https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=13670

Darunavir / cobicistat

Atorvastatin

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

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

Darunavir / cobicistat

Pharmacodynamic effects

–

Recommendations

–

Alternative solution(s)

–

Atorvastatin

Pharmacodynamic effects

Possible increased risk of HMG CoA inhibitor toxicity.

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 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
AUC
Cmax
Atorvastatin
3360
16
-
10 mg
x 1
+ 290% (3.9x)
+ 319% (4.2x)
Darunavir / cobicistat
3360
16
-
800/150 mg
QD
 
 
Comment

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
  • 3071
    Darunavir/cobicistat (Prezcobix), Janssen, Ontario, Canada, 7 avril 2017.
  • 3437
    Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (Symtuza), Janssen Inc, Ontario, Canada, 3 octobre 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.
  • 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.