AZIMAX Tablets (Azithromycin)

Table of Content

Composition

AZIMAX-250 Tablets
Each film-coated tablet contains:
Azithromycin (anhydrous)...............250 mg
(as Azithromycin Dihydrate IP)

AZIMAX-500 Tablets
Each film-coated tablet contains:
Azithromycin (anhydrous)............... 500 mg
(as Azithromycin Dihydrate IP)

AZIMAX-1000 Tablets
Each film-coated tablet contains:
Azithromycin (anhydrous)............... 1000 mg
(as Azithromycin Dihydrate IP)

AZIMAX-100 DT
Each uncoated dispersible tablet contains:
Azithromycin (anhydrous)..........100mg
(as Azithromycin dihydrate IP)

AZIMAX-200 DT
Each uncoated dispersible tablet
contains: Azithromycin (anhydrous)..........200mg
(as Azithromycin dihydrate IP)

AZIMAX-100 Dry Syrup
Each 5 ml (after reconstitution) contains:
Azithromycin dihydrate IP equivalent to
Azithromycin (anhydrous)...............100 mg

AZIMAX-200 Dry Syrup
Each 5 ml (after reconstitution) contains:
Azithromycin a dihydrate IP equivalent to
Azithromycin (anhydrous) ............... 200 mg

Dosage Forms

Oral tablets, dispersible tablets and dry syrup

Pharmacology

Pharmacodynamics

Azithromycin is a macrolide antibiotic belonging to the azalide group. It binds to the 23S rRNA of the bacterial 50S ribosomal subunit. It blocks protein synthesis by inhibiting the transpeptidation/translocation step of protein synthesis and by inhibiting the assembly of the 50S ribosomal subunit.

Azithromycin concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. The ratio of intracellular to extracellular concentration was >30 after 1-hour incubation. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.

The most frequently encountered mechanism of resistance to azithromycin is modification of the 23S rRNA at positions corresponding to A2058 and A2059 in the Escherichia coli numbering system. In addition to cross-resistance with other macrolides (erythromycin and clarithromycin), ribosomal modification may determine resistance to other antibiotic classes (lincosamides and streptogramins B) that bind to overlapping ribosomal sites.

Azithromycin has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections:

Gram-positive Bacteria
Staphylococcus aureus
Streptococcus agalactiae
Streptococcus pneumoniae
Streptococcus pyogenes

Gram-negative Bacteria
Haemophilus ducreyi
Haemophilus influenzae
Moraxella catarrhalis
Neisseria gonorrhoeae

'Other' Bacteria
Chlamydophila pneumoniae
Chlamydia trachomatis
Mycoplasma pneumoniae

The following in vitrodata are available, but their clinical significance is unknown.

At least 90% of the following bacteria exhibit an in vitrominimum inhibitory concentration (MIC) less than or equal to the azithromycin susceptible breakpoint of ≥4mcg/mL. However, safety and effectiveness of azithromycin in treating clinical infections due to these bacteria have not been established in adequate and well-controlled trials.

Gram-positive Bacteria
Beta-hemolytic streptococci (Groups C,F, G)
Viridans group streptococci

Gram-negative: Bacteria
Bordetella pertussis

Anaerobic Bacteria
Peptostreptococcus-species
Prevotella bivia

'Other' Bacteria
Ureaplasma urealyticum
Legionella pneumophila

Cardiac Electrophysiology
QTc interval prolongation was studied in a randomized, placebo-controlled parallel trial in 116 healthy subjects who received either chloroquine (1,000 mg) alone or in combination with azithromycin (500 mg, 1,000 mg and 1,500 mg once daily). Co-administration of azithromycin increased the QTc interval in a dose- and concentration-dependent manner. In comparison with chloroquine alone, the maximum mean (95% upper confidence bound) increases in QTcF were 5 (10) ms, 7 (12) ms and 9 (14) ms with the co-administration of 500 mg, 1,000 mg and 1,500 mg azithromycin, respectively.

Pharmacokinetics

Following oral administration of a single 500 mg dose (two 250 mg tablets) to 36 fasted healthy male volunteers, the mean (SD) pharmacokinetic parameters were AUC0-72= 4.3 (1.2) μg.h/mL; Cmax = 0.5 (0.2) g/mL; Tmax = 2.2 (0.9) hours.

With a regimen of 500 mg (two 250 mg capsules-1) on day 1, followed by 250 mg daily (one 250 mg capsule) on days 2 through 5, the pharmacokinetic parameters of azithromycin in plasma in healthy young adults (18-40 years of age) are portrayed in the chart below. Cminand Cmaxremained essentially unchanged from day 2 through day 5 of therapy.

Pharmacokinetic Parameters (Mean)
Total n=12
Day 1
Day 5
Cmax(μg/mL)
0.41
0.24
Tmax(h)
2.5
3.2
AUC0-24(μgh/mL)
2.6
2.1
Cmax(μg/mL)
0.05
0.05
Urinary excretion(% dose)
4.5
6.5

In a two-way crossover study, 12 adult healthy volunteers (6 males, 6 females) received 1,500 mg of azithromycin administered in single daily doses over either 5 days (two 250 mg tablets on day 1, followed by one 250 mg tablet on days 2-5) or 3 days (500 mg per day for days 1-3). Due to limited serum samples on day 2 (3-day regimen) and days 2-4 (5-day regimen), the serum concentration-time profile of each subject was fit to a 3-compartment model and the AUC(0-infinity)for the fitted concentration profile was comparable between the 5-day and 3-day regimens.

