Azithromycin for oral suspension USP 200mg/5ml Taj Pharma

  1. Name of the medicinal product

Azithromycin for oral suspension USP 200mg/5ml Taj Pharma

  1. Qualitative and quantitative composition

Each tea spoonful (5ml) contains:
Azithromycin monohydrate USP
Equivalent to Azithromycin 200mg
Excipients: Q.S.

Excipients with known effect:
Also contains 3.87 g Sucrose per 5ml.

For the full list of excipients, see section 6.1.

  1. Pharmaceutical form

Powder for Oral Suspension

  1. Clinical particulars
    • Therapeutic indications

Azithromycin is indicated for the treatment of the following infections when known or likely to be due to one or more susceptible microorganisms (see section 5.1):

  • bronchitis
  • community-acquired pneumonia
  • sinusitis
  • pharyngitis/tonsillitis (see section 4.4 regarding streptococcal infections)
  • otitis media
  • skin and soft tissue infections
  • uncomplicated genital infections due to Chlamydia trachomatis and Neisseria gonorrhoeae.

Considerations should be given to official guidance regarding the appropriate use of antibacterial agents.

  • Posology and method of administration

Posology:

Azithromycin monohydrate should be given as a single daily dose.

Azithromycin monohydrate Suspension can be taken with or without food.

Children over 45 kg body weight and adults, including elderly patients: The total dose of azithromycin is 1500mg which should be given over three days (500mg once daily).

In uncomplicated genital infections due to Chlamydia trachomatis, the dose is 1000mg as a single oral dose. For susceptible Neisseria gonorrhoeae the recommended dose is 1000mg or 2000mg of azithromycin in combination with 250mg or 500mg ceftriaxone according to local clinical treatment guidelines. For patients who are allergic to penicillin and/or cephalosporins, prescribers should consult local treatment guidelines.

Paediatric population:

In children under 45 kg body weight: Azithromycin monohydrate Suspension should be used for children under 45 kg. There is no information on children less than 6 months of age. The dose in children is 10mg/kg as a single daily dose for 3 days:

Up to 15 kg (less than 3 years): Measure the dose as closely as possible using the 10ml oral dosing syringe provided. The syringe is graduated in 0.25ml divisions, providing 10mg of azithromycin in every graduation.

For children weighing more than 15 kg, Azithromycin monohydrate Suspension should be administered using the spoon provided according to the following guidance:

15-25 kg (3-7 years): 5ml (200mg) given as 1 x 5ml spoonful, once daily for 3 days.

26-35 kg (8-11 years): 7.5ml (300mg) given as 1 x 7.5ml spoonful, once daily for 3 days.

36-45 kg (12-14 years): 10ml (400mg) given as 1 x 10ml spoonful, once daily for 3 days.

Over 45 kg: Dose as per adults.

See section 6.5 for appropriate pack size to use depending on age/body weight of child.

The specially supplied measure should be used to administer Azithromycin monohydrate suspension to children.

Renal impairment:

No dose adjustment is necessary in patients with mild to moderate renal impairment (GFR 10 – 80ml/min). Caution should be exercised when azithromycin is administered to patients with severe renal impairment (GFR < 10ml/min) (see section 4.4 and section 5.2).

Hepatic impairment:

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. No studies have been conducted regarding treatment of such patients with azithromycin (see section 4.4).

Method of administration:

Azithromycin monohydrate Suspension is for oral administration only.

  • Contraindications

Azithromycin monohydrate is contra-indicated in patients with a known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide antibiotic, or to any of the excipients (listed in section 6.1).

  • Special warnings and precautions for use

Hypersensitivity

As with erythromycin and other macrolides, serious allergic reactions including angioneurotic oedema and anaphylaxis (rarely fatal), Acute Generalized Exanthematous Pustulosis (AGEP) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have been reported. Some of these reactions with azithromycin have resulted in recurrent symptoms and required a longer period of observation and treatment.

Hepatotoxicity

Since the liver is the principal route of elimination for azithromycin, the use of azithromycin should be undertaken with caution in patients with significant hepatic disease. Cases of fulminant hepatitis potentially leading to life-threatening liver failure have been reported with azithromycin (see section 4.8). 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.

Ergot derivatives

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.

