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Administration of vonoprazan results in elevation of intragastric pH, suggesting that it may interfere with the absorption of drugs where gastric pH is an important determinant of oral bioavailability. Use of vonoprazan is therefore not recommended with some of these drugs for which absorption is dependent on acidic intragastric pH such as atazanavir and nelfinavir, due to significant reduction in their bioavailability.
Vonoprazan is metabolized mainly by hepatic drug-metabolizing enzyme CYP3A4 and partially by CYP2B6, CYP2C19 and CYP2D6.
With strong CYP3A4 inhibitors, e.g., clarithromycin, blood concentration of vonoprazan may increase. It has been reported that blood concentration of vonoprazan increased in concomitant use with clarithromycin by 1.5-fold, but no dose adjustment of vonoprazan is considered necessary.
Coadministration of vonoprazan with the antibiotic regimen clarithromycin and amoxicillin increased concentrations of vonoprazan by up to 1.9-fold. No increase was observed with the antibiotic regimen of metronidazole and amoxicillin. No dose adjustment of vonoprazan is considered necessary.
There were no clinically significant effects of NSAIDs on the pharmacokinetics of vonoprazan, and no clinically significant effects of vonoprazan on the pharmacokinetics of NSAIDs.
Co-administration of midazolam (a sensitive CYP3A4 substrate) with multiple doses of vonoprazan increased concentration of midazolam by 1.9-fold in healthy subjects. Caution is advised when vonoprazan is co-administered with other sensitive CYP3A4 substrates, notably those having a narrow therapeutic index.
