Cobicistat

Rosuvastatin

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Cobicistat may inhibit hepatic transports OATP1B1/B3 and BCRP and increase plasma concentration of Rosuvastatin.

Furthermore, inhibition of these transports may prevent the action of statin into the hepatic cell and potentially decrease clinical efficacy .

Cobicistat

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Rosuvastatin

Pharmacodynamic effects

Increased risk of toxicity associated with hypolipidemic agent.

Recommendations

Start therapy with the lowest dose and titrate to desired response while monitoring for safety.

In patients already under treatment, a reduction in dosage may be necessary.

We do not recommend more than 10 mg per day (U.S. guidelines) and 20 mg per day (European guidelines).

Or choose an alternative.

Alternative solution(s)

Pravastatin or ezetimibe.

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

Pharmacokinetic parameters

Comment

Ref #3360 : A study in two groups of 16 healthy patients studied co-administration of a single dose of rosuvastatin 10 mg with atazanavir/cobicistat 300/150 mg QD or darunavir/cobicistat 800/150 mg QD. In the atazanavir/cobicistat group, rosuvastatin AUC and Cmax increased by 3.4 and 10.6-fold, respectively, while in the darunavir/cobicistat group rosuvastatin AUC and Cmax increased by 1.9 and 3.8-fold, respectively. See atazanavir/cobicistat + rosuvastatin and darunavir/cobicistat + rosuvastatin.

Ref #2269, #2117, #2378 and #2364 : One study showed that rosuvastatin AUC with a 20 mg dose increased by 2.1-fold when coadministered lopinavir/ritonavir 400/100 mg BID. Other studies with rosuvastatin 10 mg dose showed increases in AUC with atazanavir/ritonavir 300/100 mg QD by 3.1-fold, with darunavir/ritonavir 600/100 mg BID by 1.5-fold and with tipranavir/ritonavir 500/200 mg BID by 1.4-fold. However with fosamprenavir/ritonavir 700/100 mg QD, there was no significant change in rosuvastatin AUC.

Ref # 2596: A case of rhabdomyolysis has been reported in a patient with renal failure and the combination of lopinavir/ritonavir and rosuvastatin.

For these reasons, US and European guidelines recommend to reduce the dose of rosuvastatin when it is combined with PIs. US guidelines recommend no more than 10 mg per day while European guidelines recommend no more than 20 mg per day.

Ref #1490: Rosuvastatin Canadian product monograph makes specific recommendations for some PIs. Indeed, rosuvastatin dose administered with atazanavir/ritonavir should not exceed 10 mg daily and with lopinavir/ritonavir, darunavir/ritonavir and tipranavir/ritonavir it should not exceed 20 mg daily.

Reference
  • 2570
    Elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild), Gilead, Ontario, Canada, 17 septembre 2018.
  • 2721
    Ramanathan S, Wang H, Stondell T, et al. Pharmacokinetics and drug interaction profile of cobicistat boosted-elvitegravir with atazanavir, rosuvastatin or rifabutin. 13th International Workshop on Clinical Pharmacology of HIV Therapy, April 16-18, 2012, Barcelona, Spain. Abstract O_03.
  • 1490
    Rosuvastatin (Crestor), AstraZeneca, Ontario, Canada, 21 avril 2015.
  • 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.
  • 2269
    Busti AJ, Bain AM, Hall RG, et al. Effects of atazanavir/ritonavir or fosamprenavir/ritonavir on the pharmacokinetics of rosuvastatin. J Cardiovasc Pharmacol, 2008, 51(6): 605-610.
  • 2117
    Kiser JJ, Gerber JG, Predhomme JA, Wolfe PR, Flynn DM, Hoody DW. Drug/drug interaction between lopinavir/ritonavir and rosuvastatin in healthy volunteers. JAIDS Journal of Acquired Immune Deficiency Syndromes 2008; 47(5): 570-8.
  • 2378
    Samineni D, Desai P, Sallans L and Fichtenbaum C. Steady-State Pharmacokinetic Interactions of Darunavir/Ritonavir With Lipid-Lowering Agent Rosuvastatin. The Journal of Clinical Pharmacology. 2012; 52(6): 922-931.
  • 2364
    Pham PA, la Porte CJ, Lee LS, et al. Differential effects of tipranavir plus ritonavir on atorvastatin or rosuvastatin pharmacokinetics in healthy volunteers. Antimicrob Agents Chemother, 2009, 53(10): 4385-4392.
  • 2596
    de Kanter, C, Keuter, M. van der Lee M.J., Koopmans, P.P. and Burger D.M. Rhabdomyolysis in an HIV-infected patient with impaired renal function concomitanly treated with rosuvastatin and lopinavir/ritonavir. Antiviral Therapy 2011; 16:435-437.
  • 2904
    European AIDS Clinical Society (EACS) Guidelines 7.1, Nov 2014. [En ligne]. Disponible : http://www.eacsociety.org.
  • 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.
  • 3360
    Custodio J, Wang H, Hao J, Lepist EI, Ray AS et al. Pharmacokinetics of cobicistat boosted-elvitegravir administered in combination with rosuvastatin. Clin Pharmacol, 2014, 54(6): 649-56.