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Drug Interactions between Methadone Diskets and methylene blue

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

methadone methylene blue

Applies to: Methadone Diskets (methadone) and methylene blue

CONTRAINDICATED: Coadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe and fatal adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases. The exact mechanism of interaction is unknown, but may involve excessive serotonergic activity in the central nervous system (i.e., serotonin syndrome). The interaction is unpredictable and has been reported primarily with meperidine or fentanyl and various MAOIs including phenelzine, tranylcypromine, linezolid, moclobemide, and selegiline. Fatal hyperpyrexia and hypertension have also been observed in animal studies with meperidine and phenelzine or furazolidone. In contrast, symptoms of the depressive reaction probably stem from potentiation of CNS effects by MAOIs and include respiratory depression, cyanosis, hypotension, and coma.

MANAGEMENT: Meperidine and fentanyl should not be used with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, methylene blue, procarbazine). Some manufacturers of MAOIs also contraindicate the concomitant use of propoxyphene and methadone due to their possible serotonergic effects. At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with these opioids. Although morphine may also have significant CNS interactions with MAOIs, it is generally considered a safer alternative in patients treated with MAOIs who require a narcotic analgesic. A sensitivity test should be performed in which repeated, small, incremental doses of morphine are administered over the course of several hours while overall clinical status and vital signs are carefully monitored.

References (40)
  1. Browne B, Linter S (1987) "Monoamine oxidase inhibitors and narcotic analgesics: a critical review of the implications for treatment." Br J Psychiatry, 151, p. 210-2
  2. Zornberg GL, Bodkin JA, Cohen BM (1991) "Severe adverse interaction between pethidine and selegiline." Lancet, 337, p. 246
  3. Pettinger WA, Soyangco FG, Oates JA (1968) "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther, 9, p. 442-7
  4. Schulz R, Antonin KH, Hoffmann E, et al. (1989) "Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline." Clin Pharmacol Ther, 46, p. 528-36
  5. Evans-Prosser CD (1968) "The use of pethidine and morphine in the presence of monoamine oxidase inhibitors." Br J Anaesth, 40, p. 279-82
  6. Goldberg LI (1964) "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA, 190, p. 456-62
  7. Vigran IM (1964) "Dangerous potentiation of meperidine hydrochloride by pargyline hydrochloride." JAMA, 187, p. 953-4
  8. Nierenberg DW, Semprebon M (1993) "The central nervous system serotonin syndrome." Clin Pharmacol Ther, 53, p. 84-8
  9. (2002) "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals
  10. Sternbach H (1991) "The serotonin syndrome." Am J Psychiatry, 148, p. 705-13
  11. Starr C (1991) "Interaction between pethidine and selegiline." Lancet, 337, p. 554
  12. Youssef MS, Wilkinson PA (1988) "Epidural fentanyl and monoamine oxidase inhibitors." Anaesthesia, 43, p. 210-2
  13. Noble WH, Baker A (1992) "MAO inhibitors and coronary artery surgery: a patient death." Can J Anaesth, 39, p. 1061-6
  14. (2001) "Product Information. Eldepryl (selegiline)." Somerset Pharmaceuticals Inc
  15. Insler SR, Kraenzler EJ, Licina MG, Savage RM, Starr NJ (1994) "Cardiac surgery in a patient taking monoamine oxidase inhibitors - an adverse fentanyl reaction." Anesth Analg, 78, p. 593-7
  16. Garbutt JC (1987) "Potentiation of propoxyphene by phenelzine." Am J Psychiatry, 144, p. 251-2
  17. Zornberg GL, Hegarty JD (1993) "Adverse interaction between propoxyphene and phenelzine." Am J Psychiatry, 150, p. 1270-1
  18. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  19. Limbird LE eds., Gilman AG, Hardman JG (1995) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: McGraw-Hill
  20. (2001) "Product Information. Matulane (procarbazine)." Roche Laboratories
  21. De Vita VT, Hahn MA, Oliverio VT (1965) "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med, 120, p. 561-5
  22. Michaels I, Serrins M, Shier NQ, Barash PG (1984) "Anesthesia for cardiac surgery in patients receiving monoamine oxidase inhibitors." Anesth Analg, 63, p. 1041-4
  23. Mills KC (1997) "Serotonin syndrome: A clinical update." Crit Care Clin, 13, p. 763
  24. (2001) "Product Information. Furoxone (furazolidone)." Roberts Pharmaceutical Corporation
  25. (2001) "Product Information. Actiq (fentanyl)." Abbott Pharmaceutical
  26. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG (1998) "Serotonin syndrome resulting from drug interactions." Med J Aust, 169, p. 523-5
  27. (2001) "Product Information. Nardil (phenelzine)." Parke-Davis
  28. (2001) "Product Information. Parnate (tranylcypromine)." SmithKline Beecham
  29. Weiner AL (1999) "Meperidine as a potential cause of serotonin syndrome in the emergency department." Acad Emerg Med, 6, p. 156-8
  30. Upton R, Graff A, Williamson E, et al. (1997) "American Herbal Pharmacopoeia and Therapeutic Compendium. Monograph printed in Herbalgram." Herbalgram, 40, 1-38(monograph)
  31. (2001) "Product Information. Marplan (isocarboxazid)." Roche Laboratories
  32. (2022) "Product Information. Meperidine Hydrochloride (meperidine)." Astra-Zeneca Pharmaceuticals
  33. Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
  34. Gillman PK (1995) "Possible serotonin syndrome with moclobemide and pethidine." Med J Aust, 162, p. 554
  35. Gillman PK (2005) "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity." Br J Anaesth
  36. (2006) "Product Information. Azilect (rasagiline)." Teva Pharmaceuticals USA
  37. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  38. Das PK, Warkentin DI, Hewko R, Forrest DL (2008) "Serotonin syndrome after concomitant treatment with linezolid and meperidine." Clin Infect Dis, 46, p. 264-5
  39. Cerner Multum, Inc. "Australian Product Information."
  40. (2012) "Product Information. Methylene Blue (methylene blue)." American Regent Laboratories Inc

