Azithromycin Dihydrate is indicated for the treatment of infections caused by susceptible organisms. These include lower respiratory tract infections such as bronchitis and pneumonia; upper respiratory tract infections such as sinusitis and pharyngitis/tonsillitis; otitis media; and skin and soft tissue infections. In men and women, azithromycin is also indicated for the treatment of sexually transmitted infections, including non-gonococcal urethritis and cervicitis caused by Chlamydia trachomatis.

Azithromycin is stable in acidic environments and can be administered orally without protection from gastric acid. It is well absorbed, with enhanced absorption when taken on an empty stomach. Peak plasma concentrations are typically reached within 2.1 to 3.2 hours after oral administration. Due to its high affinity for phagocytic cells, azithromycin is transported to sites of infection, where it is released in significant amounts during active phagocytosis. Tissue concentrations can exceed plasma levels by more than 50-fold, attributed to ion trapping and high lipid solubility.

The prolonged half-life of azithromycin allows for once-daily dosing and sustained bacteriostatic activity in infected tissues for several days. After a single 500 mg dose, plasma concentrations decline in a multiphasic manner, with an apparent clearance of approximately 630 mL/min and a terminal half-life of about 68 hours. This extended half-life is due to extensive tissue uptake and gradual release. Azithromycin is mainly eliminated via biliary excretion in unchanged form, while approximately 6% of the administered dose is excreted unchanged in urine over one week.

Microbiology: Azithromycin exerts its antibacterial effect by binding to the 50S ribosomal subunit of susceptible bacteria, thereby inhibiting protein synthesis without affecting nucleic acid synthesis. It is active against a wide range of microorganisms both in vitro and in clinical infections, including:

• Aerobic and facultative gram-positive microorganisms: Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes
• Aerobic and facultative gram-negative microorganisms: Haemophilus ducreyi, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae
• Other microorganisms: Chlamydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae (β-lactamase production does not affect azithromycin activity)
• Additional gram-positive organisms: Streptococci (Groups C, F, G), Viridans group streptococci
• Additional gram-negative organisms: Bordetella pertussis, Legionella pneumophila
• Anaerobic microorganisms: Peptostreptococcus species, Prevotella bivia

Oral-
Adult: 500 mg once daily orally for 3 days or 500 mg once on day 1, then 250 mg once on days 2-5 for 4 days. For sexually transmitted diseases caused by Chlamydia trachomatis in adults, the dose is 1 gm given as a single dose or 500 mg once on day 1, followed by 250 mg once daily for next 2 days may also be given.

Children:

• 10 mg/kg body weight once daily for 3 days for child over 6 months
• 200 mg (1 teaspoonful) for 3 days if body weight is 15-25 kg
• 300 mg (1½ teaspoonfuls) for 3 days if body weight is 26-35 kg; 400 mg (2 teaspoonfuls) for 3 days if body weight is 36-45 kg.
• In typhoid fever, 500 mg (2½ teaspoonfuls) once daily for 7-10 days is given.

Azithromycin Injection (For IV Infusion only): The recommended dose of Azithromycin for injection for the treatment of adult patients with community-acquired pneumonia due to the indicated organisms is:

• 500 mg as a single daily dose by the intravenous route for at least two days. Intravenous therapy should be followed by Azithromycin by the oral route at a single, daily dose of 500 mg, administered as two 250-mg tablets to complete a 7 to 10-day course of therapy. The timing of the switch to oral therapy should be done at the discretion of the physician and in accordance with clinical response.
• The recommended dose of Azithromycin for the treatment of adult patients with pelvic inflammatory disease due to the indicated organisms is: 500 mg as a single daily dose by the intravenous route for one or two days. Intravenous therapy should be followed by Azithromycin by the oral route at a single, daily dose of 250 mg to complete a 7-day course of therapy. The timing of the switch to oral therapy should be done at the discretion of the physician and in accordance with clinical response. If anaerobic microorganisms are suspected of contributing to the infection, an antimicrobial agent with anaerobic activity should be administered in combination with Azithromycin.
• Safety and effectiveness of azithromycin for injection in children or adolescents under 16 years have not been established.