Prolongation of the QT interval

Prolonged cardiac repolarisation and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with other macrolides. A similar effect with azithromycin cannot be completely ruled out in patients at increased risk for prolonged cardiac repolarisation (see section 4.8); therefore caution is required when treating patients:

  • With congenital or documented QT prolongation
  • Currently receiving treatment with other active substance known to prolong QT interval such as antiarrhythmics of Classes Ia and III, cisapride and terfenadine
  • With electrolyte disturbance, particularly in case of hypokalaemia and hypomagnesemia
  • With clinically relevant bradycardia, cardiac arrhythmia or severe cardiac insufficiency.

Superinfection

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

Clostridium difficile associated diarrhoea

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. Strains of C. difficile producing hypertoxin A and B contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. Therefore, CDAD must be considered in patients who present with diarrhoea during or subsequent to the administration of any antibiotics. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents. Discontinuation of therapy with azithromycin and the administration of specific treatment for C. difficile should be considered.

Streptococcal infections

Penicillin is usually the first choice for treatment of pharyngitis/tonsillitis due to Streptococcus pyogenes and also for prophylaxis of acute rheumatic fever. Azithromycin is in general effective against streptococcus in the oropharynx, but no data are available that demonstrate the efficacy of azithromycin in preventing acute rheumatic fever.

Renal impairment

In patients with severe renal impairment (GFR <10ml/min) a 33% increase in systemic exposure to azithromycin was observed (see section 5.2).

Myasthenia gravis

Exacerbations of the symptoms of myasthenia gravis and new onset of myasthenia syndrome have been reported in patients receiving azithromycin therapy (see section 4.8).

Diabetes

Caution in diabetic patients: 5ml of reconstituted suspension contains 3.87 g of sucrose.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Azithromycin monohydrate Suspension is for oral administration only.

  • Interaction with other medicinal products and other forms of interaction

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 24%. 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 20mg cetirizine at steady-state resulted in no pharmacokinetic interaction and no significant changes in the QT interval.

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

Digoxin and colchicine: concomitant administration of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates such as digoxin and colchicine, has been reported to result in increased serum levels of the P-glycoprotein substrate. Therefore, if azithromycin and P-glycoprotein substrates such as digoxin are administered concomitantly, the possibility of elevated serum digoxin concentrations should be considered. Clinical monitoring, and possibly serum digoxin levels, during treatment with azithromycin and after its discontinuation are necessary.

Zidovudine: Single 1000mg doses and multiple 1200mg or 600mg 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 (see section 4.4).

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

Atorvastatin: Co-administration of atorvastatin (10mg daily) and azithromycin (500mg 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 dose of 15mg 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 who were administered a 500mg/day oral dose of azithromycin for 3 days and were then administered a single 10mg/kg oral dose of ciclosporin, the resulting ciclosporin Cmax and AUC0-5 were 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 single dose of 600mg azithromycin and 400mg efavirenz daily for 7 days did not result in any clinically significant pharmacokinetic interactions.

Fluconazole: Co-administration of a single dose of 1200mg azithromycin did not alter the pharmacokinetics of a single dose of 800mg 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 1200mg azithromycin had no statistically significant effect on the pharmacokinetics of indinavir administered as 800mg 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.

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

Nelfinavir: Co-administration of azithromycin (1200mg) and nelfinavir at steady state (750mg three times daily) resulted in increased azithromycin concentrations. No clinically significant adverse effects were observed and no dose adjustment was 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 (see section 4.8.).

Sildenafil: In normal healthy male volunteers, there was no evidence of an effect of azithromycin (500mg 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.

TriazolamIn 14 healthy volunteers, co-administration of 500mg azithromycin on Day 1 and 250mg on Day 2 with 0.125mg 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 (160mg/800mg) for 7 days with 1200mg azithromycin 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.

  • Fertility, pregnancy and lactation

Pregnancy

Animal reproduction studies have been performed at doses up to moderately maternally toxic dose concentrations. In these studies, no evidence of harm to the foetus due to azithromycin was found. There are, however, 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.

Breast-feeding

There are no data on secretion in breast milk. As many drugs are excreted in human milk, azithromycin should not be used in the treatment of a lactating woman unless the physician feels that the potential benefits justify the potential risks to the infant.

  • Effects on ability to drive and use machines

There is no evidence to suggest that Azithromycin monohydrate may have an effect on a patient’s ability to drive or operate machinery.

  • Undesirable effects

Azithromycin monohydrate is well tolerated with a low incidence of side effects.

