Skip to Content

Drug interactions between methadone and Rifamate

Results for the following 2 drugs:
Rifamate (isoniazid/rifampin)

Interactions between your drugs


rifAMPin methadone

Applies to: Rifamate (isoniazid / rifampin) and methadone

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 Pharmacologic response to methadone should be monitored more closely whenever an inducer is added to or withdrawn from therapy, and the dosage adjusted as necessary.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. Raistrick D, Hay A, Wolff K "Methadone maintenance and tuberculosis treatment." BMJ 313 (1996): 925-6
  4. 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
  5. Altice FL, Friedland GH, Cooney EL "Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone." AIDS 13 (1999): 957-62
  6. Bending MR, Skacel PO "Rifampicin and methadone withdrawal." Lancet 1 (1977): 1211
  7. Kreek MJ, Garfield JW, Gutjahr CL, Giusti LM "Rifampin-induced methadone withdrawal." N Engl J Med 294 (1976): 1104-6
  8. Finelli PF "Phenytoin and methadone tolerance." N Engl J Med 294 (1976): 227
  9. Pinzani V, Faucherre V, Peyriere H, Blayac JP "Methadone withdrawal symptoms with nevirapine and efavirenz." Ann Pharmacother 34 (2000): 405-7
  10. 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
  11. Holmes VF "Rifampin-induced methadone withdrawal in AIDS." J Clin Psychopharmacol 10 (1991): 443-4
  12. "Product Information. Diskets (methadone)." Cebert Pharmaceuticals Inc, Birmingham, AL.
View all 12 references

methadone isoniazid

Applies to: methadone and Rifamate (isoniazid / rifampin)

Isoniazid may increase the blood levels and effects of methadone. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Contact your doctor if you experience increased side effects such as excessive drowsiness, tiredness, confusion, disorientation, nausea, vomiting, and shallow or difficult breathing. High blood levels of methadone can also occasionally cause an irregular heart rhythm that may be serious. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or fast or pounding heartbeats. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Switch to professional interaction data

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


isoniazid food

Applies to: Rifamate (isoniazid / rifampin)

Food decreases the levels of isoniazid in your body. Take isoniazid on an empty stomach at least 1 hour before or 2 hours after a meal. This will make it easier for your body to absorb the medication. If nausea occurs, ask your doctor if you can take isoniazid with food. Avoid alcohol while taking isoniazid. Alcohol may increase the risk of damage to the liver during isoniazid treatment. Alcohol can also cause isoniazid side effects to get worse. Contact your doctor if you experience flushing, chills, headache, nausea, vomiting, and diarrhea.

Switch to 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.