Glycoair
Glycoair
Glycoair
Transparent yellow cap and natural transparent body capsules containing a white to
practically white powder, with the product code “IGP110.50” printed in blue under
two blue bars on the body and logo ( ) printed in black on the cap.
Active substance
The delivered dose (the dose that leaves the mouthpiece of the inhaler) is equivalent
Active moieties
Indacaterol and glycopyrronium
Excipients
Capsule fill: Lactose monohydrate, magnesium stearate.
Capsule shell components: Hypromellose, purified water, carrageenan, potassium
chloride, FD&C Yellow5/Tartrazine.
INDICATIONS
Once-daily maintenance bronchodilator treatment to relieve symptoms and reduce
exacerbations in adult patients with chronic obstructive pulmonary disease (COPD).
DOSAGE AND ADMINISTRATION
General target population
The recommended dosage is the once-daily inhalation of the content of one
® inhaler.
Special populations
Renal impairment
Indacaterol/glycopyrronium can be used at the recommended dose in patients with
mild to moderate renal impairment. In patients with severe renal impairment or
end-stage renal disease requiring dialysis it should be used only if the expected
benefit outweighs the potential risk. See also sections WARNINGS AND
PRECAUTIONS and CLINICAL PHARMACOLOGY.
Hepatic impairment
Indacaterol/glycopyrronium can be used at the recommended dose in patients with
mild and moderate hepatic impairment. No data are available for subjects with
severe hepatic impairment. See also section CLINICAL PHARMACOLOGY.
Pediatric patients
Geriatric patients
Indacaterol/glycopyrronium can be used at the recommended dose in elderly
Method of administration
Indacaterol/glycopyrronium capsules must be administered only by the oral
inhalation route and only using the Breezhaler ® inhaler. Capsules must not be
instituted.
Paradoxical bronchospasm
As with other inhalation therapy, administration of indacaterol/glycopyrronium may
result in paradoxical bronchospasm that may be life-threatening. If paradoxical
bronchospasm occurs, treatment should be discontinued immediately and
alternative therapy instituted.
Anticholinergic effects related to glycopyrronium
Like other anticholinergic containing drugs, indacaterol/glycopyrronium should be
used with caution in patients with narrow-angle glaucoma or urinary retention.
Patients should be advised about signs and symptoms of acute narrow-angle
glaucoma and should be informed to stop using it and to contact their doctor
immediately should any of these signs or symptoms develop.
Patients with severe renal impairment
For patients with severe renal impairment (estimated glomerular filtration rate below
2 ) including those with end-stage renal disease requiring dialysis,
it should be used only if the expected benefit outweighs the potential risk (see
section CLINICAL PHARMACOLOGY). These patients should be monitored closely for
potential adverse drug reactions.
Systemic effects of beta-agonists
Although no clinically relevant effect on the cardiovascular system is usually seen
after the administration of indacaterol/glycopyrronium at the recommended dose,
as with other compounds containing a beta 2 -adrenergic agonist, it should be used
with caution in patients with cardiovascular disorders (coronary artery disease, acute
myocardial infarction, cardiac arrhythmias, hypertension), in patients with convulsive
disorders or thyrotoxicosis, and in patients who are unusually responsive to
beta 2 -adrenergic agonists.
As with other drugs containing an inhaled beta 2 -adrenergic agonist, it should not be
used more often or at higher doses than recommended.
Cardiovascular effects of beta-agonists
Like other drugs containing a beta 2 -adrenergic agonist, it may produce a clinically
significant cardiovascular effect in some patients as measured by increases in pulse
rate, blood pressure, and/or symptoms. In case such effects occur, the drug may
need to be discontinued. In addition, beta-adrenergic agonists have been reported to
produce ECG changes, such as flattening of the T wave, prolongation of QT interval,
and ST segment depression, although the clinical significance of these findings is
unknown.
Clinically relevant effects on prolongation of the QTc-interval have not been observed
in clinical studies of indacaterol/glycopyrronium at the recommended therapeutic
dose (see section CLINICAL PHARMACOLOGY).
Hypokalemia with beta-agonists
Beta 2 -adrenergic agonists may produce significant hypokalemia in some patients,
which has the potential to produce adverse cardiovascular effects. The decrease in
serum potassium is usually transient, not requiring supplementation. In patients
with severe COPD, hypokalemia may be potentiated by hypoxia and concomitant
treatment (see section INTERACTIONS) which may increase the susceptibility to
cardiac arrhythmias.
