Pharmacotherapy DocToonPage PDF
Pharmacotherapy DocToonPage PDF
Pharmacotherapy DocToonPage PDF
Bedside Guide
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Pharmacotherapy
Bedside Guide
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Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
Section 1 Cardiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Section 2 Infectious Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Section 3 Endocrinology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Section 4 Neurology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Section 5 Gastroenterology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Section 6 Pulmonology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Section 7 Nephrology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Section 8 Rheumatology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Section 9 Psychiatry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
Section 10 Gynecology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
Section 11 Hematology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
Section 12 Critical Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
Section 13 Fluids and Electrolytes . . . . . . . . . . . . . . . . . . . . . . . . 249
Section 14 Pain Management . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
Section 15 Urology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283
vii
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Contributors
ix
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Preface
Albert Einstein is quoted as saying “If you can’t this patient is already taking? Will cost of the medi-
explain it simply, you don’t understand it well cation be a barrier?
enough.” Provision of good medical care is anything We developed this pharmacotherapy reference
but simple. The decision of which pharmacotherapy with Einstein’s words in mind. The exclusive use of
to employ in the course of patient care is one of tables and algorithms provides a structure to display
many complex decisions to be made. The clinician many complex variables in one place. We focused
must simultaneously consider a multitude of vari- on including information that is routinely clinically
ables. What are the possible benefits of the drug relevant to produce a reference that, while not com-
treatment options relative to the risk for the patient prehensive, is high yield. Inside you will find answers
presented by this disease? What does the evidence to many of the questions posed above and some
say about which treatment should be used? How clinical pearls weaved in along the way. We hope this
does the patient’s age, gender, race, or comorbid reference helps you provide the best care for your
diseases affect the choice of pharmacotherapy? patients. Any feedback to improve future editions is
What possible harm could this medicine bring to my most welcome.
patient? Are there any interactions with medicines Chris and Bob, editors
xi
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Section
1 Cardiology
1.1 Hypertension 3
1.1.1 Antihypertensive Drug Dosing 3
1.1.2 Compelling Indications and Contraindications for Antihypertensives by Class 5
1.1.3 Guideline Recommendations for Drug Therapy of Primary Hypertension Without
Compelling Indications 6
1.1.4 Estimated Antihypertensive Blood Pressure Reduction by Drug Class 7
1.1.5 Antihypertensive Precautions and Adverse Effects by Class 8
1.1.6 Selected Cardiovascular Drug Interactions 10
1.1.7 Pharmacotherapy for Acute Hypertension 12
1.3 Dyslipidemia 20
1.3.1 Approximate LDL Lowering by Statins According to the Rule of 7 20
1.3.2 Comparative Antidyslipidemic Efficacy by Drug Class 21
1.3.3 NIH NCEP Adult Treatment Panel III LDL Cholesterol Goals 21
1.3.4 Antidyslipidemic Drug Dosing 22
1.3.5 Adverse Effects of Antidyslipidemic Drugs 23
1.4 Arrhythmias 24
1.4.1 Management Algorithm for Atrial Fibrillation 24
1.4.2 Rate and Rhythm Control Agents for Atrial Fibrillation 25
1.4.3 Antithrombotic Agents for Atrial Fibrillation 25
1.4.4 Guideline Recommendations for Antithrombotic Therapy for Primary Stroke
Prevention in Atrial Fibrillation 26
1.4.5 Antiarrhythmic Drug Indications and Dosing 27
1.4.6 Antiarrhythmic Drug Adverse Effects 28
1.5 Heart Failure 29
1.5.1 Pharmacotherapy for Heart Failure with Reduced LVEF 29
1.5.2 Digoxin Dosing for Heart Failure 32
1.5.3 Pharmacotherapy for Special Situations in Heart Failure Patients 33
1.5.4 Diuretic Algorithm for Treatment of Volume Overload in Acute Decompensated
Heart Failure 34
1.5.5 Pharmacotherapy for Acute Decompensated Heart Failure 35
A b b r e v i at i o n s
AAD Antiarrhythmic drug ESC European Society of Cardiology
ACC American College of Cardiology GFR Glomerular filtration rate
ACEI Angiotensin-converting enzyme HCTZ Hydrochlorothiazide
inhibitor HF Heart failure
ACS Acute coronary syndrome HR Heart rate
Afib Atrial fibrillation HTN Hypertension
AHA American Heart Association LVEF Left ventricular ejection fraction
AKI Acute kidney injury MI Myocardial infarction
ARA Aldosterone receptor antagonist NCEP National Cholesterol Education
ARB Angiotensin receptor blocker Program
BB Beta blocker NDCCB Non-dihydropyridine calcium channel
BP Blood pressure blocker
12
Clinical Situation Definitions and Goals Treatment
SECTION 1 | Cardiology
Hypertensive urgency • Definition: SBP ≥180 mm Hg or DBP ≥120 mm Hg • If on antihypertensives: Resume medications if noncompliant, increase doses of existing
and no symptoms of end-organ damage medications if not on max dose, add additional agent if needed
• Goal: Reduce to <160/100 over several hours or days • If not on antihypertensives: No evidence for superiority of any agent (Cochrane Database
(JAMA. 2003;289:2560) Sys Rev. 2008, Issue 1), short-acting agents such as captopril or labetalol are preferable
due to rapidity of onset and ease of titration, can transition to longer acting agent once at
goal, consider compelling indications and contraindications for long-term therapy
(see Table 1.1.2), avoid short-acting nifedipine due to risk of reflex tachycardia
Hypertensive • Definition: SBP ≥180 mm Hg or DBP ≥120 mm Hg • Treatment based on specific emergency (see below)
emergencies and symptoms of end-organ damage • In general, evidence in support of specific treatments is poor
• Goal and treatment vary by organ involvement • Avoid nitroprusside or enalaprilat if AKI
Hypertensive • Definition: Hypertensive emergency with papilledema • IV antihypertensives such as labetalol, nitroprusside, or nicardipine
encephalopathy or retinal hemorrhage and mental status changes, may • Avoid nitroprusside if AKI
(without stroke) also have AKI and proteinuria
• Goal: Reduce SBP by 15–25% of the presenting value
Ischemic stroke • Goal: <220/120 mm Hg or <185/110 mm Hg if t-PA • IV labetalol, nicardipine, or NTG
is to be administered (Stroke. 2007;38:1655)
Acute pulmonary • Goal: Improve symptoms of congestion and dyspnea, • IV NTG or nitroprusside along with loop diuretic
edema and improve LVEF • Avoid BB or hydralazine
Aortic dissection • Goal: Reduce SBP <120 mm Hg and HR <60 bpm • IV BB plus vasodilator such as NTG or nicardipine
Pregnancy • Goal: Maintain SBP 140–160 mm Hg, DBP • IV labetalol or nicardipine
90–105 mm Hg (Am J Obstet Gynecol. 2000;183:S1) • Nitroprusside and ACEIs contraindicated
Adrenergic crises • Definition: Disorders associated with high sympathetic • IV phentolamine drug of choice, phenoxybenzamine PO once stable and until resolution, start
outflow, such as cocaine use, pheochromocytoma or 10 mg BID, if needed for long term, titrate dose every few days as needed (max 100 mg/d)
clonidine withdrawal • Clonidine for clonidine withdrawal; if plan to d/c clonidine, taper by reducing dose by 50%
every 3 days
• Avoid BBs due to unopposed alpha stimulation
a
See Tables 1.1.1 and 12.4 for dosing of PO and IV antihypertensives, respectively.
TABLE 1.2.1 Pharmacotherapy for Chronic Stable Angina and Primary Prevention of ACS
Class Drug/Class Indications Dosing Comments
Antiplatelets Aspirin Primary prevention 81–325 mg QD • The potential benefit of aspirin for prevention of ischemic events must be
Clopidogrel (Plavix) Primary prevention 75 mg QD weighed against the risk of bleeding (see 1.2.2)
• Clopidogrel may be substituted for patients intolerant of aspirin
Antianginals BBs Stable angina See Table 1.1.1 • Cardioselective BB or CCB (diltiazem, amlodipine, or felodipine) preferred,
Ca++ channel blockers Stable angina See Table 1.1.1 BB and CCB efficacy similar; ACC/AHA recommends BB first line due to
post-MI efficacy (J Am Coll Cardiol. 2007;50:2264)
SL NTG Stable angina PRN 0.4 mg PRN • Add second agent from another class (BB, CCD or LA nitrate) if continued
Isosorbide Stable angina See Table 1.1.1 symptoms on monotherapy
• BB + ACE/ARB if reduced LVEF
ACEI/ARB Stable angina with See Table 1.1.1
• CCB or isosorbide preferred for variant angina
reduced LVEF
• Ranolazine does not effect BP; consider for patients who fail other
Ranolazine (Ranexa) Stable angina 500–1,000 mg BID therapies or for whom other antianginals are limited by hypotension, see
Table 1.1.6 for drug interactions
Lipid-lowering Statins Primary prevention See Tables 1.3.1 and 1.3.5 • US National Institutes of Health NCEP approach is to treat LDL target
13
14
SECTION 1 | Cardiology
TABLE 1.2.2 Aspirin Efficacy and Harms in Primary Prevention
Cohort GI Bleeding Risk Estimated Events Prevented Per 1,000 Patients by 10-Year Event Risk
(Event Measure) Age Group (Events Per 1,000) 1% Risk 5% Risk 10% Risk 15% Risk 20% Risk
Males 45–59 years 8 3.2 16 32 48 64
(MIs prevented per 60–69 years 24
1,000 men)
70–79 years 36
Females 55–59 years 4 1.7 8.5 17 25.5 34
(strokes prevented per 60–69 years 12
1,000 women)
70–79 years 18
Source: US Preventive Services Task Force. Aspirin for the Prevention of Cardiovascular Disease: Recommendation Statement. AHRQ Publication No. 09–05129-EF-2, March 2009.
Agency for Healthcare Research and Quality, Rockville, MD. http://www.uspreventiveservicestaskforce.org/uspstf09/aspirincvd/aspcvdrs.htm
1.2 | Ischemic Heart Disease 15
Early PCI planned (≤12 h Delayed PCI planned No PCI planned (e.g.,
from hospital presentation), (>12 h from hospital low-risk patient)
high-risk patient presentation)
Initial pharmacotherapy for non-ST-segment elevation ACS. (ACE, ARB, ACS, CABG, IV, intravenous; NTG, PCI,
SC, subcutaneous; SL, UFH).
a
Enoxaparin, UFH, fondaparinux plus UFH, or bivalirudin for early invasive strategy; enoxaparin or
fondaparinux if no angiography/PCI planned; fondaparinux or bivalirudin preferred if high risk of bleeding;
UFH preferred if patients going for CABG.
b
For patients unlikely to undergo CABG.
c
May require an IV supplemental dose of enoxaparin.
d
May require an IV supplemental dose of UFH.
e
For signs and symptoms of recurrent ischemia.
f
SC enoxaparin or UFH can be continued at a lower dose for venous thromboembolism prophylaxis.
Reprinted with permission from Spinler SA. Evolution of antithrombotic therapy used in acute coronary syndromes.
In: Richardson MM, Chessman KH, Chant C, Cheng JWM, Hemstreet BA, Hume AL, et al., eds. Pharmacotherapy
Assessment Program. 7th ed. Cardiology. Lenexa, KS: American College of Clinical Pharmacy; 2010:97–124.
16 SECTION 1 | Cardiology
β-blocker (oral or IV), statin, ACE inhibitor (or ARB), eplerenone (or spironolactone)d
Initial pharmacotherapy for ST-segment elevation myocardial infarction. (ACS, CABG, IV, NTG, PCI, SL, UFH).
a
For at least 48 hours.
b
See Table 1.2.5 for dosing and specific types of patients who should not receive enoxaparin.
c
For the duration of hospitalization, up to 8 days.
d
For selected patients, see Table 1.2.5.
Reprinted with permission from Spinler SA. Evolution of antithrombotic therapy used in acute coronary
syndromes. In: Richardson MM, Chessman KH, Chant C, Cheng JWM, Hemstreet BA, Hume AL, et al.,
eds. Pharmacotherapy Assessment Program. 7th ed. Cardiology. Lenexa, KS: American College of Clinical
Pharmacy; 2010:97–124.
1.2 | Ischemic Heart Disease 17
(Continued)
18 SECTION 1 | Cardiology
TABLE 1.3.3 NIH NCEP Adult Treatment Panel III LDL Cholesterol Goals
LDL Level at LDL Level at Which to
Which to Initiate Consider Drug Therapy
Risk Category LDL Goal (mg/dL) TLC (mg/dL) (mg/dL)
High risk: CHD or CHD risk <100 mg/dL (optional ≥100 ≥100
equivalents goal: <70)
(10-year risk >20%) (<100 mg/dL; consider
drug options)a
Moderately high risk: 2+ risk <130 ≥130 ≥130
factors
(10-year risk >10–20%) (100–129: consider drug
options)
Moderate risk: 2+ risk factors <130 ≥130 ≥160
(10-year risk <10%)
Lower risk: 0–1 Risk factorb <160 ≥160 ≥190
(160–189: LDL-lowering
drug optional)
LDL indicates low-density lipoprotein; CHD, coronary heart disease.
Reproduced with permission from Talbert RL. Dyslipidemia. In: Talbert RL, DiPiro JT, Matzke GR, Posey LM,
Wells BG, Yee GC, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill;
2011:chap 28. http://www.accesspharmacy.com/content.aspx?aID=7974214. Accessed June 5, 2012,
Table 28–8, page 372.
a
Some authorities recommend use of LDL-lowering drugs in this category if an LDL cholesterol level of
<100 mg/dL cannot be achieved by TLC. Others prefer use of drugs that primarily modify triglycerides
and HDL (e.g., nicotinic acid or fibrates). Clinical judgment also may call for deferring drug therapy in this
subcategory.
b
Almost all people with 0–1 risk factor have a 10-year risk <10%; thus, 10-year risk assessment in people
with 0–1 risk factor is not necessary.
22 SECTION 1 | Cardiology
1.3 | Dyslipidemia
Bile acid sequestrants • Constipation, abdominal pain, flatulence, nausea • Fecal impaction, intestinal obstruction (uncommon)
(up to 30%) • Fat-soluble vitamin deficiency (uncommon-large doses, long duration, mostly
• Steatorrhea (uncommon) children)
• Osteoporosis (rare, long-term use)
Ezetimibe • Diarrhea (2.5–4%), arthralgia (2.6–3%), URI • Anaphylaxis, angioedema (rare)
symptoms • Pancreatitis, hepatitis (0.5–3% elevated LFTs), cholelithiasis (uncommon)
• Myalgia (3.8%)
23
24 SECTION 1 | Cardiology
Atrial fibrillation/flutter
a
If AF <48 hours, anticoagulation prior to cardioversion is unnecessary; may consider TEE if patient has risk
factors for stroke.
b
Ablation may be considered for patients who fail or do not tolerate 1 AAD.
c
Chronic antithrombotic therapy should be considered in all patients with AF and risk factors for stroke
regardless of whether or not they remain in sinus rhythm.
Reproduced with permission from Sanoski CA, Bauman JL. The arrhythmias. In: DiPiro JT, Talbert RL, Matzke
GR, Posey LM, Wells BG, Yee GC, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY:
McGraw-Hill; 2011:chap 25, Figure 25–5, page 284
1.4 | Arrhythmias 25
TABLE 1.4.2 Rate and Rhythm Control Agents for Atrial Fibrillation
Drug Comments
Rate Control
BBs • BBs or NDCCBs preferred for most patients with persistent
or permanent afib, diltiazem supressed heart rate better than
carvedilol, metoprolol, or verapamil in a small prospective trial
(Am J Cardiol. 2013;111:225.)
NDCCBs (diltiazem or verapamil) • Avoid NDCCBs in HF with reduced LVEF; avoid IV NDCCBs
or BBs in patients with hypotension or acute HF (Circulation.
2006;114:e257.)
Digoxin • Digoxin effect on rate control delayed average 9.5 h after
initiation (Am J Cardiol. 1993;72:567.); digoxin induce rate
control abrogated by sympathetic stimulation during exercise
(Drugs. 2003;63:1489)
• Consider adding digoxin to BB or NDCCB if rate not controlled
with a single agent (Circulation. 2006;114:e257.)
Rhythm Control
Amiodarone • Amiodarone superior to flecainide, propafenone, and sotalol in
preventing afib recurrence (N Engl J Med. 2000;342:913)
Dronedarone • Amiodarone preferred if concurrent HF; sotalol or dronedarone
preferred if concurrent ischemic heart disease (Europace.
Dofetilide
2010;12:1360)
Flecainide • Avoid flecainide and propafenone if concurrent ischemic
heart disease due to proarrhythmia risk (N Engl J Med.
Propafenone 1991;324:781); avoid dronedarone in advanced HF due to
higher death rates (N Engl J Med. 2008;358:2678.)
Sotalol • Amiodarone is slightly more effective than dronedarone but
dronedarone may have fewer side effects (J Cardiovasc
Electrophysiol. 2010;21:597; J Am Coll Cardiol. 2009;54:1089)
(Continued)
TABLE 1.4.3 Antithrombotic Agents for Atrial Fibrillation (Continued)
Drug Dosing Comments
Anticoagulants
Warfarin Dose to target INR: • Dabigatran was better than warfarin
• 2–3 nonvalvular afib for prevention of stroke (RR 0.73, 95%
• 2–3 aortic bileaflet mechanical CI 0.52–0.81) with similar bleeding
valve outcomes in patients with intermediate
• 2.5–3.5 all other mechanical stroke risk (mean CHADS2 = 2.1) (N Engl J
valves Med. 2010;363:1875)
Dabigatran (Pradaxa) 150 mg BID if CrCl >30 mL/min • Rivaroxaban was noninferior to warfarin
150 mg tablets for both efficacy and bleeding end
75 mg BID if CrCl 15–30 mL/min points in patients with high stroke risk
Rivaroxaban (Xarelto) 20 mg QD if CrCl >50 mL/min (mean CHADS2 = 3.5) (N Engl J Med.
15 and 20 mg tablets 2011;365:883)
15 mg QD if CrCl 15–50 mL/min
• Apixiban was similar to warfarin for
Give with evening meal prevention of ischemic stroke (HR
Apixiban (Eliquis) 2.5 5 mg BID 0.92 95% CI 0.74–1.13) with lower
amd 5 mg tablets hemorrhagic stroke (0.24% vs 0.47%,
2.5 mg BID if age ≥80, weight
p<0.001, N Engl J Med. 2011;365:92)
≤60 kg or SCr ≥1.5 mg/dL
Yes No
Yes No
2 Infectious Diseases
A b b r e v i at i o n s
ABLC Amphotericin B lipid complex IE Infective endocarditis
ABM Acute bacterial meningitis LAMB Liposomal amphotericin B
AUC Area under the curve MIC Minimum inhibitory concentration
CAP Community-acquired pneumonia MRSA Methicillin-resistant Staphylococcus
CDI Clostridium difficile infection aureus
40
Recommended Dosing for Susceptible Organisms
41
(Continued)
TABLE 2.1.2 Dosing Regimens for Commonly Selected Intravenous Antimicrobials (Continued)
42
Recommended Dosing for Susceptible Organisms
43
44
SECTION 2 | Infectious Diseases
TABLE 2.1.3 Alternative Pharmacokinetic–Pharmacodynamic Dosing Strategies for Commonly Selected Intravenous
Antimicrobialsa
MIC (mg/L)
Class/Drugs ≤0.5 1 2 4 8 16
PCNsb
Pipercillin/tazobactam 2.25 g Q 8 h (4 h) 2.25 g Q 8 h (4 h) 2.25 g Q 8 h (4 h) 3.375 g Q 8 h (4 h) 3.375 g Q 8 h (4 h) 3.375 g Q 8 h (4 h)
4.5 g Q 8 h (0.5 h) 4.5 g Q 8 h (0.5 h) 4.5 g Q 8 h (0.5 h) 13.5 g (24 h) 13.5 g (24 h)
Cephalosporinsc
Cefazolin 1 g Q 8 (0.5 h) 1 g q8 (0.5 h) 2 g Q 8 h (0.5 h) — — —
3 g (24 h) 4 g (24 h) 6 g (24 h)
Cefepime 1 g Q 12 h (0.5 h) 1 g Q 8 h (0.5 h) 1 g Q 8 h (3 h) 2 g Q 8 h (3 h) 2 g Q 8 h (3 h) —
2 g Q 12 h (0.5 h) 2 g Q 8 h (0.5 h)
Carbapenemsd
Meropenem 500 mg Q 8 h (1 h) 500 mg Q 8 h (3 h) 500 mg Q 8 h (3 h) 1 g Q 8 h (3 h) — —
500 mg Q 6 h (1 h) 1 g Q 8 h (1 h)
Aminoglycosidese
Amikacin 10 mg/kg Q 24 h (1 h) 10 mg/kg Q 24 h (1 h) 10 mg/kg Q 24 h (1 h) 15 mg/kg 20 mg/kg —
Q 24 h (1 h) Q 24 h (1 h)
45
46
TABLE 2.1.4 Dosing Regimens for Commonly Selected Oral Antimicrobials
47
TABLE 2.1.5 Common Antimicrobial Adverse Effects and Monitoring
48
Ciprofloxacin/levofloxacin
Gentamicin/tobramycin
Imipenem/meropenem
Nafcillin/oxacillin
Aminopenicillins
Metronidazole
Azithromycin
Moxifloxacin
Clindamycin
Vancomycin
Daptomycin
Ceftriaxone
Tigecycline
Ertapenem
Cefepime
Amikacin
Cefazolin
Linezolid
PCN G
Daily neuro exam to monitor for X X X X
neurotoxicity
→ Altered mental status with X X X
excessive dosing
→ Seizures with excessive dosing X X X
Tinnitus and/or hearing loss X X X
ECG at baseline and follow-up if X X X
necessary
→ QTc interval if given with other X X X
QTc-prolonging drugs
Diarrhea and/or GI upset X X X X X X X X X X X Xa Xb
Antibiotic-associated colitis/CDI X X X X
ALT/AST/AlkP at baseline and weekly X X
→ Acute cholestatic liver injury X X X
→ Acute hepatocellular necrosis X
BUN/SCr at baseline and every X X X X X X X X X X X X
1–3 days
→ Acute kidney injury due to acute X X X
49
50
SECTION 2 | Infectious Diseases
TABLE 2.1.6 Susceptibility Breakpoint MIC (mg/L) Interpretive Criteria for Common Pathogensa,b
Pseudomonas
Enterobacteriaceaec Enterococcus spp. Aeruginosa Staphylococcus spp.d Streptococcus Pneumoniae
Class/Drugs CLSI EUCAST CLSI EUCAST CLSI EUCAST CLSI EUCAST CLSI EUCAST
PCNs
Ampicillin ≤8 ≤8 ≤8 ≤4 ≤0.25 ≤0.125 ≤2 ≤0.5
Amoxicillin ≤8 ≤4 ≤0.125 ≤2 ≤0.5
Ampicillin/sulbactam ≤8 ≤8 ≤4 ≤8 ≤0.5
Amoxicillin–clavulanate ≤8 ≤8 ≤4 ≤4 ≤2 ≤0.5
Nafcillin ≤2
Oxacillin (S. aureus) ≤2 ≤2
Oxacillin (S. epidermidis) ≤0.25 ≤0.25
PCN (non-CNS)e ≤0.125 ≤0.125 ≤2 ≤2
PCN G (CNS)f ≤0.06 ≤0.06
PCN VK ≤0.06
Piperacillin–tazobactamg ≤16 ≤8 ≤4 ≤16 ≤16 ≤8
Cephalosporins
Cefazolin ≤2 ≤8
Cefepime (non-CNS)e ≤8 ≤1 ≤8 ≤8 ≤8 ≤1 ≤1
Cefepime (CNS)f ≤0.5
Cefotaxime (non-CNS)e ≤1 ≤1 ≤8 ≤1 ≤0.5
Cefotaxime (CNS)f ≤0.5
Ceftriaxone (non-CNS)e ≤1 ≤1 ≤8 ≤1 ≤0.5
Ceftriaxone (CNS)f ≤1 ≤0.5
51
52
SECTION 2 | Infectious Diseases
TABLE 2.1.6 Susceptibility Breakpoint MIC (mg/L) Interpretive Criteria for Common Pathogensa,b (Continued)
Pseudomonas
Enterobacteriaceaec Enterococcus spp. Aeruginosa Staphylococcus spp.d Streptococcus Pneumoniae
Class/Drugs CLSI EUCAST CLSI EUCAST CLSI EUCAST CLSI EUCAST CLSI EUCAST
Other
Clindamycin ≤0.5 ≤0.25 ≤0.25 ≤0.5
Daptomycin ≤4 ≤1 ≤1
Linezolid ≤4 ≤4 ≤4 ≤2 ≤2
Vancomycink ≤4 ≤4 ≤2 ≤2 ≤1 ≤2
a
This table should NOT be used to compare potencies across antimicrobials. MIC breakpoints are drug-organism specific and antimicrobials have different PK properties.
b
CLSI, EUCAST.
c
Includes Escherichia coli, Klebsiella spp., Proteus spp., Enterobacter, Citrobacter, Serratia.
d
If identified as MSSA, considered susceptible to amoxicillin–clavulanate, ampicillin–sulbactam, piperacillin–tazobactam, all cephalosporins and all carbapenems.
e
Breakpoints applied to isolates NOT obtained from CSF in cases of CNS infections.
f
Breakpoints applied to isolates obtained from CSF in cases of CNS infections.
g
Penicillin-susceptible enterococci are also susceptible to imipenem, meropenem, and piperacillin—tazobactam.
h
Meropenem susceptibility breakpoint for S. pneumoniae isolate obtained from CSF in cases of CNS infections is ≤0.25 mg/L.
i
Ciprofloxacin and levofloxacin breakpoints should only be used for enterococci isolated from urine cultures.
j
Not recommended as monotherapy for the treatment of serious Staphylococcus infections.
k
Susceptibility breakpoint for coagulase-negative Staphylococcus is ≤4 mg/L.
FIGURE 2.2.1 Osteomyelitis Osteomyelitis suspected
Confirm infection Diagnostic tests/workup1,2 Empiric treatment Reevaluate/monitor 2,3 Streamline/narrow therapya
S/S: Local erythema, X-ray: Sensitivity 15–55% Etiology 2 Downtrending weekly 6–8 weeks of therapy
swelling, pain, tissue Specificity 70% CRP may indicate May consider 4 weeks in
necrosis overlying response children with acute
Usual pathogen:
bone, exposed bone, hematogenous osteo
MRI: Sensitivity 80–90% Staphylococcus aureus (>60%)
sinus tract Surgically debride
Specificity 60–90%
53
3
Lancet. 2004;364:369.
