Atazanavir / cobicistat can inhibit the metabolism (CYP 3A4) and increase the plasma concentration of Simvastatin.
Symptoms of toxicity associated with hypolipidemic agents : gastrointestinal effects, fatigue and muscular weaknesses, myalgias, muscular cramps, myopathies, rhabdomyolysis and myoglobinuria leading to renal insufficiency.
Due to the significant first-pass effect of lovastatin and simvastatin in the liver via CYP3A4, coadministration of these drugs with PIs is contraindicated. Cases of rhabdomyolysis have been reported.
A pharmacokinetic study with simvastatin 40 mg QD and saquinavir/ritonavir 400/400 mg BID demonstrated a 30-fold increase in simvastatin AUC.
See saquinavir/ritonavir + simvastatin.
Ref #911: Case report of rhabdomyolysis within several days of ritonavir being added to regimen that included simvastatin.
Ref #3112: Another case report of rhabdomyolysis and hepatotoxicity following atorvastatin substitution by simvastatin.
Atazanavir/cobicistat (Evotaz), Bristol-Myers Squibb, Québec, Canada, 8 septembre 2017.
Dube MP, Stein JH, Aberg JA, et al. Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy: recommendations of the HIV Medical Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group. Clin Infect Dis 2003 Sep 1;37(5):613-627.
Schmidt GA, Hoehns JD, Purcel JL et al. Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvasttain, amiodarone, and atazanavir. J Am Board Fam Med 2007;20 : 411-416.
Simvastatin (Zocor), Merck, Quebec, Canada, 10 août 2018.
Jacobson TA. Comparative Pharmacokinetic Interaction Profiles of Pravastatin, Simvastatin and Atorvastatin When Coadministered Whit Cytochrome P450 Inhibitors. Am J Cardiol 2004; 94 : 1140-1146.
Chauvin B, Drouot S, Barrail-Tran A and Taburet AM. Drug-Drug Interactions between HMG-coA reductase inhibitors (Statins) and Antiretroviral Protease Inhibitors. Clin Pharmacokinet 2013; 52: 815-831.
Fichtenbaum CJ, Gerber JG, Rosenkranz SL, et al. Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047. AIDS 2002 Mar 8;16(4):569-77.
Cheng CH, Miller C, Lowe C, et al. Rhabdomyolysis due to probable interaction between simvastatin and ritonavir [In Process Citation]. Am J Health Syst Pharm 2002 Apr 15;59(8):728-30.
Bastida C, Also MA, Pericas JM, et al. Rhabdomyolysis and severe hepatotoxicity due to a drug-drug interaction between ritonavir and simvastatin. Could we use the most cost-effective statin in all human immunodeficiency virus-infected patients ? Enferm Infecc Microbiol Clin. 2014 Jun 6; 32 (9): 579-82.