Ketoconazole with Felodipine Interaction Details
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Brand Names Associated with Felodipine
- Felodipine
- Lexxel® (as a combination product containing Enalapril, Felodipine)
- Plendil®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 02, 2023
Interaction Effect
Increased felodipine serum concentrations; additive negative inotropic effect
Interaction Summary
Concomitant use of felodipine and ketoconazole is contraindicated as coadministration may result increased plasma concentrations of felodipine with additive inotropic effects and an increased risk for edema and congestive heart failure. Triazole antifungals (itraconazole, fluconazole) and imidazole antifungals (ketoconazole) inhibit hepatic isoenzyme CYP3A4, an enzyme involved in the metabolism of dihydropyridine calcium channel antagonists (nifedipine, nicardipine, amlodipine, isradipine, felodipine) . Literature reports have documented substantial peripheral edema and/or elevated calcium antagonist serum concentrations during concurrent use of itraconazole and felodipine, isradipine, or nifedipine . Since the other triazole and imidazole antifungals also inhibit CYP3A4, this interaction would be expected to occur with other combinations.
Severity
Contraindicated
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Concomitant use of felodipine and ketoconazole is contraindicated as coadministration may result increased plasma concentrations of felodipine with additive inotropic effects and an increased risk for edema and congestive heart failure
Mechanism Of Interaction
Inhibition of CYP3A4-mediated metabolism of felodipine; additive negative inotropic effect
Literature Reports
A) A 68-year-old woman experienced ankle edema following treatment with nifedipine and itraconazole. The patient had been administered atenolol and nifedipine for hypertension. She was then started on itraconazole for pedal onychomycosis. Ankle edema appeared after two to three days of itraconazole and resolved two to three days after itraconazole was discontinued. The ankle edema reappeared with each subsequent course of itraconazole except the final course. Nifedipine trough concentrations were obtained with the last course of therapy. Relative to the itraconazole therapy, trough nifedipine concentrations were obtained four days prior to and three days during therapy. The mean nifedipine trough concentrations were 12.7 ng/mL and 56.1 ng/mL, respectively .
B) Peripheral edema and elevated serum felodipine levels were described in two patients receiving combined therapy with felodipine and itraconazole. Swelling of the lower extremities occurred in both cases within 3 to 7 days and resolved within 2 to 4 days following discontinuation of one of the agents. Re-challenge in one of the patients resulted in reoccurrence of the edema. In this patient, area under the felodipine plasma concentration-time curve (AUC) was found to be at least four times higher with itraconazole therapy . The authors also mention an additional patient who developed ankle swelling when itraconazole was added to isradipine therapy, however, further details were not supplied.
Ketoconazole Overview
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Ketoconazole is used to treat fungal infections when other medications are not available or cannot be tolerated. Ketoconazole should not be used to treat fungal meningitis (infection of the membranes surrounding the brain and spinal cord caused by a fungus) or fungal nail infections. Ketoconazole is in a class of antifungals called imidazoles. It works by slowing the growth of fungi that cause infection.
Felodipine Overview
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Felodipine is used to treat high blood pressure. Felodipine is in a class of medications called calcium channel blockers. It works by relaxing the blood vessels so your heart does not have to pump as hard.
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High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.