Carbamazepine and Methadone interaction

Carbamazepine and Methadone: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Carbamazepine (EQUETRO) label · effective 2025-08-19

Major

CNS Depressants The concomitant use of EQUETRO and other CNS depressants can increase the risk of respiratory depression, profound sedation, hypotension, and syncope.

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Moderate

Consider reducing the dose of CNS depressants or EQUETRO when using these drugs concomitantly.

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Minor

…channel blockers (e.g., felodipine), doxycycline, ethosuximide, everolimus, felbamate, glucocorticoids, haloperidol, imatinib, itraconazole, lamotrigine, levothyroxine, lorazepam, methadone, methsuxamide, mianserin, midazolam, mirtazapine, nefazodone, olanzapine, oral and other hormonal contraceptives, oxcarbazepine, paliperidone, phenytoin, praziquantel, quetiapine,…

Drug interactionsnames MethadoneView label on DailyMed
Minor

Cytochrome (CYP) 3A4 inhibitors, epoxide hydrolase inhibitors, CYP3A4 inducers, drugs metabolized by CYP1A2 or CYP3A4 (oral contraceptives, delavirdine, nefazodone), phenytoin, CNS depressants, lithium, chloroquine, mefloquine ( 7.1 , 7.2 , 7.3 )

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Minor

CNS depressants include: alcohol, opioid analgesics, benzodiazepines, tricyclic antidepressants, sedative/hypnotics, anticonvulsants, antipsychotics, antihistamines, anticholinergics, alpha and beta blockers, general anesthetics, muscle relaxants, and illicit CNS depressants.

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From the Methadone (METHADOSE) label · effective 2026-04-27

Major

Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )].

Boxed warningby drug classView label on DailyMed
Major

Reserve concomitant prescribing of benzodiazepines or other CNS depressants in patients in methadone treatment to those for whom alternatives to benzodiazepines or other CNS depressants are inadequate.

Boxed warningby drug classView label on DailyMed
Major

Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, and death.

Boxed warningby drug classView label on DailyMed
Major

Similarly, discontinuation of concomitant CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers in METHADOSE-treated patients may increase methadone plasma concentrations resulting in fatal respiratory depression.

Warnings and precautionsby drug classView label on DailyMed
Major

If a CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducer is discontinued, consider methadone dosage reduction and monitor for signs of respiratory depression and sedation.

Drug interactionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.