re may result in pharmacodynamic interactions.
CYP3A Inhibitors
CYP3A inhibitors such as ketoconazole, fluconazole, itraconazole, clarithromycin, erythromycin, grapefruit, nefazodone, saquinavir, indinavir, nelfinavir, and ritonavir may result in increased exposure to nifedipine when coadministered. Careful monitoring and dose adjustment may be necessary; consider initiating nifedipine at the lowest dose available if given concomitantly with these medications.
Strong CYP3A Inducers
Strong CYP3A inducers, such as rifampin, rifabutin, phenobarbital, phenytoin, carbamazepine, and St. John’s Wort reduce the bioavailability and efficacy of nifedipine; therefore nifedipine should not be used in combination with strong CYP3A inducers such as rifampin (see CONTRAINDICATIONS).
Cardiovascular Drugs
Antiarrhythmics
Quinidine
Quinidine is a substrate of CYP3A and has been shown to inhibit CYP3A in vitro. Coadministration of multiple doses of quinidine sulfate, 200 mg t.i.d., and nifedipine, 20 mg t.i.d., increased Cmax and AUC of nifedipine in healthy volunteers by factors of 2.30 and 1.37, respectively. The heart rate in the initial interval after drug administration was increased by up to 17.9 beats/minute. The exposure to quinidine was not importantly changed in the presence of nifedipine. Monitoring of heart rate and adjustment of the nifedipine dose, if necessary, are recommended when quinidine is added to a treatment with nifedipine.
Flecainide
There has been too little experience with the coadministration of TAMBOCOR®1 with nifedipine to recommend concomitant use.
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1
The following is a registered trademark of its manufacturer: TAMBOCOR®/Graceway Pharmaceuticals.
Calcium Channel Blockers
Diltiazem
Pre-treatment of healthy volunteers with 30 mg or 90 mg t.i.d. diltiazem p.o. increased the AUC of nifedipine after a single dose of 20 mg nifedipine by factors of 2.2 and 3.1, respectively. The corresponding Cmax values of nifedipine increased by factors of 2 and 1.7, respectively. Caution should be exercised when coadministering diltiazem and nifedipine and a reduction of the dose of nifedipine should be considered.
Verapamil
Verapamil, a CYP3A inhibitor, can inhibit the metabolism of nifedipine and increase the exposure to nifedipine during concomitant therapy. Blood pressure should be monitored and reduction of the dose of nifedipine considered.
ACE Inhibitors
Benazepril
In healthy volunteers receiving single dose of 20 mg nifedipine extended-release and benazepril 10 mg, the plasma concentrations of benazeprilat and nifedipine in the presence and absence of each other were not statistically significantly different. A hypotensive effect was only seen after coadministration of the two drugs. The tachycardic effect of nifedipine was attenuated in the presence of benazepril.
Angiotensin-II Blockers
Irbesartan
In vitro studies show significant inhibition of the formation of oxidized irbesartan metabolites by nifedipine. However, in clinical studies, concomitant nifedipine had no effect on irbesartan pharmacokinetics.
Candesartan
No significant drug interaction has been reported in studies with candesartan cilexitil given together with nifedipine. Because candesartan is not significantly metabolized by the cytochrome P450 system and at th |