 
3-Day Regimen
5-Day Regimen
Pharmacokinetic
Parameter
Day 1
Day 3
Day 1
Day 5
 
Cmax(serum, μg/mL)
0.44
(0.22)
0.54
(0.25)
0.43
(0.20)
0.24
(0.06)
Serum AUC(0-
infinity)
(μg hr/mL)
17.4(6.2)*
14.9(3.1)*
Serum T1/2
71.8 hours
68.9 hours

Median azithromycin exposure (AUC0-288) in mononuclear (MN) and polymorphonuclear (PMN) leucocytes following either the 5-day or 3-day regimen was more than a 1,000-fold and 800-fold greater than in serum, respectively. Administration of the same total dose with either the 5-day or 3-day regimen may be expected to provide comparable concentrations of azithromycin within MN and PMN leucocytes.

Two azithromycin 250 mg tablets are bioequivalent to a single 500 mg tablet.

1Azithromycin 250 mg tablets are bioequivalent to 250 mg capsules in the fasted state. Azithromycin 250 mg capsules are no longer commercially available.

The absolute bioavailability of azithromycin 250 mg capsules is 38%.

In a two-way crossover study in which 12 healthy subjects received a single 500 mg dose of azithromycin (two 250 mg tablets) with or without a high-fat meal, food was shown to increase the Cmax by 23% but had no effect on the AUC.

When azithromycin suspension was administered with food to 28 adult healthy male subjects, the Cmaxincreased by 56% and the AUC was unchanged.

The AUC of azithromycin was unaffected by co-administration of an antacid containing aluminum and magnesium hydroxide with azithromycin capsules; however, the Cmaxwas reduced by 24%. Administration of cimetidine (800 mg), 2 hours prior to azithromycin, had no effect on azithromycin absorption.

The serum protein binding of azithromycin is variable in the concentration range approximating human exposure, decreasing from 51% at 0.02 μg/mL to 7% at 2 μg/mL.

Following oral administration, azithromycin is widely distributed throughout the body, with an apparent steady-state volume of distribution of 31.1 L/kg. Greater azithromycin concentrations in tissues than in plasma or serum were observed. High tissue concentrations should not be interpreted to be quantitatively related to clinical efficacy. The antimicrobial activity of azithromycin is pH-related and appears to be reduced with decreasing pH. However, the extensive distribution of drug to tissues may be relevant to clinical activity.

Selected tissue (or fluid) concentration and tissue (or fluid) to plasma/serum concentration ratios are shown in the following table:

Azithromycin Concentrations Following a 500 Mg Dose (Two 250 Mg Capsules) in Adults*
Tissue Or
Fluid
Time After
Dose (h)
Tissue Or Fluid
Concentration
(μg/g or μg/mL)
Corresponding
Plasma Or
Serum
Level (μg/mL)
Tissue
(Fluid)
Plasma
(Serum)
Ratio
 
Skin
72-96
0.4
0.012
35
Lung
72-96
4.0
0.012
>100
Sputum†
2-4
1.0
0.64
2
Sputum‡
10-12
2.9
0.1
30
Tonsil§
9-18
4.5
0.03
>100
Tonsil§
180
0.9
0.006
>100
Cervix¶
19
2.8
0.04
70

The extensive tissue distribution was confirmed by examination of additional tissues and fluids (bone, ejaculum, prostate, ovary, uterus, salpinx, stomach, liver, and gallbladder). As there are no data from adequate and well-controlled studies of azithromycin treatment of infections in these additional body sites, the clinical importance of these tissue concentration data is unknown.

Following a regimen of 500 mg on the first day and 250 mg daily for 4 days, only very low concentrations were noted in cerebrospinal fluid (less than 0.01 µg/mL) in the presence of non-inflamed meninges.

In vitro and in vivo studies to assess the metabolism of azithromycin have not been performed.

Plasma concentrations of azithromycin following single 500 mg oral and intravenous doses declined in a polyphasic pattern, with a mean apparent plasma clearance of 630 mL/min and terminal elimination half-life of 68 hours. The prolonged terminal half-life is thought to be due to extensive uptake and subsequent release of drug from tissues.

Biliary excretion of azithromycin, predominantly as unchanged drug, is a major route of elimination. Over the course of a week, approximately 6% of the administered dose appears as unchanged drug in urine.

Renal Impairment
Azithromycin pharmacokinetics was investigated in 42 adults (21 to 85 years of age) with varying degrees of renal impairment. Following the oral administration of a single 1,000 mg dose of azithromycin, mean Cmaxand AUC0-120increased by 5.1% and 4.2%, respectively in subjects with mild-to-moderate renal impairment (GFR: 10 to 80 mL/min) compared with subjects with normal renal function (GFR >80 mL/min). The mean Cmaxand AUC0-120 increased 61% and 35%, respectively, in subjects with severe renal impairment (GFR <10 mL/min) compared with subjects with normal renal function (GFR >80 mL/min).

Hepatic Impairment
The pharmacokinetics of azithromycin in subjects with hepatic impairment has not been established.

Gender
There are no significant differences in the disposition of azithromycin between male and female subjects. No dosage adjustment is recommended based on gender.

Geriatric Patients
When studied in healthy elderly subjects aged 65 to 85 years, the pharmacokinetic parameters of azithromycin in elderly men were similar to those in young adults; however, in elderly women, although higher peak concentrations (increased by 30 to 50%) were observed, no significant accumulation occurred.

Paediatric Patients
In two clinical studies, azithromycin for oral suspension was dosed at 10 mg/kg on day 1, followed by 5 mg/kg on days 2 through 5 to two groups of paediatric patients (aged 1-5 years and 5-15 years, respectively). The mean pharmacokinetic parameters on day 5 were Cmax=0.216 g/mL, Tmax=1.9 hours, and AUC0-24=1.822 g?hr/mL for the 1- to 5-year-old group and were Cmax=0.383 µg/mL, Tmax=2.4 hours, and AUC0-24=3.109 µg?hr/mL for the 5- to 15-year-old group.

Two clinical studies were conducted in 68 paediatric patients aged 3-16 years to determine the pharmacokinetics and safety of azithromycin for oral suspension. Azithromycin was administered following a low-fat breakfast.

