Use caution when coadministering grazoprevir (weak CYP3A4 inhibitor) with midazolam (a CYP3A4 substrate) as this may increase midazolam plasma concentrations. If used concomitantly, monitor the patient closely and, if required, consider a dose reduction of midazolam.
Grazoprevir (single agent) vs pitavastatin, midazolam, or atorvastatin
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Study Design
The potential for grazoprevir (formerly known as MK-5172) to inhibit the organic anion transport proteins (OATP) in vivo was evaluated in a study using pitavastatin, a probe substrate for OATP. In an open label study, 9 healthy patients with ages 18-55 years old were given a single dose of pitavastatin 1 mg followed by 2-day washout. Then, they received grazoprevir 200mg daily for 9 days together with a single dose of 1 mg pitavastatin on Day 7.
Study Results
When healthy patients were given grazoprevir 200mg/day for 8 days together with a single dose of midazolam 2 mg/mL, the AUC (95% CI) of midazolam was increased by 34% [29%, 39%] potentially due to inhibition of CYP3A4.
References
Luzelena Caro, Jennifer E Talaty, Zifang Guo, Christina Reit-mann, Iain P Fraser, Raymond Evers, Dennis Swearingen, Wendy W Yeh, Joan R Butterton. Pharmacokinetic interaction between the hcv protease inhibitor mk-5172 and midazolam, pitavastatin, and atorvastatin in healthy volunteers. Hepatology. 2013; : 437-438.
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