No pharmaceutical opinion available for this interaction.
Atazanavir / ritonavir can inhibit the metabolism (CYP 3A4) and increase the plasma concentration of Simvastatin.
3A4, P-gp/3A4 > 2D6, P-gp
Ritonavir: 1A2, 2C9, 2C19, UGT, 2B6, 3A4 (auto-induction)
3A4, UGT1A1, P-gp E et 2C8/3A4 > 2D6 > 2A6, 2E1, P-gp, MRP2
3A4 (major); OATP1B1
2C8, 2C9 and 2D6 (weak); P-gp
Possible increased risk of HMG CoA inhibitor toxicity.
Contraindicated. Use alternative.
In patients already being treated with this combination and tolerating it, if deemed appropriate, keep actual treatment and exercise close monitoring of adverse effects.
See atorvastatin, rosuvastatin and pravastatin.
Symptoms of toxicity associated with hypolipidemic agents : gastrointestinal effects, fatigue and muscular weaknesses, myalgias, muscular cramps, myopathies, rhabdomyolysis and myoglobinuria leading to renal insufficiency.
Due to the significant first-pass effect of lovastatin and simvastatin in the liver via CYP3A4, coadministration of these drugs with PIs is contraindicated. Cases of rhabdomyolysis have been reported.
A pharmacokinetic study with simvastatin 40 mg QD and saquinavir/ritonavir 400/400 mg BID demonstrated a 30-fold increase in simvastatin AUC.
Ref #911: Case report of rhabdomyolysis within several days of ritonavir being added to regimen that included simvastatin.
Ref #3112: Another case report of rhabdomyolysis and hepatotoxicity following atorvastatin substitution by simvastatin.