Drug Interaction Report

MONITOR: Coadministration with human growth hormone may decrease the plasma concentrations of drugs that are metabolized by CYP450 3A4. Data from an interaction study performed in growth hormone deficient adults suggest that growth hormone (somatropin) administration can increase the clearance of compounds known to be metabolized by cytochrome P450 isoenzymes, especially CYP450 3A4. The clinical significance is unknown.

MANAGEMENT: Caution is advised when human growth hormone is used concurrently with drugs that are known CYP450 3A4 substrates, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever human growth hormone is added to or withdrawn from therapy.

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of vonoprazan, which is metabolized by the isoenzyme. When coadministered with potent and moderate CYP450 3A4 inducers, vonoprazan systemic exposure (AUC) is predicted to decrease by 80% and 50%, respectively. No data are available for other, less potent CYP450 3A4 inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of vonoprazan should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

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.

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.