https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=15580

Atazanavir / cobicistat

Rosuvastatin

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Atazanavir / 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 .

Atazanavir / cobicistat

Pharmacodynamic effects

–

Recommendations

–

Alternative solution(s)

–

Rosuvastatin

Pharmacodynamic effects

Possible increased risk of hypolipidemic agents toxicity due to the increase in rosuvastatin AUC.

Also possible decrease of clinical efficacy due to reduced liver transport of the statin.

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

AST

ALT

CK

Lipidic profile

Pharmacokinetic parameters
Parameters
Reference number
# patients
Dose
HIV
Frequency
AUC
Cmax
Atazanavir / cobicistat
3360
16
300/150 mg
-
QD
 
 
Rosuvastatin
3360
16
10 mg
-
x 1
+ 242% (3.4x)
+ 960% (10.6x)
Comment

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.

Comment
Reference
  • 2794
    Kitamura S, Maeda K, Wang Y, Sugiyama Y. Involvement of Multiple Transporters in the Hepatobiliary Transport of Rosuvastatin. Drug Metab Dispos 2008; 36 : 2014-2023.
  • 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.
  • 3151
    U.S. Department of Health and Human services (DHHS) : Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Disponible : https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new. Publié le 6 décembre 2023. Consulté le 20 février 2024.
  • 2904
    European AIDS Clinical Society (EACS) Guidelines 7.1, Nov 2014. [En ligne]. Disponible : http://www.eacsociety.org.
  • 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.
  • 2364
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  • 2117
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  • 2268
    Bottaro EG, Cravello O, Scapellanto PG et al. Rosuvastatine for treatment of dyslipidemia in HIV-infected patients receiving highly active antiretroviral therapy. Enferm Infecc Microbiol Clin. 2008 Jun-Jul;26(6):325-9.
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  • 2211
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