Clinically relevant effects of hypokalemia have not been observed in clinical studies
of indacaterol/glycopyrronium at the recommended therapeutic dose (see section
CLINICAL PHARMACOLOGY).
Hyperglycemia with beta-agonists
Inhalation of high doses of beta 2 -adrenergic agonists may produce increases in
plasma glucose. Upon initiation of treatment with indacaterol/glycopyrronium,
plasma glucose should be monitored more closely in diabetic patients. During
clinical studies, more patients on indacaterol/glycopyrronium experienced clinically
notable changes in blood glucose (4.1%) at the recommended dose than on placebo
(2.3%). It has not been investigated in patients for whom diabetes mellitus is not
well controlled.
ADVERSE EFFECTS
The presentation of the safety profile is based on the experience with combination
indacaterol/glycopyrronium and the individual components.
Summary of the safety profile
Phase III trials of 6- and 12-months duration are listed by MedDRA system organ
class (Table 1) (6 -month Core Safety database). Within each system organ class, the
adverse drug reactions are ranked by frequency based on the indacaterol/glycopyrronium
treatment arm, with the most frequent reactions first. Within each frequency
grouping, adverse drug reactions are presented in order of decreasing seriousness.
In addition, the corresponding frequency category for each adverse drug reaction is
based on the following convention (CIOMS III): very common (≥1/10); common
Indacaterol/
glycopyrronium
Placebo Frequency
Adverse drug reactions daily N=345 category
n (%)
N=699
n (%)
Immune system disorders
Hypersensitivity (0) Uncommon
Metabolism and nutrition disorders
Diabetes mellitus and
Uncommon
hyperglycemia
Psychiatric disorders
Insomnia Uncommon
Nervous system disorders
Dizziness Common
Indacaterol/
glycopyrronium
Placebo Frequency
Adverse drug reactions daily N=345 category
n (%)
N=699
n (%)
Headache Common
Paraesthesia (0) Uncommon
Eye disorders
Glaucoma* (0) Uncommon
Cardiac disorders
Ischemic heart disease Uncommon
Atrial fibrillation (0) Uncommon
Tachycardia Uncommon
Palpitations Uncommon
Indacaterol/
glycopyrronium
Placebo Frequency
Adverse drug reactions daily N=345 category
n (%)
N=699
n (%)
Respiratory, thoracic and mediastinal disorders
Cough Common
Oropharyngeal pain incl
Common
throat irritation
Epistaxis (0) Uncommon
Gastrointestinal disorders
Dyspepsia Common
Dental caries Common
Dry mouth Uncommon
Indacaterol/
glycopyrronium
Placebo Frequency
Adverse drug reactions daily N=345 category
n (%)
N=699
n (%)
Skin and subcutaneous tissue disorders
Pruritus/rash Uncommon
Musculoskeletal and connective tissue disorders
Musculoskeletal pain Common
Muscle spasm (0) Uncommon
Myalgia Uncommon
Renal and urinary disorders
Bladder obstruction and
(0) Uncommon
urinary retention
Indacaterol/
glycopyrronium
Placebo Frequency
Adverse drug reactions daily N=345 category
n (%)
N=699
n (%)
General disorders and administration site conditions
Pyrexia* Common
Chest pain Common
Peripheral edema Uncommon
Fatigue Uncommon
*new adverse drug reaction observed with the combination indacaterol/glycopyrronium
but not with the monotherapy components.
Adverse drug reactions from spontaneous reports and literature cases (frequency
not known)
The following adverse drug reaction has been reported in post-marketing
experience: angioedema (frequency not known).
Additional information on individual components
Gastroenteritis, pain in extremity and paradoxical bronchospasm have been observed
previously with the individual components but not with indacaterol/glycopyrronium
fixed dose combination in the two placebo-controlled trials and are therefore not
mild degree, none was severe. Cough was common, but usually of mild intensity.
Some serious adverse events, including hypersensitivity and ischemic heart disease,
have been reported as ADRs for indacaterol administered as monotherapy. The
reported frequencies for indacaterol/glycopyrronium for hypersensitivity and
ischemic heart disease were 0.1% versus 0.0% for placebo and 0.4% versus 0.3%
for placebo, respectively.
