Date of report: 14 Feb 2020
Reported case interaction between
Cobicistat and Simvastatin

FLS Science

Drugs suspected to be involved in the DDI

Drug A
Cobicistat (Perpetrator)
Daily Dose
150
Dose adjustment performed
No
Administration Route
Oral
Start date
Unknown
End date
Unknown
Drug B
Simvastatin (Victim)
Daily Dose
Unknown
Dose adjustment performed
No
Administration Route
Oral
Start date
Unknown
End date
Unknown

Complete list of drugs taken by the patient

Antiretroviral treatment
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir-AF
Complete list of all comedications taken by the patient, included that involved in the DDI
Simvastatin

Clinical case description

Gender
Male
Age
40
eGFR (mL/min)
>60
Liver function impairment
No
Description
A middle-aged HIV-infected homosexual patient consulted his treating physician because of progressive fatigue. His antiretroviral therapy (ART) regimen included indinavir (IDV), lamivudin (3TC) and stavudine (d4T) and his only co-medication was simvastatin. His last CD4 cell count was 1033/μl and his HIV viral load had been suppressed for the previous 8 years. Physical examination revealed a diffuse maculopapular rash and scleral icterus. Blood tests showed markedly elevated transaminases [alanine aminotransferase (ALT) >1000 U/l, aspartate aminotransferase (AST) >1000 U/l], slightly elevated cholestasis parameters and a C-reactive protein of 61 mg/l. Hepatitis A virus (HAV) IgM and hepatitis C virus (HCV) antibody tests were both positive whereas hepatitis B virus (HBV) markers were negative. Testing of a previous stored serum sample secured the diagnoses of acute HAV and chronic HCV infections. To simplify the ART regimen, the treating physician proposed a switch to a single-tablet regimen including tenofovir alafenamide (TAF), emtricitabine (FTC), cobicistat (COBI) and elvitegravir (EVG). Two weeks later, the patient presented with increased fatigue, severe muscle pain and reported reduced micturition and a dark discoloration of the urine. Laboratory analyses showed severe renal dysfunction [estimated glomerular filtration rate (eGFR) 12 ml/min, potassium 6.1 mmol/l], very high transaminases (ALT > 2279 U/L, AST > 5193 U/L) and creatinine-kinase above 200 000 U/l. The patient was diagnosed with rhabdomyolysis and secondary acute renal failure and referred for dialysis. After discontinuation of ART and simvastatin, creatinine-kinase and transaminase levels decreased rapidly so that, after 2 months, dialysis was no longer needed. This case was published by Perrone C and colleasgues in AIDS. 2018 Mar 13;32(5):676-678. doi: 10.1097/QAD.0000000000001746

Outcome

Toxicity

Drug Interaction Probability Scale (DIPS)

Score
6 - Probable

Editorial Comment

Co-administration is contraindicated due to the potential for serious or life-threatening adverse reactions, such as myopathy, including rhabdomyolysis. Genvoya Summary of Product Characteristics, Gilead Sciences International Ltd, November 2015.