Effe cts of Other Drugs on Aliskiren
Based on in-vitro studies, aliskiren is metabolized by CYP 3A4.
Co-administration of lovastatin, atenolol, warfarin, furosemide, digoxin, celecoxib, hydrochlorothiazide, ramipril, valsartan, metformin and amlodipine did not result in clinically significant increases in aliskiren exposure.
Co-administration of irbesartan reduced aliskiren Cmax up to 50% after multiple dosing.
P - glycoprotein E ffects
Pgp (MDR1/Mdr1a/1b) was found to be the major efflux system involved in absorption and disposition of aliskiren in preclinical studies. The potential for drug interactions at the Pgp site will likely depend on the degree of inhibition of this transporter.
Co-administration of aliskiren with Pgp substrates or weak to moderate inhibitors such as atenolol, digoxin, and amlodipine did not result in clinically relevant interactions.
Co-administration of atorvastatin, a potent Pgp inhibitor, resulted in about a 50% increase in aliskiren Cmax and AUC after multiple dosing.
Co-administration of 200 mg twice-daily ketoconazole, a potent Pgp inhibitor, with aliskiren resulted in an approximate 80% increase in plasma levels of aliskiren. A 400 mg once-daily dose was not studied but would be expected to increase aliskiren blood levels further.
Co-administration of 200 mg and 600 mg cyclosporine, a highly potent Pgp inhibitor, with 75 mg aliskiren resulted in an approximately 2.5 fold increase in Cmax and 5 fold increase in AUC of aliskiren. Concomitant use of aliskiren with cyclosporine is not recommended.
Effects of Aliskiren on O ther D rugs
Aliskiren does not inhibit the CYP450 isoenzymes (CYP1A2, 2C8, 2C9, 2C19, 2D6, 2E1, and CYP 3A) or induce CYP 3A4.
Co-administration of aliskiren did not significantly affect the pharmacokinetics of lovastatin, digoxin, valsartan, amlodipine, metformin, celecoxib, atenolol, atorvastatin, ramipril or hydrochlorothiazide.
The effects of aliskiren on warfarin pharmacokinetics have not been evaluated in a well-controlled clinical trial.
When aliskiren was co-administered with furosemide, the AUC and Cmax of furosemide were reduced by about 30% and 50%, respectively.