Special populations
respectively.
INTERACTIONS
Interactions linked to the indacaterol/glycopyrronium
Concomitant administration of orally inhaled indacaterol and glycopyrronium under
steady -state conditions of both drugs did not affect the pharmacokinetics (PK) of
either drug.
No specific drug-drug interaction studies were conducted. Information on the
potential for interactions is based on the potential for each of its two components.
Interactions linked to indacaterol
Indacaterol has not been shown to cause drug interactions with co-medications. In
vitro investigations have indicated that indacaterol has negligible potential to cause
metabolic interactions with medications at the systemic exposure levels achieved in
clinical practice (see section CLINICAL PHARMACOLOGY – Biotransformation/metabolism
and elimination).
Anticipated interactions resulting in concomitant use not being recommended
Beta-adrenergic blockers
Beta-adrenergic blockers may weaken or antagonize the effect of beta 2 -adrenergic
agonists.
Therefore it should not be given together with beta-adrenergic blockers (including
eye drops) unless there are compelling reasons for their use. Where required,
cardioselective beta-adrenergic blockers should be preferred, although they should
be administered with caution.
Drugs known to prolong QTc interval
As with other beta 2 -adrenergic agonist-containing drugs, it should be administered
with caution to patients being treated with monoamine oxidase inhibitors, tricyclic
antidepressants, or drugs known to prolong the QT interval, as any effect of these on
the QT interval may be potentiated. Drugs known to prolong the QT-interval may
increase the risk of ventricular arrhythmia (see section WARNINGS AND
PRECAUTIONS).
Sympathomimetic agents
Concomitant administration of other sympathomimetic agents (alone or as part of
combination therapy) may potentiate the undesirable effects of indacaterol (see
section WARNINGS AND PRECAUTIONS).
Hypokalemia
Concomitant treatment with methylxanthine derivatives, steroids, or non-potassium-
sparing diuretics may potentiate the possible hypokalemic effect of beta 2 -adrenergic
agonists (see section WARNINGS AND PRECAUTIONS).
Observed interactions to be considered
Metabolic and transporter based drug interaction
a 2-fold and 1.4-fold increase in AUC and C max , respectively. Concomitant treatment
1.8-fold increase in AUC whereas C max was unaffected. Taken together, the data
suggest that systemic clearance is influenced by modulation of both P-gp and
one hour, each) was well tolerated with no relevant effects on heart rate, QTc-
interval, serum potassium or blood glucose.
and there were no relevant effects on heart rate, QTc-interval, blood glucose or
increase in pulse rate, systolic blood pressure increase and QTc interval.
Information related to glycopyrronium
In COPD patients, repeated orally inhaled administration of glycopyrronium at total
in healthy volunteers were respectively about 50-fold and 6-fold higher than the
peak and total systemic exposure at steady-state achieved with the recommended
CLINICAL PHARMACOLOGY
Mechanism of action
Indacaterol/glycopyrronium
When indacaterol and glycopyrronium are administered together, they provide
additive efficacy due to their different mode of action targeting different receptors
and pathways to achieve small muscle relaxation. Due to the differential density of
beta 2 -adrenoceptors and M 3 -receptors in central versus smaller airways, beta 2-
agonists should be more effective in relaxing small airways whilst an anti-cholinergic
compound may be more effective in large airways. Thus for optimal bronchodilation
in all regions of the human lung, a combination of a beta 2 -adrenergic agonist and a
muscarinic antagonist may be beneficial.
Indacaterol
Indacaterol is an ‘ultra’ long-acting beta 2 -adrenergic agonist for once-daily
administration. The pharmacological effects of beta 2 -adrenoceptor agonists,
including indacaterol, are at least in part attributable to stimulation of intracellular
adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate
(ATP) to cyclic-3’, 5’-adenosine monophosphate (cyclic monophosphate). Increased
cyclic AMP levels cause relaxation of bronchial smooth muscle. In vitro studies have
shown that indacaterol has more than 24-fold greater agonist activity at beta 2-
receptors compared to beta 1 -receptors and 20-fold greater agonist activity
compared to beta 3 -receptors. This selectivity profile is similar to formoterol.
