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Drug Interactions between Dolophine and rasagiline

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

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Interactions between your drugs

Major

methadone rasagiline

Applies to: Dolophine (methadone) and rasagiline

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

  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
View all 40 references

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Drug and food interactions

Moderate

methadone food

Applies to: Dolophine (methadone)

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.

MANAGEMENT: Given the interindividual variability in the pharmacokinetics of methadone, a more significant interaction with grapefruit juice in certain patients cannot be ruled out. Patients treated with methadone should preferably avoid or limit the consumption of grapefruit juice, particularly during the induction of maintenance treatment.

References

  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
View all 4 references

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Moderate

rasagiline food

Applies to: rasagiline

GENERALLY AVOID: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with monoamine oxidase (MAO) inhibitors. The mechanism involves inhibition of MAO-A, the enzyme responsible for metabolizing exogenous amines such as tyramine in the gut and preventing them from being absorbed intact. Once absorbed, tyramine is metabolized to octopamine, a substance that is believed to displace norepinephrine from storage granules. Although rasagiline is a selective inhibitor of MAO-B at the recommended dosages of 0.5 or 1 mg/day, selectivity is not absolute and may diminish with increasing dosage. There were no cases of hypertensive crisis in the clinical development program associated with rasagiline treatment at 1 mg/day, in which most patients did not follow dietary tyramine restriction. However, rare cases of hypertensive crisis have been reported during the postmarketing period in patients who ingested unknown amounts of tyramine-rich foods while taking recommended dosages of rasagiline or selegiline, another MAO-B inhibitor.

Rasagiline peak plasma concentration (Cmax) and systemic exposure (AUC ) are decreased by approximately 60% and 20%, respectively, during coadministration with a high-fat meal. The time to peak concentration (Tmax) is not affected by food.

MANAGEMENT: Dietary restriction is not ordinarily required during rasagiline treatment with respect to most foods and beverages that may contain tyramine such as air-dried and fermented meats or fish, aged cheeses, most soybean products, yeast extracts, red wine, beer, and sauerkraut. However, certain foods like some of the aged cheeses (e.g., Boursault, Liederkrantz, Mycella, Stilton) may contain very high amounts of tyramine and could potentially cause a hypertensive reaction in patients taking rasagiline even at recommended dosages due to increased sensitivity to tyramine. Patients should be advised to avoid ingesting very high levels of tyramine (e.g., greater than 150 mg), and to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, confusion, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms. Rasagiline should not be used at dosages exceeding 1 mg/day (0.5 mg/day for patients with mild hepatic impairment or concomitant use of ciprofloxacin or other CYP450 1A2 inhibitors), as it can increase the risk of hypertensive crisis and other adverse reactions associated with nonselective inhibition of MAO. Rasagiline can be administered with or without food.

References

  1. Goldberg LI (1964) "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA, 190, p. 456-62
  2. Nuessle WF, Norman FC, Miller HE (1965) "Pickled herring and tranylcypromine reaction." JAMA, 192, p. 142-3
  3. Sweet RA, Liebowitz MR, Holt CS, Heimberg RG (1991) "Potential interactions between monoamine oxidase inhibitors and prescribed dietary supplements." J Clin Psychopharmacol, 11, p. 331-2
  4. McGrath PJ, Stewart JW, Quitkin FM (1989) "A possible L-deprenyl induced hypertensive reaction." J Clin Psychopharmacol, 9, p. 310-1
  5. Lefebvre H, Noblet C, Morre N, Wolf LM (1995) "Pseudo-phaeochromocytoma after multiple drug interactions involving the selective monoamine oxidase inhibitor selegiline." Clin Endocrinol (Oxf), 42, p. 95-8
  6. Zetin M, Plon L, DeAntonio M (1987) "MAOI reaction with powdered protein dietary supplement." J Clin Psychiatry, 48, p. 499
  7. Domino EF, Selden EM (1984) "Red wine and reactions." J Clin Psychopharmacol, 4, p. 173-4
  8. Tailor SA, Shulman KI, Walker SE, Moss J, Gardner D (1994) "Hypertensive episode associated with phenelzine and tap beer--a reanalysis of the role of pressor amines in beer." J Clin Psychopharmacol, 14, p. 5-14
  9. Pohl R, Balon R, Berchou R (1988) "Reaction to chicken nuggets in a patient taking an MAOI." Am J Psychiatry, 145, p. 651
  10. Ito D, Amano T, Sato H, Fukuuchi Y (2001) "Paroxysmal hypertensive crises induced by selegiline in a patient with Parkinson's disease." J Neurol, 248, p. 533-4
  11. (2006) "Product Information. Azilect (rasagiline)." Teva Pharmaceuticals USA
View all 11 references

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Moderate

methadone food

Applies to: Dolophine (methadone)

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. 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.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

References

  1. Linnoila M, Hakkinen S (1974) "Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving." Clin Pharmacol Ther, 15, p. 368-73
  2. Sturner WQ, Garriott JC (1973) "Deaths involving propoxyphene: a study of 41 cases over a two-year period." JAMA, 223, p. 1125-30
  3. Girre C, Hirschhorn M, Bertaux L, et al. (1991) "Enhancement of propoxyphene bioavailability by ethanol: relation to psychomotor and cognitive function in healthy volunteers." Eur J Clin Pharmacol, 41, p. 147-52
  4. Levine B, Saady J, Fierro M, Valentour J (1984) "A hydromorphone and ethanol fatality." J Forensic Sci, 29, p. 655-9
  5. Sellers EM, Hamilton CA, Kaplan HL, Degani NC, Foltz RL (1985) "Pharmacokinetic interaction of propoxyphene with ethanol." Br J Clin Pharmacol, 19, p. 398-401
  6. Carson DJ (1977) "Fatal dextropropoxyphene poisoning in Northern Ireland. Review of 30 cases." Lancet, 1, p. 894-7
  7. Rosser WW (1980) "The interaction of propoxyphene with other drugs." Can Med Assoc J, 122, p. 149-50
  8. Edwards C, Gard PR, Handley SL, Hunter M, Whittington RM (1982) "Distalgesic and ethanol-impaired function." Lancet, 2, p. 384
  9. Kiplinger GF, Sokol G, Rodda BE (1974) "Effect of combined alcohol and propoxyphene on human performance." Arch Int Pharmacodyn Ther, 212, p. 175-80
View all 9 references

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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.

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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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