The section below lists the adverse reactions identified through clinical trial experience and postmarketing surveillance by system organ class and frequency. Adverse reactions identified from post-marketing experience are included in italics. The frequency grouping is defined using the following convention: Very common (≥1/10); Common (≥ 1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥ 1/10,000 to <1/1,000); Very Rare (< 1/10,000); and Not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

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

Infections and Infestations

Uncommon (≥1/1,000 to <1/100)

Candidiasis, oral candidiasis, vaginal infection

Not known (cannot be estimated from available data)

Pseudomembranous colitis (see section 4.4)

Blood and Lymphatic System Disorders

Uncommon (≥ 1/1,000 to < 1/100)

Leukopenia, neutropenia

Not known (cannot be estimated from available data)

Thrombocytopenia, haemolytic anaemia

Immune System Disorders

Uncommon (≥1/1,000 to <1/100)

Angioedema, hypersensitivity

Not known (cannot be estimated from available data)

Anaphylactic reaction (see section 4.4)

Metabolism and Nutrition Disorders

Common (> 1/100 < 1/10)

Anorexia

Psychiatric Disorders

Uncommon (≥1/1,000 to <1/100)

Nervousness

Rare (> 1/10,000 < 1/1,000)

Agitation

Not known (cannot be estimated from available data)

Aggression, anxiety

Nervous System Disorders

Common (> 1/100 < 1/10)

Dizziness, headache, paraesthesia, dysgeusia

Uncommon (≥1/1,000 to <1/100)

Hypoaesethesia, somnolence, insomnia

Not known (cannot be estimated from available data)

Syncope, convulsion, psychomotor hyperactivity, anosmia, ageusia, parosmia, Myasthenia gravis (see section 4.4)

Eye Disorders

Common (> 1/100 < 1/10)

Visual impairment

Ear and Labyrinth Disorders

Common (> 1/100 < 1/10)

Deafness

Uncommon (≥1/1,000 to <1/100)

Hearing impaired, tinnitus

Rare (> 1/10,000 < 1/1,000)

Vertigo

Cardiac Disorders

Uncommon (≥1/1,000 to <1/100)

Palpitations

Not known (cannot be estimated from available data)

Torsades de pointes (see section 4.4), arrhythmia (see section 4.4) including ventricular tachycardia

Vascular Disorders

Not known (cannot be estimated from available data)

Hypotension

Gastrointestinal Disorders

Very common (≥1/10)

Diarrhoea, abdominal pain, nausea, flatulence

Common (> 1/100 < 1/10)

Vomiting, dyspepsia

Uncommon (> 1/1,000 < 1/100)

Gastritis, constipation

Not known (cannot be estimated from available data)

Pancreatitis, tongue discolouration

Hepatobiliary Disorders

Uncommon (> 1/1,000 < 1/100)

Hepatitis

Rare (> 1/10,000 < 1/1,000)

Hepatic function abnormal

Not known (cannot be estimated from available data)

Hepatic failure (see section 4.4), which has rarely resulted in death, hepatitis fulminant, hepatic necrosis, jaundice cholestatic

Skin and Subcutaneous Tissue Disorders

Common (> 1/100 < 1/10)

Pruritus and rash

Uncommon (> 1/1,000 < 1/100)

SJS, photosensitivity reaction, urticaria

Rare (≥1/10,000 to <1/1,000)

Acute Generalized Exanthematous Pustulosis (AGEP)

Drug reaction with eosinophilia and systemic symptoms (DRESS)

Not known (cannot be estimated from available data)

TEN, erythema multiforme

Musculoskeletal, Connective Tissue Disorders

Common (> 1/100 < 1/10)

Arthralgia

Renal and Urinary Disorders

Not known (cannot be estimated from available data)

Renal failure acute, nephritis interstitial

General disorders and Administration Site Conditions

Common (> 1/100 < 1/10)

Fatigue

Uncommon (> 1/1,000 < 1/100)

Chest pain, oedema, malaise, asthenia

Investigations

Common (> 1/100 < 1/10)

Lymphocyte count decreased, eosinophil count increased, blood bicarbonate decreased

Uncommon (> 1/1,000 < 1/100)

Aspartate aminotransferase increased, alanine aminotransferase increased, blood bilirubin increased, blood urea increased, blood creatinine increased, blood potassium abnormal

Not known (cannot be estimated from available data)

Electrocardiogram QT prolonged (see section 4.4)

*ADR identified post-marketing

  • ADR frequency represented by the estimated upper limit of the 95% confidence interval calculated using the “Rule of 3”.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Overdose

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.

  1. Pharmacological properties
    • Pharmacodynamic properties

General properties

Pharmacotherapeutic group: Antibacterials for systemic use.

