Drug Interactions between amoxicillin / clarithromycin / vonoprazan and fosamprenavir

MONITOR: Coadministration with H2-receptor antagonists or inhibitors of the proton pump (PPIs or potassium-competitive acid blockers [PCABs]) may decrease the oral bioavailability of amprenavir from its prodrug, fosamprenavir. In 30 study subjects, ranitidine (300 mg single oral dose) decreased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amprenavir from fosamprenavir (1400 mg single oral dose) by 51% and 30%, respectively, compared to administration of fosamprenavir alone. The mechanism of interaction has not been described. It is possible that fosamprenavir solubility decreases with increasing pH, thus inhibition of gastric acid secretion may interfere with dissolution of the drug. Subtherapeutic antiretroviral drug levels may lead to reduced viral susceptibility and development of resistance.

MANAGEMENT: Caution is advised if fosamprenavir is prescribed with H2-receptor antagonists or inhibitors of the proton pump. Antiretroviral response should be monitored closely during coadministration.

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

Drugs that act as both substrate and inhibitor of the CYP450 3A4 isoenzyme may alter the plasma concentration of amprenavir. Amprenavir may increase blood levels of the CYP450 3A4 inhibitor. The extent of the alterations in serum drug levels is unknown and the clinical significance is uncertain. When concomitant therapy is required, the patient should be monitored for adverse effects of both drugs and dose adjustments made when indicated.