Reconstitution procedure of suspension

• Step 01: Shake the bottle well to loosen the powder.
• Step 02: Add boiled and cooled water up to the water mark of the bottle label.
• Step 03: Shake until powder is completely mixed with water.

Azithromycin should be taken at least 1 hour before or 2 hours after meal.

Antacid: In patients taking both azithromycin and antacids, azithromycin should be taken at least 1 hour before or 2 hours after the antacid.

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

Cyclosporin: Some related macrolide antibiotics may interfere with the metabolism of cyclosporin. As there are no conclusive pharmacokinetic or clinical data regarding the potential interaction between azithromycin and cyclosporin, caution is advised when these two drugs are given together. If co-administration is necessary, cyclosporin levels should be monitored and the dose adjusted accordingly.

Digoxin: Some macrolide antibiotics have been reported to impair the metabolism of digoxin in the gut in some patients. Therefore, in patients receiving azithromycin together with digoxin, the possibility of increased digoxin levels should be considered and digoxin levels should be monitored.

Ergot derivatives: Because of the theoretical risk of ergotism, azithromycin and ergot derivatives should not be used together.

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

Theophylline: There is no evidence of any pharmacokinetic interaction when azithromycin and theophylline are co-administered to healthy volunteers. However, as a general precaution, theophylline levels should be monitored.

Warfarin: In a pharmacodynamic interaction study, azithromycin did not alter the anticoagulant effect of a single 15 mg dose of warfarin administered to healthy volunteers. Azithromycin and warfarin may be used together, but routine monitoring of prothrombin time should be continued.

Terfenadine: Azithromycin did not affect the pharmacokinetics of terfenadine when given at the recommended dose of 60 mg every 12 hours. The addition of azithromycin did not result in any significant changes in cardiac repolarization (QTc interval) during steady-state dosing of terfenadine.

Azithromycin Dihydrate is contraindicated in patients who are hypersensitive to azithromycin or any other macrolide antibiotic. Co-administration of azithromycin with ergot derivatives is contraindicated. Azithromycin is also contraindicated in patients with hepatic disease.

Azithromycin Dihydrate is generally well tolerated and is associated with a low incidence of side effects. Most reported side effects are mild to moderate in severity. The majority are gastrointestinal in nature and may include nausea, abdominal discomfort (pain or cramps), vomiting, flatulence, diarrhoea, and loose stools. Allergic reactions such as rash and photosensitivity have been reported, and there have also been rare cases of serious hypersensitivity reactions. Reversible elevations in liver transaminases have been observed at a frequency similar to that seen with other macrolides and penicillins used in clinical trials. Rare cases of cholestatic jaundice have also been reported. Transient mild reductions in neutrophil counts have occasionally been observed in clinical trials, although a causal relationship with azithromycin has not been established. In investigational studies where higher doses were used for prolonged periods, reversible hearing impairment was reported in some patients.

Azithromycin Dihydrate is classified as Pregnancy Category B. Animal reproduction studies have shown no evidence of harm to the fetus. However, there are no adequate and well-controlled studies in pregnant women. Since animal studies do not always predict human response, azithromycin should be used during pregnancy only when no adequate alternative is available. It is not known whether azithromycin is excreted in breast milk. Therefore, caution should be exercised when azithromycin is administered to nursing women.

As with erythromycin and other macrolides, rare but serious allergic reactions, including angioneurotic oedema and anaphylaxis, have been reported. Some of these reactions associated with azithromycin have resulted in recurrent symptoms and have required prolonged observation and treatment.

Use in renal impairment: No dose adjustment is required in patients with mild renal impairment (creatinine clearance >40 mL/min). However, since there are no data regarding the use of azithromycin in patients with more severe renal impairment, caution should be exercised in such cases.

Use in hepatic impairment: Since the liver is the principal route of excretion of azithromycin, it should not be used in patients with hepatic disease.

Effects on ability to drive and use machines: There is no evidence to suggest that azithromycin affects a patient’s ability to drive or operate machinery.

There are no specific data on overdose with azithromycin. Typical symptoms of overdose with macrolide antibiotics include hearing loss, severe nausea, vomiting, and diarrhoea. Gastric lavage and general supportive measures are indicated.

Macrolides

Keep in a dry place away from light and heat. Keep out of the reach of children.