Drug Interactions between amoxicillin / clarithromycin / vonoprazan and nelfinavir

GENERALLY AVOID: Concurrent use of inhibitors of the proton pump (PPIs or potassium-competitive acid blockers [PCABs]) may decrease the oral bioavailability of nelfinavir and reduce its concentrations in plasma. Nelfinavir solubility may decrease with increasing pH, thus inhibition of gastric acid secretion may interfere with dissolution of the drug. In one study, administration of omeprazole (40 mg once daily) 30 minutes before nelfinavir (1250 mg twice a day) for 4 days reduced the peak plasma concentration, trough plasma concentration, and systemic exposure (AUC) of nelfinavir by a little over one-third.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, use of inhibitors of the proton pump is not recommended in patients treated with nelfinavir.

MONITOR: Coadministration with nelfinavir may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by nelfinavir.

MANAGEMENT: Caution is advised if nelfinavir must be used concurrently with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever nelfinavir is added to or withdrawn from therapy.

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.