Mode of action:

Azithromycin monohydrate is a macrolide antibiotic belonging to the azalide group. The molecule is constructed by adding a nitrogen atom to the lactone ring of erythromycin A. The chemical name of azithromycin is 9-deoxy-9a-aza-9a-methyl-9a-homoerythromycin A. The molecular weight is 749.0. The mechanism of action of azithromycin is based upon the suppression of bacterial protein synthesis by means of binding to the ribosomal 50S sub-unit and inhibition of peptide translocation.

Mechanism of resistance:

Resistance to azithromycin may be inherent or acquired. There are three main mechanisms of resistance in bacteria: target site alteration, alteration in antibiotic transport and modification of the antibiotic.

Azithromycin demonstrates cross resistance with erythromycin resistant gram positive isolates. A decrease in macrolide susceptibility over time has been noted particularly in Streptococcus pneumoniae and Staphylococcus aureus. Similarly, decreased susceptibility has been observed among Streptococcus viridans and Streptococcus agalactiae (Group B) streptococcus against other macrolides and lincosamides.

Breakpoints

Azithromycin susceptibility breakpoints for typical bacterial pathogens published by EUCAST are:

Organism MIC breakpoints (mg/L)
Susceptible (S≤) Resistant (R>)
Staphylococcus spp. 1 2
Streptococcus groups A, B, C and G 0.25 0.5
Streptococcus pneumoniae 0.25 0.5
Haemophilus influenzae 0.12 4
Moraxella catarrhalis 0.25 0.5
Neisseria gonorrhoeae 0.25 0.5

Susceptibility

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

Table: Antibacterial spectrum of Azithromycin

Commonly susceptible species
Aerobic Gram-positive microorganisms
Staphylococcus aureus

Methycillin-susceptible

Streptococcus pneumoniae

Penicillin-susceptible

Streptococcus pyogenes (Group A)
Aerobic Gram-negative microorganisms
Haemophilus influenzae

Haemophilus parainfluenzae

Legionella pneumophila
Moraxella catarrhalis
Neisseria gonorrhoeae
Pasteurella multocida
Anaerobic microorganisms
Clostridium perfringens
Fusobacterium spp.
Prevotella spp.
Porphyromonas spp.
Other microorganisms
Chlamydia trachomatis
Species for which acquired resistance may be a problem
Aerobic Gram-positive microorganisms
Streptococcus pneumoniae

Penicillin-intermediate

Penicillin-resistant

Inherently resistant organisms
Aerobic Gram-positive microorganisms
Enterococcus faecalis
Staphylococci MRSA, MRSE*
Anaerobic microorganisms
Bacteroides fragilis group

* Methycillin-resistant staphylococci have a very high prevalence of acquired resistance to macrolides and have been placed here because they are rarely susceptible to azithromycin.

Paediatric population

Following the assessment of studies conducted in children, the use of azithromycin is not recommended for the treatment of malaria, neither as monotherapy nor combined with chloroquine or artemisinin based drugs, as non-inferiority to anti-malarial drugs recommended in the treatment of uncomplicated malaria was not established.

  • Pharmacokinetic properties

Absorption

Bioavailability after oral administration is approximately 37%. Peak plasma concentrations are attained 2 to 3 hours after taking the medicinal product.

Distribution

Orally administered azithromycin is widely distributed throughout the body. In pharmacokinetic studies it has been demonstrated that the concentrations of azithromycin measured in tissues are noticeably higher (as much as 50 times) than those measured in plasma, which indicates that the agent strongly binds to tissues.

Binding to serum proteins varies according to plasma concentration and ranges from 12% at 0.5 microgram/ml up to 52% at 0.05 microgram azithromycin/ml serum. The mean volume of distribution at steady state (VVss) has been calculated to be 31.1 l/kg.

Elimination

The terminal plasma elimination half-life closely reflects the elimination half-life from tissues of 2 to 4 days.

Approximately 12% of an intravenously administered dose of azithromycin is excreted unchanged in urine within the following three days. Particularly high concentrations of unchanged azithromycin have been found in human bile. Also in bile, ten metabolites were detected, which were formed through N- and O- demethylation, hydroxylation of desosamine and aglycone rings and cleavage of cladinose conjugate. Comparison of the results of liquid chromatography and microbiological analyses has shown that the metabolites of azithromycin are not microbiologically active.

In animal tests, high concentrations of azithromycin have been found in phagocytes. It has also been established that during active phagocytosis higher concentrations of azithromycin are released from inactive phagocytes. In animal models this results in high concentrations of azithromycin being delivered to the site of infection.

  • Preclinical safety data

Phospholipidosis (intracellular phospholipid accumulation) has been observed in several tissues (e.g. eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and/or pancreas) of mice, rats, and dogs given multiple doses of azithromycin. Phospholipidosis has been observed to a similar extent in the tissues of neonatal rats and dogs. The effect has been shown to be reversible after cessation of azithromycin treatment. The significance of the finding for animals and humans is unknown.

Carcinogenic potential:

Long-term studies in animals have not been performed to evaluate carcinogenic potential as the drug is indicated for short-term treatment only and there were no signs indicative of carcinogenic activity.

Mutagenic potential:

There was no evidence of a potential for genetic and chromosome mutations in in-vivo and in-vitro test models.

Reproductive toxicity:

In animal studies for embryotoxic effects of the substance, no teratogenic effect was observed in mice and rats. In rats, azithromycin doses of 100 and 200mg/kg bodyweight/day led to mild retardation of foetal ossification and in maternal weight gain. In peri- and postnatal studies in rats, mild retardation following treatment with 50mg/kg/day azithromycin and above was observed.

  1. Pharmaceutical particulars
    • List of excipients

Hydroxypropylcellulose

Sodium phosphate tribasic anhydrous

Sucrose

Xanthan gum

Flavours:

Artificial banana

Artificial cherry

Artificial creme de vanilla.

  • Incompatibilities

Not applicable.

  • Shelf life

Azithromycin monohydrate Powder for Oral Suspension: 3 years.

Once reconstituted with water, Azithromycin monohydrate Suspension has a shelf-life of 5 days.

  • Special precautions for storage

None

  • Nature and contents of container

Azithromycin monohydrate Powder for Oral Suspension is available as:

600mg (15ml) Pack: (Recommended for use in children up to 7 years (25 kg)).

Packs of powder equivalent to 600mg azithromycin in a polypropylene container with child resistant screw cap (with or without a tamper evident seal), in a carton box. Pack contains a double-ended multi-dosing spoon1 and 10ml oral dosing syringe with detachable adaptor. Reconstitute with 9ml of water to give 15ml suspension.

900mg (22.5ml) Pack: (Recommended for use in children aged from 8-11 years (26-35 kg)).

Packs of powder equivalent to 900mg azithromycin in a polypropylene container with child resistant screw cap (with or without a tamper evident seal), in a carton box. Pack contains a double-ended multi-dosing spoon1. Reconstitute with 12ml of water to give 22.5ml suspension.

1200mg (30ml) Pack: (Recommended for use in children aged from 12-14 years (36-45 kg)).

Packs of powder equivalent to 1200mg azithromycin in a polypropylene container with child resistant screw cap (with or without a tamper evident seal) in a carton box. Pack contains a double-ended multi-dosing spoon1. Reconstitute with 15ml of water to give 30ml suspension.

1500mg (37.5ml) Pack:

Packs of powder equivalent to 1500mg azithromycin in a polypropylene container with child resistant screw cap and tamper evident seal, in a carton box. Pack contains a double-ended multi-dosing spoon1. Reconstitute with 19ml of water to give 37.5ml suspension.

Multi-dosing spoon delivers doses as follows:

Small end to graduation 2.5ml (100mg)
brimful 5ml (200mg)
Large end to graduation 7.5ml (300mg)
brimful 10ml (400mg)

Each pack contains a patient information/ instruction leaflet.

Not all pack sizes may be marketed.

  • Special precautions for disposal and other handling

When dispensing the 15ml pack, advice should be given as to whether the dose should be measured using the oral dosing syringe or the spoon provided and on correct usage. If the dose is to be given using the oral dosing syringe, before dispensing the syringe adaptor should be detached from the syringe and inserted into the bottle neck and the cap replaced.

When dispensing 22.5ml, 30ml and 37.5ml packs, advice should be given as to the correct usage of the multi-dosing spoon.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Azithromycin Oral Suspension 200mg/5ml Taj Pharma

Package leaflet: Information for the patient

Azithromycin

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
  • If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

  1. What Azithromycin is and what it is used for
  2. What you need to know before you take Azithromycin
  3. How to take Azithromycin
  4. Possible side effects
  5. How to store Azithromycin
  6. Contents of the pack and other information

1.What Azithromycin is and what it is used for

This medicine contains azithromycin, which is one of a group of antibiotics called macrolides. It is used to treat infections caused by certain bacteria and other micro-organisms which include:

  • chest, throat or nasal infections (such as bronchitis, pneumonia, tonsillitis, sore throat (pharyngitis) and sinusitis)
  • ear infections
  • skin and soft tissue infections (such as an abscess or boil)
  • sexually-transmitted diseases caused by organisms called Chlamydia trachomatis or Neisseria gonorrhoea.

