Methylprednisolone with Ketoconazole Interaction Details
Brand Names Associated with Methylprednisolone
- Medrol®
- Methylprednisolone
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 03, 2023
Interaction Effect
An increased risk of corticosteroid side effects (neuropsychiatric reactions, fluid and electrolyte disturbances, hypertension, hyperglycemia)
Interaction Summary
Ketoconazole may inhibit the metabolism of methylprednisone and thus decrease its clearance. Ketoconazole doses at greater than 200 mg daily for at least six to seven days have been reported to decrease the metabolism of methylPREDNISolone by about 50 to 60% .
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Patients receiving methylPREDNISolone may require a dosage change when ketoconazole is added (greater than six to seven days) or deleted from their drug regimens (post five to seven days). Also, monitor for adverse effects of methylPREDNISolone (neuropsychiatric reactions, fluid and electrolyte disturbances, hypertension, hyperglycemia).
Mechanism Of Interaction
Decreased methylPREDNISolone metabolism
Literature Reports
A) MethylPREDNISolone clearance was decreased by 50% to 60% following therapy with oral ketoconazole 200 mg daily for six to seven days in 14 healthy volunteers; the methylPREDNISolone-induced adrenal suppression was also enhanced. The patients were given single intravenous methylPREDNISolone doses of 15, 20, or 30 mg before and after the ketoconazole dosing period. A 50% reduction in the methylPREDNISolone dose is recommended .
B) Six healthy male volunteers were studied by in three phases to determine the effects of ketoconazole on the disposition of methylPREDNISolone. During Phase I, the 24-hour baseline cortisol concentration was determined in each subject. Phase II consisted of methylPREDNISolone 20 mg being administered by a rapid intravenous bolus, and blood samples were drawn to define the pharmacokinetic characteristics of methylPREDNISolone. After a two-week wash-out period, ketoconazole 200 mg daily was administered for six days, followed by methylPREDNISolone 20 mg intravenously to make up Phase III. Ketoconazole was found to raise the methylPREDNISolone area under the concentration-time curve (AUC) from 829 ng/hr/mL to 1953 ng/hr/mL, representing a 135% increase. The clearance of methylPREDNISolone decreased from 423 mL/hr/kg during monotherapy to 170 mL/hr/kg with ketoconazole coadministration. The cortisol AUC was lower during ketoconazole therapy (795 ng/hr/mL) as compared to baseline (2139 ng/hr/mL) and phase II (1189 ng/hr/mL).
Methylprednisolone Overview
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Methylprednisolone, a corticosteroid, is similar to a natural hormone produced by your adrenal glands. It is often used to replace this chemical when your body does not make enough of it. It relieves inflammation (swelling, heat, redness, and pain) and is used to treat certain forms of arthritis; skin, blood, kidney, eye, thyroid, and intestinal disorders (e.g., colitis); severe allergies; and asthma. Methylprednisolone is also used to treat certain types of cancer.
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This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.
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.
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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.