When inhaled, indacaterol acts locally in the lung as a bronchodilator. Indacaterol is
a nearly full agonist at the human beta 2 -adrenergic receptor with nanomolar
potency. In isolated human bronchus, indacaterol has a rapid onset of action and a
long duration of action.
Although beta 2 -adrenergic receptors are the predominant adrenergic receptors in
bronchial smooth muscle and beta 1 -adrenergic receptors are the predominant
receptors in the human heart, there are also beta 2 -adrenergic receptors in the
human heart comprising 10% to 50% of the total adrenergic receptors. The precise
function of beta 2 -adrenergic receptors in the heart is not known, but their presence
raises the possibility that even highly selective beta 2 -adrenergic agonists may have
cardiac effects.
Glycopyrronium
Glycopyrronium is an inhaled long-acting muscarinic receptor antagonist (anti-
cholinergic) for once-daily maintenance bronchodilator treatment of COPD.
Parasympathetic nerves are the major bronchoconstrictive neural pathway in
airways, and cholinergic tone is the key reversible component of airflow obstruction
in COPD. Glycopyrronium works by blocking the bronchoconstrictor action of
acetylcholine on airway smooth muscle cells, thereby dilating the airways.
Of the five known muscarinic receptor subtypes (M 1-5 ), only subtypes M 1-3
defined physiological function in the human lung. Glycopyrronium bromide is a high
affinity muscarinic receptor antagonist of these three receptor subtypes. It
demonstrated 4- to 5-fold selectivity for the human M 3 1
human M 2
evidenced by observed receptor association/dissociation kinetic parameters and the
onset of action after inhalation in clinical studies.
The long duration of action can be partly attributed to sustained drug concentrations
in the lungs as reflected by the prolonged terminal elimination half-life of
glycopyrronium after inhalation via the glycopyrronium inhaler in contrast to the
half-life after i.v. administration (see section CLINICAL PHARMACOLOGY –
Elimination). Lung pharmacokinetic data in rats following inhalation of
glycopyrronium bromide provides further evidence for this.
Pharmacodynamics (PD)
Primary pharmacodynamic effects
The combination of indacaterol and glycopyrronium showed a rapid onset of action
QT-interval
The components (indacaterol and glycopyrronium) are not known to have a
QT-prolongation potential at clinical dose levels. A thorough QT (TQT) -study in
Pharmacokinetics (PK)
Absorption
Following inhalation, the median time to reach peak plasma concentrations of
respectively.
Based on the in vitro performance data, the dose of indacaterol delivered to the lung
is expected to be similar for indacaterol/glycopyrronium 110/50 microgram and
Indacaterol
The median time to reach peak serum concentrations of indacaterol was
Glycopyrronium
Following oral inhalation using the glycopyrronium inhaler, glycopyrronium was
About 90% of systemic exposure following inhalation is due to lung absorption and
10% is due to gastrointestinal absorption. The absolute bioavailability of orally
administered glycopyrronium was estimated to be about 5%.
Following repeated once-daily inhalation in patients with COPD, PK steady-state of
glycopyrronium was reached within one week of treatment. The steady-state mean
glycopyrronium (AUC over the dosing interval) was about 1.4-to 1.7-fold higher than
after the first dose. Urinary excretion data at steady-state compared to the first dose
suggest that systemic accumulation is independent of dose in the dose range of
Distribution
Indacaterol
After intravenous infusion the volume of distribution (V z
in vitro human serum and plasma
Glycopyrronium
After i.v. dosing, the steady-state volume of distribution (Vss) of glycopyrronium was
apparent volume of distribution in the terminal phase following inhalation (Vz/F) was
in vitro
human plasma protein binding of glycopyrronium was 38% to 41% at
magnitude as the exposure to the parent drug. Since in vitro studies did not show
In vitro enzyme
induction studies did not indicate a clinically relevant induction by glycopyrronium
Elimination
Indacaterol
In clinical studies which included urine collection, the amount of indacaterol
excreted unchanged via urine was generally lower than 2% of the dose. Renal
calculated from the accumulation of indacaterol after repeated dosing ranged from
Glycopyrronium
After i.v. administration of [ 3 H]-labelled glycopyrronium bromide to humans, the
calculated from the accumulation of indacaterol after repeated dosing ranged from
Glycopyrronium
After i.v. administration of [ 3 H]-labelled glycopyrronium bromide to humans, the
Linearity/non-linearity
Indacaterol
Special populations
Indacaterol/glycopyrronium
A population PK analysis in COPD patients after inhalation of indacaterol/glycopyrronium
indicated no significant effect of age, gender and (lean body) weight on the systemic
exposure to indacaterol and glycopyrronium. Lean body weight (which is a function
of weight and height) was identified as a covariate. A negative correlation between
systemic exposure and lean body-weight (or body weight) was observed; however,
no dose adjustment is recommended due to the magnitude of the change or the
predictive precision of lean body weight.