You must talk to a doctor if you do not feel better or if you feel worse.

  1. What you need to know before you take Azithromycin

Do not take Azithromycin:

  • if you/your child are allergic to azithromycin or any other macrolide antibiotic such as erythromycin or clarithromycin or any of the ingredients listed in section 6. An allergic reaction may cause skin rash or wheezing.

Warnings and precautions

Talk to your doctor or pharmacist before taking Azithromycin if you/your child have or have had any of the following:

  • kidney problems
  • heart conditions
  • diabetes
  • liver problems: your doctor may need to monitor your liver function or stop the treatment
  • myasthenia gravis (a condition that causes certain muscles to become weak)
  • or if you are taking any ergot derivatives such as ergotamine (used to treat migraine) as these medicines should not be taken together with Azithromycin.

Tell your doctor immediately if you feel your heart beating in your chest or have an abnormal heartbeat, or get dizzy or faint or suffer from any muscle weakness when taking Azithromycin.

If you develop diarrhoea or loose stools during or after treatment, tell your doctor at once. Do not take any medicine to treat your diarrhoea without first checking with your doctor. If your diarrhoea continues, please inform your doctor.

Other medicines and Azithromycin

Tell your doctor or pharmacist if you/your child are taking, have recently taken or might take any other medicines.

In particular, Azithromycin may interact with the medicines listed below:

  • ergot or ergotamine, see ‘Warnings and precautions’ section
  • warfarin or any similar medicine to prevent blood clots
  • ciclosporin (used to suppress the immune system to prevent and treat rejection of a transplanted organ or bone marrow)
  • antacids (for indigestion)
  • digoxin (used to treat heart failure)
  • colchicine (used for gout and familial Mediterranean fever)
  • terfenadine (for hay fever or a skin allergy).

Azithromycin with food and drink

Please refer to section 3.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

Azithromycin is not expected to affect your ability to drive or use machines.

Azithromycin suspension contains sucrose, a type of sugar (3.87 g in 5ml ). If you have been told by your doctor that you have an intolerance to some sugars contact your doctor before taking this medicine. If you are diabetic, you may need to take this into account in your diet. May be harmful to the teeth.

  1. How to take Azithromycin

Always take or give this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

The pharmacist should have advised you whether to measure the medicine using the multidosing spoon or the oral dosing syringe (15ml  pack only).

Azithromycin suspension is generally used for children under 7 stones (45 kg). It may also be used in adults and older children who have difficulty swallowing capsules.

Azithromycin suspension is not affected by food or drink.

Children under 45 kg

The recommended dose in children is 10mg for each kg of bodyweight, given as a single daily dose for 3 days.

Adults and children over 45 kg

The recommended dose in adults and in children over 7 stones (45 kg) is 500mg taken as a single dose, for 3 days. For some diseases such as Chlamydia the recommended dose is 1 g daily taken as a single dose. For gonorrhoea the recommended dose is 1 g or 2 g of azithromycin in combination with 250 or 500mg of ceftriaxone.

You should tell your doctor if you/your child have kidney or liver problems as your doctor may need to alter the normal dose.

Doctors sometimes prescribe different doses to the recommended dose. The label on the pack will tell you which dose you/your child should take. If you are still not sure, ask your doctor or pharmacist.

Always continue with the course of treatment even if you/your child feel better. If your infection gets worse or you do not start to feel better within a few days or a new infection develops, go back and see your doctor.

How to give Azithromycin Suspension in children less than 3 years of age

If your child is under three years of age or weighs up to 15 kg in bodyweight, you should measure the dose as clearly as possible using the 10ml  oral dosing syringe provided. The syringe is graduated in 0.25ml  divisions, providing 10mg of azithromycin (the active ingredient) in every graduation.

