Methadone with Atazanavir Interaction Details

Brand Names Associated with Methadone

Brand Names Associated with Atazanavir

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Feb 29, 2024

Interaction Effect

Increased methadone exposure, increased risk of QT interval prolongation and subsequent ventricular tachycardia (VT)

Interaction Summary

The coadministration of atazanavir and methadone has the potential to produce serious and/or life threatening adverse events due to an increased risk of QT interval prolongation and subsequent VT[1]. In patients initiating methadone who are taking atazanavir/cobicistat, carefully titrate methadone dose to the desired effect using the lowest feasible initial or maintenance dose. In patients initiating atazanavir/cobicistat who are taking methadone, a dose adjustment for methadone may be needed. Monitor clinical signs and symptoms [2].

Severity

Moderate

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Use caution when prescribing atazanavir concurrently with methadone. Concomitant use of atazanavir and methadone may cause QT prolongation and put the patient at risk for VT. If coadministered, consider monitoring the patient's cardiac function[1]. In patients initiating methadone who are taking atazanavir/cobicistat, carefully titrate methadone dose to the desired effect using the lowest feasible initial or maintenance dose. In patients initiating atazanavir/cobicistat who are taking methadone, a dose adjustment for methadone may be needed. Monitor clinical signs and symptoms [2].

Mechanism Of Interaction

Inhibition of CYP3A-mediated metabolism of methadone; additive QT interval prolongation

Literature Reports

A) Two case reports documented symptomatic VT associated with prolonged QT interval in patients infected with HIV. One male patient (age 47) had been controlling his infection with a combination of atazanavir (300 mg/day) and ritonavir (100 mg/day), tenofovir (300 mg/day), and emtricitabine (200 mg/day). Other medications included methadone (120 mg/day), flurazepam (30 mg/day), and diazePAM (10 mg/day). The other male patient (age 37) was stable on a combination of atazanavir (300 mg/day) and ritonavir (100 mg/day), abacavir (600 mg/day), and lamivudine (300 mg/day). Other medications included methadone (80 mg/day) and diazePAM (5 mg, 3 times/day). In the first case, the patient presented after a syncopal episode and an ECG revealed a prolonged QT interval of 589 ms. Cardiac telemetry revealed sustained VT. Atazanavir levels were therapeutic, however, antiretroviral and benzodiazepine therapies were discontinued and methadone treatment was continued. The QTc decreased to 521 ms with no further episodes of VT. The patient was discharged, and 3 months later was readmitted for commencement of non-atazanavir antiretroviral treatment and cardiac monitoring. QTc was unchanged and no further symptomatic arrhythmias occurred. In the case of the younger man, an ECG after a flurazepam overdose (twelve 30 mg tablets) and subsequent collapse revealed VT and the patient underwent emergency electrical cardioversion. A subsequent ECG revealed a persistent QTc of 541 ms and a QTc of 521 ms 1 day after presentation. All antiretrovirals were discontinued, methadone was continued, and the QTc decreased to 468 ms and 408 ms at 3 to 5 days after admission. Study authors concluded that atazanavir contributed to the prolonged QT interval and subsequent VT in both cases [1].

B) In a pharmacokinetic study, concurrent administration of atazanavir and methadone did not significantly affect methadone levels. Sixteen subjects were administered atazanavir 400 mg orally once daily concurrently with their regular dose of methadone orally once daily for 14 days. Results for total methadone indicated a 15% Cmax decrease, a 6% AUC decrease, and a 2% Cmin increase. The (R)-methadone geometric means ratio for coadministration with atazanavir relative to methadone alone were 1.03 (90% Confidence Interval (CI), 0.95 to 1.1) AUC, 0.91 (90% CI, 0.84 to 1) Cmax, and 1.11 (90% CI, 1.02 to 1.2) Cmin. Atazanavir pharmacokinetics were not significantly altered [3].

C) No clinically significant drug interactions were observed when atazanavir was coadministered with methadone [4].

References

1 ) Gallagher DP, Kieran J, Sheehan G, et al: Ritonavir-boosted atazanavir, methadone, and ventricular tachycardia: 2 case reports. Clin Infect Dis 2008; 47(3):e36-e38.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

2 ) Product Information: EVOTAZ(R) oral tablets, atazanavir cobicistat oral tablets. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2023.

3 ) Friedland G, Andrews L, Schreibman T, et al: Lack of an effect of atazanavir on steady-state pharmacokinetics of methadone in patients chronically treated for opiate addiction. AIDS 2005; 19(15):1635-1641.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

4 ) Product Information: REYATAZ(R) oral capsules, atazanavir sulfate oral capsules. Bristol-Myers Squibb Company, Princeton, NJ, 2008.

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.

Atazanavir Overview

• Atazanavir is used along with other medications to treat human immunodeficiency virus (HIV) infection in adults and children who are at least 3 months of age and weigh at least 22 lb (10 kg). Atazanavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although atazanavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Atazanavir must be given with other medications that treat HIV infection to completely treat the infection. Taking these medications along with practicing safer sex and making other lifestyle changes may decrease the risk of transmitting the HIV virus to other people.

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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.