Ketoconazole with Reboxetine Interaction Details
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 02, 2023
Interaction Effect
Increased reboxetine bioavailability
Interaction Summary
Avoid concomitant use of reboxetine with strong CYP3A4 inhibitors, as coadministration may result in increased reboxetine plasma concentrations. When reboxetine and the strong CYP3A4 inhibitor, ketoconazole, were used concurrently, plasma concentrations of reboxetine enantiomers increased by approximately 50%, although no apparent effect on vital signs or the side effect profile was seen .
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Avoid concomitant use of reboxetine with strong CYP3A4 inhibitors, as coadministration may result in increased reboxetine plasma concentrations.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated reboxetine metabolism
Literature Reports
A) Eleven healthy volunteers participated in a single-dose, open-label, randomized study to assess the extent to which ketoconazole decreases the clearance of reboxetine. Each subject was given ketoconazole 200 mg once daily on days 1 through 5 and reboxetine 4 mg on day 2, or reboxetine 4 mg on day 2 in a crossover fashion. For the R,R- enantiomer of reboxetine, ketoconazole increased the mean area under the concentration-time curve (AUC) by 58% (from 1726 ng/h/mL to 2730 ng/h/mL), decreased the oral clearance by 34% (from 41.6 mL/min to 27.5 mL/min), and increased the half-life from 14.8 hours to 21.5 hours. The AUC value for the S,S- enantiomer of reboxetine was increased by 43% (from 762 ng/h/mL to 1090 ng/h/mL), the oral clearance was decreased by 24% (from 99.3 mL/min to 75.6 mL/min), and the half-life was prolonged from 14.4 hours to 18.9 hours in the presence of ketoconazole. Peak plasma concentrations of reboxetine were not significantly altered, which coincided with the lack of any relevant changes in blood pressure, heart rate, temperature, respirations, or hematologic parameters .
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.