The first study consisted of 35 paediatric patients treated with 20 mg/kg/day (maximum daily dose 500 mg) for 3 days of whom 34 patients were evaluated for pharmacokinetics.

In the second study, 33 paediatric patients received doses of 12 mg/kg/day (maximum daily dose 500 mg) for 5 days of whom 31 patients were evaluated for pharmacokinetics. In both studies, azithromycin concentrations were determined over a 24-hour period following the last daily dose. Patients weighing above 25.0 kg in the 3-day study or 41.7 kg in the 5-day study received the maximum adult daily dose of 500 mg. Accordingly, 11 patients (weighing 25.0 kg or less) in the first study and 17 patients (weighing 41.7 kg or less) in the second study received a total dose of 60 mg/kg. The following table shows pharmacokinetic data in the subset of paediatric patients who received a total dose of 60 mg/kg.

Pharmacokinetic
Parameter
3-Day Regimen
(20 mg/kg×3
days)
5-Day Regimen
(12 mg/kg×5
days)
n
11
17
Cmax(μg/mL)
11(0.4)
0.5(0.4)
Tmax(hr)
2.7(1.9)
2.2(0.8)
AUC0-24(μg hr/mL)
7.9(2.9)
3.9(1.9)

The similarity of the overall exposure (AUC0-infinity) between the 3-day and 5-day regimens in paediatric patients is unknown.

Single-dose pharmacokinetics in paediatric patients given doses of 30 mg/kg has not been studied.

Drug Interactions
Drug interaction studies were performed with azithromycin and other drugs likely to be co-administered. The effects of co-administration of azithromycin on the pharmacokinetics of other drugs are shown in Table 1 and the effects of other drugs on the pharmacokinetics of azithromycin are shown in Table 2.

Co-administration of azithromycin at therapeutic doses had a modest effect on the pharmacokinetics of the drugs listed in Table 1. No dosage adjustment of drugs listed in Table 1 is recommended when co-administered with azithromycin.

Co-administration of azithromycin with efavirenz or fluconazole had a modest effect on the pharmacokinetics of azithromycin. Nelfinavir significantly increased the Cmaxand AUC of azithromycin. No dosage adjustment of azithromycin is recommended when administered with drugs listed in Table 2.

Table 1: Drug Interactions: Pharmacokinetic Parameters for Co-administered Drugs in the Presence of Azithromycin
Co-administered
Drug
Dose of Co
-administered
Drug
Dose of
Azithromycin
n
Ratio
(with/without
azithromycin) of
Co-administered
Drug
Pharmacokinetic
Parameters (90%
CI); No Effect =
 
 
 
 
Mean
Cmax
Mean
AUC
Atorvastatin

 

10 mg/day × 8 days

500 mg/day
PO on days 6-
8

1

2

0.83
(0.63 to 1.08)

1.01

(0.81
to 1.25)

Carbamazepine
200 mg/day×2
days, then 200
mg b.i.d.×18
days
500 mg/day
PO for days
7
0.97
(0.88 to 1.06)
0.96
(0.88
to
Cetirizine
20 mg/day×11
days
500 mg PO on
day 7, then 250
mg/day on
days 8-11

1

4

1.03

(0.93 to
1.14)

1.02

(0.92
to
1.13)

Didanosine
200 mg PO
b.i.d.×21 days

1,200 mg/day

PO on days 8-
21

6

1.44

(0.85 to
2.43)

 

(0.83
to

Efavirenz
400 mg/day×7
days
600 mg PO on
day 7

1

4

1.04*-
0.95*
Fluconazole
200 mg PO
single dose

1,200 mg PO

single dose

1

8

1.04

(0.98 to 1.11)

1.01

(0.97
to
1.05)

Indinavir
800 mg t.i.d.×5
days

1,200 mg PO

on day 5

1

8

0.96
(0.86 to
1.08)
0.90
(0.81
to
Midazolam

800 mg t.i.d. × 5 

day 3

500 mg/day
PO × 3 days

1

2

0.96

(0.89 to 1.08)

 

(1.01
to
1.56)

Nelfinavir
750 mg t.i.d.×11 days

1,200 mg PO

on day 9

1

4

0.90
(0.81 to
1.01)
0.85
(0.78
to
0.93)
Rifabutin
300 mg/day×10days
500 mg PO on
day 1, then 250
mg/day on
days 2-10
6
See
footnote
below
NA
Sildenafil
100 mg day on 1 and 4
500 mg/day
PO×3 days

1

2

1.16

(0.86 to 1.57)

0.92
(0.75
to
1.12)
Theophylline
4 mg/kg
intravenous on
days 1, 11, and
25
500 mg PO on
day 7, 250
mg/day on
days 8-11

1

0

1.19

(1.02 to 1.40)

1.02

(0.86
to 1.31)

Theophylline
300 mg PO
b.i.d.×15 days
500 mg PO on
day 6, then 250
mg/day on
days 7-10
8

1.09

(0.92 to 1.29)

1.08

(0.89
to 1.31)

Triazolam
0.125 mg on
day 2
500 mg PO on
day 1, then 250
mg/day on day
2

1

2

1.06*-
1.02*-
Trimethoprim/Sulpham
ethoxazole

160 mg/800

mg/day PO×7
days

1,200 mg PO

on day 7

1

2

0.85
(0.75 to
0.97)/
0.90
(0.78 to
0.87
(0.80
to
0.95/
0.96
(0.88
to
1.03)
Zidovudine
500 mg/day PO
×21 days
600 mg/day
PO×14 days
5

1.12

(0.42 to
3.02)

0.94
(0.52
to
1.70)
Zidovudine
500 mg/day PO
×21 days

1,200 mg/day 

PO×14 days

4

1.31

(0.43 to
3.97)

1.30

(0.69
to
2.43)

