ifedipine capsule was administered together with the last dose of rifampin. Compared to study Day 1, 14 days pretreatment with rifampin reduced Cmax and AUC of concomitantly administered nifedipine on average by 95% and 97%, respectively.
Antiviral Drugs
Amprenavir, atanazavir, delavirine, fosamprinavir, indinavir, nelfinavir and ritonavir, as CYP3A inhibitors, can inhibit the metabolism of nifedipine and increase the exposure to nifedipine. Caution is warranted and clinical monitoring of patients recommended.
CNS Drugs
Nefazodone
Nefazodone, a CYP3A inhibitor, can inhibit the metabolism of nifedipine and increase the exposure to nifedipine during concomitant therapy. Blood pressure should be monitored and a reduction of the dose of nifedipine considered.
Fluoxetine
Fluoxetine, a CYP3A inhibitor, can inhibit the metabolism of nifedipine and increase the exposure to nifedipine during concomitant therapy. Blood pressure should be monitored and a reduction of the dose of nifedipine considered.
Valproic Acid
Valproic acid may increase the exposure to nifedipine during concomitant therapy. Blood pressure should be monitored and a dose reduction of nifedipine considered.
Phenytoin, Phenobarbital and Carbamazepine
Nifedipine is metabolized by CYP3A. Coadministration of nifedipine 10 mg capsule and 60 mg nifedipine coat-core tablet with phenytoin, an inducer of CYP3A, lowered the AUC and Cmax of nifedipine by approximately 70%. Phenobarbital and carbamazepine are also inducers of CYP3A. Alternative antihypertensive therapy should be considered in patients taking phenytoin, phenobarbital, and carbamazepine.
Antiemetic Drugs
Dolasetron
In patients taking dolasetron by the oral or intravenous route and nifedipine, no effect was shown on the clearance of hydrodolasetron.
Immunosuppressive Drugs
Tacrolimus
Tacrolimus has been shown to be metabolized via the CYP3A system. Nifedipine has been shown to inhibit the metabolism of tacrolimus in vitro. Transplant patients on tacrolimus and nifedipine required from 26% to 38% smaller doses than patients not receiving nifedipine. Nifedipine can increase the exposure to tacrolimus. When nifedipine is coadministered with tacrolimus the blood concentrations of tacrolimus should be monitored and a reduction of the dose of tacrolimus considered.
Sirolimus
A single 60 mg dose of nifedipine and a single 10 mg dose of sirolimus oral solution were administered to 24 healthy volunteers. Clinically significant pharmacokinetic drug interactions were not observed.
Glucose Lowering Drugs
Pioglitazone
Coadministration of pioglitazone for 7 days with 30 mg nifedipine extended-release administered orally q.d. for 4 days to male and female volunteers resulted in least square mean (90% CI) values for unchanged nifedipine of 0.83 (0.73 to 0.95) for Cmax and 0.88 (0.80 to 0.96) for AUC relative to nifedipine monotherapy. In view of the high variability of nifedipine pharmacokinetics, the clinical significance of this finding is unknown.
Rosiglitazone
Coadministration of rosiglitazone (4 mg b.i.d.) was shown to have no clinically relevant effect on the pharmacokinetics of nifedipine.
Metformin
A single dose metformin-nifedipine interaction study in normal healthy volunteers demonstrated that coadministration of nifedipine increased plasma metformin Cmax and AUC by 20% and 9%, respectively, and increased the amount of m |
