Elvitegravir / Cobicistat

Atorvastatin

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

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

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

Elvitegravir / Cobicistat

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Atorvastatin

Pharmacodynamic effects

Possible increased risk of HMG CoA inhibitor toxicity.

Recommendations

Start therapy with a 10 mg dose once daily, and increase with caution depending on patient clinical response and tolerance.

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

We do not recommend more than 20 mg per day (U.S. guidelines) and 40 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
Parameters
Reference number
# patients
HIV
Dose
Frequency
Cmax
AUC
Cmin
Elvitegravir / Cobicistat
3417
16
-
150/150 mg *
QD
- 9%
- 8%
- 12%
Atorvastatin
3417
16
-
10 mg
x 1
+ 132% (2.3x)
+ 160% (2.6x)
 
Comment

Ref #3417 : * Administered as a fixed-dose tablet also containing emtricitabine/tenofovir alafenamide (TAF) 200/10 mg.
Increases in atorvastatin concentrations are smaller than those observed with lopinavir/ritonavir.

We observe an increase in AUC of atorvastatin with lopinavir/ritonavir, saquinavir/ritonavir, tipranavir/ritonavir, fosamprenavir/ritonavir and nelfinavir.

Ref #1695: Case report of drug-induced rhabdomyolysis in a 34-year-old HIV-infected male with a history of liver disease and concomitant use of clarithromycin, atorvastatin, and lopinavir/ritonavir.

Reference
  • 2570
    Elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild), Gilead, Ontario, Canada, 17 septembre 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.
  • 1695
    Mah Ming JB and Gill MJ. Drug-Induced Rhabdomyolysis after Concomitant Use of Clarithromycin, Atorvastatin, and Lopinavir/Ritonavir in a Patient with HIV. AIDS Patient Care and STDs 2003;17;207-210.
  • 2790
    Atorvastatin (Lipitor), Pfizer, Quebec, Canada, 20 mars 2017.
  • 2984
    Hoetelmanss R, Lasure A, Koester A. The effect of TMC 114, a potent next-generation HIV protease inhibitor, with low dose ritonavir on atorvastatine pharmacokinetics. ICAAC. 2004. Abstract H-865.
  • 3281
    Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide(Genvoya), Gilead, Ontario, Canada, 17 septembre 2018.
  • 3417
    Custodio JM, West SK, Gupta D et al. Evaluation of the Drug Interaction Potential between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide and Atorvastatin [abstract P306]. HIV Drug Therapy, October 22-26, 2016, Glasgow UK.