No pharmaceutical opinion available for this interaction.
Elvitegravir / Cobicistat may possibly inhibit the metabolism (CYP 3A4) and consequently increase the plasma concentration of Simvastatin.
Elvitegravir 3A4 and then UGT1A1/3; Cobicistat 3A4 (major) and 2D6 (minor)
Elvitegravir : 2C9 (moderate)
Cobicistat : 3A4 and 2D6 (potent), P-gp, MATE 1, BCRP, OATP1B1 and OATP1B3
3A4 (major); OATP1B1
2C8, 2C9 and 2D6 (weak); P-gp
Increased risk of toxicity associated with hypolipidemic agent.
Increased risk of myopathy and rhabdomyolysis.
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.
Ref #2570 : Potential for serious reactions such as myopathy, including rhabdomyolysis.
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.
See saquinavir/ritonavir + simvastatin.
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.