Asenapine Transdermal Patch and Methadone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Methadone
Asenapine Transdermal Patch
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased risk of respiratory and CNS depression and an increased risk of QT prolongation
Interaction Deep Dive
When concomitant use of methadone and CNS depressants are necessary, use lowest dose and shortest duration; monitor for sedation and respiratory depression. Cardiac monitoring may also be necessary2. Withholding access to medication-assisted treatment (MAT) may lead to greater risk of morbidity and mortality related to opioid use disorder, despite serious side effects that may occur. Discontinuation of the CNS depressant is preferred; if concomitant use is necessary, the CNS depressant should be tapered to the lowest effective dose or alternative options for the treatment of anxiety or insomnia should be used. An epidemiological study from Sweden reported that patients receiving methadone- or buprenorphine-based MAT along with benzodiazepines or other CNS depressants, increase the risk of death. According to a study of aggregate nationwide death certificate data from 2010 to 2014, the majority of buprenorphine- and methadone-involved overdose deaths involved concomitant CNS depressant use 1. If concomitant use is warranted, strongly consider prescribing naloxone for the emergency treatment of opioid overdose 3.
Why it happens (mechanism)
Additive CNS depression; additive QT interval prolongation
Literature reports
2 reports — tap to read
a) An epidemiological study from Sweden reported that patients receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) along with benzodiazepines or other CNS depressants (eg, drugs that treat insomnia), increase the risk of death. Between July 1, 2005 and December 31, 2012, the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods of prescribed CNS depressants to periods of time without CNS depressant therapy were analyzed in MAT prescribed patients (aged 18 to 50). The results found an elevated risk of all-cause mortality (adjusted hazard ratio (HR) 1.44; 95% CI, 0.93 to 2.23) and non-overdose related mortality (HR 1.74; 95% CI 1.00 to 3.01) with MAT and benzodiazepine treatment; however, the data was not considered statistically significant. While results demonstrated an elevated risk of fatal overdose, non-overdose morality, and all-cause mortality during periods of coadministration of MAT and non-benzodiazepines, only the data for fatal overdose and all-cause mortality was considered statistically significant; HR 2.34 (95% CI, 1.37 to 3.99) and HR 1.33 (95% CI, 1.12 to 2.45), respectively. A comparison between the benzodiazepine cohort and non-benzodiazepine cohort was not conducted due to the authors not adjusting for the indication of use for the drugs 1.
b) According to a study of aggregate nationwide death certificate data from 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were frequently reported as culprits in those deaths. Concurrent ALPRAZolam use was reported in 18.1% of cases followed by oxyCODONE (10.1%), cocaine (9.6%), heroin (9%), and diazePAM (6.6%). The FDA reported 322 drug overdose deaths in 2014 involving buprenorphine. Of these 322 deaths, 32.9% involved ALPRAZolam, 17.4% involved clonazePAM, 11.2% involved diazePAM, 11.2% involved heroin, and 9.9% involved fentaNYL. The absolute number of methadone-involved deaths was 10 times the number of buprenorphine-involved deaths, although confounding factors and differences in drug utilization were not accounted for. It is unknown whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone 1.
Common questions
Can I take Asenapine Transdermal Patch and Methadone together?
Increased risk of respiratory and CNS depression and an increased risk of QT prolongation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Asenapine Transdermal Patch and Methadone interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Asenapine Transdermal Patch or Methadone need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (3)
- US Food and Drug Administration (FDA): Drug Safety Communications: FDA urges caution about withholding opioid addiction medications from patients taking benzodiazepines or CNS depressants: careful medication management can reduce risks. US Food and Drug Administration (FDA). Silver Spring, MD. 2017.
- Product Information: DOLOPHINE(R) oral tablets, methadone HCl oral tablets. West-Ward Pharmaceuticals Corp (per FDA), Eatontown, NJ, 2019. DailyMed
- Product Information: DISKETS dispersible tablets, methadone HCl dispersible tablets. Hikma Pharmaceuticals USA Inc (per FDA), Berkeley, NJ, 2023.
Keep reading about Methadone
Keep reading about Asenapine Transdermal Patch
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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