No pharmaceutical opinion available for this interaction.
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 : 3A4 and UGT1A1, 2C8 (weak to moderate) / Cobicistat : 3A4 (potent) and 2D6 (weak), P-gp, BCRP, OATP1B1 and OATP1B3
OATP1B1, OATP1B3 and BCRP
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.
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.
Pravastatin or ezetimibe.
Symptoms of toxicity associated with hypolipidemic agents : gastrointestinal effects, fatigue and muscular weaknesses, myalgias, muscular cramps, myopathies, rhabdomyolysis and myoglobinuria leading to renal insufficiency.
|+ 242% (3.4x)|
|+ 960% (10.6x)|
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.