Elvitegravir / Cobicistat

Simvastatin

Contraindicated.

No pharmaceutical opinion available for this interaction.

Mechanism

Elvitegravir / Cobicistat may possibly inhibit the metabolism (CYP 3A4) and consequently increase the plasma concentration of Simvastatin.

Elvitegravir / Cobicistat

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Simvastatin

Pharmacodynamic effects

Increased risk of toxicity associated with hypolipidemic agent.

Increased risk of myopathy and rhabdomyolysis.

Recommendations

Contraindicated. Use alternative.

In patients already being treated with this combination and tolerating it, if deemed appropriate, keep actual treatment and exercise close monitoring of adverse effects.

Alternative solution(s)

See atorvastatin, rosuvastatin and pravastatin.

Monitor

Symptoms of toxicity associated with hypolipidemic agents : gastrointestinal effects, fatigue and muscular weaknesses, myalgias, muscular cramps, myopathies, rhabdomyolysis and myoglobinuria leading to renal insufficiency.

Tests

CK

ALT

AST

Myoglobin

Pharmacokinetic parameters

Comment

Ref #2570 : Potential for serious reactions such as myopathy, including rhabdomyolysis.

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.

Reference
  • 2570
    Elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild), Gilead, Ontario, Canada, 17 septembre 2018.
  • 901
    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.
  • 911
    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.
  • 2796
    Simvastatin (Zocor), Merck, Quebec, Canada, 10 août 2018.
  • 2983
    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.
  • 3112
    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.
  • 3151
    AIDS info, Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Disponible : https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Publié le 17 oct. 2017. Consulté le 11 janvier 2018.
  • 2904
    European AIDS Clinical Society (EACS) Guidelines 7.1, Nov 2014. [En ligne]. Disponible : http://www.eacsociety.org.
  • 3281
    Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide(Genvoya), Gilead, Ontario, Canada, 17 septembre 2018.