Smoking status and baseline FEV 1
indacaterol and glycopyrronium after inhalation of indacaterol/glycopyrronium.
Indacaterol
A population analysis of the effect of age, gender and weight on systemic exposure
in COPD patients after inhalation indicated that indacaterol can be used at the
recommended dose in all age and weight groups and regardless of gender.
The pharmacokinetics of indacaterol was investigated in two different
6 , (TA) 6 ] genotype and the low activity
[(TA) 7 , (TA) 7 ] genotype (Gilbert’s syndrome genotype). The study demonstrated that
steady-state AUC and C max of indacaterol were 1.2-fold higher in the [(TA) 7 , (TA) 7 ]
genotype, indicating that systemic exposure to indacaterol is only insignificantly
Glycopyrronium
A population PK analysis of data in COPD patients identified body weight and age as
factors contributing to inter-patient variability in systemic exposure. Glycopyrronium
dose.
Ethnicity
Indacaterol/glycopyrronium: When corrected by lean body weight, no statistically
significant effect of ethnicity (Japanese versus non-Japanese) on exposure for both
compounds was found.
Indacaterol: No difference between ethnic subgroups was identified. Limited
treatment experience is available for the black population.
Glycopyrronium: There were no major differences in total systemic exposure (AUC)
between Japanese and Caucasian subjects. Insufficient PK data is available for other
ethnicities or races.
CLINICAL STUDIES
The Phase III clinical development program [IGNITE] included five studies: one
These studies enrolled patients with a clinical diagnosis of moderate to very severe
post-bronchodilator FEV 1
post-bronchodilator FEV 1 /FVC ratio of less than 70%. The 26-week active-controlled
study, [ILLUMINATE], enrolled patients with a post-bronchodilator FEV 1
≥40% of the predicted normal value. In comparison, the 64-week [SPARK] study
enrolled patients with severe to very severe COPD, with a post-bronchodilator
FEV 1
Effects on lung function
were maintained over the 24-hour dosing interval from the first dose. Within the
26-week [SHINE] and 52-week [ENLIGHTEN] studies, there was no attenuation of
the bronchodilator effect over time.
Trough FEV 1
In the [SHINE] study, it increased post-dose trough FEV 1
placebo at the 26-week primary endpoint (p<0.001) and showed significant
increases compared to each monotherapy component treatment arm (indacaterol
and glycopyrronium) as well as the tiotropium treatment arm (see Table 2).
to glycopyrronium (70 -
<0.001) [SPARK].
Peak FEV 1
Indacaterol/glycopyrronium produced statistically significant improvement in peak
FEV
FEV AUC
Indacaterol/glycopyrronium increased post-dose FEV 1 0-12
compared to fluticasone/salmeterol.
Onset of action
In the [SHINE and ILLUMINATE] studies, indacaterol/glycopyrronium demonstrated
26.
Table 3 Onset of action versus placebo, tiotropium and fluticasone/salmeterol
Day 1 Week 26
versus placebo
versus tiotropium
Day 1 Week 26
versus fluticasone/salmeterol
1
FEV
1.40
LS Mean of FEV
1.35
1.30
1.25
1.20
1.15
1.10
1.05
1h
2h
4h
8h
12h
Baseline
30 min
23h 15m
23h 45m
Time
Figure 2 1
treatment (FAS, serial spirometry subset)
Indacaterol/glycopyrronium
Indacaterol
Glycopyrronium
1.60
Tiotropium
1.55 Placebo
1.50
1.45
1
1.40
LS Mean of FEV
1.35
1.30
1.25
1.20
1.15
1.10
1.05
1.00
1h
2h
4h
8h
−45m
12h
16h
22h
23h 45m
Time
Figure 3
1.70 1.70
LS Mean of FEV
1.65 1.65
1.60 1.60
1.55 1.55
1.50 1.50
1.45 1.45
1.40 1.40
5m
1h
2h
4h
8h
5m
1h
2h
4h
8h
12h
12h
Time
compared to placebo ( -3.01, p=0.002) and tiotropium (-2.13, p=0.009) [SHINE] and
[SPARK] study.
