Atazanavir / cobicistat

Atorvastatin

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Atazanavir / cobicistat can inhibit the metabolism (CYP 3A4) and increase the plasma concentration of Atorvastatin.

Atazanavir / 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

AST

ALT

CK

Lipidic profile

Pharmacokinetic parameters
Parameters
Reference number
# patients
HIV
Dose
Frequency
AUC
Cmax
Atazanavir / cobicistat
3360
16
-
300/150 mg
QD
 
 
Atorvastatin
3360
16
-
10 mg
x 1
+ 822% (9.2x)
+ 1790% (18.9x)
Comment

We also observe an increase in AUC of atorvastatin with lopinavir/ritonavir, saquinavir/ritonavir, darunavir/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
  • 3230
    Atazanavir/cobicistat (Evotaz), Bristol-Myers Squibb, Québec, Canada, 8 septembre 2017.
  • 2211
    Burger D, Stroes E, Reiss P et al. Drug interactions between statins and antiretroviral agents. Current opinion in HIV and AIDS 2008;3:247-251.
  • 2212
    Neuvonen PJ, Niem M and Backman JT. Drug interaction with lipid-lowering drugs: mecanisms and clinical relevance. Clin Pharmacol Ther 2006;80:565-581
  • 2790
    Atorvastatin (Lipitor), Pfizer, Quebec, Canada, 20 mars 2017.
  • 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.
  • 2789
    Lennernas H. Clinical Pharmacokinetics of Atorvastatin. Clin Pharmacokinet 2003; 42 : 1141-1160.
  • 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.
  • 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.