Methadone with Fluconazole Interaction Details
Brand Names Associated with Methadone
- Diskets®
- Dolophine®
- Methadone
- Methadose®
- Methadose® Oral Concentrate
- Westadone®
Brand Names Associated with Fluconazole
- Diflucan®
- Fluconazole
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jan 02, 2024
Interaction Effect
Increased methadone exposure and an increased risk for QT interval prolongation
Interaction Summary
Concomitant use of fluconazole with drugs that are known to prolong the QT interval and are CYP3A4 substrates, such as methadone, is contraindicated. Concomitant use may increase methadone exposure and risk for methadone-related side effects, including fatal respiratory depression and additive QT interval prolongation. Additionally, fluconazole-mediated enzyme inhibition may continue for 4 to 5 days after discontinuation because of the long half-life . A study determined that methadone and fluconazole coadministration resulted in a 35% average increase in methadone AUC; however, subjects did not display signs or symptoms of narcotic intoxication . If concomitant use is required, closely monitor for signs of respiratory or CNS depression and reduce methadone dose if needed .
Severity
Contraindicated
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Concomitant use of fluconazole with other drugs that are known to prolong the QT interval and are CYP3A4 substrates, such as methadone, is contraindicated. Concomitant use may increase methadone exposure and risk for methadone-related side effects, including fatal respiratory depression and additive QT interval prolongation. Additionally, fluconazole-mediated CYP3A4 inhibition may continue for 4 to 5 days after discontinuation because of the long half-life . If concomitant use is required, closely monitor for signs of respiratory or CNS depression and reduce methadone dose if needed .
Mechanism Of Interaction
Inhibition of CYP3A4-mediated metabolism of methadone by fluconazole; inhibition of CYP2C9-mediated metabolism of methadone by fluconazole; additive QT interval prolongation
Literature Reports
A) Twenty-five volunteers receiving methadone maintenance therapy participated in a randomized, double-blind, placebo-controlled pharmacokinetic trial to determine the effect of fluconazole on methadone disposition and any resulting clinical effects. All subjects were receiving a stable methadone dose for at least 30 days before randomization. Thirteen volunteers were given fluconazole 200 mg daily for 14 days, while the other 12 received placebo. At baseline, the methadone area under the concentration-time curve (AUC) averaged 7.8 mg x hr/L and increased to 10.14 mg/hr/L following fluconazole therapy. Mean serum methadone peak and trough concentrations also increased by 27% (from 453 to 557 nanogram/mL (ng/mL) or 1464 to 1800 nanomol/L) and 48% (from 254 to 360 ng/mL (821 to 1163 nanomol/L), respectively. The apparent oral clearance of methadone changed from 8.3 L/hr to 6.2 L/hr following fluconazole therapy, representing a 24% decrease. Despite the increased bioavailability of methadone during fluconazole coadministration, no subjects experienced signs or symptoms of narcotic overdose, suggesting that methadone dose adjustments are not required when fluconazole is co-prescribed .
B) Respiratory depression may occur with concomitant fluconazole and methadone administration. A 60-year-old patient with advanced gastric cancer achieved good pain control on a stable dose of methadone for ten days. Respiratory depression developed two days after intravenous fluconazole was administered for refractory oral candidiasis. This respiratory depression was reversed using intravenous naloxone. Acute illness and unstable disease have been identified as risk factors for clinically significant drug interactions. The authors suggests that a greater awareness is needed of the potential interactions between drugs used in palliative care .
Methadone Overview
-
Methadone is used to relieve severe pain in people who are expected to need pain medication around the clock for a long time and who cannot be treated with other medications. It also is used to prevent withdrawal symptoms in patients who were addicted to opiate drugs and are enrolled in treatment programs in order to stop taking or continue not taking the drugs. Methadone is in a class of medications called opiate (narcotic) analgesics. Methadone works to treat pain by changing the way the brain and nervous system respond to pain. It works to treat people who were addicted to opiate drugs by producing similar effects and preventing withdrawal symptoms in people who have stopped using these drugs.
Fluconazole Overview
-
Fluconazole is used to treat fungal infections, including yeast infections of the vagina, mouth, throat, esophagus (tube leading from the mouth to the stomach), abdomen (area between the chest and waist), lungs, blood, and other organs. Fluconazole is also used to treat meningitis (infection of the membranes covering the brain and spine) caused by fungus. Fluconazole is also used to prevent yeast infections in patients who are likely to become infected because they are being treated with chemotherapy or radiation therapy before a bone marrow transplant (replacement of unhealthy spongy tissue inside the bones with healthy tissue). Fluconazole is in a class of antifungals called triazoles. It works by slowing the growth of fungi that cause infection.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
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.