Table 2: Drug Interactions: Pharmacokinetic Parameters for Azithromycin in the Presence of Co-administered Drugs
Co-administered
Drug
Dose of Co
-administered
Drug
Dose of
Azithromycin
n
Ratio
(with/without
azithromycin) of
Co-administered
Drug
Pharmacokinetic
Parameters (90%
CI); No Effect =
 
 
 
 
Mean
Cmax
Mean
AUC
Efavirenz
400 mg/day×7
days
600 mg PO on
day 7
14
1.22

(1.04 to 1.42)
0.92*-
Fluconazole
200 mg PO
single dose
1,200 mg PO 

single dose
18
0.82
(0.66 to 1.02)
1.07

(0.94 to 1.22)
Nelfinavir
750 mg t.i.d.×11 days
1,200 mg PO on day 9
14
2.36(1.77 to 3.15)
2.12(1.80 to 2.50)
Rifabutin
300 mg/day×10 days
500 mg PO on
day 1, then 250
mg/day
on days
2-10
6
See footnote
below
NA

Indications

Azithromycin is indicated for the treatment of patients with mild-to-moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below. As recommended dosages, durations of therapy and applicable patient populations vary among these infections.

Adults

Acute bacterial exacerbations of chronic obstructive pulmonary disease due to Haemophilus influenzae, Moraxella catarrhalis 'or' Streptococcus pneumoniae.

Acute bacterial sinusitis due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.

Community-acquired Pneumonia due to Chlamydophila pneumoniae, Haemophilus influenzae Mycoplasma pneumoniae or Streptococcus pneumonia in patients appropriate for oral therapy.

Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy.

Note: Penicillin by the intramuscular route is the usual drug of choice in the treatment of Streptococcus pyogenes infection and the prophylaxis of rheumatic fever. Azithromycin is often effective in the eradication of susceptible strains of Streptococcus pyogenes from the nasopharynx. Because some strains are resistant to azithromycin, susceptibility tests should be performed when patients are treated with azithromycin. Data establishing the efficacy of azithromycin in subsequent prevention of rheumatic fever are not available.

Uncomplicated skin and skin structure infections due to Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae. Abscesses usually require surgical drainage.

Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae.

Genital ulcer disease in men due to Haemophilus ducreyi (chancroid). Due to the small number of women included in clinical trials, the efficacy of azithromycin in the treatment of chancroid in women has not been established.

Azithromycin, at the recommended dose, should not be relied upon to treat syphilis.

Antimicrobial agents used in high doses for short periods of time to treat non-gonococcal urethritis may mask or delay the symptoms of incubating syphilis. All patients with sexually-transmitted urethritis or cervicitis should have a serologic test for syphilis and appropriate cultures for gonorrhoea performed at the time of diagnosis. Appropriate antimicrobial therapy and follow-up tests for these diseases should be initiated if infection is confirmed.

Appropriate culture and susceptibility tests should be performed before treatment to determine the causative organism and its susceptibility to azithromycin. Therapy with azithromycin may be initiated before results of these tests are known; once the results become available, antimicrobial therapy should be adjusted accordingly.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of azithromycin and other antibacterial drugs, azithromycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Paediatric Patients

Acute otitis media caused by Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.

Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy.

Note: Penicillin by the intramuscular route is the usual drug of choice in the treatment of Streptococcus pyogenes infection and the prophylaxis of rheumatic fever. Azithromycin is often effective in the eradication of susceptible strains of Streptococcus pyogenes from the nasopharynx. Because some strains are resistant to azithromycin, susceptibility tests should be performed when patients are treated with azithromycin. Data establishing the efficacy of azithromycin in subsequent prevention of rheumatic fever are not available

Sinusitis caused by Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.

Acute bronchitis caused by Chlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae.

Community-acquired Pneumonia due to Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniaeor Streptococcus pneumoniae in patients appropriate for oral therapy.

Uncomplicated skin and soft tissues infections like furunculosis, pyoderma and impetigo due to Staphylococcus aureus, Streptococcus pyogenes and Streptococcus agalactiae.

Uncomplicated genital infections (in adolescents and older children) like urethritis and cervicitis due to Chlamydia trachomatis.

Dosage and Administration

Adults

 
Infection*
Recommended Dose/Duration of Therapy
 
Community-acquired pneumonia
(mild severity)
Pharyngitis / tonsillitis (second-
line therapy)
Skin/skin structure
(uncomplicated)
500 mg as a single dose on day 1, followed by 250
mg once daily on days 2 through 5.
Acute bacterial exacerbations of
chronic
obstructive pulmonary disease
(mild to moderate)
500 mg q.d.×3 days
OR
500 mg as a single dose on day 1, followed by 250
mg once daily on days 2 through 5.
Acute bacterial sinusitis
500 mg q.d.×3 days
Genital ulcer disease (chancroid)
One single 1-gram dose
Non-gonoccocal urethritis and
cervicitis
One single 1-gram dose
Gonococcal urethritis and
cervicitis
One single 2-gram dose
 

Renal Impairment

No dosage adjustment is recommended for subjects with mild to moderate renal impairment (GFR 10 - 80 ml/min). The mean AUC0-120 was similar in subjects with GFR at 10-80 mL/min compared with subjects with normal renal function, whereas it increased by 35% in subjects with GFR <10 mL/min compared with subjects with normal renal function. Caution should be exercised when azithromycin is administered to subjects with severe renal impairment (GFR <10 ml/min).

Hepatic Impairment

A dose adjustment is not necessary for patients with mild to moderately impaired liver function. Since azithromycin is metabolised in the liver and excreted in the bile, the drug should not be given to patients suffering from severe liver disease.

Age and Gender

No dosage adjustment is recommended based on age or gender.

