No pharmaceutical opinion available for this interaction.
Darunavir / ritonavir may possibly inhibit the metabolism (CYP 3A4) and consequently increase the plasma concentration of Atorvastatin.
2C9, 2C19, 2C8 (moderate), UGT (moderate)
3A4 (strong), 2D6 (moderate), 2B6 (probable)
3A4 (major), 2C8 (minor): metabolised in acid derivatives 2-hydroxy-atorvastatin and 4-hydroxy-atorvastatin. These active metabolites are responsable of about 70% of the inhibitory activity of HMG-CoA reductase circulating. OATP1B1 and P-gp.
3A4 (weak), OATP1B1 and P-gp.
Possible increased risk of HMG CoA inhibitor toxicity.
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.
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.
|- 15% *|
|- 44% *|
|+ 81% *|
Ref #2107 : * Compared to atorvastatin 40 mg daily alone. Hence a dosage of 10 mg is almost equivalent to 40 mg.
Ref #2984 : The AUC was only 15% lower compared to the AUC of atorvastatin 40 mg without darunavir/ritonavir. The author concludes that atorvastatin 10 mg combined with darunavir/ritonavir was approximately comparable to atorvastatin 40 mg.
We also 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.