Atazanavir

Simvastatin

Contraindicated.

No pharmaceutical opinion available for this interaction.

Mechanism

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

Atazanavir

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Simvastatin

Pharmacodynamic effects

Possible increased risk of HMG CoA inhibitor toxicity.

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

AST

ALT

CK

Myoglobin

Pharmacokinetic parameters

Comment

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
  • 1382
    Atazanavir (Reyataz), Bristol-Myers Squibb, Quebec, Canada, 23 nov. 2017.
  • 1489
    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.
  • 2334
    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.
  • 2796
    Simvastatin (Zocor), Merck, Quebec, Canada, 10 août 2018.
  • 2787
    Jacobson TA. Comparative Pharmacokinetic Interaction Profiles of Pravastatin, Simvastatin and Atorvastatin When Coadministered Whit Cytochrome P450 Inhibitors. Am J Cardiol 2004; 94 : 1140-1146.
  • 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.
  • 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.
  • 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.