Paediatric Patients

Age
Indications
Regimen
3-days
Regimen
5-days
Regimen
From 6 months
and above
Acute otitis
media
30 mg/kg
single dose
 

daily
Day 1:
10 mg/kg single
dose
Days 2-5: 5
mg/kg/day
Acute bacterial
sinusitis
 
 

daily
Day 1: 10
mg/kg single
dose
Days 2-5: 5
mg/kg/day
Community-
acquired
pneumonia/
Acute
bronchitis
 
 

daily
Day 1: 10 mg/kg single
dose
Days 2-5: 5
mg/kg/day
Uncomplicated
Skin and soft
tissue
infections
 
 

daily
Day 1: 10
mg/kg single
dose
Days 2-5: 5
mg/kg/day
From 6 months
-1 year
Pharyngitis/
Tonsillitis
--
 
 
From 1 year - 2
years
--
 

with max. daily
dose of 500 mg
 
From 2 years
and above
--
 

with max. daily
dose of 500 mg
 

once daily
Adolescents
and older
children
(weighing
above 45 kg)
Uncomplicated
genital
infections
A single 1 gram dose
Children above
45 kg weight
All above given
indications
As per adult dosage

Effectiveness of the 1-day regimen in paediatric patients with community-acquired pneumonia and acute bacterial sinusitis has not been established. The safety of re-dosing azithromycin in paediatric patients who vomit after receiving 30 mg/kg as a single dose has not been established.

Administration

AZIMAX tablets, suspension and DT can be taken with or without food.

AZIMAX DT 

Disperse the tablet in a teaspoonful (5 ml) of boiled and cooled water before administration.

AZIMAX Dry Syrup

Direction for Preparing the Suspension
At the time of dispensing, the dry powder should be reconstituted to form an oral suspension. First, shake the bottle to loosen the powder. Pour boiled and cooled water into the bottle. Recap the bottle, and shake it vigorously.

Adjust the suspension volume up to the arrow mark by adding more water, if necessary, and shake again. Store the reconstituted suspension in cool place.

After reconstitution, the contents should be consumed within 5 days. Keep tightly closed. Shake well before each use. Discard the unused portion after 5 days.

Contraindications

Azithromycin is contraindicated in patients with a known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide antibiotic or any of its excipients. Azithromycin is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.

Warnings and Precautions

Serious allergic reactions, including angio-oedema, anaphylaxis and dermatologic reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis) have been reported rarely in patients on azithromycin therapy. Although rare, fatalities have been reported. Despite initially successful symptomatic treatment of the allergic symptoms, when symptomatic therapy was discontinued, the allergic symptoms-recurred soon thereafter in some patients without further azithromycin exposure. These patients required prolonged periods of observation and symptomatic treatment. The relationship of these episodes to the long tissue half-life of azithromycin and subsequent prolonged exposure to antigen is unknown at present.

If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.

Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis and hepatic failure have been reported, some of which have resulted in death. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur.

In the treatment of pneumonia, azithromycin has only been shown to be safe and effective in the treatment of community-acquired pneumonia due to Chlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae in patients appropriate for oral therapy. Azithromycin should not be used in adult and paediatric patients with pneumonia who are judged to be inappropriate for oral therapy because of moderate to severe illness or risk factors such as any of the following: patients with cystic fibrosis, patients with nosocomially acquired infections, patients with known or suspected bacteraemia, patients requiring hospitalization, elderly or debilitated patients, or patients with significant underlying health problems that may compromise their ability to respond to their illness (including immunodeficiency or functional asplenia).

Clostridium difficile-associated diarrhoea (CDAD) has been reported with the use of nearly all antibacterial agents, including azithromycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of Clostridium difficile.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against Clostridium difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment ofClostridium difficile, and surgical evaluation should be instituted as clinically indicated.

Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with macrolides, including azithromycin. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving azithromycin. Providers should consider the risk of QT prolongation which can be fatal when weighing the risks and benefits of azithromycin for at-risk groups, including

  • patients with known prolongation of the QT interval, a history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias or uncompensated heart failure;
  • patients on drugs known to prolong the QT interval; and,
  • patients with ongoing pro-arrhythmic conditions such as uncorrected hypokalaemia or hypomagnesaemia, clinically significant bradycardia, and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, aminodarone, sotalol) anti-arrhythmic agents.

Elderly patients may be more susceptible to drug-associated effects on the QT interval.

Because azithromycin is principally eliminated via the liver, caution should be exercised when azithromycin is administered to patients with impaired hepatic function. Due to the limited data in subjects with GFR <10 mL/min, caution should be exercised when prescribing azithromycin in these patients.

Cases of fulminant hepatitis potentially leading to life-threatening liver failure have been reported with azithromycin. Some patients may have had pre-existing hepatic disease or may have been taking other hepatotoxic medicinal products.

In case of signs and symptoms of liver dysfunction, such as rapid developing asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy, liver function tests/ investigations should be performed immediately. Azithromycin administration should be stopped if liver dysfunction has emerged.

In patients receiving ergot derivatives, ergotism has been precipitated by co-administration of some macrolide antibiotics. There are no data concerning the possibility of an interaction between ergot and azithromycin. However, because of the theoretical possibility of ergotism, azithromycin and ergot derivatives should not be co-administrated.

Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy.

Prescribing azithromycin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

As with any antibiotic preparation, observation for signs of superinfection with non-susceptible organisms including fungi is recommended.

Information for Patients

Azithromycin tablets and oral suspension can be taken with or without food.

Patients should also be cautioned not to take aluminium- and magnesium-containing antacids and azithromycin simultaneously.

The patient should be directed to discontinue azithromycin immediately and contact a physician if any signs of an allergic reaction occur.

Patients should be counselled that antibacterial drugs, including azithromycin, should only be used to treat bacterial infections. They do not treat viral infections (e.g. the common cold). When azithromycin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of the therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by azithromycin or other antibacterial drugs in the future.

