Anti-Tuberculosis Treatment: DR Wong VF Sibu GH 27/7/2013

ANTI-TUBERCULOSIS
TREATMENT
DR Wong VF
Sibu GH
27/7/2013
OUTLINE
Aims of Treatment
First-line Anti-tuberculosis Drugs & Drug
Dosage
PTB in Adults
Treatment of new cases
Treatment of previously treated cases
Fix dose combination (FDC)
DOTS
Special situation: pregnancy & lactation
AIMS OF TREATMENT OF
TUBERCULOSIS
To cure patient & restore quality of life &
productivity
To prevent death from active TB or its late
effects
To prevent relapse of TB
To reduce transmission of TB to others
To prevent the development & transmission of
drug resistance TB
How to do it?
Heath education must be given to the patient

and family members/carers at the time of
starting treatment.
This should include:-
a. nature of the disease
b. necessity of strict adherence with the prolonged
treatment
c. risks of defaulting treatment
d. side effects of medication
e. risks of transmission and need for respiratory
hygiene as well as cough/sneeze etiquette
FIRST-LINE ANTITUBERCULOSIS
DRUGS
Isoniazid (H)
Rifampicin (R)
Pyrazinamide (Z)
Ethambutol (E)
Streptomycin (S)
Fixed Dose Combination anti-TB drugs
(FORECOX-Trac)
- H 75mg + R 150mg + Z 400mg + E 275mg
- Available for Intensive Phase treatment
Bactericidal
Sterilize Antiresistance
The three major actions of antituberculosis drugs are:

1) bactericidal action, defined as their ability to kill actively growing bacilli rapidly, e.g.
isoniazid, and to a lesser extent, rifampicin and streptomycin (S);
2) sterilising action, defined as their capacity to kill the semi-dormant organisms, e.g.
rifampicin and pyrazinamide (Z);
3) prevention of emergence of bacillary resistance to drugs, e.g. isoniazid and
rifampicin; less so for streptomycin, ethambutol (E) and pyrazinamide
PULMONARY TB (PTB)IN
ADULTS
Treatment of new cases
six-month regimen consisting of two

months of daily EHRZ* (2EHRZ) followed
by four months of daily HR* (4HR) is
recommended
2EHRZ 4HR
Weight is dynamic
CPG RECOMMENDATION
New patients with pulmonary tuberculosis
should receive daily 2EHRZ and followed
by daily 4HR**. (Grade A)
Regimen should contain six months of
rifampicin. (Grade A)
Rifampicin should be rounded to higher
recommended dose if tolerated. (Grade C)
If ethambutol is contraindicated,
streptomycin can be substituted. (Grade A)
TREATMENT OF PREVIOUSLY
TREATED CASES
(failure, relapse or return after default)

Interruption in the intensive phase:
a. If ≥14 days, to restart from the beginning i.e.
Day 1
b. If <14 days, to continue from the last dose
In either (a) or (b), the total number of planned
doses for the intensive phase should be given.
TREATMENT OF PREVIOUSLY TREATED
CASES, con't
Interruption in the maintenance phase:

a. If interruption occurs after patient receives 80%
of the total planned doses, the treatment may be
stopped If the sputum AFB smear was negative at
the initial presentation. If the sputum AFB smear
was positive, the treatment should be continued
to achieve the total number of planned doses
b. If patient receives <80% of total planned doses
and interruption lapse is ≥2 months, restart
treatment from the beginning
c. If patient receives <80% of total planned doses
and interruption lapse is <2 months, continue
treatment from date it stops to complete full course
Refer to physician
KURSUS PENGURUSAN TB UNTUK DRS KUCHING 20/4/2013

OPTIMAL DURATION OF TREATMENT
Current evidence suggests that the optimal

duration of treatment for sputum positive
PTB is at least six months.
EPTB: meningeal: one year
Joint & spine: 6-9 months
LN: 6 months (Nice guideline)
REGIMEN DURING THE MAINTENANCE
PHASE OF TREATMENT….
In new patients with PTB, WHO recommends

daily dosing throughout the course of antiTB
treatment.
thrice weekly maintenance phase is an option
provided that each dose is directly observed
and patient has improved clinically.
A maintenance phase with twice weekly
dosing is not recommended since missing
one dose means the patient receives only half
the total dose for that week.
FIXED-DOSE COMBINATIONS (FDCS)
FDC drugs incorporate two or more drugs in single

