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Lexxel and Nizoral

Determining the interaction of Lexxel and Nizoral and the possibility of their joint administration.

Check result:
Lexxel <> Nizoral
Relevance: 15.09.2022 Reviewer: Shkutko P.M., M.D., in

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.

Consumer:

Using felodipine together with ketoconazole is not recommended. Combining these medications can significantly increase the blood levels of felodipine. 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.

Professional:

CONTRAINDICATED: 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. In nine healthy volunteers, administration of a single 5 mg oral dose of felodipine following pretreatment with itraconazole 200 mg once daily for 4 days resulted in average increases of nearly 8-fold in felodipine peak plasma concentration (Cmax), 6-fold in systemic exposure (AUC), and 2-fold in elimination half-life compared to administration with placebo. The decreases in blood pressure and increases in heart rate were also significantly greater with itraconazole. Although not studied, ketoconazole 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 felodipine pharmacokinetics cannot be feasibly managed by dosage reduction, concomitant use with itraconazole or ketoconazole is considered contraindicated.

References
  • "Product Information. Sporanox (itraconazole)." Janssen Pharmaceutica, Titusville, NJ.
  • Neuvonen PJ, Suhonen R "Itraconazole interacts with felodipine." J Am Acad Dermatol 33 (1995): 134-5
  • Tailor SAN "Peripheral edema due to nifedipine-itraconazole interaction: a case report." Arch Dermatol 132 (1996): 1374
  • Tailor SAN, Gupta AK, Walker SE, Shear NH "Peripheral edema due to nifedipine-itraconazole interaction: a case report." Arch Dermatol 132 (1996): 350-2
  • Rosen T "Debilitating edema associated with itraconazole therapy." Arch Dermatol 130 (1994): 260-1
  • "Product Information. Nizoral (ketoconazole)." Janssen Pharmaceutica, Titusville, NJ. (1992):
  • Jalava KM, Olkkola KT, Neuvonen PJ "Itraconazole greatly increases plasma concentrations and effects of felodipine." Clin Pharmacol Ther 61 (1997): 410-5
Lexxel

Generic Name: enalapril / felodipine

Brand name:

Synonyms: n.a.

Nizoral

Generic Name: ketoconazole

Brand name: Nizoral

Synonyms: n.a.

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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