Exercise tolerance
In a 3 -week study [BRIGHT] where exercise tolerance was tested via cycle
tiotropium.
Whole-Body Plethysmography measurements of Residual Volume (RV) and
Functional Residual Capacity (FRC) give insights on airway closure and reflects the
presence of gas trapping, considered a hallmark of COPD. On the first day of
in the 13-week toxicity study was devoid of heart lesions and corresponds
of the rat female genital tract have been similarly demonstrated with other beta 2-
with indacaterol did not show any evidence of tumorigenicity at doses of at least
Published data for glycopyrronium do not indicate any reproductive toxicity issues.
Glycopyrronium was not teratogenic in rats or rabbits following inhalation
administration. Reproduction studies in rats and other data in animals did not
indicate a concern regarding fertility in either males or females or pre- and
post-natal development. Glycopyrronium and its metabolites did not significantly
cross the placental barrier of pregnant mice, rabbits and dogs. Glycopyrronium
(including its metabolites) was excreted into the milk of lactating rats and reached
up to 10-fold higher concentrations in the milk than in the blood of the dam.
INCOMPATIBILITIES
Not applicable.
AVAILABILITY
STORAGE
Do not store above 30°C.
Protect from moisture.
Do not use after the date marked “EXP” on the pack.
Drugs must be kept out of the reach and sight of children.
INSTRUCTIONS FOR USE AND HANDLING
Your indacaterol/glycopyrronium pack
One indacaterol/glycopyrronium pack contains:
t one Breezhaler ® inhaler
t one or more blisters containing indacaterol/glycopyrronium capsules to be
used in the inhaler
Mouthpiece
Cap
Screen
Blisters
Button
Base
Capsule chamber
Do not push the capsule through the foil to remove it from the blister.
Prepare capsule:
Separate one of the blisters from the
blister card by tearing along the
perforation.
Note:
As you breathe in through the inhaler, the
capsule spins around in the chamber and
you should hear a whirring noise. You will
experience a sweet flavor as the medicine
goes into your lungs.
Hold breath:
Continue to hold your breath for at least
Remove capsule:
After you have finished taking your daily
dose of indacaterol/glycopyrronium, open
the mouthpiece again, remove the empty
capsule by tipping it out of the capsule
chamber, and discard it. Close the inhaler
and replace the cap.
REMEMBER:
– Do not swallow the capsules.
– Only use the Breezhaler ®
inhaler contained in this pack.
– Capsules must always be stored in the blister, and only removed immediately
before use.
– Never place a capsule directly into the mouthpiece of the Breezhaler ®
inhaler.
– Do not press the piercing buttons more than once.
– Never blow into the mouthpiece of the Breezhaler ®
inhaler.
– Always release the push buttons before inhalation.
– Never wash the Breezhaler ® inhaler with water. Keep it dry. See below “How to
clean your inhaler”.
– Never take the Breezhaler ® inhaler apart.
– Always use the new Breezhaler ®
inhaler that comes with your new medication
pack.
– Do not store the capsules in the Breezhaler ®
inhaler.
– Always keep the Breezhaler ®
inhaler and capsules in a dry place.
Additional information
Occasionally, very small pieces of the capsule can get past the screen and enter
your mouth. If this happens, you may be able to feel these pieces on your tongue. It
is not harmful if these pieces are swallowed or inhaled. The chances of the capsule
shattering will be increased if the capsule is pierced more than once (step 7).
How to clean your inhaler
Never wash your inhaler with water. If you want to clean your inhaler wipe the
mouthpiece inside and outside with a clean, dry lint-free cloth to remove any
powder residue. Keep the inhaler dry.
For suspected adverse drug reaction, seek medical attention immediately and
productsafety@unilab.com.ph.
By reporting undesirable effects, you can help provide more information on the
safety of this medicine.
CAUTION: Foods, Drugs, Devices, and Cosmetics Act prohibits dispensing without
prescription.
Reg. IPOPHIL
UA157592IN01