Azithromycin

Azithromycin is an antibiotic, chemically a glycoside, from the group of macrolides with antibacterial properties. It is structurally closely related to erythromycin A and belongs to the group of azalides. The molecular formula is: C38H72N2O12. Azithromycin is a white powder practically insoluble in water. In medicinal products it is present as azithromycin monohydrate or azithromycin dihydrate.

After oral application the bioavailability of azithromycin is approx. 37%. 2-3 hours after oral intake the maximum plasma concentration is reached. After oral administration azithromycin is widely distributed throughout the entire organism, whereby higher azithromycin concentrations are reached in the tissues than in plasma. The degradation takes place in the liver. The degradation products are excreted renally or via the intestine.

Azithromycin is used to treat bacterial infectious diseases, including infections of the upper and lower respiratory tract, sinusitis, tonsillitis, pharyngitis, otitis media. Furthermore in skin infections and superinfected wounds, acute and chronic Borrelia infections, genital Chlamydia infections, infections with Neisseria gonorrhoeae (non multi-resistant strains). Furthermore, azithromycin is used for the prevention of intracellular Mycobacterium avium complex infections in HIV-infected persons.

Azithromycin and pregnancy: There is a great deal of experience in the use of azithromycin during pregnancy. It has been shown that the active ingredient has no harmful effect on the fetus. Therefore azithromycin may be used during pregnancy and lactation.

• Perorally: 500 mg on day 1 p.o., 250 mg from day 2 to 5 p.o. or 500 mg/day from day 1-3; sexually transmitted diseases: 1000 mg as ED p.o.
• Intravenously: 500 mg once/day slowly i.v. (over 1-3 hours) for 2 days. Then peroral application for about 7 days.

• The most common adverse events associated with peroral azithromycin intake are gastrointestinal side effects. Common (≥ 1% to < 10%): diarrhea (rarely with dehydration), soft stools, dyspepsia, abdominal discomfort (pain, cramps), anorexia, nausea, vomiting. Occasionally (≥ 0.1% to < 1%): flatulence, neutropenia, thrombocytopenia, fatigue, headache, nervousness, paraesthesia, drowsiness, erythema, urticaria, photosensitivity. Rare (≥ 0.01% to < 0.1%): discoloration of the tongue, erythema multiforme, Stevens-Johnson syndrome , toxic epidermal necrolysis, angioedema and anaphylaxis. Very rare (< 0.01%): anaphylactic shock, sporadic with lethal outcome.
• With intravenous application additional irritation at the injection site, phlebitis.

In contrast to other macrolides, the antibiotic hardly interacts with CYP450.

Drug interactions have been observed with ciclosporin, rifabutin, ergotamine, vitamin K antagonists and digoxin, among others.

Antacids: Mineral antacids may reduce the concentrations of azithromycin and should not be administered simultaneously. Concurrent use of mineral antacids and azithromycin may result in decreased serum peak concentrations without altering the bioavailability of azithromycin. They should therefore only be taken at intervals of 2 to 3 hours.

Ergotamine derivatives: Due to the theoretical possibility of ergotism, the simultaneous use of ergotamine derivatives and azithromycin is not recommended.

Statins: Some cases of rhabdomyolysis have been observed in patients taking statins and azithromycin at the same time.

Ciclosporin: Ciclosporin can significantly increase the Cmax and AUC when used concomitantly. If a combination therapy is necessary, the levels of Ciclosporin should be carefully monitored and the dose adjusted accordingly.

Oral anticoagulants of the coumarin type: Cases have been described in which anticoagulation was increased when azithromycin and oral anticoagulants of the coumarin type were administered simultaneously.

Digoxin (P-gp substrates): If digoxin is used simultaneously, the possibility of higher serum concentrations of digoxin must be taken into account.

Medication that extends the QT interval: Azithromycin should not be used together with other agents that extend the QT interval, e.g. Class IA (quinidine and procainamide) and Class III (amiodarone, dofetilide, sotalol) antiarrhythmics, cisapride and terfenadine; also antipsychotics (pimozide); antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin).

Hypersensitivity to the active substance, severe liver diseases, erythromycin-resistant Gram-positive strains and methicillin-resistant staphylococci.

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