FIGURE 2.2.2 Septic Arthritis
54
Septic arthritis suspected
(Continued)
55
FIGURE 2.2.3 Catheter-Related Bloodstream Infections (Continued)
56
SECTION 2 | Infectious Diseases
Uncomplicated: Treatment c Vancomycin
1. Negative blood cx <72 h
2. Afebrile <72 h May consider adding
3. No intravascular hardware echinocandin or
4. No active malignancy fluconazole if Candida
5. Immunocompetent is suspected
Vancomycin
57
(Continued)
FIGURE 2.2.4 Infective Endocarditis (Continued)
58
Consider surgical Viridans streptococci
intervention: native valve:
a
Oscillating intracardiac mass on valve, abscess, or new partial dehiscence of prosthetic valve.
b
Two blood cultures drawn >12 h apart or 3 of 4 positive blood cultures drawn >1 h apart
c
See chapter 2.1 for dosing and monitoring.
d
Daptomycin is noninferior to therapy for right-sided IE (N Engl J Med. 2006;355:653).
e
If PCN MIC ≥0.25 → Duration is 6 weeks of b-lactam AND gentamicin.
1
Clin Infect Dis. 2000;30:633.
2
JAMA. 2005;293:3012.
3
J Am Coll Cardiol. 2008;52:1.
4
Circulation 2005;111:e394.
FIGURE 2.2.5 Clostridium difficile Infection
Clostridium difficile infection (CDI) suspected
59
1
Infect Control Hospital Epidemiol. 2010;31:431.
FIGURE 2.2.6 Intra-Abdominal Infections
60
Intra-abdominal infection (IAI) suspected
S/S: Abdominal Imaging: Abdominal CT has ↑ Drain-infected site Follow up culture and Duration is 4–7 days
discomfort, loss of sensitivity and specificity vs. in all cases. Only 1° susceptibility results for culture-confirmed
appetite, N/V, bloating, ultrasonography peritonitis treated infection
fever, leukocytosis (94/94% vs. 83/93%) with antibiotics alone.
>50% IAI are
Refer to Figure 2.2.7 polymicrobial infections 24-h duration:
PE: Abdominal guarding, Cultures: Obtain >1 mL of 1. Acute stomach or
abdominal distention fluid or >1 g tissue for proximal jejunum
aerobic/anaerobic cultures Infection should perforationsa
resolve within 4–5 2. Bowel injury due to
Assess severity: Mild-to- days of antimicrobial trauma or intra-op
moderate infections include therapy and source contamination
perforated appendicitis or acute control: repaired within 12 h
diverticulitis ↓ peritoneal irriation 3. Acute appendicitis
Normal bowel function without perforation,
Resolution of abscess or
Severe or high risk: leukocytosis peritonitisb
1. APACHE II ≥15 Defervescence
a
2. Age ≥65
In absence of acid-reducing therapy or malignancy AND source 3. Serum albumin <3.0
control within 24 h. 4. Diffuse peritonitis
b
Prophylactic antibiotics in acute pancreatitis is not recommended 5. Inadequate source control
prior to culture-confirmed infection. 6. Immunocompromised
1
Clin Infect Dis. 2010;50:133.
2.2 | Bacterial Disease Treatment by Organ System 61
Severe or high-risk,
and enterococcus risk:
Imipenem–cilastatin,
meropenem, OR
piperacillin–tazobactam
a
Not observed in cholecystitis or cholangitis unless biliary-enteric anastomosis present; ↑ risk in distal small
bowel, appendiceal, colonic, paralytic ileus, or proximal GI perforations with obstruction.
b
Not pathogenic in biliary infections; ↑ risk with post-op infection, previous receipt of cephalosporins,
immunocompromised, valvular heart diseases, or intravascular devices.
c
Presence of invasive device, history of surgery, hospitalization, residence in long-term care facility, or
dialysis within 12 months, onset >48 h of hospital admission.
d
See chapter 2.1 for dosing and monitoring.
e
Fluoroquinolones should only be used if antibiogram shows >90% susceptibility to E. coli.
FIGURE 2.2.8 Acute Bacterial Meningitis
62
Acute bacterial meningitis (ABM) suspected
S/S: Neck stiffness, HA, CT head Perform PCN G and cefotaxime/ S. pneumoniae (10 days)
photophobia, fever, CT prior to lumbar puncture See Figure ceftriaxone MIC testing if IF PCN MIC:
malaise, seizures is recommended: 2.2.10 Streptococcus pneumoniae or <0.125: PCN G
(children>adults) 1. Immunocompromised N. meningitidis isolated 0.125–1: Third-generation
Meningococcal disese: 2. History of CNS disease cephalosporins
1. Purpuric and petechial 3. New onset seizure ≥2: Vancomycin +
skin lesions 4. Papilledema May narrow therapy for third-generation cephalosporins
2. Waterhouse– 5. Impaired consciousness community-acquired meningitis
Friderichsen syndrome 6. Focal neurologic deficit based on Gram stain results alone
N. meningitidis (7 days)
CSF analysis and culture IF PCN MIC:
PE: Nuchal rigidity, Age <1 month GPC in
Lumbar puncture sent for chemistry, <0.125: PCN G
presence of Kernig's or pairs/chains or gram-positive
hematology with cell count, Gram 0.125–1: Third-generation
Brudzinki's signs (poor rods PCN G or ampicillin +/−
stain, and culture (see Figure 2.2.9 cephalosporins
sensitivity), bulging gentamicin
for interpretation of results) Gram
fontanelle in neonates
stain sensitivity is 75–90% if done
BEFORE antibiotic administration Listeria or S. agalactiae
Age >1 month–50 years (21 days)
GPC in pairs/chains Ampicillin or PCN G
Vancomycin + third-generation
cephalosporins (cefotaxime or
ceftriaxone)
Age >1 month gram–negative H. influenzae (7 days)
PCR testing of CSF diplococci or gram Ampicillin or third-generation
1. Enterovirus RT-PCR (sensitivity negative rods cephalosporins
86–100%; specificity 92–100%) Third-generation cephalosporins
2. If no organisms identified on (cefotaxime or ceftriaxone)
Gram stain, consider Neisseria
meningitidis, streptococcus, and
63
64
SECTION 2 | Infectious Diseases
TABLE 2.2.9 Cerebrospinal Fluid Analysis
Normal Bacterial Viral Fungal TB
WBC <5 1,000–5,000 100–1,000 40–400 100–500
Diff% >90 monos ≥80 PMNs 50 lymphs >50 lymphs >80 lymphs
Protein <50 100–500 30–150 40–150 <40–150
Glucose 50–60% of blood glucose <60% of blood glucose <30–70 <30–70 <30–70
FIGURE 2.2.10 Empiric Therapy for ABM
Empiric Therapy for ABM
65
d
Can be used without affecting vancomycin CSF concentration (Clin Infect Dis. 2007;44:250).
FIGURE 2.2.11 Acute Otitis Media
66
Otitis media suspected
Sources: Wald ER. Acute otitis media and acute bacterial sinusitis. CID. 2011;52(S4):S277–S283; Gould JM, Matz PS. Otitis media. Pediatr Rev. 2010;31:102–116.
a
~35–45% of H. influenzae and 100% of M. catarrhalis produce b-lactamase.
b
See Figure 2.1.4 for dosing.
c
Nonsevere illness is mild otalgia and temperature <39°C in the past 24 h.
d
A certain diagnosis meets all three criteria: (1) rapid onset, (2) signs of middle ear effusion, and (3) signs and symptoms of middle ear inflammation.
e
Treatment failure is defined as (1) persistent or recurrent ear pain or fever or both after 48–72 h or (2) development of a suppurative complication (Pediatr Rev. 2010;31:102).
67
FIGURE 2.2.12 Pharyngitis
68
Pharyngitis suspected
S/S: Sudden onset sore throat (may be Rapid antigen detection Fever and constitutional If obtained, use cultures
severe), fever, headache, abdominal test (RADT): Test has symptoms disappear to narrow therapy
pain, nausea, vomiting 95–98% specificity and spontaneously within 3–4
75–85% sensitivity, thus, days of onset, even without
more prone to false negatives antibiotic therapy Treat for 10 days unless
PE: Pharyngeal erythema and exudates, benzathine PCN is used
tender, and enlarged anterior cervical (one-time dose)
nodes, palatal petechiae, tonsilar Throat swab culture: Faster resolution of signs
hypertrophy, scarlet fever rash Recommended for children, and symptoms may be
adolescents, parents, and observed in patients who
schoolteachers who have receive antibiotics
negative antigen tests or in
Streptococcal vs. viral the setting of an outbreak
Differentiating is key in determining if
antibiotic therapy is required
Only patients with a
positive rapid strep test
or RADT should receive
antibiotics
Source: Bisno AL, et al. Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. CID. 2002;35:113–125.
69
FIGURE 2.2.13 Community-Acquired Pneumonia
70
Community acquired pneumonia (CAP) suspected
S/S: Cough, fever, sputum CXR: Dense lobar or Refer to Figure 2.2.14 Patient should be If obtained, use cultures to
production, pleuritic chest segmented infiltrates hemodynamically stable narrow therapy
pain (must have to confirm and improving clinically
diagnosis)
PE: Bronchial breath sounds, Afebrile and WBC Before discontinuing therapy,
tachycardia, tachypnea Blood culture: Not obtained decreasing patient must be
routinely as it is unlikely to • Treated for at least 5 days
Assess severity: Must alter treatment Switch from IV to PO if • Able to maintain oral intake
determine inpatient vs. criteria from above are met, • Afebrile for 48 to 72 h
outpatient treatment Sputum culture: Not and patient is able to ingest • HR <100, RR <24,
obtained routinely as it meds/has a functional GI • SBP >90, arterial O2
is hard to obtain reliable, tract • Saturation >90%
CURB-65: 1 or more
then hospitalize uncontaminated samples
(confusion, BUN >20,
RR≥30, DBP<60, ≥65 Sputum and blood cultures may be helpful in patients
years) with leukopenia, alcohol abuse, chronic liver disease,
asplenia, recent travel (2 weeks), severe obstructive/
PSI: structural lung disease, admitted to the ICU, and
Class I-II: Outpatient failed outpatient treatment
Class III-V: Inpatient
Source: Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, et al. Infectious Diseases Society of America /American Thoracic Society consensus guidelines on the
management of community-acquired pneumonia. CID. 2007;44:S27–S72.
FIGURE 2.2.14 Empiric Therapy for CAP
Empiric Therapy for CAP
Usual pathogens
Healthy and no risk Non-ICU
Streptococcus pneumoniae (70% cases),
factors for DRSP Respiratory FQd or
Haemophilus influenza, Moraxella catarrhalis,
Macrolidec or β-Lactam + macrolide
atypicals (Mycoplasma pneumoniae,
71
e
See figures 2.1.2 and 2.1.3 for dosing.
FIGURE 2.2.15 Hospital-Acquired Pneumonia /Ventilator-Associated Pneumonia
72
Hospital-acquired/ventilator-associated pneumonia (HAP/VAP) suspected
Stenotrophomonas
Treat × 14 days
Use monotherapy with
a susceptible agent
Clinical diagnosis: Treatmenta
New or progressive infiltrate
on chest x-ray and ≥2 of
the following signs: Early-onset Late-onsetb
1. Temp >38°C Ceftriaxone, Antipseudomonal β-lactamc
2. Leukocytosis or fluoroquinolones, AND aminoglycosides OR
Antipseudomonal FQd
Other labs
1. Arterial blood gas
2. Diagnostic thoracentesis
if effusion is present
a
See chapter 2.1 for dosing and monitoring.
b
Strongly consider two antipseudomonal agents if local susceptiblility to one drug is <90% and patient critically ill.
c
Imipenem-cilastatin, meropenem, doripenem.
d
Ciprofloxacin or levofloxacin.
73
FIGURE 2.2.16 Abscesses and Cellulitis
74
Cellulitis/abscess suspected
S/S: Erythema, edema, Wound culture: Usually Refer to Figure 2.2.17 Patient should be If obtained, use cultures to
warmth, inflammation, only obtained in patients hemodynamically stable and narrow therapy
lymphadenopathy, pain. who are hospitalized and if improving clinically
Deeper skin structure able to culture specimen (i.e.,
Before discontinuing therapy,
infections such as cellulitis purulent cellulitis or abscess)
Erythema and edema should patient must be treated for at
may cause fever, chills,
be receding. Fever and WBC least 5–10 days (outpatient)
and malaise
Blood culture: Obtained in decreasing or 7–14 days (inpatient)
patients with serious or long-
Assess severity: Must standing infections
Switch from IV to PO if
determine inpatient vs.
criteria from above are met
outpatient treatment
and patient is able to ingest
meds/has a functional GI
Erona classification: tract
Class I: Outpatient
Class II: Outpatient or
24-hr ER
observation
Class III: Inpatient
Class IV: ICU
a
Eron classification (J Antimicrob Chemother. 2003;52(Suppl S1):3–17)
Class I: Afebrile and healthy, other than cellulitis.
Class II: Febrile and ill-appearing, but no unstable comorbidities (PVD, DM, antibiotic use in the last 2 weeks, alcohol abuse, advanced age, chronic liver and/or renal disease, asplenia).
Class III: Toxic appearance, or at least one unstable comorbidity, or a limb-threatening infection.
Class IV: Sepsis syndrome or life-threatening infection (i.e., necrotizing fasciitis).
2.2 | Bacterial Disease Treatment by Organ System 75
Antibiotic choices
CA-MRSA: Clindamycin,
TMP/SMX, doxycycline,
minocycline, linezolid
CA-MRSA and β-hemolytic
streptococci: Clindamycin,
linezolid
Sources: (1) Eron LJ, et al. Managing skin and soft tissue infections: expert panel recommendations on key
decision points. J Antimicrob Chemother. 2003;52:S1:i3–i17; (2) Stevens DL, et al. Practice guidelines for
the diagnosis and management of skin and soft tissue infections. CID. 2005;41:1373–1406; (3) Liu C, Bayer
A, Cosgrove SE, Daum RS, Fridkin SK, et al. Clinical practice guidelines by the Infectious Diseases Society
of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.
CID. 2011;52(1):1.
a
See chapter 2.1 for dosing and monitoring.
b
Severe or extensive disease (e.g., involving multiple sites of infection) or rapid progression in
presence of associated cellulitis, signs and symptoms of systemic illness, associated comorbidities or
immunosuppression, extremes of age, abscess in an area difficult to drain (e.g., face, hand, and genitalia),
associated septic phlebitis, and lack of response to incision and drainage.
FIGURE 2.2.18 Diabetic Foot Ulcers
76
Diabetic foot ulcer suspected
+/− vancomycine
Etiologyb
Etiologyb
Moderate to severe
Patient has ≥1 of the following: Cellulitis without and open skin
• Cellulitis extends >2 cm wound or infected ulcer and β-hemolytic streptococcus, Staphylococcus aureus
• Lymphangitic streaking antibiotic naive
• Spread beneath the superficial
fascia
• Deep-tissue abcess Infected ulcer that is chronic
or was previously treated with β-hemolytic streptococcus, S. aureus,
• Gangrene
antibiotics enterobacteriaceae
Sources: (1) Eron LJ, et al. Managing skin and soft tissue infections: expert panel recommendations on key decision points. J Antimicrob Chemother. 2003;52:S1:i3–i17; (2) Lipsky
BA. Medical treatment of diabetic foot infections. CID. 2004;39(S2):S104–S114; (3) Stevens DL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue
infections. CID. 2005;41:1373–1406; (4) Lipsky BA, et al. Diagnosis and treatment of diabetic foot infections. CID. 2004;39:885–910; (5) Liu C, Bayer A, Cosgrove SE, Daum RS,
Fridkin SK, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and
children. CID. 2011;52(1):1–38.
a
Diagnosis cannot be made based on microbiological results as most open wounds are colonized.
b
Pseudomonas is usually found in ulcers that are macerated because of soaking.
c
Aerobic gram-positive: cocci: S. aureus, coagulase-negative staphylococci, enterococci.
d
See chapter 2.1 for dosing and monitoring.
77
e
Consider using vancomycin if high rates of methicillin-resistant S. aureus are found in the hospital or community.
FIGURE 2.2.19 Urinary Tract Infections
78
Urinary tract infection (UTI) suspected
S/S: Increased urinary UA: Leukocyte esterase +, Refer to Figure 2.2.20 Patient should be If obtained, use cultures
frequency, dysuria, urgency, nitrite +, bacteria present, hemodynamically stable to narrow therapy
+/– hematuria, +/– vaginal cloudy/straw colored and improving clinically
discharge/pain No need to narrow therapy
Pyelonephritis: Flank Urine culture: Only obtained Afebrile and WBC for uncomplicated UTIs,
pain, N/V, dehydration in patients with complicated decreasing since treatment usually only
UTIs. Infection if >104 cfu/mL for 3 days and cultures
If no improvement, not obtained
PE: CVA tenderness
CBC: WBC in patients with reculture urine and
complicated UTIs get blood cultures Complicated UTIs are usually
Assess severity treated for 10–14 days.
Follow-up culture should be
Uncomplicated obtained for 2 weeks after
Young (15–45 years), nonpregnant, healthy women the end of antibiotic
treatment
Complicated:
All others. Require hospitalization ifpatient severely ill
or unable to tolerate medications by mouth
Source: (1) Drekonja DM, et al. Urinary tract infections. Prim Care Clin Office Pract. 2008;35:345–367; (2) Simerville JA, et al. Urinalysis: A comprehensive review. Am Fam
Physician. 2005;71:1153–1162; (3) Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, et al. International clinical practice guidelines for the treatment of acute uncomplicated
cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. CID.
2011;52(5):e103–e120.
2.2 | Bacterial Disease Treatment by Organ System 79
Sources: (1) Drekonja DM, et al. Urinary tract infections. Prim Care Clin Office Pract. 2008;35:345–367;
(2) Simerville JA, et al. Urinalysis: A comprehensive review. Am Fam Physician. 2005;71:1153–1162;
(3) Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, et al. International clinical practice guidelines for the
treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious
Diseases Society of America and the European Society for Microbiology and Infectious Diseases. CID.
2011;52(5):e103–e120.
a
See chapter 2.1 for dosing and monitoring.
b
UTIs are considered complicated if they occur in men, the elderly (>65 years), include sites other than the
bladder, or the patient has “predisposing factors”. Such factors include diabetes, congenital abnormalities
of the urinary tract, a stone, indwelling catheter, prostatic hypertrophy, obstruction, or neurologic deficit that
interfere with the normal flow of urine or voiding mechanism.
80
SECTION 2 | Infectious Diseases
TABLE 2.3.1 Antifungal Formulations and Dosing
Drug Brand Name Available Formulations General Dose Range
Azoles
Fluconazole Diflucan Oral (tablets and suspension) 100–800 mg once daily
Intravenous (6–12 mg/kg/day for systemic infections)
Itraconazole Sporanox Capsules and oral solution 200 mg QD to three times dailya,b
(solution contains cyclodextrin)
Posaconazole Noxafil Oral suspension 200 mg three to four times daily
400 mg once to twice dailyc
Voriconazole Vfend Oral (tablet and suspension) 6 mg/kg IV every 12 h for 24 h, then 4 mg/kg IV (200–300 mg PO) every
Intravenous (IV formulation contains cyclodextrin) 12 hd
Echinocandins
Anidulafungin Eraxis Intravenous Invasive candidiasis—200 mg IV on day 1, then 100 mg IV every 24 h
Esophageal candidiasis—100 mg IV on day 1, then 50 mg IV every 24 h
Caspofungin Cancidas Intravenous 70 mg IV on day 1, then 50 mg IV every 24 h
Micafungin Mycamine Intravenous Invasive candidiasis—100–150 mg IV every 24 h
Esophageal candidiasis—150 mg IV every 24 h
Prophylaxis—50 mg IV every 24 h
Polyenes
Amphotericin B Fungizone Intravenous 0.5–1.0 mg/kg IV every 24 h
deoxycholate
Amphotericin B colloidal Amphotec (ABCD) Intravenous 3–5 mg/kg IV every 24 h
dispersion
Amphotericin B lipid complex Abelcet (ABLC) Intravenous 3–5 mg/kg IV every 24 h
Liposomal amphotericin B Ambisome (LAMB) Intravenous 3–5 mg/kg IV every 24 h
Miscellaneous
Flucytosine Ancobon Oral (capsules) 25 mg/kg PO every 6 h
Terbinafine Lamisil Oral (granules and tablets) 250 mg PO once daily
a
Administer oral solution on empty stomach.
b
Administer capsules with food.
c
Administer with food (preferably a fatty meal).
d
Administer tablets and suspension on empty stomach.
83
84
SECTION 2 | Infectious Diseases
TABLE 2.3.3 Treatment of Superficial Fungal Infections (Continued)
Infection Topical Therapy Systemic Therapy Comments
Tinea capitis Shampoo (ketoconazole, selenium sulfide, Terbinafine 250 mg QD × 4–8 weeks • Shampoo alone may be used in
povidone-iodine) in conjunction with oral asymptomatic carriers
therapy
Onychomycosis Ciclopirox 8% nail lacquer, apply nightly for up • Fluconazole 50 mg QD or 300 mg once • Usually secondary to dermatophytes,
(fingernails) to 48 weeks weekly for 6 (finger) or 12 (toe) months may be caused by candida in
• Itraconazole 200 mg QD × 6 (finger) or 12 immunosuppressed patients
(toe) weeks or 200 mg BID × 1 week and • More common in toenails than fingernails
repeated 4 weeks after initial treatment
(finger) or repeated at 4 and 8 weeks (toe)
• Terbinafine 250 mg QD × 6 (finger) or
12 (toe) weeks
Sources: (1) Pappas PG, Kauffman CA, Andes D, Benjamin DK, Calandra TF, (2) Edwards JE, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the
Infectious Diseases Society of America. Clin Inf Dis. 2009;48:503–535; (3) Brown TE, Dresser LD, Chin TW. Superficial fungal infections. In: Dipiro JT, Talbert RL, Matzke GR, Posey
LM, Wells BG, Yee GC, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill; 2011:chap. 29.
TABLE 2.3.4 Treatment of Invasive Fungal Infections
Condition Therapy Comments
Aspergillosis
Invasive pulmonary Primary: • Treatment of other aspergillosis conditions (e.g., sinus,
aspergillosis • Voriconazole 6 mg/kg every 12 h for 1 day, then 4 mg/kg every 12 h (oral dose tracheobronchial, CNS, endocarditis, endophthalmitis)
200–300 mg) similar to invasive pulmonary aspergillosis
Alternative: • Prolonged therapy and the use of other modalities may
• LAMB 3–5 mg/kg/day be required
• ABLC 5 mg/kg/day
• Caspofungin 70 mg loading dose, then 50 mg/day
• Posaconazole 200 mg QID, then 400 mg BID once stable
Empiric or preemptive therapy • LAMB 3 mg/kg/day
• Caspofungin 70 mg loading dose, then 50 mg/day
• Itraconazole 200 mg/day IV or 200 mg BID PO
• Voriconazole 6 mg/kg every 12 h for 1 day, then 4 mg/kg every 12 h
(oral dose 200)
Prophylaxis Primary
Posaconazole 200 mg every 8 h
85
(Continued)
TABLE 2.3.4 Treatment of Invasive Fungal Infections (Continued)
86
Condition Therapy Comments
87
TABLE 2.3.4 Treatment of Invasive Fungal Infections (Continued)
88
Condition Therapy Comments
89
(Continued)
90
SECTION 2 | Infectious Diseases
TABLE 2.3.4 Treatment of Invasive Fungal Infections (Continued)
Condition Therapy Comments
Meningitis—maintenance • Fluconazole 200 mg/day for ≥1 year (HIV patients) or 6 months–1 year (non-HIV,
non-transplant patients)
• Fluconazole 200–400 mg/day for 6 months–1 year (transplant patients)
Pulmonary, mild-to-moderate • Fluconazole 400 mg/day for 6 months–1 year
Pulmonary, severe or • Treat as meningitis
cryptococcemia
Histoplasmosis
Acute pulmonary • Mild to moderate and symptoms >4 weeks—itraconazole 200 mg TID for 3 days, • Chronic suppressive therapy required in HIV/AIDS
then 200 mg QD or BID for 6–12 weeks patients who do not achieve immune reconstitution with
• Moderately severe or severe—lipid amphotericin B 3–5 mg/kg/day or antiretroviral therapy; this may also be needed in other
amphotericin B deoxycholate 0.7–1.0 mg/kg/day for 2 weeks, then itraconazole patients with immunosuppressive disorders and in those
200 mg/day for 12 additional weeks who relapse despite appropriate therapy
Chronic cavitary pulmonary • Itraconazole 200 mg TID for 3 days, then 200 mg BID for ≥1 year • Monitoring of itraconazole serum levels should be
• Amphotericin B deoxycholate 0.7 mg/kg/day for 12–16 weeks considered in patients being treated for chronic
pulmonary, disseminated, or CNS histoplasmosis; a
Progress disseminated • Moderately severe to severe—lipid amphotericin B 3–5 mg/kg/day for 2 weeks, random serum concentration of >1.0 mg/mL should be
then 200 mg TID for 3 days, then 200 mg BID for ≥1 year achieved
• Mild to moderate—itraconazole 200 mg TID for 3 days, then 200 mg BID for
≥1 year
CNS • Lipid amphotericin B 5 mg/kg/day for a 4–6 weeks (up to a total of 175 mg/kg),
then itraconazole 200 mg BID or TID daily for ≥1 year
TABLE 2.3.5 Antifungal Drug Interactions
Antifungal Interacting Drugs Comments
Azolesa
Fluconazole Warfarin, rifampin CYP isoenzyme inhibition by fluconazole increases with higher doses; rifampin significantly reduces
fluconazole concentrations
Itraconazole Midazolam, nisoldipine, pimozide, quinidine, Inhibitors inducers of CYP 3A4 affect metabolism of itraconazole; co-administration with drugs that
dofetilide, triazolam, lovastatin, simvastatin, prolong the QT interval may result in Torsades de pointes; rhabdomyolysis may occur with HMG CoA-
ergot alkaloids, warfarin, rifampin proton reductase inhibitors; o-administration may result in toxic concentrations of the calcineurin inhibitors
pump inhibitors H2 blockers cyclosporine tacrolimus; o-administration of proton pump inhibitors H2 blockers may significant reduce
the oral bioavailability of itraconazole
Posaconazole Sirolimus, pimozide, quinidine, lovastatin, Drugs that induce UDP-glucuronidase (phenytoin, rifampin/rifabutin, efavirenz) will significantly reduce
simvastatin, ergot alkaloids, cyclosporine, posaconazole concentrations; co-administration with drugs that prolong the QTc interval may result in
tacrolimus, midazolam, warfarin, rifampin/ Torsades de pointes; rhabdomyolysis may occur with HMG CoA-reductase inhibitors; co-administration
rifabutin, efavirenz, proton pump inhibitors, may result in toxic concentrations of the calcineurin inhibitors cyclosporine and tacrolimus; co-
and H2 blockers administration of proton pump inhibitors and H2 blockers may significantly reduce the oral bioavailability
of posaconazole
91
TABLE 2.3.5 Antifungal Drug Interactions (Continued)
92
Antifungal Interacting Drugs Comments
3 Endocrinology
A b b r e v i at i o n s
DKA Diabetic ketoacidosis GLP-1 Glucagon-like peptide-1
DM Diabetes mellitus HbA1C Hemoglobin A1C
DPP-4 Dipeptidyl peptidase-4 MNT Medical nutrition therapy
DSC Digoxin serum concentration TPOab Thyroperoxidase antibodies
FT4 Free T4 TSH Thyroid-stimulating hormone
GIP Gastric inhibitory peptide
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3.1 | Diabetes Mellitus 95
Diabetes diagnosis
Type 1 Type 2
Metformin barring
contraindications
Glycemic control?