Drug and food interactions

Major

methadone food

Applies to: Methadone Diskets (methadone)

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of methadone. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of methadone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In 8 study subjects stabilized on methadone maintenance treatment, ingestion of regular strength grapefruit juice (200 mL one-half hour before and 200 mL simultaneously with the daily methadone dose) for five days resulted in an approximately 17% mean increase in methadone peak plasma concentration (Cmax) and systemic exposure (AUC) and a 14% mean decrease in apparent clearance for both the R(+) and S(-) enantiomers. Grapefruit juice did not affect the time to peak level (Tmax), terminal half-life, or apparent volume of distribution of methadone. No signs or symptoms of methadone toxicity or changes in intensity of withdrawal symptoms were reported in the study. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict. In addition, high dosages (particularly above 200 mg/day) and high serum levels of methadone have been associated with QT interval prolongation and torsade de pointes arrhythmia.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with methadone. Any history of alcohol or illicit drug use should be considered when prescribing methadone, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. In addition, patients treated with oral methadone should preferably avoid or limit the consumption of grapefruit juice, particularly during the induction of maintenance treatment. Given the interindividual variability in the pharmacokinetics of methadone, a significant interaction with grapefruit juice in certain patients cannot be ruled out. Patients should be advised to seek immediate 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.

References (11)
  1. Iribarne C, Berthou F, Baird S, Dreano Y, Picart D, Bail JP, Beaune P, Menez JF (1996) "Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes." Chem Res Toxicol, 9, p. 365-73
  2. Oda Y, Kharasch ED (2001) "Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation." J Pharmacol Exp Ther, 298, p. 1021-32
  3. Benmebarek M, Devaud C, Gex-Fabry M, et al. (2004) "Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone." Clin Pharmacol Ther, 76, p. 55-63
  4. Foster DJ, Somogyi AA, Bochner F (1999) "Methadone N-demethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4." Br J Clin Pharmacol, 47, p. 403-12
  5. (2023) "Product Information. Methadone Hydrochloride (methadone)." SpecGx LLC
  6. (2023) "Product Information. Methadose (methadone)." Mallinckrodt Medical Inc
  7. (2024) "Product Information. Methadone (methadone)." Martindale Pharmaceuticals Ltd
  8. (2023) "Product Information. Physeptone (methadone)." Martindale Pharmaceuticals Ltd
  9. (2023) "Product Information. Metharose (methadone)." Rosemont Pharmaceuticals Ltd
  10. (2023) "Product Information. methADONe (AFT) (methADONe)." AFT Pharmaceuticals Pty Ltd
  11. (2022) "Product Information. Apo-Methadone (methadone)." Apotex Inc

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.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
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 interaction information available.

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