Floctil 250

Azithromycin dihydrate.

Each capsule contains: Azithromycin dihydrate eq. to Azithromycin 250 mg.

Pharmacology: The mode of action of Azithromycin is inhibition of protein synthesis in bacteria by binding to the 50s ribosomal subunit and preventing translocation of peptides.
Pharmacokinetics: Absorption: Bioavailability - 37%; Effects of food - reduces bioavailability about 50%.
Distribution: Widely distributed throughout the body; Heavily tissue-bound (up to 50 times the maximum concentration observed in plasma).
Time to peak plasma concentration: 2-3 hours.
Excretion: Biliary - Very high concentration of unchanged drug found; Renal.
Plasma terminal elimination half-life: 2-4 days.

Uncomplicated genital infections due to Chlamydia trachomatis.
Infection due to Mycobacterium avium-intracellulare complex (MAC), an opportunistic infection prevalent in patients with advanced human immunodeficiency virus (HIV); Prophylaxis.
Disseminated Mycobacterium avium-intracellulare complex (MAC) in persons with advanced HIV infection (treatment).
Infections caused by susceptible organisms.
Lower respiratory infections including bronchitis and pneumonia.
Skin and soft tissue infection.
Acute otitis media.
Upper respiratory infections including sinusitis and pharyngitis/tonsillitis.
Chancroid.

Usual adult dose: Uncomplicated genital infections due to Chlamydia trachomatis: 1,000 mg given as a single dose.
Infection due to Mycobacterium avium-intracellulare complex (MAC), an opportunistic infection prevalent in patients with advanced human immunodeficiency virus (HIV); Prophylaxis: 1,200 mg once a week.
Disseminated Mycobacterium avium-intracellulare complex (MAC) in persons with advanced HIV infection (treatment): 600 mg once a day.
Note: Azithromycin should be administered in combination with other antimycobacterial agents that have shown in vitro activity against MAC e.g. Ethambutol at approved dose.
Other indications taken in oral formulation: Total dosage of 1,500 mg should be given as 500 mg daily for 3 days. As an alternative, the same total dose can be given over 5 days with 500 mg given on day 1, then 250 mg daily on days 2-5.
Usual pediatric dose: Mycobacterium avium-intracellulare complex (MAC) infections: Safety and efficacy for the prevention or treatment in children have not been established.
Acute otitis media*: 10 mg/kg on day 1 followed by 5 mg/kg on days 2-5. Safety and effectiveness in the treatment of children with otitis media under 6 months of age have not been established.
Pharyngitis/ Tonsillitis*: 12 mg/kg on days 1-5. Safety and effectiveness in the treatment of children with pharyngitis/ tonsillitis under 2 years of age have not been established.
Elderly: The same dosage as in adult patients.
Patients with renal impairment: The same dosage as in patients with normal renal function may be used in patients with mild renal impairment (creatinine clearance > 40 mL/min). There are no data regarding Azithromycin usage in patients with more severe renal impairment (see Precautions).
Patients with hepatic impairment: The same dosage as in patients with normal hepatic function may be used in patients with mild to moderate hepatic impairment (see Precautions).
Instructions for Use and Handling: Tablet/Capsule: To be swallowed whole.

Patients with a history of allergic reactions to Azithromycin or any of the macrolide antibiotics.

Erythromycin and other macrolides: Rare serious allergic reactions, including angioedema and anaphylaxis (rarely fatal). Some of these reactions with Azithromycin have resulted in recurrent symptoms and required a longer period of observation and treatment.
Patients with a creatinine clearance > 40 mL/min: There are no data regarding Azithromycin usage, thus, caution should be exercised before prescribing Azithromycin.
Patients with significant hepatic disease: Usage should be undertaken with caution since liver is the principal route of elimination for Azithromycin.
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 an ergotism, Azithromycin and ergot derivatives should not be co-administered.
With any antibiotic preparation: Observation for signs of superinfection with nonsusceptible organisms including fungi is recommended.
Hypersensitivity^: Dermatologic reactions including Drug Reaction with Eosinophilia and Systemic symptoms (DRESS) have been reported in patients on Azithromycin therapy.
QT Prolongation^^: 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 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.
Patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (Quinidine, Procainamide) or Class III (Dofetilide, Amiodarone, Sotalol) antiarrhythmic agents.
Elderly patients may be more susceptible to drug-associated effects on the QT interval.
Effects on the ability to drive or operate machinery: There is no evidence to suggest that Azithromycin may have an effect on a patient's ability to drive or operate machinery.

Animal reproduction studies have demonstrated that Azithromycin crosses placenta, but have revealed no evidence of harm to the fetus. There are no data on secretion in breast milk. Safety for use in human pregnancy and lactation has not been established. Azithromycin should only be used in pregnant or lactating women where adequate alternatives are not available.

