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Drug interactions between methadone and Ultram

Results for the following 2 drugs:
Ultram (tramadol)

Interactions between your drugs


methadone traMADol

Applies to: methadone and Ultram (tramadol)

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Concomitant use of tramadol with other central nervous system (CNS) depressants including other opioids may result in profound sedation, respiratory depression, coma, and death. The risk of hypotension and seizures may also be increased. In patients who have been previously dependent on or chronically using opioids, tramadol can reinitiate physical dependence or precipitate withdrawal symptoms.

MONITOR CLOSELY: Methadone may cause dose-related prolongation of the QT interval. Tramadol may also prolong the QT interval, and theoretically, coadministration of multiple agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. High dosages of methadone alone have been associated with QT interval prolongation and torsade de pointes. In a retrospective study of 17 methadone-treated patients who developed torsade de pointes, the mean daily dose was approximately 400 mg (range 65 to 1000 mg) and the mean corrected QT (QTc) interval on presentation was 615 msec. The daily methadone dose correlated positively with the QTc interval. Fourteen patients had at least one predisposing risk factor for arrhythmia (hypokalemia, hypomagnesemia, concomitant use of a medication known to prolong the QT interval or inhibit the metabolism of methadone, and structural heart disease), but these were not predictive of QTc interval. It is not known if any of the patients had congenital long QT syndrome. The effect of tramadol on the QT interval was evaluated in a randomized, double-blind, 4-way crossover, placebo- and positive-controlled, multiple-dose ECG study of 62 healthy subjects. The maximum placebo-adjusted mean change from baseline in the Fridericia-corrected QT interval (QTcF) was 5.5 msec in the 400 mg/day treatment arm (100 mg every 6 hours on days 1 through 3 with a single 100 mg dose on day 4) and 6.5 msec in the 600 mg/day treatment arm (150 mg every 6 hours on days 1 through 3 with a single 150 mg dose on day 4), both occurring at the 8-hour time point.

MANAGEMENT: Concomitant use of tramadol with methadone should generally be avoided. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect. Patients should be monitored closely for development of seizures, respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. In addition, tramadol should not be used in opioid-dependent patients, and use in patients who are chronically on opioids is also not recommended. Tramadol is contraindicated in patients with acute opioid intoxication. Particular care should be exercised in patients suspected to be at an increased risk of torsade de pointes. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.


  1. Walker PW, Klein D, Kasza L "High dose methadone and ventricular arrhythmias: a report of three cases." Pain 103 (2003): 321-4
  2. Canadian Pharmacists Association "e-CPS. Available from: URL:"
  3. De Bels D, Staroukine M, Devriendt J "Torsades de pointes due to methadone." Ann Intern Med 139 (2003): E156
  4. Krantz MJ, Lewkowiez L, Hays H, et al "Torsade de pointes associated with very-high-dose methadone." Ann Intern Med 137 (2002): 501-4
  5. Cerner Multum, Inc. "Australian Product Information." O 0
  6. Martell BA, Arnsten JH, Krantz MJ, Gourevitch MN "Impact of methadone treatment on cardiac repolarization and conduction in opioid users." Am J Cardiol 95 (2005): 915-8
  7. Ehret GB, Desmeules JA, Broers B "Methadone-associated long QT syndrome: improving pharmacotherapy for dependence on illegal opioids and lessons learned for pharmacology." Expert Opin Drug Saf 6 (2007): 289-303
  8. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  9. Krantz MJ, Kutinsky IB, Robertson AD, Mehler PS "Dose-related effects of methadone on QT prolongation in a series of patients with torsade de pointes." Pharmacotherapy 23 (2003): 802-5
  10. Sala M, Anguera I, Cervantes M "Torsade de pointes due to methadone." Ann Intern Med 139 (2003): W64
  11. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical, Raritan, NJ.
  12. Mokwe EO, Ositadinma O "Torsade de pointes due to methadone." Ann Intern Med 139 (2003): W64
  13. Krantz MJ, Mehler PS "Synthetic opioids and QT prolongation." Arch Intern Med 163 (2003): 1615; author reply 1615
  14. EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring. Available from: URL:" ([2013 - ]):
  15. Gil M, Sala M, Anguera I, et al. "QT prolongation and Torsades de Pointes in patients infected with human immunodeficiency virus and treated with methadone." Am J Cardiol 92 (2003): 995-7
View all 15 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.

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traMADol food

Applies to: Ultram (tramadol)

Alcohol can increase the nervous system side effects of traMADol such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. You should avoid or limit the use of alcohol while being treated with traMADol. Do not use more than the recommended dose of traMADol, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. Talk to your doctor or pharmacist if you have any questions or concerns.

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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.