  1. Instructions for the syringe

Filling the syringe with medicine

  1. Shake the bottle before use and remove the child-proof cap.
  2. An adaptor for the syringe should have been fitted into the neck of the bottle of medicine by the pharmacist. If this has not been done, take off the adaptor from the syringe and fit to the neck of the bottle as shown. The adaptor is so that you can fill the syringe with medicine from the bottle.
  3. Check the dispensing label attached by your pharmacist to see how much medicine needs to be taken.
  4. While the bottle is sitting on a firm, flat surface, hold it steady with one hand. With the other hand insert the tip of the syringe into the adaptor.
  5. Turn the bottle upside down while holding the syringe in place.
  6. Slowly pull back the plunger of the syringe so that the top edge is level with the graduation mark corresponding to the quantity in the millilitres (ml) prescribed by your doctor.
  7. If large bubbles can be seen in the syringe, slowly push the plunger back into the syringe. This will force the medicine back into the bottle. Repeat step 6 again.
  8. Hold the syringe and bottle firmly. Turn the bottle upright, with the syringe still in place.
  9. Remove syringe from bottle.

Giving the medicine using the syringe

  1. Make sure your child is supported in an upright position.
  2. Put the tip of the syringe carefully into your child’s mouth. Point the tip of the syringe towards the inside of your child’s cheek.
  3. Slowly push down the plunger of the syringe: Do not squirt it out quickly. The medicine will trickle into your child’s mouth.
  4. Allow your child some time to swallow the medicine.
  5. Replace the child-proof cap on the bottle. Wash the syringe as instructed below.
  6. Where daily doses of less than 5ml have been given for three days, some suspension will remain in the bottle. This remaining suspension should be discarded.

Cleaning and storing the syringe

  1. Pull the plunger out of the syringe and wash both parts by holding under warm running water or by immersing in sterilising solution used for baby’s feeding bottles, etc.
  2. Dry the two parts. Push the plunger back into the syringe. Keep it in a clean safe place with the medicine. After you have given your child the final dose of medicine, wrap the syringe in a sheet of newspaper and put it in the rubbish bin.

How to give Azithromycin Suspension in children between 3 and 14 years of age

Bodyweight and age Dose and duration
15-25 kg bodyweight (3-7 years):
(Between 2½ and 4 stones)
5ml  (200mg), given as 1 x 5ml  spoonful, once daily for 3 days.
26-35 kg bodyweight (8-11 years): (Between
4 and 5½ stones)
7.5ml  (300mg), given as 1 x 7.5ml  spoonful, once daily for 3 days.
36-45 kg bodyweight (12-14 years): (Between
5½ and 7 stones)
10ml  (400mg), given as 1 x 10ml  spoonful, once daily for 3 days.

  1. Instructions for the plastic spoon the spoon should not be used for children less than 3 years of age (less than 2½ stones). Giving the medicine using the spoon.
  2. A plastic double-ended spoon is provided with the medicine. Check which end of the spoon and to which level gives you your required dose. If you are unsure, check with your doctor or pharmacist. This multi-dosing spoon delivers doses as follows: 2.5ml (100mg) Small end to graduation (illustration) 5ml  (200mg) Small end brimful (illustration) 7.5ml  (300mg) Large end to graduation (illustration) 10ml  (400mg) Large end brimful (illustration)
  3. Shake the bottle well and then remove the child-proof cap.
  4. Gently pour the medicine into the spoon as required to give the correct dose.
  5. Allow the patient to swallow the medicine slowly.
  6. Wash the spoon under warm, running water. Dry and store it with the medicine in a safe place.

Warning: if giving this medicine to a child, ensure that while receiving the medicine he/she is supported in an upright position to avoid the risk of choking.

If you/your child takes more Azithromycin than they should

If you/your child take too much Azithromycin they may feel unwell. Tell your doctor or contact your nearest hospital casualty department immediately. Take any remaining medicine with you.

If you forget to take or give Azithromycin

If you forget to take Azithromycin take it as soon as you can. Take your next dose at the right time. Do not take a double dose to make up for a forgotten dose.

If you stop taking Azithromycin

If you/your child stop taking Azithromycin too soon, the infection may return. Take Azithromycin for the full time of treatment, even when you/your child begin to feel better.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

  1. Possible side effects

Like all medicines, this medicine can cause side effects although not everybody gets them.

Tell your doctor immediately if you experience any of the following symptoms after taking this medicine as the symptoms can be severe.