HbA1C <7% for most
No—consider Yes—continue
add-on therapy current strategy
96
Insulin Onset Peak Duration Considerations
SECTION 3 | Endocrinology
Rapid Acting
Aspart (Novolog) 0.25–0.5 h 0.5–1.5 h <5 h • Inject immediately prior to meal (some patients dose with or
Glulisine (Apidra) after meal)
• Do not use IV: increased cost with no advantage vs. regular
Lispro (Humalog) 0.5–2 h
Short Acting
Regular 0.5–1 h 2–4 h 5–8 h • Inject ~30 min prior to eating
Intermediate
NPH (Humulin N, Novolin N) 1–2 h 4–10 h 10–18 h • Peak and duration highly variable, especially in elderly; be
aware of nocturnal hypoglycemia
Long Acting
Glargine (Lantus) 1.5–4 h No peak 24 h • Some patients do not get full 24 h effect and require BID
dosing
• Burning at injection site—pH 4.0
Detemir (Levemir) Slow steady rise ~3–4 h <0.4 units/kg highly • Administer BID for low doses (<0.4 units/kg)
variable; <24 h; • Only insulin to show (minor) weight loss vs. gain (Diabetes
>0.4 units/kg ~24 h Care. 2011;34:1487)
Combination Products
70% aspart protamine/30% aspart 0.25–0.5 h Dual peak 10–16 h • Longer-acting insulin always listed 1st
50% lispro protamine/50% lispro • Time to onset determined by faster-acting insulin; duration by
intermediate insulin
75% lispro protamine/25% lispro
70% NPH/30% regular 0.5–1 h 10–18 h
TABLE 3.1.3 Selected Non-Insulin Antihyperglycemic Agents
Class Drug (Brand) Dosing Comments
a-Glucosidase inhibitors Acarbosea (Precose) 25, 50, 25 mg QD-TID @ meals w/1st bite • MOA: Enzyme inhibitor, delays hydrolysis of complex carbohydrates
100 mg tabs of food, titrate Q 4–8 weeks; adjust • 0.5–0.8% decrease in A1C
Miglitol (Glyset) 25, 50, 100 based on 1° postprandial glucose; • Contraindications: Renal dysfunction (Scr ≥ 2 mg/dL); inflammatory bowel
mg tabs 100 mg TID max disease; GI obstruction
• AEs: Flatulence, diarrhea, abdominal pain, may avoid through slow titration;
acarbose ~14% have ↑ AST/ALT– monitor Q 3 months
• Dosing requirements may decrease compliance
Biguanide Metformina (glucophage, IR 500 mg BID; increase by 500 mg • Decrease hepatic glucose production and intestinal glucose absorption;
glucophage XL) 500, 850, Q week up to 2550 mg/day (850 increases insulin sensitivity
1,000 mg tabs; 500, 750, mg TID) • 1–2% decrease in A1C
1,000 mg XR tabs XR 500–1,000 mg/day max 2,500 • Contraindicated in renal dysfunction (Scr ≥1.5 mg/dL males, ≥1.4 mg/dL
mg/day; if not controlled with max females); acute/chronic acidosis; discontinue in AKI or if patient to receive
dose, split BID contrast
• Considered weight neutral—typically causes weight loss
• AEs: Abdominal pain, cramping, flatulence; GI effects worse with IR vs. XR;
take w/food and titrate slowly, B12 deficiency
(Continued)
97
TABLE 3.1.3 Selected Non-Insulin Antihyperglycemic Agents (Continued)
98
Class Drug (Brand) Dosing Comments
SECTION 3 | Endocrinology
D2 agonist Bromocriptine (Cycloset) 0.8 mg QAM; titrate by 0.8 mg Q • MOA: Unknown, believed to reset circadian rhythm and reverse insulin
0.8 mg tabs week up to 4.8 mg/day resistance
• 0.6–0.9% decrease in A1C
• Contraindicated with a, b agonists, azole antifungals; risk of serotonin
syndrome with serotonergic agents; caution with psychiatric history
• Extensive hepatic metabolism
• AEs: Increased CNS effects including dizziness, HA, fatigue, drowsiness;
hypotension, syncope; GI upset—take with food
DPP-IV inhibitors Linagliptin (Tradjenta) 5 5 mg QD; no renal adjustments • MOA: Inhibits enzyme responsible for metabolism of incretin hormones and
mg tabs increased [GLP-1], [GIP]
Saxagliptin (Onglyza) 2.5, 2.5–5 mg QD; • 0.5–0.8% decrease in A1C
5 mg tabs • AEs: Headache, peripheral edema, hemorrhagic pancreatitis
CrCl <50 mL/min: 2.5 mg QD • Weight neutral
Sitagliptin (Januvia) 25, 50, 100 mg QD; • Linagliptin, saxagliptin—CYP3A4 substrates; decrease saxagliptin to
100 mg tabs 2.5 mg QD w/strong 3A4 inhibitor
CrCl ≥30–50 mL/min: 50 mg QD;
CrCl <30 mL/min: 25 mg QD
GLP-1 agonists Liraglutide (Victoza) 6 mg/ 0.6 mg SQ QD × 1 week, then 1.2 mg • MOA: GLP-1 analog, increases glucose-dependent insulin secretion,
mL soln; 3 mL pen SQ QD; may titrate to 1.8 mg QD decreases glucagon secretion, delays gastric emptying and increases
Exenatide (Byetta) 250 mg/ IR–5 mg BID within 60 min of meal; satiety
mL soln; 2.4 mL = 60 IR 10 mg BID after 1 month if needed; • 0.5–1.0% decrease in A1C; 1.5–1.9% decrease in A1C –XR exenatide
doses; (Bydureon) 2 mg XR–2 mg Q week • Weight loss
soln = 1 XR dose • Contraindications: Multiple endocrine neoplasia syndrome type 2; family
CrCl <30 mL/min not recommended history of medullary thyroid carcinoma
• AEs: N/V/D, dose-related, decreases with exposure, hemorrhagic
pancreatitis, injection side irritation
• AEs: N/V/D, dose-related, decreases with exposure, hemorrhagic
pancreatitis, injection side irritation
Meglitinides Nateglinidea (Starlix) 60, 120 mg TID • MOA: Stimulates glucose-dependent insulin release
120 mg tabs • 0.5–1.5% decrease in A1C
Repaglinide (Prandin) 0.5, Initial: 0.5 mg (untreated or A1C <8%); • Weight gain (↑insulin secretion)
1, 2 mg tabs 1–2 mg (prior treatment or A1C >8%); • Take within 15–30 min of meal; skip dose if skip meal
max 4 mg/dose (16 mg/day) • AEs: Hypoglycemia
• Nateglinide—CYP 2C9/3A4 substrate; CI—conivaptan
CrCl 20–40 mL/min: initiate @ • Repaglinide—CYP3A4/2C8 substrate; CI—conivaptan; also metabolized
0.5 mg/dose via glucuronidation; CI—gemfibrozil
Sulfonylureas Glimepiridea (Amaryl) 1, 2, 1–2 mg QAM with breakfast (or 1st • MOA: Stimulates pancreatic insulin release, decreases hepatic glucose
4 mg tabs meal); max 8 mg/day production
Glipizidea (Glucotrol) 5, 10 IR–5 mg QD; 40 mg max; divide • 1–2% decrease in A1C
mg tabs doses >15 mg • Weight gain (↑insulin secretion)
• AE: Dizziness, HA, hypoglycemia (>w/↑age)
(Glucotrol XL) 2.5, 5, 10 mg XR–5 mg QD; 20 mg max • Sulfonylureas associated w/ increased CV mortality vs. diet/insulin
XR tabs CrCl <50 mL/min: decrease dose • Caution in sulfonamide allergy, G6PD deficiency
by 50% • Glimepiride, glipizide—CYP2C9 substrates, metabolites excreted in urine
• Secondary failure common with beta-cell destruction; pancreas unable to
Glyburidea (DiaBeta) 1.25, Regular tabs ≠ micronized tabs
continue insulin production
2.5, 5 mg tabs 2.5–5 mg (1.5–3 mg micronized)
(Micronase) 1.5, 3, 6 mg initial; max 20 mg/day (12 mg/day
micronized tabs micronized); max doses more effective
99
(Continued)
100
SECTION 3 | Endocrinology
TABLE 3.1.3 Selected Non-Insulin Antihyperglycemic Agents (Continued)
Class Drug (Brand) Dosing Comments
Amylinomimetic Pramlintide (Symlin, DM1–15 mg SQ just prior to meals; • MOA: Amylin analog; delays gastric emptying, centrally mediated appetite
Symlinpen 60, Symlinpen titrate Q 3 days (if nausea tolerable) suppression, decreases glucagon secretion
120) 1,000 mg/mL; 1.5 mL target 30–60 mg • 0.5–1.0% decrease in A1C
(60 pen), 2.7 mL (120 pen) DM2–15 mg SQ just prior to meals; • Weight loss (secondary to decreased intake)
injectors titrate Q 3 days (if nausea tolerable) • Decrease insulin 50% at initiation to mitigate risk of hypoglycemia
target 30–60 mg • AEs: Severe hypoglycemia, N/V, gastroparesis, HA,
• Contraindications: Gastroparesis, hypoglycemic unawareness (caution w/
beta blockers secondary to masking hypoglycemic symptoms)
AEs—hypoglycemia listed only for products that frequently cause hypoglycemia as monotherapy.
Source: Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: A patient centered approach. Position statement of the American Diabetes
Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35:1364.
a
Generic available.
TABLE 3.1.4 Hyperglycemic Crises
Criteria DKA HHS
Pathophysiology • Insulin deficiency leads to lipolysis (breakdown of adipose tissue • Residual insulin protects against lipolysis; peripheral muscle tissue used
to free fatty acids) for energy production, ketone formation, and for energy production, no ketones
metabolic acidosis • Precipitating factors—develops slowly
• Precipitating factors—develops quickly • Undiagnosed/untreated DM
• Illness/infection • Illness/infection
• Inadequate insulin
• Initial presentation of diabetes (type 1 typically)
Presentation • Signs/symptoms • Signs/symptoms
• N/V, abdominal cramps • Similar to DKA; milder GI symptoms
• Polyuria, polydipsia, polyphagia • No Kussmaul’s respirations
• Kussmaul’s respirations • Mental status changes common
• Mental status changes • Typically profound dehydration
• Fruity “ketone breath”
Glucose >250 mg/dL >600 mg/dL
pH (arterial) <7.2 >7.3
Serum bicarbonate <15 mEq/L >18 mEq/L
(Continued)
101
102
SECTION 3 | Endocrinology
TABLE 3.1.4 Hyperglycemic Crises (Continued)
Treatment
Volume
• Expand extracellular volume/restore renal perfusion
• 15–20 mL/kg NS, ½ NS
• Switch to D5W + ½ NS when glucose ≈ 200–250 mg/dL
Electrolytes
• Assess hydration state, electrolyte levels and urinary output
• K+ <5.3 mEq/L
• Initiate after urinary output verified; before/with insulin in DKA → insulin will worsen existing hypokalemia by shifting K+ intracellularly
• Bicarbonate replacement controversial, may be detrimental
• Consider if pH <7.0
Glycemic control
• Use regular insulin only; rapid acting insulins do NOT offer any benefit; increased cost
• Optional bolus: 0.1 units/kg
• Infusion 0.1 units/kg/h (5–10 units/h)
• Slow steady fall in glucose ~50–75 mg/dL/h
• Goal 200–250 mg/dL—do NOT stop insulin at this point
• Initiate D5W + ½ NS and continue insulin infusion to allow ketones to clear (close anion gap)
3.2 | Thyroid Disorders 103
Hyperthyroidism suspected
4–8 weeks
TSH TSH
low, low, FT4
FT4 high low or normal
Continue or increase
antithyroid drugs:
Asymptomatic Hypothyroid symptoms
Consider
|131 therapy
Discontinue drugs
TSH
high,
FT4 normal
or low
5–6 weeks
Increase Decrease
levothyroxine levothyroxine
sodium dose by sodium dose by
12.5–25 µg/day 12.5–25 µg/day
increments increments
4 Neurology
Cardioembolic
Atrial fibrillation
• Dose-adjusted warfarin (INR 2–3), apixiban,
dabigatran or rivaroxaban (See 1.4.3)
LV thrombus or rheumatic heart valve disease
• Dose-adjusted warfarin (INR 2–3)
Nonrheumatic native heart valve disease
• Aspirin 81–325 mg QD
Prosthetic heart valve
• Dose-adjusted warfarin (INR 2.5–3.5) unless
bi-leaflet aortic valve (INR 2–3)
Sources: (1) Furie KL, Kasner SE, Adams RJ, et al.; on behalf of the American Heart Association Stroke
Council, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Interdisciplinary Council on
Quality of Care and Outcomes Research. Guidelines for the prevention of stroke in patients with stroke or
transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/
American Stroke Association. Stroke. 2011;42:227–276. (2) Lansberg MG, O’Donnell MJ, Khatri P, et al.
Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: Antithrombotic Therapy and Prevention of
Thrombosis, 9th ed.: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
Chest. 2012;141:e601S–636S.
a
See also Table 4.1.3 for details on selection and dosing of specific agents.
b
See tables 1.3.1 and 1.3.4
TABLE 4.1.3 Pharmacotherapy for Secondary Prevention of Ischemic Stroke
Drug Dosing Comments
Antiplatelet Agents
Aspirin 160–325 mg QD acutely, • For secondary prevention of stroke of atherosclerotic origin, AHA/ASA guidelines
81–325 mg QD thereafter recommend aspirin or aspirin/dipyridamole ER as first line and clopidogrel for aspirin
intolerance (Stroke. 2011;42:227); ACCP guidelines recommend either aspirin/
dipyridamole ER or clopidogrel over aspirin due to modestly better efficacy despite
Aspirin/dipyridamole ER (Aggrenox) 25/200 mg 1 tablet BID higher cost (Chest. 2012;141:e601S)
• Both guidelines recommend aspirin for cardioembolic source due to PFO or
nonrheumatic native valve disease
• Aspirin plus clopidogrel may be considered for patients with atrial fibrillation
Clopidogrel (Plavix) 75 mg tablet 1 tablet QD who cannot take anticoagulation for reasons other than bleeding risk (Chest.
2012;141:e601S) but should be otherwise avoided due to a lack of efficacy and
higher bleeding risk (Lancet. 2004;364:331)
Anticoagulants
Warfarin Dose to target INR • ACCP guidelines recommend dabigatran over warfarin for secondary prevention of
Dabigatran (Pradaxa) 150 mg tablets See table 1.4.3 stroke in patients with atrial fibrillation (Chest. 2012;141:e601S)
• Initiate within 1–2 weeks of stroke, unless high bleeding risk; aspirin should be used
Rivaroxaban (Xarelto) 15 and 20 mg tablets until anticoagulation started unless contraindicated
Apixiban (Eliqius) 2.5 and 5 mg tablets
4.1 | Stroke
Statins
Atorvastatin (Lipitor) 10, 20, 40 or 80 mg tablets Choose dose to reduce LDL <100 • Evidence for statins supported by 1 trial of high-dose atorvastatin (Stroke.
mg/dL or by 50% (see table 1.3.1 2007;38:3198); thus, AHA/ASA recommends aggressive dosing (Stroke. 2011;42:227)
for dosing) • Could be a class effect at similar doses and LDL target (see table 1.3.1 for other
statins)
111
112
SECTION 4 | Neurology
FIGURE 4.2.1 Diagnostic Criteria for Epilepsy
Epilepsy
Criteria required for diagnosis: at least Symptoms of seizure depends on type Need to rule out (r/o) provoked cause of
two unprovoked seizures separated by 24 h of seizure: seizure: electrolyte disturbance, metabolic
• Generalized type: associated with disturbance (i.e., hypoglycemia, infection,
LOC with convulsive activity that hypotension, drug-induced)
can be tonic/clonic or both
• May also have very brief LOC that is
EEG is useful in MRI of brain is useful to almost undectable (absence seizure)
Need to r/o pseudoseizure: prolactin level can
diagnosis but is positive look for structural or can have atonic drop attacks with
be elevated 10–20 min after tonic–clonic
in only 50% of patients abnormality especially of brief LOC
seizure but not after pseudoseizure; does not
who have epilepsy hippocampus • Partial type: simple partial not
differentiate cause of seizure (i.e., epilepsy
CT is helpful initially to rule associated with LOC but has focal
vs. syncope)
out tumor or bleed (repetitive) motor or sensory
component
• Complex partial associated with
altered consciousness and has focal
(repetitive) motor and/or sensory
component
4.2 | Epilepsy 113
Yes Yes
Increase AED dose;
No
go to box 3
No
Reproduced with permission from Rogers SJ, Cavazos JE. Epilepsy. In: Dipiro JT, Talbert RL, Yee GC, Matzke
GR, Wells BG, Posey LM, eds. Pharmacotherapy. A Pathophysiologic Approach. 8th ed. New York, NY:
McGraw-Hill Companies; 2011.
a
Favorable factors include single type of partial or primary GTC seizures, normal neurologic exam, normal IQ
and an EEG that has normalized with treatment; repeated episodes of status epilepticus or history of high
frequency of seizures are poor risk factors for successful withdrawal of AED.
114
TABLE 4.2.3 Antiepileptic Drug Dosing and Treatment Considerations
Drug Initial Dose (Frequency), Titration, and Usual Maximum Seizure Type Comments
SECTION 4 | Neurology
Carba Initial 400 mg/day (BID) Partial, primary GTC CNS side effects including diplopia, nausea,
Titration 200 mg every week hyponatremia, rash, blood dyscrasias
Levetiracetam Initial 500–1,000 mg/day (BID, QD if XR used) Partial, primary GTC, JME Sedation, behavioral disturbance, psychosis
(Keppra) Titration Increase by 1,000 mg every 2 weeks
Maximum 3,000–4,000 mg/day (BID, QD if XR used)
Oxcarbazepine Initial 300–600 mg/day (BID) Partial, primary GTC CNS side effects, nausea, rash, hyponatremia
(Trileptal) Titration 600 mg or less every week
Maximum 2,400–3,000 mg/day (BID)
Phenobarbital Initial 10–20 mg/kg loading dose, then 1–3 mg/kg/day (QD) Partial, primary GTC Very strong hepatic inducer, abrupt discontinuation
(PB) Titration As tolerated especially dangerous, CNS side effectsa, behavior
changes, cognitive impairment, metabolic bone
Maximum 180–300 mg/day (QD or BID depending on dose/tolerability) disease, blood dyscrasias
Phenytoin (PHT) Initial 15–20 mg/kg load, then 3–5 mg/kg (200–400 mg) PO Partial, primary GTC CNS side effects, cognitive impairment,
QD or BID or TID based on tolerability immunologic reactions, gingival hyperplasia,
Titration Increase every 7–10 days connective tissue changes blood dyscrasias, rash,
cerebellar syndrome
Maximum 500–600 mg/day (QD or BID or TID based on tolerability and
control of seizures)
Pregabalin Initial 150 mg/day (BID or TID) Partial Dizziness, somnolence, blurred vision, pedal
(Lyrica) Titration As tolerated edema, behavior changes, weight gain
4.2 | Epilepsy
Titration Increase every 3 days by 125–250 mg/d (BID or TID) due to greater conversion to PB, not as strong
hepatic inducer, first dose effect start slowly, CNS
Maximum 750–2,000 mg/day (BID or TID) side effects, blood dyscrasias
Rufinamide Initial 400–800 mg/day (BID) Lennox–Gastaut Dizziness, nausea, vomiting, somnolence,
(Banzel) Titration Increase by 400–800 mg every 2 days syndrome multiorgan hypersensitivity, status epilepticus,
leukopenia, QT shortening
Maximum 3,200 mg/day (BID)
115
(Continued)
116
TABLE 4.2.3 Antiepileptic Drug Dosing and Treatment Considerations (Continued)
SECTION 4 | Neurology
Drug Initial Dose (Frequency), Titration, and Usual Maximum Seizure Type Comments
Tiagabine Initial 4–8 mg/day (QD or BID with higher dose) Partial CNS side effects, depression, spike-wave stupor,
(Gabitril) Titration Increase by 4–8 mg every week tremor, nervousness, weakness
4.2 | Epilepsy
PHT A10–34; C5–14 7–28 CYP2C9, CYP2C19, 5% CYP3A, CYP2C, GT None Total: 10–20 mg/mL
(renal) (40–79 mmol/L)
Unbound: 0.5–3 mg/mL
(2–12 mmol/L)
Pregabalin (Lyrica) A6–7 1–2 100% (renal) None None Not defined
117
(Continued)
118
SECTION 4 | Neurology
TABLE 4.2.4 Pharmacokinetic Characteristics of Antiepileptic Drugs (Continued)
Time to Steady
Drug Half-Life (Hours) State (Days) Elimination Induces Inhibits Target Serum Concentration
PRM A3.3–19; 1–4 Mostly renal, same as PBa Same as PB (weak) None 5–10 mg/mL (23–46 mmol/L)
C4.5–14
RUF (Banzel) 6–10 2 Hydrolysis, 2% (renal) CYP3A4 (weak) CYP2E1 (weak) Not defined
TGB (Gabitril) 5–13 2 CYP3A4, 2% (renal) None None 0.02–0.2 mg/mL
(0.05–0.5 mmol/L)
TPM 18–21 4–5 Hepatic enzymes not CYP3A4 (dose CYP2C19 5–20 mg/mL (15–59 mmol/L)
known, 70% (renal) dependent)
Valproic acid A8–20; C7–14 1–3 GT, β-oxidation, 2% None CYP2C9, GT, 50–100 mg/mL
(renal) epoxide hydrolase (347–693 mmol/L)
Vigabatrin (Sabril) 5–8 N/A Almost 100% (renal) CYP2C9 None 0.8–36 mg/mL (6–279 mmol/L)
ZON 24–60 5–15 CYP3A4, 35% (renal) None None 10–40 mg/mL (47–188 mmol/L)
A, adult; C, child; Co, combination therapy; M, monotherapy; N/A, not applicable since effect depends on inhibiting enzyme.
Sources: (1) Faught E. Pharmacokinetic considerations in prescribing antiepileptic drugs. Epilepsia. 2001;42(Suppl 4):19–23. (2) Patsalos PN, Berry DJ, Bourgeois BFD, et al.
Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on
Therapeutic Strategies. Epilepsia. 2008;49:1239–1276. (3) Halford JJ, Lapointe M. Clinical perspectives on lacosamide. Epilepsy Curr. 2009;9:1–9. (4) Sabril [product information].
Deerfield, IL: Lundbeck Inc; Feb 2012.
a
Clinically relevant concentration of PB formed only when patient is on a hepatic enzyme inducer.
TABLE 4.2.5 Interactions Between Antiepileptic Drugs
AED Added Drug Effect AED Added Drug Effect
CBZ FBM ↑10,11 epoxidea Pregabalin No known interactions
↓CBZ PRM CBZ ↓PRM, ↑PB
Oxcarbazepine ↓CBZ PHT ↓PRM,↑PB
PB ↓CBZ VPA ↑PRM, ↑PB
PHT ↓CBZ RUF CBZ ↓RUF
Valproic acid (VPA) ↑10,11 epoxidea PB ↓RUF
Ethosuximide CBZ ↓Ethosuximide PHT ↓RUF
PB ↓Ethosuximide PRM ↓RUF
PHT ↓Ethosuximide VPA ↑RUF
FBM CBZ ↓FBM TGB CBZ ↓TGB
PHT ↓FBM PB ↓TGB
VPA ↑FBM PHT ↓TGB
Gabapentin No known interactions PRM ↓TGB
LAC CBZ ↓LAC TPM CBZ ↓TPM
PB ↓LAC PB ↓TPM
PHT ↓LAC PHT ↓TPM
4.2 | Epilepsy
LTG CBZ ↓LTG PRM ↓TPM
PB ↓LTG VPA ↓TPM
PHT ↓LTG
PRM ↓LTG
VPA ↑LTG
119
(Continued)
120
TABLE 4.2.5 Interactions Between Antiepileptic Drugs (Continued)
AED Added Drug Effect AED Added Drug Effect
SECTION 4 | Neurology
LEV CBZ ↓LEV VPA CBZ ↓VPA
PB ↓LEV FBM ↑VPA
PHT ↓LEV LTG ↓VPA
Oxcarbazepineb CBZ ↓MHD PB ↓VPA
PB ↓MHD PHT ↓VPA
PHT ↓MHD PRM ↓VPA
PB FBM ↑PB TPM ↓VPA
Oxcarbazepine ↑PB Vigabatrin No known interactions
PHT ↑PB ZON CBZ ↓ZON
VPA ↑PB PB ↓ZON
PHT CBZ ↑ or ↓PHT PHT ↓ZON
FBM ↑PHT PRM ↓ZON
Methsuximide ↑PHT
Oxcarbazepine (>1200 mg/d) ↑PHT
PB ↑ or ↓PHT
TPM ↑PHT
VPA ↓PHT, then may ↑PHT
Vigabatrin ↓PHT
Reproduced with permission from Rogers SJ, Cavazos JE. Epilepsy. In: Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy. A Pathophysiologic
Approach. 8th ed. New York, NY: McGraw-Hill Companies; 2011.
a
Carbamazepine-10,11-epoxide is an active metabolite of CBZ.
b
Oxcarbazepine is a prodrug that is converted to the active 10-monohydroxy derivative (10 MHD) by glucuronidation.
FIGURE 4.3.1 Diagnostic Criteria for Parkinson’s Disease
Parkinson’s disease
121
Source: Chen JJ, Lew MF, Siderowf A. Treatment strategies and quality-of-care indicators for patients with Parkinson’s disease. JMCP. 2009;15(3):S1–S21.
