Interaction between Nisoldipine and Ketoconazole
Major
Metabolism
| ID | DDInter1298 and DDInter1008 |
| Interaction | Coadministration with ketoconazole or itraconazole may significantly increase the plasma concentrations of nisoldipine. The proposed mechanism is decreased first-pass metabolism and hepatic clearance of nisoldipine due to inhibition of CYP450 3A4. Although not studied, itraconazole is expected to interact similarly, since it is a known potent inhibitor 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). |
| Management | Because the alterations in nisoldipine pharmacokinetics cannot be feasibly managed by dosage reduction, concomitant use with ketoconazole or itraconazole is considered contraindicated. Some authorities consider concomitant administration of nisoldipine and itraconazole to be contraindicated during and for 2 weeks after treatment with itraconazole. |
| References | |
| Alternative for Nisoldipine |
C08C
|
| Alternative for Ketoconazole |
G01A
Tinidazole
Methazolamide
Sulfacetamide (ophthalmic)
Brinzolamide (ophthalmic)
Amphotericin B (cholesteryl sulfate)
More
|
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.