Drug Interactions between amoxicillin / clarithromycin / omeprazole and boceprevir

MONITOR: Coadministration of a macrolide or ketolide antibiotic (clarithromycin, erythromycin, telithromycin) with a hepatitis C virus (HCV) NS3/4A protease inhibitor (boceprevir, telaprevir) is expected to increase the plasma concentrations of both drugs. The mechanism may involve both competitive and noncompetitive inhibition of CYP450 3A4, since these drugs are all substrates as well as inhibitors of the isoenzyme. No pharmacokinetic data are currently available. Clinically, high plasma levels of macrolide or ketolide antibiotics may increase the risk of QT interval prolongation and torsade de pointes arrhythmia.

MANAGEMENT: Caution and close clinical monitoring are recommended if clarithromycin, erythromycin, or telithromycin are used in combination with a HCV NS3/4A protease inhibitor. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope.

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.

Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH.