Strong and moderate CYP3A4 inhibitors increased the exposure of Zinobrest® plus its active metabolites to a clinically meaningful extent and may lead to increased toxicity.
In patients with recommended starting doses of 200 mg twice daily or 150 mg twice daily, reduce the Zinobrest® dose to 100 mg twice daily with concomitant use of strong CYP3A inhibitors other than ketoconazole, followed by careful monitoring of toxicity. In patients who have had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the Zinobrest® dose to 50 mg twice daily with concomitant use of strong CYP3A inhibitors. If a patient taking Zinobrest® discontinues a strong CYP3A inhibitor, increase the Zinobrest® dose (after 3-5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor. Patients should avoid grapefruit products.
- Moderate CYP3A Inhibitors
With concomitant use of moderate CYP3A inhibitors, monitor for adverse reactions and consider reducing the Zinobrest® dose in 50 mg decrements as demonstrated in the following table, if necessary. No dose adjustment is necessary for patients treated with moderate or weak CYP3A4 inhibitors. There should, however, be close monitoring for signs of toxicity.
Examples of strong CYP3A4 inhibitors include, but not limited to: clarithromycin, itraconazole, ketoconazole, lopinavir/ritonavir, posaconazole or voriconazole.
- Strong and Moderate CYP3A Inducers
Coadministration of strong or moderate CYP3A inducers (rifampicin, carbamazepine, phenytoin, and St. John’s wort) decreased the plasma concentrations of Zinobrest® plus its active metabolites and may lead to reduced activity. Avoid concomitant use of strong or moderate CYP3A inducers and consider alternative agents.