FIGURE 4.3.2 Pharmacotherapy of Early Parkinson’s Disease
122
Newly diagnosed Parkinson’s diseasea Consider patient’s age, symptom severity, whether
SECTION 4 | Neurology
employed, concern for developing motor
complications and treatment preferences
Moderate
or severe Relief of disabling
symptoms
Physiologic age >65 years Tremor predominate
No No
No
and/or cognitive decline symptoms
No
No Yes
Reconsider Yes
Relief of disabling symptoms No Relief of disabling
diagnosis
symptoms
Yes Relief of disabling No
No
symptoms
No
No Yes
Continue current therapy Continue current therapy Reconsider diagnosis Continue current therapy
Adapted with permission from Algorithm for the early treatment of Parkinson’s disease developed by VA PADRECC Clinical Care Committee. In: Duda J, Robinson R. Diagnosing and
managing Parkinson’s disease: practical strategies for the federal healthcare professional. U.S. Medicine Supplement. Med-IQ; 2011.
a
Evaluate for presence and treatment of nonmotor symptoms of Parkinson’s disease (i.e., sleep dysfunction, sensory symptoms, autonomic dysfunction, mood disorder, and cognitive
abnormalities). Refer to: Zesiewicz TA, Sullivan KL, Arnulf I, et al. Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: treatment of nonmotor
symptoms of Parkinson disease: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010;74(11):924–931.
b
Patients should be evaluated at least annually for QOL measures pertaining to safety, nonmotor symptoms, and current review of Parkinson disease diagnosis or treatment. Refer to:
Cheng EM, Tonn S, Swain-Eng R, et al. American Academy of Neurology Parkinson Disease Measure Development Panel. Quality improvement in neurology: AAN Parkinson disease
quality measures: report of the Quality Measurement and Reporting subcommittee of the American Academy of Neurology. Neurology. 2010;75(22):2021–2027.
c
Assess history of impulse control disorder-type behaviors (pathological gambling, eating, spending, sexual, etc.) and consider using other agents if significant history and/or concerns
exist; monitor impulse control disorder symptoms periodically during dopamine-agonist therapy.
124
Levodopa-induced motor complicationsa
SECTION 4 | Neurology
Wearing-off effect Dyskinesias (choreic, ballistic, Consider deep brain stimulation
Treatment options: myoclonic) or ablative surgery if:
• Increase dose or frequency of dosing Treatment options: • Motor complications are
especially if on lower levodopa dose • Add amantadine disabling
• Add COMT inhibitor or dopamine agonist or • Decrease dose of levodopa • Patient is cognitively intact
MAO-B inhibitor [may result in increase in • Add COMT inhibitor or and
dyskinesias or side effects (i.e., constipation, dopamine agent with • Patient is responsive to
hallucinations,vomiting)] decrease in dose of levodopa levodopa
Akathisia—occurs at bedtime when levodopa wears
off; treat with levodopa or dopamine agonist at bedtime
a
More common in patients with young onset (i.e., <age 50 Parkinson’s disease).
b
May also occur in levodopa-naïve patients.
TABLE 4.3.4 Considerations for Anti-Parkinson’s Agents
Therapy Comments
Dopamine agonists As a class associated with nausea, vomiting, confusion, hallucinations, postural hypotension, lower-extremity edema, vivid dreaming
and less commonly compulsive behaviors (hypersexuality, gambling, Internet use, hoarding, shopping), and sleep attacks; are
ineffective in patients who do not respond to levodopa; avoid stopping abruptly due to possible dopamine withdrawal syndrome
associated with symptoms of anxiety, panic attacks, depression, sweating, nausea, fatigue, dizziness, pain; levodopa does not treat
this withdrawal
Dopamine replacement Common side effects are nausea, vomiting, orthostasis, hallucinations, dyskinesias, and wearing- off motor fluctuations
Monamine oxidase type B inhibitors Use of these agents contraindicated in patients taking meperidine and other selected opioid analgesics due to risk of serotonin
syndrome; not contraindicated in patients on serotonin reuptake inhibitor antidepressants; higher doses are more likely to have some
MAO-A inhibitory activity
125
126
TABLE 4.3.5 Drug Products and Dosing in Parkinson’s Disease
Medications Daily Dose Comments
SECTION 4 | Neurology
Dopamine Agonists
Apomorphine injection 10 mg/mL Initial 2 mg subcutaneous test dose, then 1 mg less than tolerated Premedicate 3 days before with trimethobenzamide due to
test dose; increase by 1 mg every few days; maintenance dose nausea and vomiting; use contraindicated with serotonin
2–6 mg divided 3 times/day; rotate injection sites to avoid receptor blocker class drugs due to severe hypotension and
developing subcutaneous nodules syncope; avoid prochlorperazine and metoclopramide since
they reduce apomorphine’s effectiveness
Bromocriptine tablet, capsule Initial dose 1.25 mg/day; increase slowly over 4–6 weeks; Ergot-derived agonist with possible associated side effect,
maintenance dose 10–40 mg divided 3 times/day rarely cardiovascular valve fibrosis, Raynaud phenomenon,
erythromelalgia, retroperitoneal/pulmonary fibrosis
Pramipexole tableta 0.125 mg 3 times/day; titrate weekly by 0.125–0.25 mg/dose; Renally excreted; adjust dose function in renally impaired
maintenance dose 1.5–4.5 mg divided 3 times/day patient
Ropinirole tableta 0.25 mg 3 times/day; titrate weekly by 0.25 mg/dose Metabolized by CYP1A2 therefore potent inhibitors (i.e.,
fluoroquinolone antibiotics) and inducers (i.e., cigarette
smoking) may change serum levels of this drug
Carbidopa/Levodopa tableta 25/100 once/day (regular or oral disintegrating tablet); increase by Avoid high-protein meals; take regular release product
25/100 weekly to desired effect and as tolerated; maintenance dose 60 minutes before meals; take controlled release product
is 30/300–150/1500 in divided doses given 3–5 times/day with food
25/100 2 times/day (controlled release tablet); space at least Controlled release product is not very effective for managing
6 hours apart and increase every 3–7 days; maintenance dose is levodopa-induced motor fluctuations
50/200–500/2,000 divided 4 times/day
COMT Inhibitors
Entacapone tablet One tablet with each administration of levodopa/carbidopa up to Diarrhea 10% patients—occurs 6–12 weeks after starting
8 tablets daily; maintenance dose is 3–8 tablets/day drug; can cause urine discoloration
Entacapone/levodopa/carbidopa Use only after stabilized on dose of levodopa/carbidopa
combination tablet
Tolcapone tablet 100–200 mg 3 times/day; maintenance dose is 300–600 mg More effective than entacapone; can cause fatal liver failure
divided 3 times/day especially first 6 months; need frequent liver enzyme testing;
diarrhea 10% patients—occurs 6–12 weeks after starting drug
Monamine Oxidase Type B Inhibitors
Selegiline tablet, capsule, oral disintegrating 5 mg/day; may increase to 5 mg 2 times/day; maintenance dose Hepatically metabolized to l-methamphetamine and
tablet, transdermal patchb oral tablet is 5–10 mg/day given as 5 mg with breakfast and 5 mg l-amphetamine; side effects can include insomnia, jitteriness,
with lunch and hallucinations; increases peak affects of l-dopa and can
Oral disintegrating tablet maintenance dose is 1.25–2.5 mg/day worsen preexisting dyskinesias or psychiatric symptoms; oral
disintegrating tablet less likely to cause above effects since
product avoids first-pass hepatic metabolism with decreased
production of amphetamine metabolites
Rasagiline tablet 0.5 mg/day; may increase to 1 mg/day; maintenance dose is Drug not metabolized to amphetamine metabolites;
0.5–1 mg/day metabolized by CYP1A2; studies indicate probably more
effective than selegiline as adjunctive agent
Anticholinergics
127
b
Transdermal patch not FDA approved for treatment of Parkinson’s disease.
FIGURE 4.4.1 Diagnostic Criteria for Episodic Headaches
128
Episodic headachesa
SECTION 4 | Neurology
Migraine headache w/o aura Cluster headache Tension-type headache
W/o aura W/aura A. Severe unilateral orbital, supraorbital A. Headache <15 days/month
A. 2 or > of the following: Migraine w/o aura criteria plus: and/or temporal pain lasting B. Lasts 30 min 7 days
• Unilateral location • 1 or > reversible aura symptoms 15–180 min untreated C. 2 or > present:
• Pulsating/throbbing • 1 or > aura develops over B. Attack associated with 1 or > signs • Pressing/tightening (nonpulsating)
• Moderate-to-severe intensity >4 min or 2 or > symptoms on pain side: quality
• Aggrevated by routine activity occur in succession • Conjunctival injection • Mild-to-moderate pain intensity
AND one of the foollowing: • Aura symptoms do not last • Lacrimation • Bilateral location
• Nausea and/or vomiting >60 min • Nasal congestion • Not aggrevated by routine physical
• Photophobia and phonophobia • Migraine attack follows within • Rhinorrhea activity
B. Previous similar attacks 60 min • Forehead and facial swelling D. Both of the following:
C. Headache lasts 4–72 h • Miosis • No nausea or vomiting (anorexia may
(untreated or unsuccessfully • Ptosis occur)
treated) • Eyelid edema • Photophobia/phonophobia is absent or
• Agitation, unable to lie down only 1 of 2 is present
C. Frequency from 1 every other day
to 8/day
Reproduced with permission from Institute for Clinical Systems Improvement. Health care guideline: diagnosis and treatment of headache. http://www.icsi.org/headache/headache_
diagnosis_and_treatment_of_2609.html. January 2011. Accessed June 2, 2011.
a
Rule out organic disorder by evaluation and diagnostic studies in workup.
FIGURE 4.4.2 Pharmacotherapy of Episodic Headaches
Episodic headaches
• Nondrug modalities • Determination of mild vs. moderate • Oxygen inhalation via • Nondrug modalities
• Triptans (see Tables 4.4.7, vs. severe symptoms may dictate non-rebreathing facial mask • NSAIDs (see Table 4.4.6)
4.4.8) which treatment modality(s) to try (7–15 L/min)—usually effective • Nonopioid analgesics (see Table 4.4.6)
• NSAIDs initially as well as concommittant within 15 minutes if used early in
(see Table 4.4.6) medical problems headache presentation; may have
• Nonopioid analgesics • Mild: able to continue daily routine to be repeated due to reoccurrence
(see Table 4.4.6) with minimal alteration of headache
• Adjunctive drug therapy • Moderate: headache inhibits daily • Triptan (subcutaneous or intranasal)
(see Table 4.4.9) activities but is not incapacitating (see Tables 4.4.7, 4.4.8)
• Severe: headache is incapacitating • DHE (intravenous) (see Table 4.4.7
• Status: headache lasts >72 h • Will need bridging (corticosteroids,
(see Figure 4.4.5) ergotamine, occipital nerve block)
4.4 | Headache
• Evaluate for triggers: environmental, and preventative therapy in majority
lifestyle habits, hormonal, of sufferers (see Table 4.4.8)
emotional, medication, dietary
129
FIGURE 4.4.3 Diagnostic Criteria for Chronic Headaches.
130
Chronic headaches
SECTION 4 | Neurology
Chronic migraine headache Chronic tension-type headache Medication overuse headache Hemicrania continua
A. Tension type and/or migraine a Risk factors for development: A. Average frequency A. Headache ≥15 days/month A. Headache >3 months fulfulling
headache ≥15 days/month • Attack frequency >1/month ≥15 attacks/month B. Regular oversuse >3 criteria B–D listed below:
× ≥3 months (use diary to • Body mass index >30 B. ≥2 pain characteristics months of following: B. All the following present:
document at least 1 month • Medication overuse listed under episodic tension- • Ergotamine, triptans, • Unilateral pain w/o side-shift
time period) • Life stressors type headache Section C opioids, or combination • Daily and continuous, w/o
B. Occurs in patient with ≥5 • Snoring/sleep apnea/sleep of Figure 4.4.1 analgesic medication ≥10 pain-free periods
attacks fulfilling criteria for disturbance C. Both of the following: days/month or regular basis • Moderate intensity, but with
migraine w/o aura • Caffeine consumption • No vomiting >3 months exacerbations of severe pain
C. ≥8 days/month × ≥3 months • Female gender • No more than 1 of the • Simple analgesic or any C. ≥1 occuring during exacerbations
with headache fulfilling criteria • Head injury following—nausea, combination of ergotamine, and ipsilateral to the side of pain:
listed for migraine w/o aura • Low education/ photophobia, phonophobia triptan, analgesic opioids • Conjunctival injection and/or
(see Migraine headache w/o socioeconomic factors D. Organic disorder has been ≥15 days/month on a lacrimation
aura Section A, Figure 4.4.1) • Prior hx of episodic migraine r/o and headaches should not regular basis for >3 months • Nasal congestion and/or
and/or is treated and relieved have started in close temporal w/o overuse of any single rhinorrhea
by triptan(s) or ergot before relationship with another class alone • Ptosis and/or miosis
the expected development of disorder if present C. Headache has developed or D. Complete response to
symptoms listed in Section A, markedly worsened during indomethacin
Figure 4.4.1 medication overuse E. Another disorder is not causative
D. No medication overuse and
not another possible
causative disorder
Reproduced with permission from Institute for Clinical Systems Improvement. Health care guideline: diagnosis and treatment of headache. http://www.icsi.org/headache/headache_
diagnosis_and_treatment_of_2609.html. January 2011. Accessed June 3, 2011.
a
Neurology: Clinical Practice 2011;76(suppl2):S37-542
FIGURE 4.4.4 Pharmacotherapy of Chronic Headaches
Chronic headaches
Chronic migraine headache Chronic tension-type headache Medication overuse headache Hemicrania continua
4.4 | Headache
• Evaluate for depression/anxiety phenobarbital may help with those
and treat if present on other barbs
• Educate sufferer that headaches may get
worse initially and offer follow-up support
• Can use symptomatic analgesics in limited
doses (NSAIDs, DHE, corticosteroids
≤2×/week) from drug classes not being
currently overused
131
1Neurology: Clinical Practice 2001;76 (suppl2):S37-S42
132 SECTION 4 | Neurology
Adjunctive therapya
(see Table 4.4.9)
IV metoclopramide 10 mg
a
Patient should be hydrated prior to neuroleptic treatment with 250–500 mL fluid to avoid orthostatic
hypotension.
b
Avoid in a pregnant patient or who has a history of heart disease or Prinzmetal’s angina, severe peripheral
vascular disease, onset of chest pain following test dose of DHE, within 24 hours of receiving a triptan or
ergot derivative, elevated blood pressure, cerebrovascular disease, patients with hemiplegic or basilar-type
migraines (defined as any three of the following: diplopia, dysarthria, tinnitus, vertigo, transient hearing loss,
or mental confusion)
c
See Institute for Clinical Systems Improvement. Health care guideline: diagnosis and treatment of headache.
http://www.icsi.org/headache/headache_diagnosis_and_treatment_of_2609.html.January2011.
4.4 | Headache 133
4.4 | Headache
135
136 SECTION 4 | Neurology
5 Gastroenterology
A b b r e v i at i o n s
ANV Anticipatory nausea and vomiting NK-1 Neurokinin 1
CINV Chemotherapy-induced nausea and NSAID Nonsteroidal anti-inflammatory drug
vomiting PONV Postoperative nausea and vomiting
COX-2 Cyclooxygenase-2 PPI Proton pump inhibitor
GERD Gastroesophageal reflux disease PUD Peptic ulcer disease
5-HT3 5-Hydroxytryptamine-3 RINV Radiation-induced nausea and
H2RA Histamine 2 receptor antagonist vomiting
MALT Mucosa-associated lymphoid tissue
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5.1 | Nausea and Vomiting 141
TABLE 5.1.2 Drugs and Dosing for Prophylaxis of CINV and RINV
Drug Indication Dosing Dosage Forms
5-HT3 Receptor Antagonists
Dolasetron (Anzemet) CINV 100 mg before chemo Tab
Delayed CINV 100 mg QD Tab
Granisetron (Kytril) CINV, RINV 2 mg before chemo/radiation Tab
Delayed CINV 1–2 mg QD Tab
CINV 1 mg before chemo IV
CINV 34.3 mg applied 24 h prior to Transdermal patch
chemo
Ondansetron (Zofran) CINV 16-24 mg before chemo Tab, ODT
CINV 8–12 mg before chemo/radiation IV
RINV 8 mg BID Tab, ODT
Delayed CINV 8 mg QD-BID Tab, ODT
Palonosetron (Aloxi) CINV 0.25 mg before chemo IV
CINV 0.5 mg before chemo Tab
NK-1 Receptor Antagonist
Aprepitant (Emend) CINV 125 mg before chemo Cap
Delayed CINV 80 mg days 2 and 3 after chemo Cap
Fosaprepitant (Emend) CINV 150 mg before chemo IV
Benzodiazepines
Alprazolam (Xanax) ANV 0.5–2 mg TID prior to Tab
chemotherapy
Lorazepam (Ativan) ANV 0.5–2 mg on night before and Tab
morning of chemotherapy
Corticosteroid
Dexamethasone (Decadron) CINV 8–12 mg before chemoa Tab, IV
Delayed CINV 8 mg QD days 2 and 3 after Tab, IV
chemo
RINV 4 mg with fractions 1–5 Tab, IV
Sources: (1) Prevention of chemotherapy and radiotherapy-induced emesis. Results of the 2004 Perugia
International Antiemetic Consensus Conference. Ann Oncol. 2006;17:20–28. (2) Basch E, Prestrud AA,
Hesketh PJ, et al. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update.
J Clin Oncol. 2011;29:4189–4198.
a
12 mg for high emetic risk regimens or for moderate risk regimens including an NK1 antagonist, 8 mg for
all other regimens.
5.1 | Nausea and Vomiting 143
On NSAID?
Endoscopy to assess
ulcer status
Yes No
Consider continuation
of PPI or H2RA Consider NSAID use,
antibiotic resistance,
nonadherence, other
diagnosis
Reproduced with permission from Berardi RR, Fugit RV. Peptic ulcer disease. In: DiPiro JT, Talbert RL, Matzke
GR, Posey LM, Wells BG, Yee GC, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY:
McGraw-Hill; 2011:chap 40. Figure 40-5.
146
SECTION 5 | Gastroenterology
TABLE 5.2.3 Acid Suppression Agents for GERD and PUD
Drug Dosing Comments
Proton Pump Inhibitors
Esomeprazole (Nexium) 20–40 mg QD • PPIs reduce recurrent ulcer risk in NSAID- treated patients by 4–6% (Ann Int Med. 2010;
Dexlansoprazole (Dexilant) 30–60 mg QD 152:101)
• PPI therapy is associated with increased risk of fractures (Arch Int Med. 2010;170:765); risk
Lansoprazole (Prevacid, generics) 15–30 mg QD appears both dose and duration related
Pantoprazole (Protonix, generics) 40 mg QD • Hypomagnesemia occurs with long-term therapy, measures serum [Mg++] and considers Mg++
supplementation, especially in patients taking thiazide diuretics or digoxin
Omeprazole (Prilosec, generics) 20–40 mg QD
• PPI use associated with increased incidence of pneumonia and Clostridium difficile infection
Omeprazole sodium bicarbonate (Zegerid) 20–40 mg QD
Rabeprazole (Aciphex) 20 mg QD
H2-Receptor Antagonists
Cimetidine (Tagamet, generics) 200–400 mg BID • Low doses (available nonprescription) effective for episodic dyspepsia but not for GERD with
800 mg QHS esophagitis or PUD
• Higher doses effective for mild-to-moderate GERD but less effective than PPIs for severe GERD
Famotidine (Pepcid, generics) 10–20 mg BID • Multiple drug interactions with cimetidine
40 mg QHS
Nizatidine (Axid, generics) 75–150 mg BID
300 mg QHS
Ranitidine (Zantac, generics) 75–150 mg BID
300 mg QHS
TABLE 5.2.4 Eradication Regimens for Helicobacter pylori
Category Triple Therapy Quadruple Therapy Sequential Therapy Indications for H. pylori Testing
147
TABLE 5.3.1 Pharmacotherapy for Complications of Cirrhosis
148
Clinical Situation Pharmacotherapy Comments
SECTION 5 | Gastroenterology
Ascites Spironolactone 100–400 mg QD • Spironolactone directly targets hyperaldosteronism; one of the primary causes of ascites formation
Furosemide 40–100 mg QD • Furosemide used for additional fluid removal; preferentially decreases vascular/peripheral fluid vs.
peritoneal fluid; use caution with intravascular volume depletion
Albumin 25% 8 g/L of fluid removed via • Ratio of 100:40 mg spironolactone; furosemide helps maintain potassium balance
paracentesis • Only give albumin, if ≥5 L fluid removed via paracentesis
Hepatic Lactulose 15–-45 mL TID up to Q 1–2 h • Titrate lactulose to 3–4 soft bowel movements/day or as tolerated by patient
encephalopathy Rifaximin 400 mg TID; max 1,200 mg/day • Ammonia levels do not correlate with level of impairment; assess patient symptoms
(HE) • Consider rifaximin in those refractory to or intolerant of lactulose
Hepatorenal Albumin 25% 1 g/kg day 1; then 20–40 g/day • Discontinue if serum albumin ≥4.5 g/L
syndrome (HRS) Midodrine 5–7.5 mg TID up to 12.5 mg TID
Octreotide 100 mg SQ TID up to 200 mg TID
Portal hypertension Propranolol 10 mg BID up to 80 mg/day • Decrease risk of variceal bleeding secondary to portal hypertension
Nadolol 20 mg QD up to 160 mg QD • Goal: Decrease HR by 25% or to 55–60 BPM (noninvasive surrogate marker for portal hypertension)
• Initiate at low doses and titrate slowly; cirrhotic patients often have low BP at baseline
Spontaneous Cefotaxime 2 g IV Q 8 h • Primarily Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae—monomicrobial;
bacterial peritonitis Ceftriaxone 1 g IV Q 12 h or 2 g Q 24 h narrow antibiotic spectrum when pathogen identified
(SBP) • Alternative prophylactic ceftriaxone dose during variceal bleeding is 1 g IV QD
Piperacillin/tazobactam 3.375 g IV Q6 h • Albumin decreases incidence of HRS in patients with SBP
Albumin 25% 1.5 g/kg on day 1; 1 g/kg day 3
Long-term SBP Ciprofloxacin 750 mg Q week • Decreases mortality in those with prior episode of SBP
prophylaxis • Daily vs. intermittent therapy may be preferred due to resistance concerns
Trimethoprim/sulfamethoxazole 1 DS tab 5X/ week
Variceal bleeding Octreotide 50–100 mg IV bolus, then 25–50 mg/h • Duration controversial; continue at least 24 h after banding of varices; some recommend 5 days total
continuous infusion • Prophylactic antibiotics recommended during acute variceal bleeding with or without ascites
Prophylactic antibiotics: see empiric therapy for
SBP above
Section
6 Pulmonology
A b b r e v i at i o n s
CAT COPD assessment test MDI Metered-dose inhaler
DPI Dry powder inhaler mMRC Modified British Medical Research
FEV1 Forced expiratory flow in 1 second Council questionnaire
FEV1 or PEF ≥ 40% (Mild-to-moderate) FEV1 or PEF < 40% (severe) Impending or actual respiratory arrest:
• O2 to achieve SaO2 ≥ 90% • O2 to achieve SaO2 ≥90% • Intubation and mechanical ventilation
• SABA by nebulizer or MDI up to 3 doses first hour • High-dose SABA + ipratropium by nebulizer with 100% O2
• Oral systemic corticosteroids if no immediate or MDI Q 20 min or continuously over 1 h • Nebulized SABA and ipratropium
response or if patient recently took systemic steroids • Oral systemic corticosteroids • IV corticosteriods
Repeat assessment: Symptoms, PEF, SaO2, physical exam See “Admit to ICU” on next page
6.1 | Asthma
Good response: FEV1 or PEF ≥70%, 60 min Incomplete response: FEV1 or PEF Poor response: FEV1 or PEF <40%, PCO2 ≥ 42 mm Hg,
sustained response, no distress, exam normal 40–69%, mild-to-moderate symptoms physical exam symptoms severe, drowsiness, confusion
Discharge home: See “Discharge Discharge home or admit to Admit to hospital: See “Admit to Hospital” on
151
Home” on next page hospital, individualized decision next page
(Continued)
152
FIGURE 6.1.1 Hospital Management of Acute Asthma Exacerbations (Continued)
SECTION 6 | Pulmonology
Discharge home Admit to hospital ward: Admit to hospital intensive care:
• Continue treatment with inhaled SABA • O2 • O2
• Continue course of oral systemic corticosteroid • Inhaled SABA • Inhaled SABA hourly or continuously
• Consider initiation of an ICS • Systemic (oral or intravenous) • Intravenous corticosteroid
• Patient education corticosteroid • Consider adjunct therapies
• Review medications and inhaler technique • Consider adjunct therapies • Possible intubation and mechanical
• Review/initiate action plan • Monitor vital signs, FEV1 or PEF, SaO2 ventilation
• Recommend close medical follow-up
Improve Improve
Adapted from NHLBI. National Asthma Education and Prevention Program Expert Panel Report 3. Guidelines for the Diagnosis and Management of Asthma. NIH Publication No.
08-5846. Bethesda, MD: US Department of Health and Human Services; 2007.
TABLE 6.1.2 Drug Dosing in Acute Asthma Exacerbations
Medications Adult Dose Children Dose (≤12 Years Old) Comments
SABAs
Albuterol nebulizer solution 2.5–5 mg every 20 min for 3 0.15 mg/kg (minimum dose 2.5 mg) every Directly supervised MDI is equivalent to nebulizer for most
doses, then 2.5–10 mg every 20 min for 3 doses, then 0.15–0.3 mg/kg (up patients, no data in most severe patients however (Chest.
1–4 h PRN, or 10–15 mg/h to 10 mg) every 1–4 h PRN, or 0.5 mg/kg/h by 2005;127:335)
continuously continuous nebulization
Albuterol MDI 4–8 puffs every 30 min up to 4–8 puffs every 20 min for 3 doses, then every Use valved holding chamber-type spacer for children
4 h, then every 1–4 h PRN 1–4 h PRN ≤4 years old.
Levalbuterol (Xopenex) 1.25–2.5 mg every 20 min for 0.075 mg/kg (minimum dose 1.25 mg) every Majority of studies indicate no efficacy or tolerability
nebulizer solution 3 doses, then 2.5–5 mg every 20 min for 3 doses, then 0.075–0.15 mg/kg advantage vs. albuterol (Formulary. 2009;44:108); individual
1–4 h PRN, or 5–7.5 mg/h (up to 5 mg) every 1–4 h PRN, or 0.25 mg/kg/h exceptions may be encountered; 2.5 mg albuterol = 1.25 mg
continuously by continuous nebulization levalbuterol
Levalbuterol MDI (Xopenex) 4–8 puffs every 30 min up to 4 4–8 puffs every 20 min for 3 doses, then every
h, then every 1–4 h PRN 1–4 h PRN
Short-Acting Anticholinergics (SAMAs)
Ipratropium bromide 500 mg every 30 min for 3 250 mg every 20 min for 3 doses, then Must use with albuterol. May mix in same nebulizer with
nebulizer solution doses, then every 2–4 h PRN 250 mg every 2–4 h 0.5 mL albuterol 0.5% solution.