Diarrhoea is a common problem caused by antibiotics, which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Drug Interactions

Antacids
In a pharmacokinetic study investigating the effects of simultaneous administration of antacid with azithromycin, no effect on overall bioavailability was seen, although peak serum concentrations were reduced by approximately 25%. In patients receiving both azithromycin and antacids, the drugs should not be taken simultaneously.

Cetirizine
In healthy volunteers, co-administration of a 5-day regimen of azithromycin with cetirizine 20 mg at steady-state resulted in no pharmacokinetic interaction and no significant changes in the QT interval.

Didanosine(Dideoxyinosine)
Co-administration of 1200 mg/day azithromycin with 400 mg/day didanosine in 6 HIV-positive subjects did not appear to affect the steady-state pharmacokinetics of didanosine as compared with placebo.

Digoxin
Some of the macrolide antibiotics have been reported to impair the microbial metabolism of digoxin in the gut in some patients. In patients receiving concomitant azithromycin, a related azalide antibiotic, and digoxin the possibility of raised digoxin levels should be borne in mind.

Zidovudine
Single 1000 mg doses and multiple 1200 mg or 600 mg doses of azithromycin had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. However, administration of azithromycin increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of this finding is unclear, but it may be of benefit to patients.

Azithromycin does not interact significantly with the hepatic cytochrome P450 system. It is not believed to undergo the pharmacokinetic drug interactions as seen with erythromycin and other macrolides. Hepatic cytochrome P450 induction or inactivation via cytochrome-metabolite complex does not occur with azithromycin.

Ergot derivatives
Due to the theoretical possibility of ergotism, the concurrent use of azithromycin with ergot derivatives is not recommended.

Pharmacokinetic studies have been conducted between azithromycin and the following drugs known to undergo significant cytochrome P450 mediated metabolism.

Atorvastatin
Co-administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter the plasma concentrations of atorvastatin (based on a HMG CoA-reductase inhibition assay).

Carbamazepine
In a pharmacokinetic interaction study in healthy volunteers, no significant effect was observed on the plasma levels of carbamazepine or its active metabolite in patients receiving concomitant azithromycin.

Cimetidine
In a pharmacokinetic study investigating the effects of a single dose of cimetidine, given 2 hours before azithromycin, on the pharmacokinetics of azithromycin, no alteration of azithromycin pharmacokinetics was seen.

Coumarin-Type Oral Anticoagulants
In a pharmacokinetic interaction study, azithromycin did not alter the anticoagulant effect of a single 15 mg dose of warfarin administered to healthy volunteers. There have been reports received in the post-marketing period of potentiated anticoagulation subsequent to co-administration of azithromycin and coumarin-type oral anticoagulants. Although a causal relationship has not been established, consideration should be given to the frequency of monitoring prothrombin time when azithromycin is used in patients receiving coumarin-type oral anticoagulants.

Ciclosporin
In a pharmacokinetic study with healthy volunteers that were administered a 500 mg/day oral dose of azithromycin for 3 days and were then administered a single 10 mg/kg oral dose of ciclosporin, the resulting ciclosporin Cmaxand AUC0-5were found to be significantly elevated (by 24% and 21% respectively), however no significant changes were seen in AUC0-∞. Consequently, caution should be exercised before considering concurrent administration of these drugs. If co-administration of these drugs is necessary, ciclosporin levels should be monitored and the dose adjusted accordingly.

Efavirenz
Co-administration of a 600 mg single dose of azithromycin and 400 mg efavirenz daily for 7 days did not result in any clinically significant pharmacokinetic interactions.

Fluconazole
Co-administration of a single dose of 1200 mg azithromycin did not alter the pharmacokinetics of a single dose of 800 mg fluconazole. Total exposure and half-life of azithromycin were unchanged by the co-administration of fluconazole, however, a clinically insignificant decrease in Cmax (18%) of azithromycin was observed.

Indinavir
Co-administration of a single dose of 1200 mg azithromycin had no statistically significant effect on the pharmacokinetics of indinavir administered as 800 mg three times daily for 5 days.

Methylprednisolone
In a pharmacokinetic interaction study in healthy volunteers, azithromycin had no significant effect on the pharmacokinetics of methylprednisolone.

Midazolam
In healthy volunteers, co-administration of azithromycin 500 mg/day for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of a single 15 mg dose of midazolam.

Nelfinavir
Co-administration of azithromycin (1200 mg) and nelfinavir at steady state (750 mg three times daily) resulted in increased azithromycin concentrations. No clinically significant adverse effects were observed and no dose adjustment is required.

Rifabutin
Co-administration of azithromycin and rifabutin did not affect the serum concentrations of either drug.

Neutropenia was observed in subjects receiving concomitant treatment of azithromycin and rifabutin. Although neutropenia has been associated with the use of rifabutin, a causal relationship to combination with azithromycin has not been established.

Sildenafil
In normal healthy male volunteers, there was no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC and Cmax, of sildenafil or its major circulating metabolite.

Terfenadine
Pharmacokinetic studies have reported no evidence of an interaction between azithromycin and terfenadine. There have been rare cases reported where the possibility of such an interaction could not be entirely excluded; however there was no specific evidence that such an interaction had occurred.

Theophylline
There is no evidence of a clinically significant pharmacokinetic interaction when azithromycin and theophylline are co-administered to healthy volunteers.

Triazolam
In 14 healthy volunteers, co-administration of azithromycin 500 mg on Day 1 and 250 mg on Day 2 with 0.125 mg triazolam on Day 2 had no significant effect on any of the pharmacokinetic variables for triazolam compared to triazolam and placebo.

Trimethoprim/sulfamethoxazole
Co-administration of trimethoprim/sulfamethoxazole DS (160 mg/800 mg) for 7 days with azithromycin 1200 mg on Day 7 had no significant effect on peak concentrations, total exposure or urinary excretion of either trimethoprim or sulfamethoxazole. Azithromycin serum concentrations were similar to those seen in other studies.

