RiteMED Felodipine Drug Interactions

Felodipine is metabolised in the liver by cytochrome P450 3A4 (CYP3A4). Concomitant administration of substances which interfere with CYP3A4 enzyme system may affect plasma concentrations of felodipine.
Enzyme interactions: Enzyme inhibiting and enzyme inducing substances of cytochrome P450 isoenzyme 3A4 may exert an influence on the plasma level of felodipine.
Interactions leading to increased plasma concentration of felodipine: CYP3A4 enzyme inhibitors have been shown to cause an increase in felodipine plasma concentrations.
Felodipine C_max and AUC increased 8-fold and 6-fold, respectively, when felodipine was coadministered with the strong CYP3A4 inhibitor itraconazole. When felodipine and erythromycin were coadministered, the C_max and AUC of felodipine were increased by about 2.5-fold. Cimetidine increased the felodipine C_max and AUC by approximately 55%. The combination with strong CYP3A4 inhibitors should be avoided.
In case of clinically significant adverse events due to elevated felodipine exposure when combined with strong CYP3A4 inhibitors, adjustment of felodipine dose and/or discontinuation of the CYP3A4 inhibitor should be considered.
Examples: Cimetidine, erythromycin, itraconazole, anti-HIV/protease inhibitors (e.g. ritonavir), certain flavonoids present in grapefruit juice.
Felodipine tablets should not be taken together with grapefruit juice.
Interactions leading to decreased plasma concentration of felodipine: Enzyme inducers of the cytochrome P450 3A4 system have been shown to cause a decrease in plasma concentrations of felodipine.
When felodipine was coadministred with carbamazepine, phenytoin or phenobarbital, the C_max and AUC of felodipine were decreased by 82% and 96% respectively. The combination with strong CYP3A4 inducers should be avoided.
In case of lack of efficacy due to decreased felodipine exposure when combined with potent inducers of CYP3A4, adjustment of felodipine dose and/or discontinuation of the CYP3A4 inducer should be considered.
Examples: Phenytoin, carbamazepine, rifampicin, barbiturates, efavirenz, nevirapine, Hypericum perforatum (Saint John's wort).
Additional interactions: Tacrolimus: Felodipine may increase the concentration of tacrolimus. When used together, the tacrolimus serum concentration should be followed and the tacrolimus dose may need to be adjusted.
Cyclosporin: Felodipine does not affect plasma concentrations of cyclosporin.