Table.

Drug interactions with methadone

Drug	Interaction type	Clinical effect	Practitioner considerations
Naloxone, naltrexone, pentazocine, nalbuphine-mixed opiate antagonists/partial agonists	Pharmacodynamic—receptor blockade	Precipitate abstinence syndrome	Must avoid in patients on methadone therapy; may use naloxone to treat overdose
Rifampin, carbamazepine, phenytoin,26 nevirapine27	Pharmacokinetic—enhance elimination	Reduce blood concentrations and effectiveness and may produce abstinence syndrome	Increase dose of methadone
Benzodiazepines, ethanol	Pharmacodynamic—additive/synergistic CNS depression	Increased sedation and risk of respiratory failure	Avoid in patients on methadone therapy
Ritonavir,28 fluvoxamine29	Pharmacokinetic—decreased metabolism	Produce methadone toxicity	Reduce dose of methadone
Zidovudine,30 desipramine31	Pharmacokinetic—reduced clearance	Increased risk of zidovudine and desipramine toxicity	Reduce zidovudine dosage and monitor for toxicity; monitor desipramine serum concentrations
Thyroxine	Laboratory increased concentrations of thyroxine binding globulin	Altered thyroid function tests (increased T3, T4, FTI, and TBG).	Monitor for euthyroid state with free T3 and T4 and TSH levels
Opiate analgesics	Pharmacodynamic cross-tolerance between opioid agents	Partial tolerance to analgesic effect of opioids	Titrate and adjust dosage interval to attain analgesia, avoid mixed agonist-antagonists (eg. pentazocine) or substitute with non-narcotic analgesics (eg. NSAIDs)
T3 = triiodothyronine, T4 = thyroxine, FTI = free thyroxine index, TBG = thyroxine binding globin; TSH = thyroid-stimulating hormone; NSAIDs = nonsteroidal anti-inflammatory drugs