Ketoconazole (Systemic) and Nisoldipine

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Using nisoldipine together with ketoconazole is not recommended. Combining these medications can significantly increase the blood levels of nisoldipine. This may increase the risk of serious side effects such as irregular heart rhythm, fluid retention, swelling, heart failure, and excessively low blood pressure. Talk to your doctor or pharmacist if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

CONTRAINDICATED: 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. In seven healthy male volunteers, nisoldipine mean peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 11- and 24-fold, respectively, following pretreatment and during concomitant administration with ketoconazole. 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). 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. Heart failure was more frequently reported in patients receiving a dosage of 400 mg/day, although there were also cases reported among those receiving lower daily dosages.

MANAGEMENT: Because the alterations in nisoldipine pharmacokinetics cannot be feasibly managed by dosage reduction, concomitant use with ketoconazole or itraconazole is considered contraindicated.

Ketoconazole (Systemic)

Generic Name: ketoconazole

Brand name: Nizoral

Synonyms: Ketoconazole

What is Ketoconazole (Systemic)?

Nisoldipine

Generic Name: nisoldipine

Brand name: Sular

Synonyms: n.a.

What is Nisoldipine?