tablet and offer reduction in number of pills that need to
be consumed.
The following FDC preparations are registered in
Malaysia:-
Forecox-Trac Film Coated Tab: Isoniazid, Rifampicin,
Ethambutol and Pyrazinamide
Rimactazid 300 Sugar Coated Tab: Isoniazid and Rifampicin
Rimcure 3-FDC Film Coated Tab: Isoniazid, Rifampicin and
Pyrazinamide
Akurit-Z Tab: Isoniazid, Rifampin (Rifampicin) and
Pyrazinamide
Akurit Tab:Isoniazid and Rifampin (Rifampicin)
Akurit-Z Kid Dispersible Tab: Isoniazid, Rifampin (Rifampicin)
and Pyrazinamide
Akurit-4: Ethambutol, Isoniazid, Rifampin (Rifampicin) and
Pyrazinamide
FDC…
The recommended dosages for the two
FDCs are:-
30 - 37 kg body weight: 2 tablets daily
More than 70 kg body weight: 5 tablets
daily
ADVANTAGE OF FDC
reduce the risk of non-compliance by 17% and
consequently improve effectiveness of therapy.
Smaller number of tablets to be ingested may also
encourage patient adherence.
RCTs showed that FDCs are as effective as
separate-drug regimens for the treatment of
tuberculosis
Prescription errors are likely to be less frequent for
FDCs due to easy adjustment of dosage according
to patient weight.
In term of bioavailability, FDCs are proven to be
bioequivalent to separate-drugs formulations at the
same dose levels .
Corticosteroid in TB
Proven benefit in Tb meningitis and

pericarditis
No one fix recommendation dose,
dexamethasone vs steroid, high dose
tapering off over 6-12 weeks.
Also useful in uveitis and urinary TB
(Dose may be 20 mg tds-qid 4-6 weeks)
Caution: immunosuppresion, sugar control,
bioavailability of rifampicin may be
reduced.
DIRECTLY OBSERVED TREATMENT (DOT)
“… an observer* watches the patient swallowing

their tablets, …
… patient take the right antituberculosis drug, in
the right doses, at the right interval.”
The observer may be a health care worker or a
trained and supervised community member
Treatment of Tuberculosis Guidelines for national programmes WHO 2003

DIRECTLY OBSERVED THERAPY (DOT)
WHO launched Direct Observed Therapy, Short Course (DOTS) in

1995. This strategy combines drug treatment with political commitment,
sputum smear microscopy for diagnosis and directly observed therapy
(DOT) to ensure adherence and good management practice.
DOT increased the completion rate compared to those on SAT
The practice of DOT in Malaysia was reported to be 97% (ranging from
93% to 100%).
A study in Thailand in 2002 , only 65% to 89% of those assigned
actually watched the patients taking the drugs.
Involve process of negotiation and support, incorporating patients’
characteristics and choices.
A controlled trial in Tanzania comparing patient-centred approach
where patient was given the choice to receive treatment at home
observed by a supporter of their own choice vs daily treatment at health
facilities observed by healthcare worker showed a better treatment
success rate in the patient-centred approach
What to consider when starting anti-tb
treatment
Weight
- must calculate anti-TB dose based on patients weight
Creat level
- especially patient with low weight, with normal value Sr
creat (may need to calculate eGFR)
- if renal impairment may need to give renal dose anti-TB
Patient general well being / social support
Other co-morbidities
Drug Interactions
- ask about drug history
Ensure DOTS
RIFAMPICIN AND ORAL CONTRACEPTIVE
PILLS
Women using oral contraceptives, should either use an
oral contraceptive pill containing a higher dose of
estrogen (50 μg) or use a nonhormonal method of
contraception may be used throughout rifampicin
treatment and for at least one month subsequently.
Breast feeding and pregnancy
• Untreated tuberculosis >>> greater hazard to a
pregnant woman and her fetus than does
treatment of her disease.
• BF is allowed, as far as mother is not infective
and treated.
• Potential toxic effects of drugs delivered in
breast milk have not been reported
• Pyridoxine supplement in pregnancy should be
at a dose of 50 mg/day (instead of 25 mg/day).
Should I extend the intensive
phase?
• Get the C&S result back!

• Repeat the C&S!
• In patients (newly diagnosed) treated with the

regimen containing rifampicin throughout
treatment, if a positive sputum smear is found
at completion of the intensive phase, the
extension of the intensive phase is not
recommended (WHO TB guideline 2009)
Patient
empowerment Education
Adherence
Thank you

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ANTI-TUBERCULOSIS

Heath education must be given to the patient

The three major actions of antituberculosis drugs are:

six-month regimen consisting of two

(failure, relapse or return after default)

Interruption in the maintenance phase:

KURSUS PENGURUSAN TB UNTUK DRS KUCHING 20/4/2013

Current evidence suggests that the optimal

In new patients with PTB, WHO recommends

FDC drugs incorporate two or more drugs in single

Proven benefit in Tb meningitis and

“… an observer* watches the patient swallowing

Treatment of Tuberculosis Guidelines for national programmes WHO 2003

WHO launched Direct Observed Therapy, Short Course (DOTS) in

• Get the C&S result back!

• In patients (newly diagnosed) treated with the

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