Skip to Content

Drug interactions between methadone and modafinil

Results for the following 2 drugs:

Interactions between your drugs


methadone modafinil

Applies to: methadone and modafinil

Consumer information for this interaction is not currently available.

MONITOR CLOSELY: Coadministration with inducers of various CYP450 isoenzymes may decrease the plasma concentrations of methadone, which is metabolized by CYP450 3A4, 2B6, 2C19, 2C9, and 2D6. Reduced analgesic efficacy or withdrawal symptoms may occur in patients maintained on methadone following the addition of an inducer. Conversely, discontinuation of the inducer may increase methadone plasma concentrations and potentiate the risk of overdose and fatal respiratory depression. The interaction has been reported with several moderate and potent inducers including rifampin, phenytoin, phenobarbital, nevirapine, and efavirenz. In one report, evidence of withdrawal was observed in 21 of 30 patients maintained on methadone who received rifampin for tuberculosis, compared to zero out of 26 who received other antituberculous agents. In a study of 11 patients on stable methadone maintenance treatment, mean methadone peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 48% and 57%, respectively, following initiation of antiretroviral therapy containing efavirenz 600 mg once a day. Nine patients developed symptoms consistent with methadone withdrawal an average of 8 to 10 days after start of efavirenz, which required a 22% mean increase in methadone dosage. In a similar study with nevirapine given at 200 mg once daily for 2 weeks followed by 200 mg twice daily, the reduction in mean methadone Cmax and AUC was 36% and 52%, respectively, in 8 patients stabilized on methadone treatment. Withdrawal symptoms occurred in six patients 8 to 10 days after start of nevirapine, and methadone dosage was subsequently increased an average of 16%. Dosage increases of up to 100% and eventual discontinuation of the non-nucleoside reverse-transcriptase inhibitor have also been described in some reports.

MANAGEMENT: Caution is advised if methadone is prescribed with CYP450 2B6, 2C19, 2C9 and/or 3A4 inducers. Pharmacologic response to methadone should be monitored more closely whenever an inducer is added to or withdrawn from therapy, and the dosage adjusted as necessary.


  1. Tong TG, Pond SM, Kreek MJ, et al "Phenytoin-induced methadone withdrawal." Ann Intern Med 94 (1981): 349-51
  2. Liu S-J, Wang RI "Case report of barbiturate-induced enhancement of methadone metabolism and withdrawal syndrome." Am J Psychiatry 141 (1984): 1287-8
  3. Kreek MJ, Garfield JW, Gutjahr CL, Giusti LM "Rifampin-induced methadone withdrawal." N Engl J Med 294 (1976): 1104-6
  4. Bell J, Seres V, Bowron P, Lewis J, Batey R "The use of serum methadone levels in patients receiving methadone maintenance." Clin Pharmacol Ther 43 (1988): 623-9
  5. Holmes VF "Rifampin-induced methadone withdrawal in AIDS." J Clin Psychopharmacol 10 (1991): 443-4
  6. "Product Information. Diskets (methadone)." Cebert Pharmaceuticals Inc, Birmingham, AL.
  7. Raistrick D, Hay A, Wolff K "Methadone maintenance and tuberculosis treatment." BMJ 313 (1996): 925-6
  8. Otero MJ, Fuertes A, Sanchez R, Luna G "Nevirapine-induced withdrawal symptoms in HIV patients on methadone maintenance programme: an alert." AIDS 13 (1999): 1004-5
  9. Altice FL, Friedland GH, Cooney EL "Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone." AIDS 13 (1999): 957-62
  10. Bending MR, Skacel PO "Rifampicin and methadone withdrawal." Lancet 1 (1977): 1211
  11. Finelli PF "Phenytoin and methadone tolerance." N Engl J Med 294 (1976): 227
  12. Pinzani V, Faucherre V, Peyriere H, Blayac JP "Methadone withdrawal symptoms with nevirapine and efavirenz." Ann Pharmacother 34 (2000): 405-7
View all 12 references

Drug and food interactions


methadone food

Applies to: methadone

Grapefruit juice can increase the blood levels and effects of methadone. If you regularly consume grapefruits or grapefruit juice, you should be monitored for side effects and/or changes in methadone levels. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor. Orange juice is not expected to interact.

Switch to professional interaction data


modafinil food

Applies to: modafinil

Consumer information for this minor interaction is not currently available. Some minor drug interactions may not be clinically relevant in all patients. Minor drug interactions do not usually cause harm or require a change in therapy. However, your healthcare provider can determine if adjustments to your medications are needed.

For clinical details see professional interaction data.

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

Drug Interaction Classification

The classifications below are a guideline only. The relevance of a particular drug interaction to a specific patient is difficult to determine using this tool alone given the large number of variables that may apply.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No information available.

Do not stop taking any medications without consulting your healthcare provider.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.