Interactions with the drugs listed below have not been reported in clinical trials with azithromycin; however, no specific drug interaction studies have been performed to evaluate potential drug-drug interaction. Nonetheless, they have been observed with macrolide products. Until further data are developed regarding drug interactions when azithromycin and these drugs are used concomitantly, careful monitoring of patients is advised: Terfenadine, hexobarbital and phenytoin concentrations.

Laboratory Test Interactions
There are no reported laboratory test interactions.

Renal Impairment

No dosage adjustment is recommended for subjects with mild to moderate renal impairment (GFR 10 - 80 ml/min). Caution should be exercised when azithromycin is administered to subjects with severe renal impairment (GFR

Hepatic Impairment

A dose adjustment is not necessary for patients with mild to moderately impaired liver function.

Pregnancy

Pregnancy Category B
There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, azithromycin should be used during pregnancy only if clearly needed.

Lactation

It is not known whether azithromycin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when azithromycin is administered to a nursing mother.

Paediatric Use

There is no information on children less than 6 months of age. Studies evaluating the use of repeated courses of therapy have not been conducted. Safety and efficacy for prevention or treatment of MAC in children have not been established.

Geriatric Use

Pharmacokinetic parameters in older volunteers (aged 65-85 years) were similar to those in younger volunteers (aged 18-40 years) for the 5-day the rapeutic regimen. Dosage adjustment does not appear to be necessary for older patients with normal renal and hepatic function receiving treatment with this dosage regimen.

In multiple-dose clinical trials of oral azithromycin, 9% of patients were at least 65 years of age (458/4,949) and 3% of patients (144/4,949) were at least 75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in response between the elderly and younger patients, but the greater sensitivity of some older individuals cannot be ruled out.

Elderly patients may be more susceptible to development of torsades de pointes arrhythmia than younger patients.

Undesirable Effects

In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Potentially serious side effects of angio-oedema and cholestatic jaundice were reported rarely. Approximately 0.7% of the patients (adults and paediatric patients) from the 5-day multiple-dose clinical trials discontinued azithromycin therapy because of treatment-related side effects. In adults given 500 mg/day for 3 days, the discontinuation rate due to treatment-related side effects was 0.6%. In clinical trials in paediatric patients given 30 mg/kg, either as a single dose or over 3 days, discontinuation from the trials due to treatment-related side effects was approximately 1%. Most of the side effects leading to discontinuation were related to the gastrointestinal tract, e.g. nausea, vomiting, diarrhoea or abdominal pain.

Clinical

Adults
Multiple-dose Regimens
Overall, the most common treatment-related side effects in adult patients receiving multiple-dose regimens of azithromycin were related to the gastrointestinal system, with diarrhoea/loose stools (4-5%), nausea (3%), and abdominal pain (2-3%) being the most frequently reported.

No other treatment-related side effects occurred in patients on the multiple-dose regimens of azithromycin with a frequency greater than 1%. Side effects that occurred with a frequency of 1% or less included the following:
Cardiovascular: Palpitations, chest pain.
Gastrointestinal: Dyspepsia, flatulence, vomiting, melaena and cholestatic jaundice.
Genitourinary: Monilia, vaginitis and nephritis.
Nervous System: Dizziness, headache, vertigo and somnolence.
General: Fatigue.
Allergic: Rash, pruritus, photosensitivity and angio-oedema.

Single 1-gram dose Regimen
Overall, the most common side effects in patients receiving a single-dose regimen of 1 gram of azithromycin were related to the gastrointestinal system and were more frequently reported than in patients receiving the multiple-dose regimen.

Side effects that occurred in patients on the single 1-gram dosing regimen of azithromycin with a frequency of 1% or greater included diarrhoea/loose stools (7%), nausea (5%), abdominal pain (5%), vomiting (2%), dyspepsia (1%), and vaginitis (1%).

Single 2-gram dose Regimen
Overall, the most common side effects in patients receiving a single 2-gram dose of azithromycin were related to the gastrointestinal system. Side effects that occurred in patients in this study with a frequency of 1% or greater included nausea (18%), diarrhoea/loose stools (14%), vomiting (7%), abdominal pain (7%), vaginitis (2%), dyspepsia (1%) and dizziness (1%). The majority of these complaints were mild in nature.

Paediatric Patients
Single- and Multiple-dose Regimens
The types of side effects in paediatric patients were comparable with those seen in adults, with different incidence rates for the dosage regimens recommended in paediatric patients.

Acute Otitis Media
For the recommended total dosage regimen of 30 mg/kg, the most frequent side effects (≥1%) attributed to treatment were diarrhoea, abdominal pain, vomiting, nausea and rash.

The incidence, based on dosing regimen, is described in the table below:

Dosage
Regimen
Diarrhoea,
%
Abdominal
Pain, %
Vomiting,
%
Nausea,
%
Rash,
%
1-day
4.3%
1.4%
4.9%
1.0%
1.0%
3-day
2.6%
1.7%
2.3%
0.4%
0.6%
5-day
1.8%
1.2%
1.1%
0.5%
0.4%

Community-acquired Pneumonia
For the recommended dosage regimen of 10 mg/kg on day 1 followed by 5 mg/kg on days 2-5, the most frequent side effects attributed to treatment were diarrhoea/loose stools, abdominal pain, vomiting, nausea and rash.

The incidence is described in the table below:

Dosage
Regimen
Diarrhoea/Loose
stools, %
Abdominal
Pain, %
Vomiting,
%
Nausea,
%
Rash,
%
5-day
5.8%
1.9%
1.9%
1.9%
1.6%

Pharyngitis/Tonsillitis
For the recommended dosage regimen of 12 mg/kg on days 1-5, the most frequent side effects attributed to treatment were diarrhoea, vomiting, abdominal pain, nausea and headache.

