Ketoconazole with Levomethadyl Interaction Details
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 02, 2023
Interaction Effect
Increased plasma concentrations of levomethadyl and reduced active metabolites plasma concentrations
Interaction Summary
The concurrent administration of ketoconazole, which inhibits cytochrome P450 isoform CYP3A4, have increased the plasma concentrations of levomethadyl and reduced the plasma concentrations of its active metabolites. This increase in serum concentration could potentially prolong QT intervals while simultaneously provoking symptoms of opiate withdrawal.
Severity
Major
Onset
Rapid
Evidence
Probable
How To Manage Interaction
Close observation of patients receiving levomethadyl and ketoconazole is advised to allow early detection of any need to adjust the dose or dosing interval. Observe patient for signs and symptoms of opiate withdrawal and the prolongation of QT intervals.
Mechanism Of Interaction
Inhibition of cytochrome P450 3A4-mediated metabolism of levomethadyl leading to increased plasma concentrations of levomethadyl
Literature Reports
A) The concurrent administration of ketoconazole with levomethadyl (LAAM) resulted in a significant increase in levomethadyl parent compound while significantly reducing plasma concentrations of both active metabolites (norLAAM and dinorLAAM). In a single-blind, randomized, cross-over study, healthy subjects (n=13) were entered into a 1-month washout period prior to receiving a single oral dose of either ketoconazole 400 milligrams (mg) or placebo. One hour later, each subject received a single oral dose of LAAM 5 mg/70 kilogram (kg) body weight. Serial blood analysis was then performed over 240 hours in conjunction with subject-rated measures of LAAM effect. Following a 1-month washout, each subject crossed over the opposing study arm. The concurrent administration of ketoconazole increased the LAAM mean maximum serum concentration (Cmax) and area under the concentration-time curve (AUC 0-240 hours) by 322% and 529%, respectively (p less than 0.001, both measures) while simultaneously reducing the norLAAM mean Cmax by 23% and extending the time to maximum concentration (Tmax) by 243% (p less than 0.005 and 0.001, respectively). DinorLAAM mean Cmax also declined (by 45%) with concomitant ketoconazole administration, and Tmax increased simultaneously by 1160% (p less than 0.001, both measures). AUC (0-240 hours) for norLAAM and dinorLAAM were both increased, by 225% and 121%, respectively (p less than 0.001 and 0.005, respectively). Subjects receiving concurrent ketoconazole reported significantly less sedation (p less than 0.05) while showing an upwards trend (over baseline) toward subjectively reported feelings of stomach distress, shaking tremors of hands, and other opiate withdrawal effects .
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.