Azithro-Natrapharm Drug Interactions

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes: Many drug interactions reported in clinical trials with macrolides (eg, erythromycin, clarithromycin) have not been reported to date with azithromycin. While azithromycin appears to have no effect on the cytochrome P-450 (CYP) enzyme system and interactions mediated by this enzyme system would not be expected to occur. It should be kept in mind that azithromycin and other macrolides have similar pharmacologic effects and the possibility that similar drug interactions may occur cannot be ruled out.
Macrolide antibiotics may inhibit metabolism of pimozide, resulting in increased plasma concentrations of unchanged drug. Because such alterations in pharmacokinetics of pimozide may be associated with prolongation of the QT and QTc interval, the manufacturer of pimozide states that concomitant administration of pimozide and azithromycin, clarithromycin or erythromycin is contraindicated. Unlike some macrolides (ie, erythromycin, clarithromycin), azithromycin does not appear to alter the metabolism of terfenadine (no longer commercially available in the US).
Antacids: Giving azithromycin with antacids containing aluminium or magnesium salts can reduce the rate, but not the extent of its absorption; azithromycin should be given at least 1 hr before or 2 hrs after the antacid.
Antilipidemic Agents: Azithromycin states that concomitant use of atorvastatin and azithromycin results in only a modest effect on the pharmacokinetics of the antilipidemic agent and that dosage adjustments are not necessary when azithromycin and atorvastatin are used concomitantly. However, in a patient receiving long-term therapy with lovastatin, administration of oral azithromycin (250 mg daily tor 5 days) appeared to precipitate rhabdomyolysis. Rhabdomyolysis has occurred rarely in patients receiving lovastatin and some evidence suggests that concomitant administration of erythromycin may increase the risk of this adverse effect. While the mechanism of this interaction remains to be determined, the risk of drug-induced rhabdomyolysis should be considered in patients receiving azithromycin, erythromycin or clarithromycin concomitantly with lovastatin or another hydroxymethylgtutaryl-CoA (HMG-CoA) reductase inhibitor.
Antimalarial Agent (Quinine): There is in vitro evidence of additive to synergistic effects between azithromycin and quinine against P. falciparum, including multidrug-resistant strains.
Antiretroviral Agents: HIV Protease Inhibitors (Nelfinavir): In healthy adults receiving nelfinavir (750 mg 3 times daily), administration of a single 1.2-g oral dose of azithromycin at steady state resulted in a 15% decrease in the mean AUC_0-8 of nelfinavir and its M8 metabolite, but C_max of nelfinavir and its M8 metabolite were not affected. However, concomitant use of these drugs increases the C_max and area under the concentration-time curve (AUC) of azithromycin by about 2-fold. Although dosage adjustments are not necessary when azithromycin and nelfinavir are used concomitantly, patients should be closely monitored for azithromycin adverse effects (eg, hepatic enzyme abnormalities, hearing impairment).
Cyclosporine: Although specific drug interaction studies have not been performed with azithromycin, concomitant use with other macrolides has resulted in increased cyclosporine concentrations. Therefore, the patient should be carefully monitored if azithromycin and cyclosporine are used concomitantly.
Pimozide: Because concomitant use of pimozide and other macrolides (eg, clarithromycin) has increased pimozide concentrations and is associated with a risk or prolonged QT interval and serious cardiovascular effects, thus concomitant use of pimozide and macrolides (including azithromycin) is contraindicated.