Ipratropium bromide MDI 4–8 puffs PRN every 2–4 h 4–8 puffs PRN every 2–4 h Use valved holding chamber-type spacer for children ≤4
(Atrovent) years old.
6.1 | Asthma
Corticosteroids
Prednisone tablets/ 40–80 mg/day PO in 1–2 doses 1–2 mg/kg (up to 60 mg/day) PO in 2 divided Give until PEF is 70% predicted/personal best; 7–10-day
Prednisolone oral solution doses courses do not need to be tapered in most patients, especially
(15 mg/5 mL) if they are taking an ICS
Methylprednisolone 32–64 mg/day PO in 1–2 doses 2–4 mg/kg (up to 60 mg/day) IV Reserve IV for NPO or severe exacerbation requiring ICU
40–80 mg/day IV in 1–2 doses management and/or intubation. Depo-Medrol 160 mg IM at
153
discharge equivalent to 8 days PO taper (Chest. 2004;126:362)
154
SECTION 6 | Pulmonology
TABLE 6.1.3 Classification of Asthma Severity in Patients Not Taking Long-Term Control Medications
Children 0–11 Years of Age
Components Intermittent Mild Persistent Moderate Persistent Severe Persistent
Symptom frequency ≤2 days/week >2 days/week but not daily Daily Throughout the day
Nighttime awakenings (0–4 years) None Once or twice per month 3–4 times per month >Once per week
Nighttime awakenings (5–11 years) ≤twice per month 3–4 times per month >Once per week but not nightly Often 7 times per week
Impairment
SABA use for symptoms ≤2 days/week >2 days/week but not daily Daily Several times per day
Interference with normal activity None Minor limitation Some limitation Extremely limited
Lung function (5–11 years) FEV1 >80% FEV1 >80% FEV1 60%–80% FEV1 <60%
FEV1/FVC >85% FEV1/FVC >80% FEV1/FVC 75%–80% FEV1/FVC <75%
Exacerbation frequency (0–4 years) 0–1 per year ≥2 in 6 months or ≥4 wheezing episodes per year lasting >1 day
Risk
SABA use for symptoms ≤2 days/week >2 days/week but not >once Daily Several times per day
per day
Interference with normal activity None Minor limitation Some limitation Extremely limited
Lung function FEV1 >80% FEV1 >80% FEV1 60–80% FEV1 <60%
FEV1/FVC normal FEV1/FVC normal FEV1/FVC reduced 5% FEV1/FVC reduced >5%
Exacerbation frequency 0–2 per year >2 in 1 year
Risk
Step for initiating treatment Step 1 Step 2 Step 3 and consider short course of Step 4 or 5
systemic oral corticosteroids
Adapted from NHLBI. National Asthma Education and Prevention Program, Expert Panel Report 3. Guidelines for the Diagnosis and Management of Asthma. NIH Publication No.
08-5846. Bethesda, MD: US Department of Health and Human Services; 2007:72–77.
6.1 | Asthma
155
156
TABLE 6.1.4 Recommendations for Chronic Asthma Pharmacotherapy in Children and Adults
Age 0–4 Years Age 5–11 Years Adults and Youth Age ≥12 Years
SECTION 6 | Pulmonology
Step Preferred Alternative Preferred Alternative Preferred Alternative
1 SABA PRN N/A SABA PRN N/A SABA PRN N/A
2 Low-dose ICS Montelukast or Low-dose ICS LTRA, cromolyn, or Low-dose ICS LTRA, cromolyn, or
cromolyn theophylline theophylline
3 Medium-dose ICS N/A Medium-dose ICS Low-dose ICS + either Medium-dose ICS or low- Low-dose ICS + either
LABA, LTRA, or theophylline dose ICS + LABA LABA, LTRA, theophylline,
or zileuton
4 Medium-dose ICS + either N/A Medium-dose ICS + LABA Medium-dose ICS + either Medium-dose ICS + LABA Medium-dose ICS + either
montelukast or LABA LTRA or theophylline LABA, LTRA, theophylline,
or zileuton
5 High-dose ICS + either N/A High-dose ICS + LABA High-dose ICS + either High-dose ICS + LABA and N/A
montelukast or LABA LTRA or theophylline consider omalizumab in
patients with allergic asthma
6 High-dose ICS + either N/A High-dose ICS + LABA + High-dose ICS + either High-dose ICS + LABA + oral N/A
montelukast or LABA + oral corticosteroid LTRA or theophylline + oral corticosteroid, and consider
oral corticosteroids corticosteroid omalizumab in patients with
allergic asthma
Other Measures SABA PRN Use for short-term symptom relief in all patients. May give Q 20 min × 3 in acute situations.
SQ allergy immunotherapy Consider in all patients >4 years old with allergy triggers at treatment step 2 or above.
Asses Control Step up treatment If inadequate control by symptoms or if using SABA >2 times per week. Assess compliance with therapy and
environmental measures.
Step down treatment If well controlled for 3 months.
Adapted from NHLBI. National Asthma Education and Prevention Program, Expert Panel Report 3. Guidelines for the Diagnosis and Management of Asthma. NIH Publication No.
08-5846. Bethesda, MD: US Department of Health and Human Services; 2007:305, 306, and 343.
TABLE 6.1.5 Drug Products and Dosing in Chronic Asthma Management
Children Dose
Medications Products Adult Dose (≤12 Years Old) Comments
SABAs
Albuterol 0.021% (0.63 mg/3 mL); 0.042% 2.5–5 mg 0.63–1.25 mg
nebulizer solution (1.25 mg/3 mL); 0.083% (2.5 mg/3 mL); Q 4–6 h PRN Q 4–6 h PRN
0.5% (2.5 mg/0.5 mL)
Albuterol MDI Ventolin HFA, Proventil HFA, ProAir HFA 2 puffs Q 4–6 h PRN 1–2 puffs Q 4–6 h PRN Use valved holding chamber-type spacer for children
(all are 90 mg/puff) ≤4 years old
Levalbuterol Xopenex 0.31 mg/3 mL; 0.63 mg/3 mL; 1.25–2.5 mg Q 6–8 0.31–0.63 mg Q 6–8 Majority of studies indicate no efficacy or tolerability advantage
nebulizer solution 1.25 mg/3 mL; 1.25 mg/0.5 mL h PRN h PRN vs. albuterol (Formulary. 2009;44:108); individual exceptions may
Levalbuterol MDI Xopenex HFA (45 mg/puff) 2 puffs Q 4–6 h PRN 1–2 puffs Q 4–6 h PRN be encountered; 2.5 mg albuterol = 1.25 mg levalbuterol
6.1 | Asthma
nebulizer solution per day per day use
Short-Acting Anticholinergics (SAMAs)
Ipratropium 0.03% (0.5 mg/2.5 mL) 0.5 mg Q 6–8 h PRN 0.25–0.5 mg Q 6–8 Not as effective as SABAs in chronic asthma; only use as a
nebulizer solution h PRN replacement for patients who cannot tolerate SABAs or in
Ipratropium MDI Atrovent HFA 17 mg/inhalation 2 inhalations Q 6 1–2 inhalations Q 6 addition to an SABA in acute asthma
h PRN h PRN
157
(Continued)
158
TABLE 6.1.5 Drug Products and Dosing in Chronic Asthma Management (Continued)
Children Dose
SECTION 6 | Pulmonology
Medications Products Adult Dose (≤12 Years Old) Comments
Leukotriene Modifiers (LTRAs)
Montelukast Singulair 10 mg tablet, 4 mg chewable, 10 mg QD 6 months–5 years:
5 mg chewable, 4 mg granules 4 mg QPM
5–12 years: 5 mg QPM
Zafirlukast Accolate 10 mg tablet, 20 mg tablet 20 mg BID 5–12 years: 10 mg BID
Zileuton Zyflo CR 1200 mg tablet 1200 mg BID Not recommended AST/ALT >3 times normal occurs in 3% of patients; monitor
LFTs monthly for the first 3 months of therapy
IgE Inhibitor
Omalizumab Xolair 150 mg injection See Table 6.1.9 Not recommended
LABA/ICS Combination Products (see Table 6.1.6 for ICS only products)
Salmeterol/ Advair Diskus 100/50, 250/50 and 1 inhalation Q 12 h 1 inhalation Q 12 h
fluticasone DPI 500/50 (fluticasone mg/salmeterol mg) (100/50 max if 4–11
years old)
Salmeterol/ Advair HFA 45/21, 115/21 and 230/21 2 puffs Q 12 h 2 puffs Q 12 h
fluticasone MDI (fluticasone mg/salmeterol mg)
Formoterol/ Symbicort 80/4.5 or 160/4.5 2 inhalations Q 12 h 2 inhalations Q 12 h Patients on low-to-medium-dose ICS should take the
budesonide MDI (budesonide mg/ formoterol mg) (max dose 80/4.5, not 80/4.5 mg dose; patients on medium to high-dose ICS
for use <5 years old) should take the 160/4.5 mg (Prod Info: Symbicort, 2010)
Methylxanthines
Theophylline Theo-24 extended release capsules (Q 24 See Figure 6.1.7 See Figure 6.1.7 Theophylline is a narrow therapeutic index drug and should
h) 100, 200, 300, and 400 mg; Uniphyl for dosing initiation, for dosing initiation, be considered as additive therapy for patients not controlled
controlled release tablets (Q 24 h) 400 and titration and monitoring titration and monitoring on the preferred agents. Common adverse effects include
600 mg; Elixophyllin elixir 80 mg/15 mL; nausea, insomnia, tremors, and anxiety. For clinically
(generics) extended release tablets (Q 12 h) important drug interactions see Table 6.1.8
100, 200, 300, 400, 450, and 600 mg.
TABLE 6.1.6 Inhaled Corticosteroid Comparative Dosinga
Medication Products Low Dose Medium Dose High Dose
Children 0–4 Years of Age
Budesonide suspensionb Pulmicort Respules 0.25 mg/2 mL (2 mL); 0.25–0.5 mg QD (or split BID) 0.75–1 mg QD (or split BID) >1 mg QD
0.5 mg/2 mL (2 mL); 1 mg/2 mL (2 mL)
Fluticasone MDI Flovent HFA 44, 110, or 220 mg/inhalation 88 mg BIDc 110–176 mg BID >176 mg BID
Children 5–11 Years of Age
Beclomethasone MDI QVAR 40 or 80 mg/inhalation 40–80 mg BID 120–160 mg BID >160 mg BID
Budesonide DPI Pulmicort Flexhaler 90 or 180 mg/inhalation 90–180 mg BID 270–360 mg BID >360 mg BID
Budesonide suspensionb Pulmicort Respules 0.25 mg/2 mL (2 mL); 0.5 mg QD (or split BID) 1 mg QD (or split BID) 2 mg QD (or split BID)
0.5 mg/2 mL (2 mL); 1 mg/2 mL (2 mL)
Ciclesonide MDI Alvesco 80 or 160 mg/inhalation 80 mg QD-BID 160 mg BID >160 mg BID
Flunisolide MDI Aerospan 80 mg/inhalation 80 mg BID 160 mg BID >160 mg BID
6.1 | Asthma
Fluticasone MDI Flovent HFA 44, 110 or 220 mg/inhalation 44–88 mg BIDc 110–176 mg BID >176 mg BID
(Continued)
159
160
SECTION 6 | Pulmonology
TABLE 6.1.6 Inhaled Corticosteroid Comparative Dosing (Continued)
Medication Products Low Dose Medium Dose High Dose
Adults and Youth ≥12 years of Age
Beclomethasone MDI QVAR 40 or 80 mg/inhalation 40–160 mg BID 200–240 mg BID > 240 mg BID
Budesonide DPI Pulmicort Flexhaler 90 or 180 mg/inhalation 90–270 mg BID 360–540 mg BID >540 mg BID
Ciclesonide MDI Alvesco 80 or 160 mg/inhalation 80 mg QD-BID 160 mg BID >160 mg BID
Flunisolide MDI Aerospan 80 mg/inhalation 160 mg BID 240–320 mg BID >320 mg BID
Fluticasone MDI Flovent HFA 44, 110 or 220 mg/inhalation 44–132 mg BID 176–220 mg BID >220 mg BID
Mometasone DPI Asmanex Twisthaler 110 or 220 mg/inhalation 220 mg QD 440 mg QD >440 mg QD
Sources: (1) NHLBI, Expert Panel Report 3. Guidelines for the Diagnosis and Management of Asthma. NIH Publication No. 08-5846. (2) Global Strategy for Asthma Management
and Prevention, Global Initiative for Asthma (GINA) 2011. http://www.ginasthma.org/. (3) Inhaled corticosteroid dose comparison. Pharmacist’s Letter/Prescriber’s Letter
2009;25(8):250801.
a
ICS Pearls: Initial symptom improvement takes 1–2 weeks with peak improvement in 4–6 weeks. Improvement in FEV1 and PEF can be seen in 3–6 weeks. Bronchial
hyperresponsiveness will improve after 2–3 weeks with peak improvement in 1–3 months. Exercise challenge sensitivity improves after 4 weeks. In well controlled patients with
mild asthma, taking an inhaled ICS as needed for symptom control along with albuterol may provide similar control as scheduled ICS with less overall steroid exposure (JAMA
2012;308:987, Lancet 2011;377:650)
b
May mix with albuterol (0.5% solution), levalbuterol (1.25 mg/5 mL), or ipratropium in the same nebulizer. Use only with jet nebulizers.
c
Use higher dose of fluticasone HFA (88 mg BID) with face mask valved chamber-type spacer due to reduced drug delivery.
6.1 | Asthma 161
Yes
Yes
Dose titration
Any level If dose not tolerated, reduce dose and recheck in 3 days
Level <10 Increase dose by 25% and redraw level in 3 days
Level 10–15 Maintain current dose
Level 15.1–19.9 Consider reduced dose by 10%
Level 20–25 Reduce dose by 25% and redraw in 3 days
Level >25 Hold next dose, reduce dose 25–50%, monitor for toxicity
and redraw in 3 days
a
See table 6.1.8 for factors effecting theophylline clearance.
162 SECTION 6 | Pulmonology
6.1 | Asthma
in children dependent months (Pediatr Drugs. 2011;13:11); final adult height was 1.2 cm shorter on average for patients
receiving 400 mcg/day inhaled budesonide versus nedocromil or placebo (N Engl J Med.
2012;367:904.); short-term studies show less growth effect with ciclesonide vs. fluticasone
(Pediatr Allergy Immunol. 2010;21:e199) and vs. budesonide (Pediatr Allergy Immunol.
2007;18:391)
a
See Table 6.2.3 for bronchodilator adverse effects.
163
164
TABLE 6.2.1 GOLD Guideline Initial Pharmacotherapy for Stable COPDa
Patient Group Spirometric Classification Symptoms and Risk First Choice Second Choice Alternative Choiceb
SECTION 6 | Pulmonology
A FEV1/FVC <0.70 and • Low risk, less symptoms SAMA PRN LAMA or LABA Theophylline
• GOLD 1 (FEV1 >80%) or • ≤1 exacerbation per year or or
• GOLD 2 (FEV1 50–80%) • mMRC 0–1 SABA PRN SABA and SAMA
• CAT <10
B FEV1/FVC <0.70 and • Low risk, more symptoms LAMA LAMA and LABA SABA and/or SAMA
• GOLD 1 (FEV1 >80%) or • ≤1 exacerbation per year or or
• GOLD 2 (FEV1 50–80%) • mMRC ≥2 LABA Theophylline
• CAT ≥10
C FEV1/FVC <0.70 and • High risk, less symptoms ICS and LABA LAMA and LABA PDE-4 inhibitor
• GOLD 3 (FEV1 30–49%) or • ≥2 exacerbations per year or or
• GOLD 4 (FEV1 <30%) • mMRC 0–1 LAMA SABA and/or SAMA
• CAT <10 or
Theophylline
D FEV1/FVC <0.70 and • High risk, more symptoms ICS and LABA ICS and LAMA Carbocysteinec
• GOLD 3 (FEV1 30–49%) or • ≥2 exacerbations per year or or or
• GOLD 4 (FEV1 <30%) • mMRC ≥2 LAMA ICS and LABA and LAMA SABA and/or SAMA
• CAT ≥10 or or
ICS and LABA and PDE-4 inhibitor Theophylline
or
LAMA and LABA
or
LAMA and PDE-4 inhibitor
Adapted by the author from the Global Strategy for Diagnosis, Management and Prevention of COPD 2011; used with permission from the Global Initiative for Chronic Obstructive
Lung Disease (GOLD), www.goldcopd.org.
a
Medications in each box are mentioned in alphabetical order, and therefore not necessarily in order of preference.
b
Medications in this column can be used alone or in combination with other options in the first and second columns.
c
Carbocysteine is not available in the United States.
TABLE 6.2.2 Drug Dosing for Stable COPD
Medication Products Class Dosing Comments
Short-Acting Bronchodilators
Albuterol MDI (90 mg/puff) Ventolin HFA, ProAir HFA, Proventil HFA SABA 2 puffs Q 4–6 h PRN SABA on an as needed basis provides similar
Albuterol nebulizer solution 2.5 mg/3 mL (0.083%); SABA 2.5 mg Q 4–6 h PRN clinical benefit to scheduled SABA with overall
2.5 mg/0.5 mL (0.5%) lower drug dose requirement (Am J Respir Crit
Care Med. 2001;163:85)
Levalbuterol MDI (45 mg/puff) Xoponex HFA SABA 2 puffs Q 4–6 h PRN
Levalbuterol nebulizer solution Xoponex 1.25 mg/3 mL SABA 1.25 mg Q 4–6 h PRN
Pirbuterol MDI Maxair Autohaler SABA 2 puffs Q 4–6 h PRN
Ipratropium (17 mg/puff) Atrovent HFA SAMA 2 puffs Q 6 h PRN Ipratropium is longer acting than albuterol
165
(Continued)
166
TABLE 6.2.2 Drug Dosing for Stable COPD (Continued)
Medication Products Class Dosing Comments
SECTION 6 | Pulmonology
ICS
Budesonide DPI Pulmicort Flexhaler 90 or 180 mg/ ICS 360 mg BID Majority of data in COPD is with fluticasone and
inhalation budesonide. ICS efficacy without a bronchodilator
Fluticasone MDI Flovent HFA 44, 110, or 220 mg/ ICS 440 mg BID is modest and limited to patients with FEV1
inhalation <50% (Chest. 2010;137:318)
Mometasone DPI Asmanex Twisthaler 110 or 220 mg/ ICS 440 mg BID
inhalation
Fluticasone/salmeterol DPI Advair Diskus 100/50, 250/50, and ICS/LABA 500/50 mg 1 inhalation Combination therapy with an ICS + LABA is
500/50 (fluticasone mg/salmeterol mg) combination BID superior to monotherapy with ICS (Cochrane
Fluticasone/salmeterol MDI Advair HFA 45/21, 115/21, and ICS/LABA 230/21 mg 2 inhalations Database Sys Rev. 2007), LABA (N Engl J Med.
230/21 (fluticasone mg/salmeterol mg) combination BID 2007;356:775), or tiotropium (Am J Respir
Crit Care Med. 2008;177:19.); Some advocate
Budesonide/formoterol MDI Symbicort 80/4.5 or 160/4.5 ICS/LABA 160/4.5 mg 2 combining tiotropium, ICS, and LABA, but this
(budesonide mg/ formoterol mg) combination inhalations BID approach has not been studied
PDE-4 Inhibitor a
Roflumilast Daliresp 500 mg tablet PDE-4 inhibitor 500 mg QD Improves FEV1 when combined with LABA
or LAMA (Lancet. 2009;374:695); reduced
exacerbations in patients with chronic bronchitis,
but reduction not significant when patients with
emphysema were included in the analysis (Br J
Pharmacol. 2011;163:53)
Sources: (1) Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011. http://www.goldcopd.org
(2) National Clinical Guideline Centre (2010). Chronic Obstructive Pulmonary Disease: Management of Chronic Obstructive Pulmonary Disease in Adults in Primary and Secondary Care.
London: National Clinical Guideline Centre. http://guidance.nice.org.uk/CG101/Guidance/pdf/English
a
Recommended as second line agent in combination with LAMA or LABA in GOLD C or in the combinations noted in table 6.2.1 for GOLD D patients by the 2013 update of the GOLD
COPD Guidelines (http://www.goldcopd.org)
(2) National Clinical Guideline Centre (2010). Chronic Obstructive Pulmonary Disease: Management of Chronic Obstructive Pulmonary Disease in Adults in Primary and Secondary Care.
London: National Clinical Guideline Centre. http://guidance.nice.org.uk/CG101/Guidance/pdf/English
a
Recommended as second line agent in combination with LAMA or LABA in GOLD C or in the combinations noted in table 6.2.1 for GOLD D patients by the 2013 update of the GOLD
COPD Guidelines (http://www.goldcopd.org)
167
168 SECTION 6 | Pulmonology
• Start SABA
On home long-acting bronchodilators? Yes
• Consider
adding SAMA
• Consider LABA or LAMA Consider theophylline
No upon discharge or aminophylline
• Avoid SAMA with LAMA if poor bronchodilator
response (see Figure
6.1.7 for dosing)
Glucocorticoids
• Give prednisone 30–40 mg daily for 7–14 days
• Continue ICS if taking one
Antibiotics
Antibiotic indications
• Increased sputum purulence with increased sputum
volume or dyspnea
• Severe exacerbation requiring mechanical ventilation COPD exacerbation pathogens
• Clinical signs of pneumonia • Haemophilus influenzae —20–30%
• Streptococcus pneumoniae —10–15%
Antibiotic selection • Moraxella catarrhalis —10–15%
• Empiric treatment based on likely pathogen, local • Pseudomonas aeruginosa—5–10%
susceptibility patterns, disease severity, and the • Clamydophilia pneumoniae —3–5%
presence of pseudomonas risk factors
• Optimal antibiotic regimen is poorly studied and Severe exacerbation or risk factors
comparisons between agents are limited for pseudomonas
• Risk factors include hospitalization >48 h
Mild-to-moderate exacerbation in past 90 days, history of pseudomonas
(no p. aerug. risk factors) infection, severe exacerbation
In no particular order: • Anti-pseudomonas beta-lactam: piperacillin/
• Amoxicillin (with clavulanate in areas with high tazobactam, cefepime, imipenem/cilastatin,
H. influenzae resistance rates) meropenem, doripenem
• Azithromycin or clarithromycin (avoid in areas with • Anti-pseudomonas flouroquinolone:
high S. pneumoniae resistance to macrolides) ciprofloxacin (do not use as monotherapy if
• Doxycycline S. pneumoniae possible), levofloxacin
• Levofloxacin, moxifloxacin 750 mg QD
Sources: (1) Global Strategy for the diagnosis Management and Prevention of COPD, Global initiative for
Chronic Obstructive Lung Disease (GOLD) 2013. http://www.goldcopdorg (2) National Clinical Guideline
Centre (2010). Chronic Obstructive Pulmonary Disease Management of Chronic Obstructive Pulmonary
Disease in Adults in Primary and Secondary Care. London: National Clinical Guideline Centre. http://
guidancenice org.uk/CG101.Guidance/pdf/English (3) Sethi, S, Murphy, TF. Infection in the pathogenesis
and course of chronic obstructive pulmonary disease. N Engl J Med. 2008;359:2355.
