What the FDA labels say about taking them together
Clozapine and methadone
Clozapine's FDA label of June 6, 2025 names methadone in its drug interactions section; methadone's label does not name clozapine itself but warns about its class (Atypical antipsychotics). The clozapine label: “Drugs that cause QT prolongation include: specific antipsychotics, specific antibiotics, Class 1A antiarrhythmics or Class III antiarrhythmics, and others.”
Check it at the source: the clozapine FDA label on DailyMed (effective June 6, 2025, HLS Therapeutics (USA), Inc.); the methadone FDA label on DailyMed (effective December 8, 2025, Epic Pharma, LLC).
What does the clozapine label say about methadone?
Clozapine label, drug interactionsDrugs that cause QT prolongation include: specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, thioridazine, mesoridazine, droperidol, and pimozide), specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin), Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class III antiarrhythmics (e.g., amiodarone, sotalol), and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus) [see Warnings and Precautions ( 5.9 )].
Source: FDA drug label (Clozaril), NDA019758 (Heritage Life), as published by HLS Therapeutics (USA), Inc., effective June 6, 2025 (SPL set 90876802-0e3a-44c9-9ff7-1754dfbe736a), via openFDA; the full label on DailyMed
What does the methadone label say about clozapine?
Methadone's label does not name clozapine itself; it warns about its class (Atypical antipsychotics):
Methadone label, warnings and precautionsRisks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Methadone hydrochloride tablets with benzodiazepines and/or other CNS depressants (e.g., alcohol, non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids).
Methadone label, warnings and precautionsRisks from Concomitant Use of Benzodiazepines or Other CNS Depressants with Methadone Concomitant use of methadone and benzodiazepines and/or other CNS depressants (e.g., alcohol, non-benzodiazepine sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids), increases the risk of adverse reactions, including overdose and death.
Source: FDA drug label (Methadone Hydrochloride), Epic Pharma, LLC, effective December 8, 2025 (SPL set 6da7501b-b881-4bc7-891a-74214a00a3ac), via openFDA; the full label on DailyMed
These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.
Both medicines on the record
| Clozapine | Methadone | |
|---|---|---|
| Labeled for | Schizophrenia | Pain, Opioid use disorder |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $0.610 per tablet 100 mg tablet | $0.177 per tablet 10 mg tablet |
| Shortage now | No current entry | No current entry |
Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)
What next?
- Check more medicines together
- up to five at once