Interaction between Isradipine and Itraconazole
Major
Synergy
Metabolism
| ID | DDInter993 and DDInter995 |
| Interaction | Itraconazole exhibits a dose-related negative inotropic effect which may be additive to those of calcium channel blockers (CCBs). Theoretically, 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). In addition, both itraconazole and its major metabolite, hydroxyitraconazole, inhibit CYP450 3A4 metabolism and may interfere with the clearance of certain CCBs like the dihydropyridines (amlodipine, felodipine, isradipine, lacidipine, nicardipine, nifedipine, nimodipine, nisoldipine), diltiazem, and verapamil. Significant increases of severalfold in felodipine and nifedipine plasma concentrations have been observed during coadministration with itraconazole, and there have been case reports of leg and ankle edema in patients treated with various itraconazole-dihydropyridine combinations. 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. |
| Management | Caution is advised if itraconazole must be used concomitantly with CCBs. Close monitoring of clinical response and tolerance is recommended, and patients should be advised to seek medical attention if they experience edema or swelling of the lower extremities; sudden, unexplained weight gain; difficulty breathing; chest pain or tightness; or hypotension as indicated by dizziness, fainting, or orthostasis. Appropriate dosage adjustment of the CCB may be necessary when used with itraconazole. Some authorities consider concomitant administration of bepridil and itraconazole to be contraindicated during and for 2 weeks after treatment with itraconazole. |
| References | |
| Alternative for Isradipine |
C08C
|
| Alternative for Itraconazole |
J02A
|
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.