Section
7 Nephrology
A b b r e v i at i o n s
ACEI Angiotensin-converting enzyme CKD Chronic kidney disease
inhibitor 25(OH)D 25 Hydroxyvitamin D (calcidiol)
ARB Angiotensin receptor blocker 1,25(OH)2D 1,25 Dihydroxyvitamin D
BB Beta-blocker (calcitriol)
CCB Calcium channel blocker
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TABLE 7.1.1 Pharmacotherapy for Management of CKD Complications
Complication Pharmacotherapy Comments
Hypertension ACEIs/ARBs first line • Target blood pressure is <130/80 mm Hg
• Most patients will require multiple agents; choose additional agents based on comorbid illnesses
(see Table 1.1.2); thiazide diuretic (if CrCl > 30 mL/min) preferred second agent if no other compelling
indications; CCB or BB preferred third agents (Am J Kidney Dis. 2004;43(Suppl 1):S1)
Proteinuria ACEIs/ARBs • Both ACEIs and ARBs reduce protein excretion by 35–40% (Am J Kidney Dis. 2004;43:S1)
• An ACEI plus ARB regimen can decrease proteinuria greater than either alone but may worsen kidney disease
(Lancet. 2008;372:547)
• Spironolactone combined with an ACEI or ARB may reduce proteinuria greater than either alone (Clin J Am Soc
Nephrol. 2006;1:256); monitor serum K+ closely with this combination
• Titrate ACE/ARB to maximum tolerated dose (see Table 1.1.1 for dosing), monitor serum K+ and SCr 1 week
after initiation
(Continued)
171
172
SECTION 7 | Nephrology
TABLE 7.1.1 Pharmacotherapy for Management of CKD Complications (Continued)
Complication Pharmacotherapy Comments
CKD mineral and bone Activated vitamin D, vitamin D • See 7.1.2 for indications and dosing
disorder (CKD-MBD) precursors or analogs; calcimimetic • K/DOQI (2003) treatment goals: PTH = (35-70 pg/mL for CKD stage 3 or 70–110 pg/mL for CKD stage 4); serum
Hyperphosphatemia Phosphate binders phosphate 2.7–4.6 mg/dL; serum Ca++ in normal range; Ca-P product < 55 (Am J Kidney Dis. 2003;42:S1)
• KDIGO (2009) treatment goals: PTH, serum Ca++ and phosphate in normal range for the assay measured
(Kidney Int. 2009;76(Suppl 113):S1)
Metabolic acidosis • NaHCO3 tablets (650 mg = 7.7 • Goal is to maintain serum HCO3 @ 24 mEq/L
mEq Na+ and HCO3-) • Calculate base deficit: [0.5 L/kg × (weight (kg)] × [(normal CO2) – (measured CO2)]
• Na+ citrate solution (Bicitra = 1 • Replace total deficit over several days to avoid volume overload
mEq/L Na+ and HCO3-) • Once base deficit replaced, titrate maintenance dose to achieve serum HCO3 @ 24 mEq/L
• Na+/K+ citrate solution (Polycitra • Use of Na+/K+ citrate solution can lead to hyperkalemia
= 1 mEq/L Na+ and K+ and
2 mEq/L HCO3-)
TABLE 7.1.2 Pharmacotherapy for Maintenance of Calcium and Phosphorus Homeostasis in Pre-dialysis Patients
Drug Dosing Comments
Vitamin D Precursors
Cholecalciferol (vitamin D3) • Serum 25(OH)D = 16-30 ng/mL: 800–1000 IU PO daily • Ergocalciferol may be preferred (Am J Kidney Dis. 2003;42:S1)
Ergocalciferol (vitamin D2) • Serum 25(OH)D = 16-30 ng/mL: 800 IU PO daily or • Measure serum 25(OH)D after 6 months of therapy and reassess
50,000 IU PO monthly • Vitamin D precursors lose efficacy as CKD progresses due to a loss of renal
• Serum 25(OH)D = 5-15 ng/mL: 50,000 IU PO weekly conversion to activated vitamin D
× 4, then monthly • Patients with osteomalacia should receive an active vitamin D product
• Serum 25(OH)D <5 ng/mL: 50,000 IU PO weekly × 12, instead of a precursor
then monthly, alternatively 500,000 IU IM × 1
Activated Vitamin D and Analogs
(Continued)
173
174
SECTION 7 | Nephrology
TABLE 7.1.2 Pharmacotherapy for Maintenance of Calcium and Phosphorus Homeostasis in Pre-dialysis Patients (Continued)
Drug Dosing Comments
Calcimimetic
Cinacalcet (Sensipar) • 30–180 mg PO daily • Use of cinacalcet in non-dialysis patients is controversial and carries
an appreciable risk of hypocalcemia and hyperphosphatemia; weekly
monitoring is warranted until stable, titrate dose upward every 2–4 weeks
as needed
• Consider for patients refractory to all other available treatments
Phosphate Binders
Calcium acetate (Phos-Lo) • 3–6 tablets (168 mg elemental Ca++ per tablet) 3 times • Calcium products are preferred unless corrected serum Ca++ >10.2 mg/dL
daily with meals (0.5–1 gram elemental Ca++ per dose) • Calcium acetate contains less elemental calcium (25% versus 40%) and is
Calcium carbonate • 0.5–1 gram elemental Ca++ 3 times daily with meals preferred for patients in whom calcium intake should be limited
8 Rheumatology
8.2 Osteoarthritis (see Tables 14.1.1 and 14.1.2 for NSAID dosing and adverse effects) 265
A b b r e v i at i o n s
DMARD Disease-modifying antirheumatic MTX Methotrexate
drug NSAID Nonsteroidal anti-inflammatory drug
HCQ Hydroxychloroquine TNF Tumor necrosis factor
LEF Leflunomide
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TABLE 8.1.1 Pharmacotherapy for Early Rheumatoid Arthritis
Treatment by Disease Activityb
Prognostic Features Low Disease Activity Moderate Disease Activity High Disease Activity
No poor prognostic DMARD monotherapy DMARD monotherapy DMARD monotherapy or HCQ PLUS MTX
featuresa
With poor prognostic Combination DMARD therapy: (MTX + HCQ Combination DMARD therapy: (MTX + HCQ or Anti-TNF +/− MTX or combination DMARD therapy:
featuresa or LEF or sulfasalazine) or (sulfasalazine + LEF or sulfasalazine) or (sulfasalazine + HCQ) or (MTX + HCQ or LEF or sulfasalazine) or (sulfasalazine
HCQ) or (MTX + HCQ + sulfasalazine) (MTX + HCQ + sulfasalazine) + HCQ) or (MTX + HCQ + sulfasalazine)
Source: Singh JA, Furst DE, Bharat A, et al. 2012 Update of the 2008 American College of Rheumatology Recommendations for use of disease-modifying antirheumatic drugs and
177
178
TABLE 8.1.2 Dosing, Adverse Effects, and Monitoring of DMARDs
Agent Dosing Adverse Effects Monitoring
SECTION 8 | Rheumatology
Nonbiologic DMARDS
HCQ Initial: 400–600 mg PO QD for • Common: GI side effects, photosensitivity, hair bleaching • Eye exam at baseline and every 5 years or sooner
4–12 weeks; max 200–400 mg • Serious: Retinopathy (1% after 5–7 years of use), (some experts recommend annual exams);
PO QD angioedema, hepatotoxicity, bronchospasm, exfoliative do not exceed the retinopathy threshold
dermatitis, Stevens–Johnson syndrome, bone marrow 200–400 mg QD; cumulative dose of 1,000 g is
toxicity associated with retinopathy
• CBC with platelet counts during prolonged therapy
MTX 10–15 mg PO once weekly, • Common: Alopecia (0.5–3%), diarrhea (1–3%), nausea and • Pregnancy category X
increase by 5 mg/week every vomiting (>10%), leukopenia (1–3%), thrombocytopenia • Hepatic function baseline and 1–2 months
2–3 weeks to a maximum of (3–10%), dizziness (1–35) intervals; renal function (80–90% unchanged
20–30 mg/week • Serious: Hepatic fibrosis (7%), pancytopenia (1–3%), toxic in urine)
epidermal necrolysis, GI hemorrhage, stomatitis (2–10%), • Chest x-ray prior to initiation, pulmonary function
acquired infections testing prior to initiation
LEF (Arava) • Loading dose: 100 mg PO QD • Common: Alopecia (9–17%), rash (10–12%), diarrhea • Pregnancy category X
× 3 days (17–27%), mouth ulcer (3–5%), headache (7–13%) • CBC with platelet counts and LFTS at baseline,
• Maintenance: 20 mg PO QD, • Serious: Stevens–Johnson syndrome, toxic epidermal then monthly for 6 months, then every
reduce to 10 mg QD if not necrolysis, bone marrow toxicity, hepatic necrosis (increased 6–8 weeks thereafter
tolerated LFTs 1.5–4.4%), opportunistic infections, interstitial lung • Signs and symptoms of interstitial lung disease
disease and serious infection
Minocycline 100 mg PO BID • Common: Tooth discoloration in forming teeth; dizziness • LFTs if hepatitis symptoms occur
(9%), vertigo, photosensitivity • SCr and adjustment perhaps with CKD (no
• Serious: Hypersensitivity, pseudotumor cerebri guidelines)
Sulfasalazine Initial 0.5–1 g/day PO BID • Common: Pruritus (3–4%), rash (3–13%), GI complaints (up • CBC with platelet counts and LFTS at baseline,
Maximum dose up to 3 g QD to 33%), headache (9–33%), fever (3–5%) then every 3 months thereafter
• Serious: Stevens–Johnson syndrome (rare), bone marrow • Urinalysis for crystals
toxicity, hepatotoxicity, hypersensitivity, male infertility,
interstitial pulmonary fibrosis
Biologic Non-TNF DMARDs
Abatacept (Orencia) • <60 kg: 500 mg IV over 30 • Common: Nausea (~10%), infections (37–54%), headache • Signs and symptoms of infection; screen for TB
min, repeat doses at 2 and 4 12–18%), UTI (6%), COPD exacerbation (43%) before starting therapy
weeks; then every 4 weeks • Serious: UTI (0.2–0.5%), pneumonia (0.2–0.5%), cancer
thereafter (1.3%)
• 60–100 kg: 750 mg IV over
30 min then similar to above
• >100 kg: 1000 mg IV over
30 min then similar to above
Rituximab (Rituxan) 1000 mg IV followed by • Common: Infusion reactions, fever, lymphopenia, chills, • Premedicate with methylprednisolone 100 mg IV
1,000 mg IV 2 weeks later in infections 30 min prior to infusion, antihistamine and APAP
combination with MTX repeated • Serious: Severe infusion reactions (urticaria, hypotension, • JC virus infection resulting in PML, and death
every 16–24 weeks angioedema, hypoxia, bronchospasm, pulmonary infiltrates, can occur in rituximab-treated patients
acute respiratory distress syndrome, myocardial infarction,
ventricular fibrillation, cardiogenic shock, anaphylactoid
events, or death) in up to 77% with the first infusion
Tocilizumab (Actemra) • 4 mg/kg IV infusion over • Common: Hypertension (4–6%), rash (2–4%), diarrhea • Neutrophil count (ANC) 500–1,000/mm3,
1 h every 4 weeks; increase (>5%), LFT elevation (up to 48%), nasopharyngitis (4%) interrupt therapy and resume at 4 mg/kg when
to 8 mg/kg based on clinical • Serious: Injection site reaction (5%), GI perforation, ANC is greater than 1000/mm3, increase to
179
180
SECTION 8 | Rheumatology
TABLE 8.1.2 Dosing, Adverse Effects, and Monitoring of DMARDs (Continued)
Agent Dosing Adverse Effects Monitoring
Biologic Anti-TNF DMARDs
Adalimumab (Humira) 40 mg SQ every other week; • Common: Injection site reaction/pain (12–19%), rash (12%), • Discontinue therapy if lupus-like syndrome
other DMARDs may be continued antibody development, adalimumab (1–12%), antinuclear develops
during therapy; may increase to antibody positive (12%), headache (12%), sinusitis (11%), • Signs/symptoms of fungal infections and other
40 mg SQ every week in patients upper respiratory infection (17%) serious systemic infections during and after
not receiving concomitant MTX • Serious: Heart failure (<5%), aplastic anemia (rare), treatment, especially patients with a history of
erythrocytosis (less than 5%), leukopenia (less than recurrent infection
5%), pancytopenia (less than 5%), thrombocytopenia
(infrequently), immune hypersensitivity reaction
(approximately 1%), risk of malignancy and infections
Etanercept (Enbrel) 50 mg SQ weekly given as one • Common: Injection site reaction (37–43%), rhinitis • ESR, rheumatoid factor, and C-reactive protein
50 mg injection or two 25 mg (12–14%), URI (17–65%) may be measured for indication of efficacy
injections in one day, or one • Serious: Heart failure (0.1% or less), erythema multiforme, • Evaluate for TB at baseline and monitor during
25 mg injection given twice malignant melanoma, necrotizing fasciitis, primary therapy, increased risk for fungal infections, LFT
weekly, 72–96 h apart cutaneous vasculitis, skin cancer, squamous cell during therapy, some risk for heart failure
carcinoma of skin, Stevens–Johnson syndrome, toxic
epidermal necrolysis, aplastic anemia (less than 0.01%),
leukopenia, neutropenia, pancytopenia (less than 0.1%),
thrombocytopenia, autoimmune hepatitis (less than 1%),
risk of infection and malignancy
Certolizumab (Cimzia) • Initial: 400 mg SQ (as 2 SQ • Common: Infections (e.g., nasopharyngitis, laryngitis, viral • Increased risk for developing serious infections
injections of 200 mg) once infection), urinary tract infections (e.g., bladder infection, that may lead to hospitalization or death and
and then repeat at weeks bacteriuria, cystitis), and arthralgia lymphoma and other malignancies
2 and 4 • Serious: Potential cardiovascular adverse effect, TB and
• Maintenance: 200 mg SQ once other infections, bone marrow toxicity
every 2 weeks or 400 mg (as
2 SQ injections of 200 mg)
every 4 weeks
Golimumab (Simponi) 50 mg SQ once monthly in • Common: Hypertension (3%), injection site reaction (6%), • Baseline screening for TB
combination with MTX LFT elevation (3–4%), bronchitis (2%), sinusitis (2%), URI • Monitor for new or worsening heart failure
(16%)
• Serious: Increased risk for malignancy and infections (28%
overall), optic neuritis, demyelinating disease of central
nervous system, Guillain–Barré syndrome
Yes No
Inadequate response
1 >1
Yes No
Intraarticular Contraindication to
corticosteroid corticosteroids?
Yes No
From Ernst ME, Clark EC. Chapter 102: Gout and hyperuricemia. In: DiPiro JT, Talbert RL, Yee GC, et al., eds.
Pharmacotherapy: A Pathophysiological Approach. 8th ed. New York, NY: McGraw-Hill; 2011:1627, with
permission.
8.3 | Gout 183
9 Psychiatry
Initial assessment: At least five of the following have been present for at least 2 weeks: (1) Depressed mood, (2) markedly diminished interest or pleasure in activities,
(3) significant changes in weight or appetite, (4) insomnia or hypersomnia, (5) psychomotor agitation or retardation, (6) fatigue or loss of energy, (7) feelings of worthlessness or
excessive or inappropriate guilt, (8) diminished ability to think or concentrate, (9) recurrent thoughts of death or suicide. The symptoms cause clinically significant distress or
impairment in daily functioning.
Identify comorbid conditions and medications Medications associated with depressive symptoms:
• Obtain a complete medical, family, and psychiatric history including previous hospitalizations and suicide Antihypertensive agents: Clonidine, diuretics, hydralazine,
• Consider medications and medical conditions that may be contributing to symptoms methyldopa, propranolol, resperpine
• Rule out other psychiatric disorders such as bipolar disorder. If present, refer to psychiatrist for Hormonal therapies: Oral contraceptives, steroids,
evaluation adrenocorticotropic hormone
Acne therapy: Isotretinoin
Other: Interferon-β
Initial treatment
• Identify target symptoms and goals of therapy
• Develop a detailed safety plan with patient in case suicidal ideation or behaviors develop
Medical conditions associated with depressive
• Initiate antidepressant pharmacotherapy based on patient preference, prior response, safety, tolerability/
symptoms:
adverse effects, comorbid disorders, potential drug interactions, pharmacokinetic parameters, and cost Cardiovascular: Coronary artery disease, heart failure,
• Consider administration of standardized rating scale such as QIDS-SR or PHQ-9
myocardial infarction
Endocrine: Hypothyroidism, Cushing’s
Infections: HIV, mononucleosis, tuberculosis
9.1 | Depression
Weeks 1–4 assessment Metabolic: Hyponatremia, hypokalemia, encephalopathy
Full response: Neurologic: Alzheimer’s, epilepsy, Huntington’s, multiple
Maintain current treatment if there are no issues with tolerability sclerosis, Parkinson’s
Partial or nonresponse: Other: Anemia, systemic lupus erythematosus, malignancy
1. Assess adherence
2. Increase dose if clinically indicated and if no issues with tolerability
3. For severe symptoms, consider ECT
187
(Continued)
FIGURE 9.1.1 Assessment and Management of Depression Algorithm (Continued)
188
SECTION 9 | Psychiatry
Weeks 4–8 assessment Considerations for nonresponse:
Full response/remission: • Incorrect diagnosis
Move to continuation phase • Comorbid disorders, including substance abuse
• Inadequate dose of medication
Partial response:
• Inadequate duration of therapy
1. Increase dose if no issues with tolerability OR
• Pharmacokinetic and pharmacodynamic factors
2. Initiate pharmacotherapeutic augmentation strategy OR
• Persistent adverse effects
3. Augment with psychotherapy OR
• Nonadherence
4. Change to an alternate antidepressant
• Unaddressed psychosocial stressors or psychological issues
Nonresponse:
1. Consider reasons for non-response
2. Change to an alternate antidepressant
3. Consider ECT
Continuation phase:
Continue current therapy for additional 4–9 months
Maintenance phase:
Continue current therapy indefinitely for those with chronic
symptoms or with a history of three or more depressive episodes who
successfully complete the continuation phase.
Other considerations for maintenance therapy:
• Presence of residual symptoms
• Psychosocial stressors
• Family history
• Episode severity
Source: American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 3rd ed. Arlington, VA: American Psychiatric Association; 2010.
9.1 | Depression 189
Psychological: Pharmacologic:
Cognitive behavioral therapy, See Figure 9.2.2
other behavioral therapies
Sources : Canadian Psychiatric Association clinical practice guidelines for the management of anxiety
disorders. Can J Psychiatry. 2006;51(Suppl. 2):1S–92S; National Institute for Health and Clinical Excellence
(2011) [Generalized anxiety disorder and panic disorder (with or without agoraphobia) in adults]. [113]
London: National Institute for Health and Clinical Excellence.
9.2 | Anxiety Disorders 193
First-line
SSRI
SNRI
Second-line
Third-line
Source : Canadian Psychiatric Association clinical practice guidelines for the management of anxiety
disorders. Can J Psychiatry. 2006;51(Suppl. 2):1S–92S.
a
BZD may be added to first-line treatments at the initiation of therapy while waiting for first-line treatment to
take effect.
b
Consider referral to mental-health specialist.
194 SECTION 9 | Psychiatry
Source: World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological
treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders—first revision. World J Biol
Psychiatry. 2008;9(4):248–312.
a
Consider referral to mental-health specialist.
b
Canadian Psychiatric Association clinical practice guidelines for the management of anxiety disorders. Can J
Psychiatry. 2006;51(Suppl. 2):1S–92S.
9.2 | Anxiety Disorders 195
Sources : (1) Canadian Psychiatric Association clinical practice guidelines for the management of anxiety
disorders. Can J Psychiatry. 2006;51(Suppl. 2):1S–92S. (2) National Institute for Health and Clinical
Excellence (2011) [Generalized anxiety disorder and panic disorder (with or without agoraphobia) in adults].
[113] London: National Institute for Health and Clinical Excellence.
196 SECTION 9 | Psychiatry
First-line
Second-line
Third-line
Source: Canadian Psychiatric Association clinical practice guidelines for the management of anxiety
disorders. Can J Psychiatry. 2006;51(Suppl. 2):1S–92S.
a
Short-term adjunctive clonazepam at the initiation of treatment can lead to an increased rapid response
b
Consider referral to mental-health specialist.
9.2 | Anxiety Disorders 197
First consider: Appropriate diagnosis, compliance, adequate dosing, adequate trial period, drug
interactions with concurrent medications, psychosocial stress factors, substance abuse
Atypical antipsychotica
Clomipramine, imipramine,
mirtazapine, BZD
Sources : (1) World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the
pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders—first
revision. World J Biol Psychiatry. 2008;9(4):248–312. (2) Canadian Psychiatric Association clinical practice
guidelines for the management of anxiety disorders. Can J Psychiatry. 2006;51(Suppl. 2):1S–92S.
a
Consider referral to mental-health specialist.
198 SECTION 9 | Psychiatry
Generic Trade GAD Initial Dose GAD Dosage PD Initial Dose PD Dosage
Name Name (mg/day) Range (mg/day) (mg/day) Range (mg/day)
Gabapentina Neurontin — — 300 TID 900–3600
divided TID
Pregabalin Lyrica 75 BID 200–450 divided — —
BID or TID
Buspironea Buspar 5 TID or 7.5 BID 20–30 divided Not Not
BID or TID recommended recommended
Max 60
Sources: (1) Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Reuters
(Healthcare) Inc. (2) Canadian Psychiatric Association clinical practice guidelines for the management of
anxiety disorders. Can J Psychiatry 2006;51(Suppl. 2):1S–92S. (3) World Federation of Societies of Biological
Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and
post-traumatic stress disorders—first revision. World J Biol Psychiatry. 2008;9(4):248–312. (4) Bech P.
Dose-response relationship of pregabalin in patients with generalized anxiety disorder. A pooled analysis of
four placebo-controlled trials. Pharmacopsychiatry. 2007;40:163–168.
a
Generic formulations available
Initial assessment: Reported difficulty initiating or maintaining sleep; wakingup too early or sleep that is nonrestorative despite adequate opportunities and circumstance for sleep
and includes at least 1 daytime impairment (fatigue, concentration or memory impairment, mood changes or irritability, loss of motivation or energy, worries about loss of sleep,
errors at work or while driving, headaches or GI upset in response to lost sleep)
201
(Continued)
FIGURE 9.3.1 Evaluation and Management of Insomnia (Continued)
202
SECTION 9 | Psychiatry
Pharmacologic therapy: (May be used alone or in combination with non-pharmacologic therapy or while treating comorbid conditions)
Not improved
Not improved
Not improved
Source: Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med.
2008;4(5):487–504.
TABLE 9.3.2 Drug Products and Dosing for Insomnia
Name Availability Dose (mg QHS) T1/2 (h) Comments Adverse Effects/ Precautions
BZD
Diazepam Generic A: 5–10 50–100 Long T1/2—Carry-over effects Respiratory depression (avoid in comorbid OSA, COPD, or opiates)
(Valium) T: 2, 5, 10 mg CNS depression (may impair abilities, increase fall risk, avoid with
S: 5 mg/mL alcohol and CNS depressants)
Estazolam Generic A: 1–2 10–24 Behavioral changes, sleep-related activities (such as driving, cooking,
(Prosom) T: 1, 2 mg E: 0.5 phone calls while sleeping), amnesia
Flurazepam Generic A: 15–30 40–114 Long T1/2—Carry-over effects Dependence (withdrawal symptoms possible after 2 weeks, may
(Dalmane) C: 15, 30 mg E: 15 require taper before discontinuation)
Lorazepam Generic A: 2–4 10–20 No active metabolites Abuse potential (all benzos are controlled (C-IV), avoid in hx of
(Ativan) T: 0.5, 1, 2 mg substance abuse)
S: 2 mg/mL Not recommended for long-term use due to risk of dependence
Temazepam Generic A: 15–30 10–40 No active metabolites
203
204
TABLE 9.3.2 Drug Products and Dosing for Insomnia (Continued)
Name Availability Dose (mg QHS) T1/2 (h) Comments Adverse Effects/ Precautions
SECTION 9 | Psychiatry
BZRA “Z Drugs”
Eszopiclone Brand only A: 2–3 6 “Z Drugs” are preferred Respiratory depression (avoid in comorbid OSA, COPD, or opiates)
(Lunesta) T: 1, 2, 3 mg E: 1–2 over BZDs due to ↓risk of CNS depression (may impair mental/physical abilities, increase fall
Zaleplon (Sonata) Generic A: 10–20 1 dependence/abuse risk, avoid with alcohol, avoid with other CNS depressants)
C: 5, 10 mg E: 5 Both eszopiclone and zolpidem Behavioral changes, sleep-related activities (such as driving, cooking,
have been shown safe and phone calls while sleeping), amnesia
Zolpidem Generic Tabs only A: 10 2.5
effective for up to 6 months of
(Ambien) T: 5, 10 mg E: 5 Abuse potential (Lower risk than with benzos but all Z Drugs are
nightly use
SL: 5, 10 mg controlled (C-IV), avoid with hx of substance abuse)
Spray: 8.2 g Zaleplon and zolpidem are
ideal for sleep initiation,
Zolpidem No generic A: 12.5 2.5
zolpidem CR able to be used
Controlled-Release T: 6.25, 12.5 mg E: 6.25
for sleep maintenance
(Ambien CR)
Melatonin Agonists
Ramelteon Brand only A: 8 1–2.5 Not controlled Behavioral changes, sleep-related activities (such as driving, cooking,
(Rozerem) T: 8 mg Approved for sleep phone calls while sleeping), changes in reproductive hormones
maintenance (decreased libido or change in menses)
Sedating Antidepressants
Doxepin (Silenor) Brand only A: 6 15–31 Contraindicated with MAOIs or glaucoma and severe urinary retention
T: 3, 6 mg E: 3 CNS depressant, behavioral changes, sleep-related activities (such as
driving, cooking, phone calls while sleeping)
Amitriptyline Generic A: 25–50 9–27 Anticholinergic, orthostasis, EKG changes, lowers seizure threshold
(Elavil) E: 10–25
Mirtazapine Generic A: 15 20–40 Weight gain, hyperlipidemia,
(Remeron) G: 7.5
Trazodone Generic A: 25–200 7–10 Orthostasis, priapism, QTc prolongation, hyponatremia, dizziness,
(Desyrel) blurry vision, dry mouth
9.3 | Sleep Disorders 205
Initial assessment:
Narcolepsy with cataplexy
• Excessive daytime sleepiness for the past 3 months
• Definite history of cataplexy (Sudden bilateral loss of postural muscle tone occurs in association with
intense emotion)
• May be confirmed by polysomnography or CSF-hypocretin-1 level <110 pg/mL
Source : Morgenthaler TI, Kapur VK, Brown TM, et al. Practice parameters for the treatment of narcolepsy and
other hypersomnias of central origin. Sleep. 2007;30:1705–1711.
206
SECTION 9 | Psychiatry
TABLE 9.3.4 Drug Dosing for Narcolepsya
Drug Availability Dose Adverse Effects Comments
Stimulants
Dextroamphetamine salts Generic 10 mg/day, ↑ by 10 mg/week to max Psychosis,↑HR, ↑BP, anorexia, FDA-approved for narcolepsy
(Adderall) T: 5, 10, 15, 20, 30 mg 60 mg/day divided BID-TID insomnia, irritability, headache, dry Controlled (C-II)
Methylphenidate (Ritalin) Generic 10 mg daily (↑ by 10 mg/week) up to mouth, abdominal pain, dysphoria Avoid in hx of substance abuse
T: 5, 10, 20 mg 60 mg/day divided BID-TID
Armodafinil (Nuvigil) Brand only 150 mg–250 mg daily Headache, anxiety, nausea, dry mouth, FDA-approved for narcolepsy
T: 50, 150, 250 mg diarrhea, asthenia, insomnia,↑HR Controlled (C-IV)
Modafinil (Provigil) Brand only Initially 200–400 mg/day, add 200 mg
T: 100, 200 mg at noon if residual sleepiness
Sodium oxybate (Xyrem) Brand only 4.6–9 g divided evenly QHS and then Avoid activities requiring mental FDA-approved for narcolepsy
500 mg/mL 2.5–4 h later alertness for 6 h, confusion, dizziness, Controlled (C-III)
nausea, enuresis
Prescribers must be registered
with Xyrem Program
a
SSRIs, SNRIs and TCAs may all be used for cataplexy at standard doses, see table 9.1.2 for dosing.
9.3 | Sleep Disorders 207
Initial assessment:
A. Reported symptoms of excessive daytime sleepiness not better explained by other factors,
choking/gasping during sleep, witness apneas by partner, recurrent awakenings from sleep,
unrefreshing sleep, daytime fatigue, or impaired concentration
B. Physical features: Neck circumference >16 cm (female) and >17 cm (male), BMI >30, HTN,
upper airway narrowing
C. High-risk populations (BMI>35, CHF, Afib, treatment-refractory HTN, type 2 diabetes, nocturnal
dysrhythmias, stroke, pulmonary hypertension, and commercial truck drivers)
D. Confirm with polysomnography demonstrating >5 obstructed apnea episodes per hour during sleep
Source : Epstein LJ, Kristo D, Strollo PJ, et al. Clinical guidelines for the evaluation, management and long-
term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009;5:263–276.
