Date of report 03 Feb 2020
Reported case interaction between
Cobicistat and SIMVASTATIN
Cobicistat and SIMVASTATIN
Drugs suspected to be involved in the DDI
Complete list of drugs taken by the patient
simvastatin
Clinical case description
Middle aged HIV infected patient who developed a severe rhabdomyolysis 2 weeks after being switched to elvitegravir/cobicistat, emtricitabine, tenofovir alafenamide while on treatment with simvastatin (dose unknown). Within 2 weeks, the patient developed severe muscle pain and reduced micturition as well as a dark discoloration of the urine. Laboratory analyses showed severe renal impairment (eGFR 12 mL/min), postassium 6.1 mmol/L, very high transaminase levels (ALT > 2279 U/L; AST > 5193 U/L) and creatinine kinase > 200000 U/L. The patient was diagnosed with rhabdomyolysis and secondary acute renal failure and underwent dialysis. After discontinuation of the antiretroviral treatment and simvastatin, creatinine kinase and transaminase levels decreased rapidly so that dialysis could be stopped after 2 months. This case has been published by Perrone C et al. AIDS 2018; 32:676-677.
Clinical Outcome
Drug Interaction Probability Scale (DIPS)
Editorial Comment
This drug-drug interaction occurred because of cobicistat strong inhibitory effect on CYP3A4, the main enzyme contributing to simvastatin metabolism. Coadministration of simvastatin with strong CYP3A4 inhibitors is estimated to increase simvastatin exposure by 100 fold (Stader F et al. Antimicrob Agent Chemother 2018). Given the large magnitude of the drug-drug interaction and related high risk of rhabdomyolysis, coadministration of simvastatin with boosted antiretroviral agents is contra-indicated.
University of Liverpool Recommendation
These drugs should not be coadministered