The incidence is described in the table below:

Dosage
Regimen
Diarrhoea
%
Abdominal
Pain, %
Vomiting,
%
Nausea,
%
Rash,
%
Headache,
%
5-day
5.4%
3.4%
5.6%
1.8%
0.7%
1.1%

With any of the treatment regimens, no other treatment-related side effects occurred in paediatric patients treated with azithromycin with a frequency greater than 1%. Side effects that occurred with a frequency of 1% or less included the following:
Cardiovascular: Chest pain.
Gastrointestinal: Dyspepsia, constipation, anorexia, enteritis, flatulence, gastritis, jaundice, loose stools and oral moniliasis.
Haematologic and Lymphatic: Anaemia and leucopenia.
Nervous System: Headache (otitis media dosage), hyperkinesia, dizziness, agitation, nervousness and insomnia.
General: Fever, face oedema, fatigue, fungal infection, malaise and pain.
Allergic: Rash and allergic reaction.
Respiratory: Cough increased, pharyngitis, pleural effusion and rhinitis.
Skin and Appendages: Eczema, fungal dermatitis, pruritus, sweating, urticaria and vesiculobullous rash.
Special Senses: Conjunctivitis.

Postmarketing Experience

Adverse events reported with azithromycin during the postmarketing period in adult and/or paediatric patients for which a causal relationship may not be established included the following:
Allergic: Arthralgia, oedema, urticaria and angio-oedema.
Cardiovascular: Arrhythmias, including ventricular tachycardia and hypotension. There have been rare reports of QT prolongation and torsades de pointes.
Gastrointestinal: Anorexia, constipation, dyspepsia, flatulence, vomiting/diarrhoea rarely resulting in dehydration, pseudomembranous colitis, pancreatitis, oral candidiasis, pyloric stenosis, and rare reports of tongue discolouration.
General: Asthenia, paraesthesia, fatigue, malaise and anaphylaxis (rarely fatal).
Genitourinary: Interstitial nephritis and acute renal failure and vaginitis.
Haematopoietic: Thrombocytopenia.
Liver/Biliary: Adverse reactions related to hepatic dysfunction have been reported in postmarketing experience with azithromycin.
Nervous System: Convulsions, dizziness/vertigo, headache, somnolence, hyperactivity, nervousness, agitation and syncope.
Psychiatric: Aggressive reaction and anxiety.
Skin/Appendages: Pruritus; rarely, serious skin reactions, including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.
Special Senses: Hearing disturbances, including hearing loss, deafness and/or tinnitus, and reports of taste/smell perversion and/or loss.

Laboratory Abnormalities

Adults
Clinically significant abnormalities (irrespective of drug relationship) occurring during the clinical trials were reported as follows:
With an Incidence of Greater Than 1%
Decreased haemoglobin, haematocrit, lymphocytes, neutrophils and blood glucose; elevated serum creatine phosphokinase, potassium, ALT, GGT, AST, BUN, creatinine, blood glucose, platelet count, lymphocytes, neutrophils and eosinophils

With an Incidence of Less Than 1%
Leucopenia, neutropenia, decreased sodium, potassium, platelet count, elevated monocytes, basophils, bicarbonate, serum alkaline phosphatase, bilirubin, LDH and phosphate. The majority of subjects with elevated serum creatinine also had abnormal values at baseline.

When follow-up was provided, changes in laboratory tests appeared to be reversible.

In multiple-dose clinical trials involving more than 5,000 patients, 4 patients discontinued therapy because of treatment-related liver enzyme abnormalities and 1 because of a renal function abnormality.

Paediatric Patients
Regimens for 1, 3 and 5 Days
Laboratory data collected from comparative clinical trials employing two 3-day regimens (30 mg/kg or 60 mg/kg in divided doses over 3 days), or two 5-day regimens (30 mg/kg or 60 mg/kg in divided doses over 5 days) were similar for regimens of azithromycin and all comparators combined, with most clinically significant laboratory abnormalities occurring at incidences of 1-5%. Laboratory data for patients receiving 30 mg/kg as a single dose were collected in one single-centre trial. In that trial, an absolute neutrophil count between 500 and 1,500 cells/mm3was observed in 10/64 patients receiving 30 mg/kg as a single dose, 9/62 patients receiving 30 mg/kg given over 3 days, and 8/63 comparator patients. No patient had an absolute neutrophil count 3.

In multiple-dose clinical trials involving approximately 4,700 paediatric patients, no patients discontinued therapy because of treatment-related laboratory abnormalities.

Other adverse reactions
Other adverse reactions possibly or probably related to azithromycin based on clinical trial experience and post-marketing surveillance:

Common(> 1/100<1/10):Dysgeusia, visual impairment, lymphocyte count decreased, eosinophil count increased, blood bicarbonate decreased

Uncommon (≥1/1,000 to <1/100):Candidiasis, angioedema, hypersensitivity, Hypoaesethesia, photosensitivity reaction

Not known (cannot be estimated from available data): Haemolytic anaemia, anaphylactic reaction, psychomotor hyperactivity, anosmia, ageusia, parosmia, renal failure acute, nephritis interstitial.

Overdosage

Adverse events experienced in higher than recommended doses were similar to those seen at normal doses. The typical symptoms of an overdose with macrolide antibiotics include reversible loss of hearing, severe nausea, vomiting and diarrhoea. In the event of overdose, the administration of medicinal charcoal and general symptomatic treatment and supportive measures are indicated as required.

Storage And Handling Instructions

Store at room temperature. Protect from moisture

Packaging Information

AZIMAX 250: Strip pack of six tablets
AZIMAX 500: Strip pack of three tablets
AZIMAX 1000: Strip pack of one tablet
AZIMAX 100: Bottle of 15 ml dry syrup
AZIMAX 200: Bottle of 15 ml dry syrup
AZIMAX 100: Strip pack of six dispersible tablet
AZIMAX 200: Strip pack of six dispersible tablet