Interaction between Felodipine and Itraconazole
Major
Metabolism
| ID | DDInter716 and DDInter995 |
| Interaction |
Coadministration with itraconazole or ketoconazole may significantly increase the plasma concentrations of felodipine. The proposed mechanism is decreased first-pass metabolism and hepatic clearance of felodipine due to inhibition of CYP450 3A4.There have been case reports of leg and ankle edema in patients treated with itraconazole and dihydropyridine calcium channel blockers. Pharmacodynamically, itraconazole exhibits a dose-related negative inotropic effect, which may be additive to those of calcium channel blockers (CCBs). It is conceivable that coadministration may potentiate the risk of ventricular dysfunction, congestive heart failure, and peripheral and pulmonary edema, particularly in patients with preexisting risk factors (e.g., a history of congestive heart failure; cardiac disease such as ischemic and valvular disease; significant pulmonary disease such as chronic obstructive pulmonary disorder; edematous disorders such as renal failure). Itraconazole alone has also been associated with postmarketing reports of congestive heart failure, peripheral edema, and pulmonary edema in patients treated for onychomycosis and/or systemic fungal infections.
pleural pain
confusion
drowsiness
dyspepsia
Difficulty breathing
edema
eruption
Fatigue
body temperature increased
acid reflux
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| Management | Because the alterations in felodipine pharmacokinetics cannot be feasibly managed by dosage reduction, concomitant use with itraconazole or ketoconazole is considered contraindicated. Some authorities state that coadministration with felodipine is considered contraindicated during and for 2 weeks after treatment with itraconazole (AU). |
| References | |
| Alternative for Felodipine |
C07F
C08C C09B
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| Alternative for Itraconazole |
J02A
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Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.