When co-administering GZR and atorvastatin, the daily dose of atorvastatin should not exceed 20 mg per day. It is recommended to monitor for signs of toxicity such as rhabdomyolysis, myopathy and elevated liver enzymes.
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
DrugAUC GMR (90% CI)Cmax GMR (90% CI)atorvastatin3.00 (2.42-3.72)5.66 (3.99-9.45)The authors state that GZR PK was not not significanty impacted by administration of atorvastatin, however, no values were included. There was a 3-fold increase in atorvastatin AUC when co-administered with GZR, likely due to an inhibition of CYP3A4 and potentially BCRP.
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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