  • sudden wheeziness, difficulty in breathing, swelling of eyelids, face or lips, rash or itching (especially affecting the whole body)
  • severe or prolonged diarrhoea, which may have blood or mucus in it, during or after treatment with Azithromycin as this may be a sign of serious bowel inflammation
  • severe skin rash causing redness and flaking
  • rapid or irregular heartbeat
  • low blood pressure
  • Serious skin reactions:
  • blistering of the skin, mouth, eyes and genitals (Stevens-Johnson Syndrome (SJS))
  • blistering of the skin, severe skin reaction (Toxic Epidermal Necrosis (TEN))
  • Skin rash accompanied by other symptoms such as fever, swollen glands and an increase of eosinophils (a type of white blood cell). A rash appears as small, itchy red bumps (Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS))
  • skin eruption that is characterised by the rapid appearance of areas of red skin studded with small pustules (small blisters filled with white/yellow fluid) (Acute Generalized Exanthematous Pustulosis (AGEP)).

Stop taking azithromycin if you develop these skin symptoms and contact your doctor or seek medical attention immediately.

The most common side effects that occur when taking Azithromycin are listed below. These may go away during treatment as your body adjusts to the medicine. Tell your doctor if any of these side effects continue to bother you:

Very common: may affect more than 1 in 10 people

  • Stomach cramps, feeling sick, diarrhoea, wind.

Common: may affect up to 1 in 10 people

  • dizziness, headache
  • numbness or pins and needles
  • being sick, indigestion
  • loss of appetite, taste disturbance
  • visual disturbances, deafness
  • skin rash and /or itching
  • joint pain
  • low numbers of lymphocytes (a type of white blood cell), higher number of eosinophils (type of white blood cells)
  • low blood bicarbonate
  • tiredness or weakness.

Uncommon: may affect up to 1 in 100 people

  • yeast infections of the mouth and vagina (thrush)
  • low numbers of leukocytes (a type of white blood cell), low number of neutrophils (a type of white blood cell)
  • allergic reactions of various severity
  • skin more sensitive to sunlight than normal
  • feeling nervous
  • reduced sense of touch or sensation (hypoesthesia)
  • sleepiness or sleeplessness (insomnia)
  • poor hearing or ringing in the ears
  • heart palpitations, chest pain
  • constipation, stomach pain associated with diarrhoea and fever
  • Inflammation of the liver (hepatitis), changes in liver enzymes.
  • general loss of strength
  • swelling
  • general discomfort
  • Abnormal laboratory test values (e.g. blood or liver tests).

Rare: may affect up to 1 in 1,000 people

  • agitation
  • vertigo
  • changes in liver function

Not known: frequency cannot be estimated from the available data

  • fits or fainting
  • aggression or anxiety
  • feeling hyperactive
  • localised muscle weakness
  • loss of smell or altered sense of smell, loss of taste
  • tongue discolouration
  • inflammation of the pancreas (pancreatitis)
  • inflammation of the kidney or kidney failure
  • yellowing of the skin or eyes (jaundice) or liver failure (rarely life-threatening)
  • bruising or prolonged bleeding after injury
  • abnormal electrocardiogram (ECG)
  • reduction in red blood cells which can make the skin pale and cause weakness or breathlessness.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

  1. How to store Azithromycin

Keep this medicine out of the sight and reach of children.

Do not take or give this medicine after the expiry date which is stated on the bottle after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Any unused medicine should be discarded after 5 days.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

  1. Contents of the pack and other information

What Azithromycin contains

The active substance is azithromycin (200mg in 5ml). Other ingredients are sucrose (3.87 g per 5ml) (see section 2, Azithromycin contains sucrose) hydroxypropylcellulose, sodium phosphate tribasic anhydrous, xanthan gum and flavourings: artificial banana, artificial cherry and artificial creme de vanilla.

What Azithromycin looks like and contents of the pack

Azithromycin Suspension is a dry powder which reconstitutes with water sizes: 15ml (600mg), 22.5ml (900mg), 30ml (1200mg) and 37.5ml (1500mg) bottles.

Each pack contains a multi-dosing spoon and the 15ml size contains an oral dosing syringe.

Not all pack sizes may be marketed.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

 

Related Products

Taj Generics (Taj Pharma) provides a wide range of products to the Indian market, including an extensive range of generics and specialty products; Our products cover a vast array of therapeutic categories, and we offer an extensive range of dosage forms and delivery systems including oral solids, controlled-release, steriles, injectables, topicals, liquids, transdermals, semi-solids and high-potency products. Our Generics portfolio offers over 1500 products in the major therapeutic areas of gastro-intestinal, cardiovascular, pain management, oncology, anti-infectives, paediatrics and dermatology.