Initial assessment:
Diagnosis
Essential criteria (all must be present): Urge to move (generally with uncomfortable sensation) starting in
the legs, Onset or exacerbation during periods of rest/inactivity, Relief with movement or stretching, Sx
occur or are worse in the evening or night
Supportive criteria (used to help confirm dx): 3–5× more likely among first-degree relatives; Most people
with RLS show response to dopamine agonists; periodic limb movement occurs in 85% of cases
Associated features: Age of onset >50 sx are abrupt and severe, if <50 then sx are insidious, sleep
disturbances are common, physical exam is normal and does not contribute to diagnosis except to ruleout
other disorders
Labs: Obtain iron studies (ferritin, %iron saturation), kidney function, folic acid, b12, and thyroid function
to rule out secondary causes or mimicking disorders
Identify contributing medications: Antidepressants (except bupropion), antipsychotics, metoclopramide,
prochlorperazine, promethazine
Iron deficiency: If ferritin<25 µg/L or iron saturation <20%, then initiate FeSO4 325 mg TID with vitamin C
100–200 mg TID, obtain follow-up iron studies after 3–4 months; if ferritin >50 µg/L and iron sturation
>20%, then FeSO4 can be discontinued
Pharmacologic therapy
Source: Rye DM, Adler CH, Allen RP, et al. RLS Switch to untried dopamine agonist, gabapentin,
medical bulletin: a publication for healthcare tramadol, oxycodone, or try combination of
providers. Restless Legs Syndrome Foundation. dopamine agonist with gabapentin, tramadol, or
2005. www.rls.org. Accessed November 20, 2011. oxycodone
TABLE 9.4.2 Drug Dosing for RLS
Drug Availability Dose Adverse Effects Comments
Dopamine Agonists
Carbidopa/levodopa Generic 25/100 QHS Orthostasis, dyskinesias, Off-label for RLS
(Sinemet, Sinemet CR) T: 25/100 compulsive gambling, binge eating, IR can be used PRN for plane rides, movie theaters, and
hypersexuality, rebound (early midnight awakenings
morning RLS), augmentation (earlier
RLS symptoms) Not preferred for daily RLS due to rebound/ augmentation
Do not take with protein-foods do to ↑ absorption
Pramipexole (Mirapex) Generic 0.125 mg × 3 days, double dose Nausea, headache, orthostasis, Both FDA-approved IR formulation for RLS
T: 0.25, 0.5, 1, every 4–7 days, usual dose dyskinesias, compulsive gambling, Give 2–3 h before bed
1.5 mg 0.5 mg/day (max 2 mg/day) binge eating, hypersexuality,
rebound (early morning RLS), Give earlier in the day if augmentation occurs
Ropinirole (Requip) Generic 0.25 mg × 3 days, then 0.5 × Convert from ropinirole to pramipexole 3:1 ratio
augmentation (earlier RLS
T: 0.25, 0.5, 1, 3 days then ↑ by 0.5 mg/week
symptoms )
2, 3, 4 mg to usual dose 2 mg/day (max 4
mg/day)
Anticonvulsants
209
constipation, abuse/dependence
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Section
10 Gynecology
A b b r e v i at i o n s
DSG Desogestrel NGM Norgestimate
DSP Drospirenone NTE Norethindrone
EE Ethinyl estradiol NTE ac Norethindrone acetate
HFI Hormone-free interval OCs Oral contraceptives
IUD Intrauterine device VTE Venous thromboembolism
LVN Levonorgestrel
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TABLE 10.1.1 Marketed OC Products
Original Brand
Namea Branded Generic Namesb Estrogen Component Progestin Component Regimenc Comments
Alesse Aviane-28, Lessina, Lutera, Sronyx EE 20 mg LVN 0.1 mg 27/7 HFI Monophasic
Loestrin Fe 1/20 Junel Fe 1.5/20, Microgestin Fe 1/20 EE 20 mg NTE ac 1 mg 21/7 HFI Monophasic; HFI contains
ferrous fumarate
Nordette Levora, Portia 28 EE 30 mg LVN 0.15 mg 21/7 HFI Monophasic
Lo/Ovral Low-Ogestrel, Cryselle 28 EE 30 mg Norgestrel 0.3 mg 21/7 HFI Monophasic
Loestrin Fe 1.5/30 Junel 1.5/30, Microgestin Fe 1.5/30 EE 30 mg NTE ac 1.5 mg 21/7 HFI Monophasic; HFI contains
ferrous fumarate
Desogen, Ortho-Cept Apri, Reclipsen, Solia EE 30 mg DSG 0.15 mg 21/7 HFI Monophasic
Yasmin Ocella, Zarah EE 30 mg DSP 3 mg 21/7 HFI Monophasic
Demulen Kelnor 1/35, Zovia 1/35 EE 35 mg Ethynodiol diacetate 1 mg 21/7 HFI Monophasic
Ortho-Cyclen MonoNessa, Previfem, Sprintec EE 35 mg NGM 0.25 mg 21/7 HFI Monophasic
Ortho Novum 1/50 Norinyl 1 + 50, Necon 1/50 Mestranol 50 mg NTE 1 mg 21/7 HFI Monophasic; mestranol is
converted into EE
10.1 | Contraception
Ovcon-35 Balziva, Zenchent EE 35 mg NTE 0.4 mg 21/7 HFI Monophasic
Femcon Fe Chewable Zeosa, Generess Fe EE 35 mg NTE 0.4 mg 21/7 HFI Monophasic; HFI contains
ferrous fumarate; chewable
Modicon-28 Brevicon-28, Necon 0.5/35; EE 35 mg NTE 0.5 mg 21/7 HFI Monophasic
Nortrel 0.5/35
Ortho-Novum 1/35 Necon 1/35; Norinyl 1 + 35; Nortrel EE 35 mg NTE 1 mg 21/7 HFI Monophasic
1/35
Ovcon-50 EE 50 mg NTE 1 mg 21/7 HFI Monophasic; high dose
213
(Continued)
214
TABLE 10.1.1 Marketed OC Products (Continued)
Original Brand Namea Branded Generic Nameb Estrogen Component Progestin Component Regimenc Comments
10.1 | Contraception
(2) http://www.watson.com/products/product-database-detail.asp?group=business&c=18. Accessed August 4, 2011. (3) Teva Pharmaceuticals. http://www.tevausa.com/
default.aspx?pageid=76&TherapeuticCategory=Contraceptives Accessed August 8, 2011.
a
Some original products are no longer available
b
May not contain all current products; products may be discontinued. Not all products are AB rated for substitution.
c
Days of each dose per pillpack
215
216 SECTION 10 | Gynecology
Epilepsy Some antiepileptic If taking lamotrigine: All If taking phenytoin, If taking lamotrigine: Estrogen- Anticonvulsants that do not
medications may induce forms except estrogen- carbamazepine, barbiturates, containing contraceptives affect OC levels: Ethosuximide,
hepatic enzymes and reduce containing contraceptives primidone, topiramate, or If taking phenytoin, gabapentin, levetiracetam,
serum concentrations of (see Table 10.1.8) oxcarbazepine: Implants carbamazepine, barbiturates, tiagabine, valproic acid, and
contraceptive hormones If taking phenytoin, primidone, topiramate, or zonisamide
carbamazepine, barbiturates, oxcarbazepine: OCs (both types)
primidone, topiramate, Some experts recommend
or oxcarbazepine: Depot higher dose OCs instead
medroxyprogesterone or IUDs (see Table 10.1.8)
Hypercoagulable Increased coagulability and Not receiving anticoagulant Not receiving anticoagulant Not receiving anticoagulant Family history does not
conditions risk of thromboembolism therapy or for ≤3 months: therapy or for ≤3 months: therapy or for ≤3 months: preclude any agents
with history of due to estrogen content Copper IUD Progestin-only contraceptives Estrogen-containing
deep venous Taking anticoagulant therapy contraceptives unless no
thrombosis for at least 3 months: All current identifiable risk factors
(DVT) or forms of contraception other Taking anticoagulant
pulmonary than estrogen containing therapy for at least 3
embolism (PE) months: Estrogen-containing
contraceptives (although some
experts feel that this is an
acceptable option)
Headache/ Estrogen-containing Nonmigraine headaches: Migraines without aura: Migraines without aura and Women who develop migraine
migraine contraceptives may increase All forms If younger than age 35, age 35 or older: Estrogen- headaches (with or without
risk of stroke (migraine Migraines without aura: Copper all others are acceptable. containing contraceptives aura) or have worsening
with aura) IUD or progestin-only OCs If 35 or older, all others Migraines with aura: Estrogen- headaches on estrogen-
except estrogen-containing containing contraceptives containing contraceptives
Migraines with aura: Copper contraceptives should discontinue their use
IUD
Migraines with aura: All
Menstrual migraine: others except estrogen-
Continuous or extended containing contraceptives
combined estrogen/progestin
10.1 | Contraception
hormonal contraceptives
Hyperlipidemia Oral estrogen may increase Copper IUD Use estrogen/progestin- Consider an OC with less
triglycerides and progestins containing OCs with caution androgenic progestin
may increase LDL if total cholesterol, LDL, and/ compared with more
cholesterol or triglycerides are elevated. androgenic progestin
All others are acceptable. Monitor fasting lipids in women
with controlled dyslipidemias
using a combination OC
219
(Continued)
220
TABLE 10.1.7 Contraception with Chronic Medical Problems (Continued)
Preferred Method of
10.1 | Contraception
immunosuppressive therapy
(and antiphospholipid
antibody negative): Copper
IUD
Adapted with permission from Contraception for women with chronic medical conditions. Pharmacist’s Letter/Prescriber’s Letter 2011;27(3):270306. www.therapeuticresearch.com.
221
222
TABLE 10.1.8 Anti-infective, Antiviral, Antibiotic, and Anticonvulsant Drug Interactions with OCs
Drug Class Generic Name Decrease OC Efficacy? Comments
10.1 | Contraception
Ritonavir Yes Backup method of contraception
Tipranavir Yes Backup method of contraception
(Continued)
223
224
SECTION 10 | Gynecology
TABLE 10.1.8 Anti-infective, Antiviral, Antibiotic, and Anticonvulsant Drug Interactions with OCs (Continued)
Drug Class Generic Name Decrease OC Efficacy? Comments
Non-nucleoside Efavirenz No Plasma concentrations of EE were increased in a small study; significance is not fully known
reverse Nevirapine Yes Backup method of contraception
transcriptase
inhibitors
Nucleoside and Various No Not all agents have data, but are not expected to interact with OCs as they do not commonly affect
nucleotide reverse liver enzymes such as CYP450
transcriptase
inhibitors
CCR5 antagonist Maraviroc No
Sources: (1) Shenfield GM, Griffin JM. Clinical pharmacokinetics of contraceptive steroids. An update. Clin Pharmacokinet. 1991;20:15–37. (2) Oral contraceptive (OC) drug
interactions. Pharmacist’s Letter/Prescriber’s Letter 2005:21(9):210903. (3) Johannsen LC, Patsalos PN. Drug interactions involving the new second and third generation antiepileptic
drugs. Expert Rev Neurother 2010;10:119–140. (4) GlaxoSmithKline. Lamictal® (lamotrigine) tablets and chewable dispersible tablets prescribing information. Research Triangle Park;
NC; 2011 Jul. (5) El-Ibiary SY, Cocohoba JM. Effects of HIV retrovirals on the pharmacokinetics of hormonal contraceptives. Eur J Contracept Reprod Health Care. 2008;13:123–132.
10.1 | Contraception 225
11 Hematology
A b b r e v i at i o n s
ACCP American College of Chest LMWH Low-molecular-weight heparin
Physicians NCCN National Comprehensive Cancer
APA Antiphospholipid antibody syndrome Network
CKD Chronic kidney disease PCC Prothrombin complex concentrate
ESA Erythropoietin-stimulating agent PPI Proton pump inhibitor
FFP Fresh frozen plasma VTE Venous thromboembolism
HIT Heparin-induced thrombocytopenia
K/DOQI The Kidney Disease Outcomes
Quality Initiative
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TABLE 11.1.1 Iron Products for Treatment of Anemia
Drug Dosing Comments
Oral Iron
Ferrous fumarate • 150–200 mg elemental per day for most patients • K/DOQI guidelines suggest 200 mg elemental per day for dialysis patients
200 mg (66 mg elemental) • Common adverse effects are constipation, diarrhea, nausea,
325 mg (106 mg elemental) vomiting, and darkened stools
• Food, PPIs, and antacids decrease absorption
Ferrous gluconate
• Taking with a vitamin C source (orange juice or 50–100 mg ascorbic
246 mg (28 mg elemental)
acid tablet) can improve tolerability and absorption (Hum Nutr Appl
300 mg (34 mg elemental)
Nutr. 1986;40:97)
325 mg (36 mg elemental)
• Sustained release formulations may bypass site of absorption
Ferrous sulfate • Hemoglobin will rise slowly, generally 2 g/L over 2–3 weeks
325 mg (65 mg elemental) • A trial of IV iron or 1-3 months of PO iron can be considered for any
220 mg/5 mL (44 mg/5 mL elemental) CKD patient with TSAT ≤30% and ferritin ≤500 ng/mL (Kidney Int
300 mg/mL (60 mg/5 mL elemental) Suppl. 2012;2:279.)
Parental Irona
Ferumoxytol (Feraheme) • CKD: 510 mg IV push every 3–8 days • Common indications for IV iron therapy include ongoing blood loss,
30 mg/mL (17 mL) intolerance of or difficulty absorbing PO iron and cancer or dialysis
patients taking ESAs who do not respond to or cannot take PO iron
Iron dextran (INFeD, Dexferrum) • Cancer: 25 mg test dose, followed 1 h later by
• Anaphylactic reactions have occurred with both iron dextran and
50 mg/ml (1, 2 mL) 100 mg over 5 minutes
sodium ferric gluconate, the reported frequency is 8.7 and 3.3 events
• Labeled dosing = 0.0442 (desired Hgb – observed
per million, respectively (Am J Kidney Dis. 1999;33:464)
11.1 | Anemia
Hgb) × LBW + (0.26 × LBW)b
• A 25 mg test dose is recommended by NCCN guidelines for sodium
Iron sucrose (Venofer) • CKD: 100–200 mg over 2–5 minutes 1–3 times per ferric gluconate in patients with history of anaphylaxis to iron dextran
20 mg/mL (5, 10 mL) week up to 1 g cumulative dose • Delayed (1–2 days) infusion reactions reported with iron dextran
• Cancer: 200 mg infused over 1 h every 2–3 weeks including arthralgias, dizziness, chills, and fever
Sodium ferric gluconate (Ferrlecit) • CKD: 125 mg over 1 h per dialysis session × 8 doses
12.5 mg/mL (5 mL) • Cancer: 125 mg over 1 h weekly × 8 doses
229
a
Parenteral iron product strengths reflect elemental iron content.
b
LBW, lean body weight.
230
SECTION 11 | Hematology
TABLE 11.1.2 Erythropoietin-Stimulating Agents for Treatment of Anemia
Drug Indication Dosing and Titration Comments
Epoetin CKD Initial dose: • Adverse effects include Hypertension (5–24%),
alfa • 50–100 units/kg 3 times/week thrombotic events, edema, fever, dizziness,
(Epogen, Titration: insomnia, headache, pruritus, rash, nausea,
Procrit) • If Hgb ↑ >1 g/dL in 2 weeks, ↓ dose ≥25% constipation, vomiting, diarrhea, dyspepsia,
• If Hgb <10 g/dL and does not ↑ by 1 g/dL after 4 weeks,↑ dose 25% injection site reactions, arthralgias, cough,
• Dialysis: If Hgb @ 11 g/dL ↓ dose or discontinue seizure
• Nondialysis: If Hgb @ 10 g/dL ↓ dose or discontinue • Hgb response 2–6 weeks
• Discontinue if response inadequate at 8 weeks
Cancer Initial dose: (chemo) or 12 weeks (CKD) with appropriate
• 150 units/kg 3 times/week or 40,000 units/week doses
Titration: • Evaluate BP, seizure, and VTE risk prior to
• If Hgb ↑ >1 g/dL in 2 weeks, ↓ dose ≥25% initiating therapy
• If Hgb <10 g/dL and does not ↑ by 1 g/dL after 2 weeks, ↑ dose 25% • Epogen and Procrit contain human albumin
Darbepoetin CKD Initial dose: • Adverse effects include edema (21%),
alfa • Dialysis: 0.45 mg/kg/week, or 0.75 mg/kg/2 weeks hypertension (4–20%), hypotension (20%),
(Aranesp) • Nondialysis: 0.45 mg/kg/4 weeks fatigue, fever, headache, dizziness, diarrhea,
Titration: constipation, vomiting, nausea, muscle spasm,
• If Hgb ↑ >1 g/dL in 2 weeks, ↓ dose 25%; if Hgb continues to increase, discontinue and arthralgia, upper respiratory infection
resume when needed at ↓ dose • Aranesp available in albumin-containing and
• If Hgb <10 g/dL and does not ↑ by 1g/dL after 4 weeks, dose 25% albumin-free
• Dialysis: If Hgb @11 g/dL ↓ dose or discontinue • IV dosing recommended for dialysis patients
• Nondialysis: If Hgb @10 g/dL ↓ dose or discontinue • Aranesp SingleJect contains latex packaging
• Discontinue if response inadequate at 8 weeks
Cancer Initial dose: (chemo) or 12 weeks (CKD) with appropriate
• 2.25 mg/kg/week or 500 mg/3 weeks until completion of chemo doses
Titration: • Evaluate blood pressure, seizure, and VTE risk
• If Hgb <10 g/dL and does not ↑ by 1 g/dL after 6 weeks, ↑ dose to 4.5 mg/kg/week (weekly prior to initiating therapy
dosing; do not adjust if Q3 week dosing)
• If Hgb ↑ >1 g/dL in 2 weeks, or if sufficient to avoid RBC transfusion, ↓ dose 40%; if Hgb
exceeds concentration needed to avoid transfusion, hold, and resume at 40% ↓ dose
Reproduced with permission from Ryan L. Anemia. In: Attridge R, Miller M, Moote R, Ryan L, eds. Internal Medicine: A Guide to Clinical Therapeutics. New York, NY: McGraw-Hill; 2012:chap 21.
11.1 | Anemia
231
232
SECTION 11 | Hematology
TABLE 11.2.1 Risk Stratification and Indications for VTE Prophylaxis in Medical Inpatients
Category VTE Risk (Padua Prediction Score) VTE Risk (IMPROVE Risk Score) Hemorrhagic Risk (IMPROVE Bleeding Risk)
Strongest risk factors • Active cancer (3 pts) • Previous VTE (3 pts) • Active gastroduodenal ulcer
• Prior VTE (3 pts) • Known thrombophilia (3 pts) • Bleeding w/in 3 months prior to admission
• Reduced mobility (bed rest for at least 3 days—3 pts) • Platelet count <50,000/mm3
• Known thrombophilia (3 pts)
Other risk factors • Trauma and/or surgery within past 1 month (2 pts) • Cancer (1 pt) • Increased age (≥85 vs. <40)
• Age ≥70 years old (1 pt) • Age >60 years old (1 pt) • Hepatic failure (INR >1.5)
• Heart or respiratory failure (1 pt) • Severe renal failure (GFR <30 mL/min)
• Acute MI or ischemic stroke (1 pt) • ICU or CCU admission
• Acute infection or rheumatologic disease (1 pt) • Central venous catheter
• BMI ≥30 (1 pt) • Rheumatic disease
• Ongoing hormonal therapy (1 pt) • Current cancer
• Male sex
Score calculation • Add points for each risk factor • Calculate risk score at http://www.outcomes-umassmed.org/IMPROVE
• ≥4 points is considered high risk (11% VTE risk)
Prophylaxis • No risk score has been prospectively and independently validated; use clinical judgement in determining use of prophylaxis
indications • Consider pharmacologic prophylaxis for medical inpatients with high VTE risk (including critically ill patients) and low bleeding risk
• Consider mechanical prophylaxis for medical inpatients with high VTE risk and high bleeding risk
• See reference no. 4 for an in depth discussion of the risks, benefits, and indications for VTE prophylaxis
Sources: (1) Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua
Prediction Score. J Thromb Haemost. 2010;8:2450–2457. (2) Spyropoulos AC, Anderson FA, Fitzgerald G, et al. Predictive and associative models to identify hospitalized patients
at risk for VTE. Chest. 2011;140:706–714. (3) Decousus H, Tapson VF, Bergmann JF, et al. IMPROVE investigators. Factors at admission associated with bleeding risk in medical
inpatients. Chest. 2011;139:69–79. (4) Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in non-surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed:
American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2)(Suppl):195s–226s.
TABLE 11.2.2 Pharmacotherapy for VTE Prophylaxis
Drug Indication Dose Comments
Parenteral Anticoagulants
Unfractionated heparin All indications 5000 U SC Q 8–12 h • Enoxaparin 30–60 mg SC BID has been studied in bariatric surgery
Enoxaparin (Lovenox) General medical or critically ill patients 40 mg SC Q 24 h patients, it is unclear if these doses are beneficial in obese medical
inpatients
Hip replacement surgery 40 mg SC Q 24 h • Dalteparin half-life prolonged if CrCl <30, no dose adjustment
30 mg SC Q 12 h provided by manufacturer, no significant accumulation with 5000
Knee replacement surgery 30 mg SC Q 12 h U SC daily dose for 7 days in patients with CrCl <30 (Arch Int Med.
2008;168:1805)
Abdominal surgery 40 mg SC Q 24 h
• Fondaparinux is contraindicated in patients weighing ≤50 kg or with
CrCl ≤30 mL/min 30 mg SC Q 24 h CrCl <30 mL/min
Dalteparin (Fragmin) General medical or critically ill patients 5000 U SC Q 24 h • ACCP guidelines recommend prophylaxis for orthopedic procedures
be initiated ≥12 h prior to or after surgery and continued for
Hip replacement surgery 2500 U SC × 1 after surgery,
10–14 days (Chest. 2012;141(2)(Suppl):e278)
then 5000 U SC Q 24 h
• ACCP guidelines recommend pharmacologic prophylaxis in abdominal
233
dose of rivaroxaban, wait 6 hours to give subsequent dose.
234
TABLE 11.2.3 Pharmacotherapy for VTE Treatment
Drug Dose Comments
(Continued)
235
236
SECTION 11 | Hematology
TABLE 11.2.4 Monitoring Anticoagulants for VTE Prophylaxis and Treatment (Continued)
Drug Indication Assay Target Range Comments
Warfarin VTE prophylaxis or INR 2–3 • Most patients with VTE should be treated for 3 months
treatment • Consider longer term therapy for patients with VTE
Recurrent VTE with APA INR 2.5–3.5 secondary to cancer or with an unprovoked VTE at low
syndrome risk of bleeding
• See reference no. 3 for full recommendations
Sources: (1) Nutescu EA, Spinler SA, Wittkowski A, Dager WE. Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice
recommendations across medical and surgical settings. Ann Pharmacother. 2009;43:1064–1083. (2) Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants:
antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2)(Suppl):e24S–
e43S. (3) Kearon C, Akl E, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest
Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2)(Suppl):e419S–e494S.
TABLE 11.2.5 Selected Warfarin Drug Interactions
Interacting Drug INR Typical Onset Clinical Implications
Amiodarone ↑ 1–3 months Potent 3A4 inhibitor, high incidence of interaction
Valproic acid ↑ <24 h Transient effect, no warfarin dose adjustment needed
Simvastatin, lovastatin, fluvastatin, rosuvastatin ↑ Within 1 week, potentially later Simvastatin increased the INR 27% in one study (Thromb Haemost.
2003;89:949); consider atorvastatin or pravastatin
Phenobarbital ↓ Between 1 week and 1 month Decreases warfarin levels 38–40%
Fenofibrate ↑ Within 1 week Supported by multiple case reports; consider empiric 20% reduction in warfarin
dose (Ann Pharmacother. 2003;37:212); interaction is possible but appears
less likely with gemfibrozil
Trimethoprim/Sulfamethoxazole ↑ 2 days to 1 week Supported by multiple case reports; consider empiric dose decrease or
237
238
SECTION 11 | Hematology
TABLE 11.3.1 Management of Excess Anticoagulation
Clinical Situation Recommended Management
INR >5.0 If no significant bleed, omit or decrease dose
INR 5.0–9.0 If no significant bleed, omit 1–2 doses, hold warfarin, and give vitamin K 2.5 mg PO × 1
INR >9.0 If no significant bleeding, hold warfarin and give vitamin K 2.5–5 mg PO × 1
Serious bleeding on warfarin Hold warfarin, give vitamin K 10 mg IV (administer over at least 10 minutes) plus FFP or PCC
Serious bleeding on unfractionated heparin drip Stop heparin drip, administer protamine sulfate, 1 mg per 100 U heparin administered within the past 3 h
Serious bleeding while on subcutaneous unfractionated heparin Hold heparin, administer protamine sulfate 1 mg per 100 U heparin dosed, give first 50 mg IV push over
10 minutes, infuse the remainder over 8–12 h
Serious bleeding while on subcutaneous enoxaparin Hold enoxaparin, administer protamine sulfate 1 mg per 1 mg enoxaparin administered; may repeat 0.5 mg
protamine per 1 mg enoxaparin if bleeding continues
Serious bleeding while on subcutaneous dalteparin Hold dalteparin, administer protamine sulfate 1 mg per 100 U dalteparin administered; may repeat 0.5 mg
protamine per 100 U dalteparin if bleeding continues
Sources: (1) Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest
Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2)(Suppl):e24S–e43S. (2) Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin K
antagonists, 8th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2008;133:160–198. (3) Ryan L. Anticoagulation. In: Attridge R, Miller
M, Moote R, Ryan L, eds. Internal Medicine: A Guide to Clinical Therapeutics. New York, NY: McGraw-Hill; 2012.
