Methadone with Erythromycin Interaction Details

Brand Names Associated with Methadone

Brand Names Associated with Erythromycin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Jan 02, 2024

Interaction Effect

Increased risk of QT interval prolongation; increased risk of opioid adverse effects

Interaction Summary

Concomitant use of methadone (a CYP3A4 substrate) with a CYP3A4 inhibitor may result in an increase in methadone plasma levels resulting in increased or prolonged opioid effects, and may result in a fatal overdose, particularly when an inhibitor is added after a stable dose of methadone is achieved. Additionally, coadministration of drugs that affect cardiac conduction increases the risk of QT prolongation. If coadministered, closely monitor the patient for the development of prolonged QT interval. Consider a dosage reduction of methadone until stable clinical effects are achieved. Monitor for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, observe signs of opioid withdrawal and consider increasing the methadone dosage until stable clinical effects are achieved

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Concomitant use of methadone (a CYP3A4 substrate) with a CYP3A4 inhibitor may result in an increase in methadone plasma levels resulting in increased or prolonged opioid effects, and may result in a fatal overdose, particularly when an inhibitor is added after a stable dose of methadone is achieved. Additionally, coadministration of drugs that affect cardiac conduction increases the risk of QT prolongation. If coadministered, closely monitor the patient for the development of prolonged QT interval. Consider a dosage reduction of methadone until stable clinical effects are achieved. Monitor for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, observe signs of opioid withdrawal and consider increasing the methadone dosage until stable clinical effects are achieved

Mechanism Of Interaction

Additive effects on QT interval; inhibition of CYP3A4-mediated methadone metabolism

Literature Reports

A) In a pharmacokinetic study, oral voriconazole (400mg every 12 hours for 1 day, then 200mg every 12 hours for 4 days) administered to patients receiving maintenance methadone doses of 30 to 100 mg/day increased the Cmax and AUC of R-methadone by 31% and 47%, respectively, and increased the Cmax and AUC of (S)-methadone by 65% and 103% .

B) Coadministration of multiple oral doses of voriconazole in patients with steady-state methadone levels increased the methadone exposure according to a pharmacokinetic study in 23 male patients receiving methadone for opiate abstinence syndrome. Patients receiving methadone 32 to 100 mg orally once a day for at least 30 days were randomized to receive either placebo or voriconazole 400 mg orally twice a day for one day, followed by 200 mg orally twice a day for 4 days. Effects on active (R)-methadone included a 47.2% (range 20% to 113%) increase AUC and a 30.7% (range 9% to 85%) increase in Cmax. The Tmax did not appreciably change from 2 hours (range 1 to 3 hours) to 2.5 hours (range 1 to 6 hours). Compared to historical data, methadone has no effect on voriconazole pharmacokinetic parameters. There was no correlation between increasing voriconazole doses and the magnitude of increase in methadone exposure or the frequency and severity of adverse events .

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.

Erythromycin Overview

• Erythromycin is used to treat certain infections caused by bacteria, such as infections of the respiratory tract, including bronchitis, pneumonia, Legionnaires' disease (a type of lung infection), and pertussis (whooping cough; a serious infection that can cause severe coughing); diphtheria (a serious infection in the throat); sexually transmitted diseases (STD), including syphilis; and ear, intestine, gynecological, urinary tract, and skin infections. It also is used to prevent recurrent rheumatic fever. Erythromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as erythromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.