Clinical trials: Gastrointestinal: Nausea, vomiting, diarrhea, loose stools, abdominal discomfort (pain/cramps) and flatulence.
Hematopoietic: Transient episoded of mild neutropenia have occasionally been observed in clinical trials, although a causal relationship to Azithromycin has not been established.
Liver/ Biliary: Abnormal liver function.
Skin/ Appendages: Allergic reactions including rash and angioedema.
Special senses: Hearing impairment (including hearing loss, deafness and/or tinnitus) has been reported in some patients receiving Azithromycin. Many of these have been associated with prolonged use of high doses in investigational studies. In those cases where follow-up information was available, the majority of these events were reversible.
HIV-infected patients for prophylaxis for DMAC: Diarrhea, abdominal pain, nausea, loose stools, flatulence, vomiting, dyspepsia, rash, pruritus and arthralgia.
Treatment of DMAC infection (prolonged periods): Abdominal pain, nausea, vomiting, diarrhea, flatulence, headache, abnormal vision and hearing impairment.
Post-marketing: Body as a whole: Asthenia has been reported, although causal relationship has not been established; Fatigue, malaise, moniliasis and anaphylaxis (rarely fatal) (see Precautions).
Cardiovascular: Palpitations and arrhythmias including ventricular tachycardia (as seen with other macrolides) have been reported, although a causal relationship to Azithromycin has not been established hypotension.
Central and peripheral nervous system: Dizziness/ vertigo, convulsions (as seen with other macrolides), headache, hyperactivity, paresthesia, somnolence and syncope.
Gastrointestinal: Anorexia, dyspepsia, constipation, pseudomembranous colitis, pancreatitis, rare reports of tongue discoloration and vomiting/ diarrhea (rarely resulting in dehydration).
Genitourinary: Intestinal nephritis and acute renal failure.
Hematopoietic: Thrombocytopenia.
Liver/ Biliary: Hepatitis and cholestatic jaundice have been reported, as well as rare cases of hepatic necrosis and hepatic failure, which rarely resulted to death. However, a causal relationship has not been established.
Musculoskeletal: Arthralgia.
Psychiatric: Aggressive reaction, nervousness, agitation and anxiety.
Reproductive: Vaginitis.
Skin/ Appendages: Allergic reactions including pruritus, rash, photosensitivity, edema, urticaria and angioedema. Rarely, serious skin reactions including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.
Special cases: There have been rare reports of taste perversion.

Antacids: Bioavailability- no effect; peak serum concentration- reduced by approximately 25% with simultaneous in-take with Azithromycin.
Cetirizine: No pharmacokinetic interaction and no significant changes in the QT interval with co-administration of a 5-day regimen of Azithromycin with Cetirizine 20 mg at steady state.
Didanosine (Dideoxyinosine): Co-administration of daily doses of 1,200 mg/day Azithromycin with 400 mg/day Didanosine did not appear to affect the steady-state pharmacokinetics of Didanosine as compared to placebo.
Digoxin: Possibility of raised Digoxin levels.
Zidovudine or its glucuronide metabolite: Plasma pharmacokinetics/ Urinary excretion- little effect when taken with single 1,000-mg doses and multiple 1,200- or 600-mg doses of Azithromycin; increased concentration of phosphorylated Zidovudine.
Ergot: Concurrent use of Azithromycin with ergot derivatives is not recommended due to theoretical possibility of ergotism.
Atorvastatin: Plasma concentration- Not altered with co-administration of Atorvastatin (10 mg daily) and Azithromycin (500 mg daily).
Carbamazepine or its active metabolite: Plasma levels- no significant effect in patient receiving concomitant Azithromycin.
Cimetidine: No alteration of Azithromycin pharmacokinetics was seen with single dose of Cimetidine given 2 hours before Azithromycin.
Coumarin-type oral anticoagulants: Azithromycin did not alter the anticoagulant effect of a single 15-mg dose of Warfarin, athough there have been reports received in the post-marketing period of potentiated anticoagulation subsequent to co-administration of Azithromycin and Coumarin-type oral anticoagulants.
Cyclosporin: C_max and AUC_0-50 of Cyclosporin - significantly elevated with administation of 500-mg/day oral dose of Azithromycin for 3 days and a single dose of 10-mg/kg oral dose of Cyclosporine. Levels of Cyclosporine should be monitored and dose adjusted accordingly if co-administration of these drugs is necessary.
Efavirenz: No clinically significant pharmacokinetic interactions with co-administration of a 600-mg single dose of Azithromycin and 400-mg Efavirenz daily for 7 days.
Fluconazole: Co-adminsitration with 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, but a clinically decrease in C_max (18%) of Azithromycin was observed.
Indinavir: No statistically significant effect on the pharmacokinetics of Indinavir 800 mg 3 times daily when co-administered with 1,200 mg single dose of Azithromycin.
Methylprednisolone: No significant effect on the pharmacokinetics of Methylprednisolone.
Midazolam: No clinically significant changes in the pharmacokinetics and pharmacodynamics of a single 15-mg dose of Midazolam co-administered with Azithromycin 500 mg/day.
Nelfinavir: A decrease of approximately 16% in mean AUC_0-8 hrs of Nelfinavir and its M₈ metabolite, and an increase of approximately 113% in Azithromycin AUC_0- and 136% increase in C_max with co-administration of 1,200 mg of Azithromycin and steady-state Nelfinavir (750 mg 3 times daily).
Rifabutin: No effect on the serum concentrations of either drug. Neutropenia was observed in subjects receiving concomitant treatment of Azithromycin and Rifabutin.
Sildenafil: No evidence of an effect of Azithromycin (500 mg daily for 3 days) on the AUC and C_max of Sildenafil or its major circulating metabolite.
Terfenadine: No evidence reported on the interaction between Azithromycin and Terfenadine. But rare cases have been reported where possibility of such interaction could not entirely excluded; however, there are no specific evidence that such an interaction had occurred.
Theophylline: No evidence of any pharmacokinetic interaction with co-administration of Azithromycin and Theophylline.
Triazolam: Co-administartion 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 1,200 mg on day 7 had no significant effect on peak concentrations, total exposure or urinary excretion of either Trimethoprim or Sulfamethoxazole.

Store at temperature not more than 30°C.

Macrolides

J01FA10 - azithromycin ; Belongs to the class of macrolides. Used in the systemic treatment of infections.

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