TABLE 11.3.2 Pharmacotherapy for HIT
Drug Dose Comments
Argatroban • Initial infusion 2 mg/kg/min (actual body weight) 4Ts Pre-test probability for HIT:
• Lower initial infusion to 0.5–1.2 mg/kg/min in heart failure, • Thrombocytopenia: Platelet count fall: >50% and nadir >20,000 = 2 points;
anasarca, critically ill patients with multiorgan dysfunction or 30–50% or nadir 10–19,000 = 1 points; <30% or nadir <10,000 = 0 points
postcardiac surgery • Timing of platelet count fall: Clear onset between days 5 and 10 or platelet
• Measure aPTT 2 h after initiation, then maintain aPTT count fall at ≤1 day if prior heparin exposure within the last 30 days = 2 points;
1.5–3 times baseline consistent with fall at 5–10 days but unclear (e.g., missing platelet counts), onset
• Transition to warfarin alone once INR on argatroban ≤2 mg/ after day 10, or fall ≤1 day with prior heparin exposure within 30–100 days = 1 point;
kg/min and warfarin combined >4.0 platelet count fall at <4 days without recent exposure = 0 points
• If argatroban dose >2 mg/kg/min, reduce dose to 2 mg/kg/ • Thrombosis or other sequelae: Confirmed new thrombosis, skin necrosis, or
min and measure INR 4–6 h post-dose reduction acute systemic reaction after intravenous unfractionated heparin bolus = 2 points;
progressive or recurrent thrombosis, nonnecrotizing (erythematous) skin lesions, or
239
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Section
12 Critical Care
12.5 Drugs for Atrial Fibrillation with Rapid Ventricular Response 246
A b b r e v i at i o n s
ACS Acute coronary syndrome PEA Pulseless electrical activity
ACLS Advanced cardiovascular life support RASS Richmond agitation sedation scale
CI Cardiac index RSI Rapid sequence intubation
CVD Cardiovascular disease SBP Systolic blood pressure
CVP Central venous pressure ScvO2 Central venous oxygen saturation
HR Heart rate SvO2 Venous oxygen saturation
ICP Intracranial pressure VF Ventricular fibrillation
IO Intraosseous VT Ventricular tachycardia
MAP Mean arterial pressure
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12.1 | Rapid Sequence Intubation 243
TABLE 12.5 Drugs for Atrial Fibrillation with Rapid Ventricular Response
Maintenance
Agent Loading Dose Dose Titration (Goal) Comments
Diltiazem 0.25 mg/kg 5–15 mg/h 5 mg/h Q 15 min Avoid in systolic heart failure
(SBP <160; HR <100)
Verapamil 0.075–0.15 mg/kg No infusion N/A Avoid in systolic heart failure
Esmolol 500 mg/kg 50–200 mg/ 50 mg/kg/min Q Avoid in asthmatics
kg/min 5–10 min
(SBP <160; HR <100)
Metoprolol 2.5–5 mg No infusion N/A Give for 3 doses; caution in
asthmatics
Propranolol 0.15 mg/kg No infusion N/A Avoid in asthmatics
Amiodarone 150 mg 0.5–1 mg/min Fixed Several toxicities: pulmonary,
skin, thyroid, optic, hepatic;
can be used in patients with
an accessory pathway
Digoxin 0.5 mg × 1, then 0.125–0.25 N/A Check digoxin level
0.25 mg Q 6 h × 2 mg/day (HR <100) (0.8–2.0 ng/mL); reduce
doses; OR 0.25 Q maintenance dose in renal
2 h, up to 1.5 mg insufficiency
12.6 | Advanced Cardiovascular Life Support 247
A b b r e v i at i o n s
ADH Antidiuretic hormone NDI Nephrogenic diabetes insipidus
CDI Central diabetes insipidus ½ NS Half-normal saline (0.45% saline)
D5W Dextrose 5% NS Normal saline
DDAVP Desmopressin UOP Urine output
DI Diabetes insipidus SIADH Syndrome of inappropriate
HCTZ Hydrochlorothiazide antidiuretic hormone
LR Lactated ringers
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TABLE 13.1.1 Fluid Composition and Uses
Fluid Composition Main Indications Comments Dosing
Hypotonic Fluids
D5W Fluid maintenance May impair glucose control in • Maintenance dosing according to the 4:2:1 rule:
diabetes; provides free water to all • 4 mL/kg/hr for 1–10 kg
compartments • Add 2 mL/kg/h for 10–20 kg
½ NS—0.45% NaCl Fluid maintenance Hyponatremia with long-term use; • Add 1 mL/kg/h for every kg over 20 kg
(Na+ 77 mEq/L, Cl- 77 mEq/L) increased risk of IV infiltration vs.
isotonic
Isotonic Fluids
NS—0.9% NaCl Fluid replacement; Monitor for fluid overload; • Dose varies widely depending on patient fluid status and clinical
(Na+ 154 mEq/L; Cl- 154 mEq/L) hypovolemia, shock hyperchloremic metabolic acidosis situation
251
= 1/(Effect of 1 L 3% saline on serum [Na+])
FIGURE 13.1.2 Evaluation Algorithm for Hyponatremia
252
Measured serum osmolality (mOsm)
Severe acute hyponatremia: (severe Moderate acute hyponatremia: Mild chronic hyponatremia:
headache, obtundation, seizures, coma) (confusion, lethargy, dizziness) (absent or mild, stable symptoms)
253
(Continued)
FIGURE 13.1.3 Treatment Algorithm for Hyponatremia (Continued)
254
SECTION 13 | Fluids and Electrolytes
Additional diagnosis- Additional diagnosis-
specific treatment specific treatment
UOP
Treatment Treatment
• Calculate and replace • D5W IV (combine with a loop
water deficit (PO if possible) diuretic if hypervolemic) >300 mOsmol/kg H2O <300 mOsmol/kg H2O
DDAVP response?
Treatment Treatment
+
• Dietary Na restriction <2,000 mg/d
• DDAVP 10 µg intranasal QD, titrate to UOP 1.5–2 L/D.
+ • HCTZ—alone or combined with
a
TBW = 0.5 × weight (kg) females: • Monitor plasma [Na ] frequently during titration
255
0.6 × weight (kg) males. • May add other agents as needed (see Table 13.1.5) indomethacin or amiloride
256
SECTION 13 | Fluids and Electrolytes
TABLE 13.1.5 Pharmacotherapy of Sodium Disorders
Drug Indication Dosing Comments
Hyponatremia
3% saline Acute hyponatremia with severe Infusion rate = desired [Na+] • Limit serum [Na+] correction to ≤12 mEq/L/d for acute,
symptoms ↑ per hour (mEq/h) × weight (kg) ≤8 mEq/L/d for chronic hyponatremia to prevent osmotic
(see Table 13.1.1) demyelination
• Total daily correction more predictive of osmotic demyelination
than hourly correction rate (Kidney Int. 1992;41(6):1662)
Demeclocycline Chronic, mild SIADH Initiate 300 mg BID; max 600 mg • Dizziness, headache, nausea, and common diarrhea can be
BID; 3–4 days for max effect nephrotoxic
• Take on empty stomach; do not take with dairy products or
antacids due to deactivation from chelation
• Avoid in renal dysfunction
• Peak effect in 3–4 days
Conivaptan (Vaprisol) Hypervolemic hyponatremia Load 20 mg IV over 30 min, • May cause hypotension or infusion site pain (use central line)
secondary to heart failure or acute then 20 mg infused over 24 h; up • Limit serum [Na+] correction to ≤12 mEq/L/d for acute,
symptomatic SIADH to 4 days ≤8 mEq/L/d for chronic hyponatremia to prevent osmotic
demyelination
• Avoid in patients with cirrhosis due to potential for hypotension
from V1 a receptor blockade (Kidney Int. 2006;69:2124)
Tolvaptan (Samsca) Chronic SIADH, hypervolemic Initiate 15 mg PO QD; max • Onset within 24 h
hyponatremia 60 mg PO QD • Dosing can be limited by thirst stimulation
Hypernatremia
DDAVP CDI along with fluid restriction Intranasal: Initial 0.1 mg QD; • 1 st line for CDI
max 0.2 mg BID • Titrate to UOP 1.5–2 L/d
SC: 0.1–0.2 mg BID • More predictable response with intranasal than PO
• SC and PO forms are approximately 1/10th the potency of
PO: 0.1 mg QD intranasal with high inter-patient variability
HCTZ NDI; CDI along with DDAVP 25 mg QD up to BID • 1 st line for NDI
Indomethacin NDI along with HCTZ 50 mg Q8–12 h • Counteracts renal prostaglandin inhibition of ADH
Amiloride NDI along with HCTZ 5–10 mg QD • 1 st line for NDI secondary to Li++
• Monitor for hyperkalemia
• May combine with HCTZ
259
260
SECTION 13 | Fluids and Electrolytes
TABLE 13.3.1 Calcium and Phosphorus Repletion
Drug Dosage Forms Dosinga Comments
Oral Calcium
Calcium carbonate Tablets and suspension 1,000–2,000 mg per day elemental • 40% elemental calcium
(many strengths) calciumb given with meals • Acidic pH required for maximal absorption; take with food; absorption reduced by
PPIs and H2 blockers
Calcium citrate Tablets (many strengths) 1,000–2,000 mg elemental calciumb • 21% elemental calcium
divided 2 to 3 times per day • pH-independent absorption (may take with or without food)
IV Calcium
Calcium chloride 100 mg/mL injection 1 g slow IV push (over 10 min) in a • 27.3% elemental calcium
central line or 1–2 g in 100 mL • Requires central line secondary to vein irritation
(D5 W or NS) infused over 1 h, repeat • Do not give IM or SC due to severe tissue injury
as needed • IV calcium reserved for symptomatic hypocalcemia
Calcium gluconate 500 mg tablet; 100 mg/mL 1 g IV push or 1–2 g in 100 mL • 9.3% elemental calcium
injection (D5 W or NS) infused over 15 min, • IV calcium reserved for symptomatic hypocalcemia
repeat as needed • May infuse in peripheral vein or give IM
Oral Phosphate
Potassium phosphate Neutra-Phos-K (8 mmol 1–3 packets 3 times daily • 8 mmol PO4 = 250 mg PO4
PO4/14.25 mEq K+) • Use low K+ formulation if normal or high serum [K+] (see sodium–potassium
granules phosphate below)
Sodium–potassium 8 mmol PO4 with varying 1–3 packets/tablets 3 times daily • Neutra-Phos (8 mmol PO4/7 mEq Na+/7 mEq K+) granules
phosphate amounts of Na+ and K+ • K-Phos Neutral (8 mmol PO4/13 mEq Na+/1.1 mEq K+) tablets
(see comments) • Uro-KP-Neutral (8 mmol PO4/10.9 mEq Na+/1.27 mEq K+) tablets
IV Phosphate
Sodium phosphate 3 mmol PO4/4 mEq Na+ per 15 mmol PO4 in 250 mL (D5W or • 15 mmol in 250 mL ½ NS or 30 mmol in 250 mL D5W produce an isotonic
mL injection ½NS) or 30 mmol in 250 mL D5W solution
infused over 3 h, repeat as needed • Do not administer to patients with hypercalcemia or co-administer with IV
calcium
261
262
TABLE 13.3.2 Pharmacotherapy of Hypercalcemia
14 Pain Management
A b b r e v i at i o n s
AKI Acute kidney injury IR Immediate release
COX Cyclooxygenase NSAID Nonsteroidal anti-inflammatory drug
CR Controlled release TDS Transdermal system
ER Extended release VAS Visual analog scale
ICP Intracranial pressure XR Extended release
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14.1 | Non-Opioid Analgesics 265
Lamotrigine (Lamictal): 25, 50, 100, 200 mg Neuropathic pain Initial 25 mg QOD 2 weeks; then 25 mg QD Do not discontinue abruptly
tabs; 2, 5, 25 mg chewable tabs; 25, 50, 100, 2 weeks; then by 25–50 mg/day Q 1–2 weeks; up
200, 300 mg XR tabs; 25, 50, 100 mg ODTs to 50–400 mg/day typical
Topiramate (Topamax): 15, 25 mg sprinkle Neuropathic pain Initial 25–50 mg QD; ↑ by 25–50 mg Q week; Limited data
caps; 25, 50, 100, 200 mg tabs 200 mg BID studied; max 1,600 mg/day
Valproic acid: 125, 250, 500 mg softgel IR and Neuropathic pain Initial 125 mg TID; maint; 500–1,000 mg TID Monitor levels (<100 mg/mL); CYP-450 inhibitor;
XR; 250/5 mL PO solution monitor for drug interactions
267
(Continued)
268
SECTION 14 | Pain Management
TABLE 14.1.3 Adjuvant Analgesics (Continued)
Drug Syndrome Dosing Comments
Corticosteroids
Dexamethasone: 0.5, 0.75, 1, 1.5, 2, 4, 6 Spinal cord Load 40–100 mg IV dex or equivalent High dose ≤72 h; if no benefit, dose can be rapidly
mg tabs; 0.5/5 mL, 1 mg/30 mL PO solution; compression, ↑ ICP (methylprednisolone 40–80 mg IV) or 10–20 mg IV tapered; if pain improves, taper to lowest effective
solution for injection Q 6 for initial 24–72h dose
Methylprednisolone: 4, 8, 16, 32 mg tabs; Nerve compression, Dex 4–8 mg PO Q 8–12 h; methylprednisolone Usefulness limited to 2–3 months before steroid-
solution and suspension for injection visceral distension, 20–40 mg PO Q 8–12 h induced side effects outweigh benefit
↑ ICP
Bone pain, nausea, Dex 4–12 mg/day
anorexia
Other
Lidocaine patch (Lidoderm) 5% Postherpetic 1 patch for 12h/day; 1–3 patches Clinical experience supports use in painful
neuralgia peripheral neuralgia
Pamidronate (Aredia): 3, 6, 9 mg/mL injection Bone pain 90 mg IV Q 4 weeks, may ↓ interval to Q 3 weeks; Decreased impact of disease progression in
solution; 30, 90 mg powder for reconstitution ↓ dose renal dysfunction patients with osteolytic lesions secondary to
multiple myeloma, breast cancer, prostate cancer
Zoledronic acid (Zometa, Reclast): 4, 5 mg/ 4 mg IV Q 4 weeks; may ↓ interval to Q 3 weeks;
100 mL, 4 mg/5 mL injection solution ↓ dose renal dysfunction
Reproduced with permission from Scullion BF, Ryan L. Pain. In: Attridge R, Miller M, Moote R, Ryan L, eds. Internal Medicine: A Guide to Clinical Therapeutics. New York, NY: McGraw-Hill;
2012:chap 45. Table 45-3.
TABLE 14.2.1 Suggested Opioid Regimens by Clinical Situation
Situation Opioid Regimen
Acute episodic pain in opioid • Provide short-acting IV or PO opioid on PRN basis (see Table 14.2.2)
naïve patient • Monitor pain response and increase dose or consider scheduling opioid if pain poorly controlled
Acute severe pain in opioid • Morphine 1–5 mg IV (or equivalent dose of another opioid)
naïve patient • Reassess pain in 15 min; if pain level has not dropped 2–4 points on VAS, then double morphine dose
• Repeat for 1 more cycle if pain uncontrolled
• Monitor respiratory rate and sensorium closely; have naloxone available
• Schedule an appropriate opioid regimen once acute control achieved
Chronic pain in opioid naïve • Schedule either short-acting or long-acting opioid at appropriate dosing intervals (see Table 14.2.2)
patient • Provide PRN opioid for breakthrough pain; rule of thumb is to provide breakthrough dose equivalent to 10–15% of the total daily scheduled
regimen (per dose)
• Example: Morphine CR 15 mg Q 12 h and morphine IR 5 mg Q 4 h PRN
Uncontrolled pain in a patient • Mild-to-moderate pain: increase total daily opioid dose by 25–50%
already taking opioids • Moderate-to-severe pain: increase total daily opioid dose by 50–100%
269
270
TABLE 14.2.2 Opioid Dosing in Naïve Patients
Drug Products Typical Dosing Onset Duration Comments
271
272
SECTION 14 | Pain Management
TABLE 14.2.3 Opioid Equianalgesic Dose Conversions
Equianalgesic Dose (mg)
Drug Oral Parenteral Stepwise Conversion Procedure
Morphine 30 10 • Calculate total 24-h opioid dose of each different opioid being taken
Hydromorphone 7.5 1.5 • Convert total 24-h dose of each opioid to an equivalent dose in oral morphine equivalents using the table.
Add equivalent doses of each opioid being taken together to get the total daily oral morphine equivalent dose
Oxycodone 20 — • Determine the dose of the new opioid regimen equal to the calculated daily oral morphine equivalent using
Hydrocodone 30 — the table
• Reduce calculated dose of new opioid by 25–50% to prevent overdose from incomplete cross-tolerance
Oxymorphone 10 1
between opioids
Fentanyl — 0.1 (100 mg)
Meperidine 300 75
Tramadol 120 —
Buprenorphine 0.4 0.3
TABLE 14.2.4 Fentanyl Transdermal Patch Conversions
Morphine (mg/day)
Fentanyl TDS (g/h) PO IV Stepwise Conversion Procedures
25 50 17 Conversion from another opioid regimen to fentanyl TDS
50 100 33 1. Calculate total daily dose of opioid including long- and short-acting agents
2. Use conversion chart (Table 14.2.1) to convert total daily dose to oral morphine equivalents
75 150 50 3. Convert oral morphine equivalents to fentanyl TDS and round to patch size per individual patient
100 200 67 characteristics:
• Round down if patient is elderly, has renal or liver impairment, or was well controlled on prior regimen
125 250 83
• Round up if pain control was inadequate on previous regimen
150 300 100 4. Perceptible analgesia is delayed 12 h and peak analgesia occurs around 36 h after patch application
175 350 117 • Give prior long-acting opioid for the first 12 h and short-acting breakthrough doses until pain controlled.
200 400 133 Conversion from fentanyl TDS to another opioid regimen
• Use conversion chart to determine daily oral morphine equivalent dose to fentanyl TDS
225 450 150
273
274
SECTION 14 | Pain Management
TABLE 14.2.5 Methadone Conversions
Total Daily Oral Morphine Equivalent Oral Morphine:Methadone Equivalent Daily
Dose (mg) Dose (mg:mg) Comments
<100 4:1 • Conversion from morphine to methadone is complex and highly variable
101–300 8:1 from patient to patient
• The conversion is not linear; higher daily doses of morphine (or
301–600 10:1 equivalent) require lower doses of methadone on a mg per mg basis
601–800 12:1 • This table reflects one of several published conversion ratios; these ratios
are more conservative than many others in the literature
801–1,000 15:1
>1,000 20:1
Stepwise Conversion Procedure (Using Ratios) Alternative Conversion Procedure
1. Add total 24-h opioid dose of each different opioid being taken 1. Follow steps 1 and 2 of the stepwise conversion procedure
2. Convert total 24-h dose of each opioid to an equivalent dose in oral morphine equivalents using 2. Convert total daily morphine equivalent dose to methadone dose using
the table. Add equivalent doses of each opioid being taken together to get the total daily oral 10:1 ratio (or 20:1 ratio if patient >65 years old or daily morphine
morphine equivalent dose >1,000 mg)
3. Convert total daily oral morphine equivalent dose to methadone dose using above ratios 3. Give calculated methadone dose (up to 30 mg) every 3 h PRN
4. Reduce calculated dose of methadone by 30–50% to account for incomplete cross-tolerance. 4. Continue for 6 days. After 6 days, average total methadone requirement
Give in divided dose Q 8 h from day 5 and 6. This average dose is the new daily scheduled dose of
methadone (divided BID)
Sources: (1) Scullion BF, Ryan L. Pain. In: Attridge R, Miller M, Moote R, Ryan L, eds. Internal Medicine: A Guide to Clinical Therapeutics. New York, NY: McGraw-Hill;2012:chap 45. (2)
McPherson, MLM. Methadone: A Complex and Challenging Analgesic, But Its Worth It. In: Demystifying Opioid Conversion Calculations: A Guide for Effective Dosing. Bethesda, MD:
American Society of Health-System Pharmacists;2009:chap 6. (3) Gazelle G, Fine PG. Methadone for the Treatment of Pain. 2nd ed. Fast Facts and Concepts. July 2006; 75.
http://www.eperc.mcw.edu/fastfact/ff_075.htm
TABLE 14.2.6 Opioid Adverse Effects
Effected System Symptoms Comments
Cardiovascular • Hypotension (more common with IV push opioids) • Cardiac monitoring for methadone: obtain ECG at baseline, at 30 days and annually,
• QTc prolongation (methadone) inform patient of risks, discontinue if QTc >500 ms, check for interacting drugs
(Ann Int Med. 2009;150:387)
Central nervous system (CNS) • Withdrawal: mydriasis, diaphoresis, tachycardia, • Patients receiving continuous opioids for 1–2 weeks are at risk of withdrawal if opioid
anxiety, hypertension discontinued
• CNS depression: sedation, somnolence, confusion • Onset usually 6–12 h after last dose (short-acting opioid) or 72–96 h following
• Other: euphoria, confusion, delirium, hallucinations methadone
• Can avoid withdrawal by tapering by 25% every 2 days
Gastrointestinal Nausea, vomiting, constipation • Patients taking scheduled opioids should be on a scheduled bowel regimen including
a stimulant laxative (typically Senna) to prevent constipation
275
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Section
15 Urology
A b b r e v i at i o n s
BPH Benign prostatic hyperplasia PSA Prostate-specific antigen
IR Immediate release XR Extended release
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15.1 | Benign Prostatic Hyperplasia 279
BPH
Reproduced with permission from Talbert RL, DiPiro JT, Matzke GR, Posey LM, Wells BG, Yee GC.
Benign Prostatic Hyperplasia. In: Talbert RL, DiPiro JT, Matzke GR, Posey LM, Wells BG, Yee GC, eds.
Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill; 2011:chap 93
280
SECTION 15 | Urology
TABLE 15.1.2 Pharmacotherapy for BPH
Drug Dosing Peak Onset Comments
Nonselective α-Adrenergic Antagonists
Alfuzosin (Uroxatral) 10 mg QD 1 week • Orthostatic hypotension, syncope and dizziness common with doxazosin, prazosin and
Doxazosin (Cardura) 1–8 mg QD 2–6 weeks terazosin; in particular with the first few doses; 10% of patients will stop taking due to side
effects (Int J Clin Pract. 2008;62:1547); start with low dose and titrate up as tolerated over the
Doxazosin GTS (Cardura XL) 4–8 mg QD 1 week course of 4–6 weeks
Prazosin (Minipress) 0.5–2 mg BID 2–6 weeks • Prazosin not recommended due to more side effects (J Urol. 2003;170:530)
• Alfuzosin has a low incidence of cardiovascular side effects due to its low serum and high
Terazosin (Hytrin) 1–10 mg QD 2–6 weeks
prostate concentration; dose titration is not needed
• These agents will not effect PSA, prostate size, or alter disease progression
Selective α-Adrenergic Antagonists
Silodosin (Rapaflo) 8 mg QD 1 week • Tamsulosin and silodosin have low incidence of cardiovascular side effects
Tamsulosin (Flomax) 0.4–0.8 mg QD 1 week • Common side effects include flu-like illness, fatigue, nasal congestion, and ejaculatory
dysfunction
5α-Reductase Inhibitors
Dutasteride (Avodart) 0.5 mg QD 3–6 months • Sexual side effects occur in approximately 10% of patients and include erectile dysfunction,
Finasteride (Proscar) 5 mg QD 3–6 months ejaculatory dysfunction, and decreased libido
• Will reduce prostate size and PSA; measured PSA should be doubled to reflect true value in
patients taking these agents (J Urol. 2003;170:530)
• Finasteride and dutasteride reduced prostate cancer incidence by ~25% over 7 and 4 years,
respectively (N Engl J Med. 2003;349:215; N Engl J Med. 2010;362:1192)
TABLE 15.2.1 Pharmacotherapy of Urinary Incontinence
Drug Indications Dosing Comments
Antimuscarinic Agents
Darifenacin (Enablex) Urge incontinence 7.5–15 mg QD • Antimuscarinics are first-line therapy for urge incontinence
Fesoterodine (Toviaz) Urge incontinence 4–8 mg QD • A systematic review of comparative trials found that
tolterodine IR was better tolerated than oxybutynin IR;
Oxybutynin (Ditropan, Anturol, Urge incontinence IR (Ditropan): 2.5–5 mg BID-QID solifenacin and fesoterodine had better efficacy than
Gelnique, Oxytrol) XR (Ditropan XL): 5–30 mg QD tolteridine XR, but fesoterodine had higher incidence
of adverse effects (Cochrane Database Syst Rev.
Patch (Oxytrol): 3.9 mg patch applied Q 3–4 days
2012;1:CD005429)
Gel (Gelnique): One sachet applied QD • Dry mouth, constipation, dizziness, and visual disturbances
Gel (Anturol): 84 mg (3 pumps) applied QD are common, highest incidence with oxybutynin IR and
tolterodine IR, lowest incidence with oxybutynin patch and
Tolterodine (Detrol) Urge incontinence IR (Detrol): 1–2 mg BID
281
282
SECTION 15 | Urology
TABLE 15.2.1 Pharmacotherapy of Urinary Incontinence (Continued)
Drug Indications Dosing Comments
Antidepressants
Duloxetine (Cymbalta) Stress incontinence 40–80 mg QD • Anticholinergic side effects (dry mouth, dizziness,
Imipramine Urge incontinence, stress 25–100 mg QHS constipation) and orthostasis common with imipramine;
incontinence start at low dose and take at night to minimize
• Nausea common with duloxetine; improves over time
• Both agents have modest efficacy
α-Adrenergic Agonists
Pseudoephedrine Stress incontinence 15–60 mg TID • Avoid in patients with hypertension, ischemic heart disease,
Phenylephrine Stress incontinence 10 mg QID arrhythmias, or renal failure
Cholinomimetic
Bethanechol Atonic bladder 25–50 mg TID–QID • Take on empty stomach
Index
283
284 Index
Bronchodilators Cefdinir
adverse effects of, 167 for acute otitis media, 67
for stable COPD, 165 oral, dosing regimens for, 46
Budesonide DPI, 159, 160, 166 Cefepime
Budesonide/formoterol MDI, 166 adverse effects and monitoring, 48–49
Budesonide suspension, 159 intravenous, 41, 44
Bumetanide, 31 susceptibility breakpoint MIC interpretive
Buprenorphine, 270, 272 criteria, 50
Bupropion, 13, 189, 190, 193, 196, 198 Cefotaxime
Buspirone, 190, 193, 199 for cirrhosis complications, 148
Butorphanol nasal spray, 133 intravenous, dosing regimens for, 41
susceptibility breakpoint MIC interpretive criteria,
C 50, 51
Calcitonin, 262 Cefotetan, 41
Calcitriol, 172 Cefoxitin, 41
Calcium acetate, 173 Cefpodoxime
Calcium carbonate, 173, 260 for acute otitis media, 67
Calcium channel blockers oral, dosing regimens for, 46
adverse effects, 9 Cefprozil, 46
for antihypertensive blood pressure reduction, 7 Ceftaroline, 41
dose ranges, 4 Ceftibuten, 46
for headache, 136 Ceftriaxone
indications and contraindications for, 5 for acute otitis media, 67
for stable angina, 13 adverse effects and monitoring, 48–49
Calcium chloride, 260 for cirrhosis complications, 148
Calcium citrate, 260 for hospital-acquired/ventilator-associated
Calcium gluconate, 259, 260 pneumonia, 73
Candesartan, 136 intravenous, dosing regimens for, 41
dose range, 3 for septic arthritis, 54
for heart failure with reduced LVEF, 30 susceptibility breakpoint MIC interpretive
Captopril criteria, 51
dose range, 3 Cefuroxime
for heart failure with reduced LVEF, 29 for acute otitis media, 67
Carbapenems oral, dosing regimens for, 46
intravenous, 41, 44 Celecoxib, 265
susceptibility breakpoint MIC interpretive Cephalexin
criteria, 51 for diabetic foot ulcers, 76
Carbidopa/levodopa, 126, 209 oral, dosing regimens for, 46
Carvedilol for pharyngitis, 69
dose range, 3 Cephalosporins
for heart failure with reduced LVEF, 30 intravenous, 40–41, 44
Caspofungin oral, dosing regimens for, 46
adverse effects, 82 susceptibility breakpoint MIC interpretive criteria,
drug interactions, 92 50–51
formulations and dosing, 80 for urinary tract infections, 79
CCR5 antagonist Certolizumab, 181
interactions with OCs, 224 Chlorpromazine, 141
Cefazolin Chlorthalidone, 4
for abscesses and cellulitis, 75 Cholecalciferol, 172
adverse effects and monitoring, 48–49 Cholestyramine, 22
intravenous, 40, 44 Cholinomimetic, 282
susceptibility breakpoint MIC interpretive Ciclesonide MDI, 159, 160
criteria, 50 Cimetidine, 146
286 Index