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Drug Interactions between amitriptyline and rasagiline

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

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Major

amitriptyline rasagiline

Applies to: amitriptyline and rasagiline

CONTRAINDICATED: Coadministration of monoamine oxidase inhibitors (MAOIs) and dibenzazepine derivatives (e.g., tricyclic and tetracyclic antidepressants, cyclobenzaprine, carbamazepine) may produce significant adverse reactions including nausea, vomiting, flushing, dizziness, tremor, myoclonus, rigidity, diaphoresis, hyperthermia, autonomic instability, hypertensive crises, disseminated intravascular coagulation, severe convulsive seizures, coma, and death. The exact mechanism of interaction is unknown, but may involve excessive serotonergic activity in the central nervous system (i.e., serotonin syndrome). Clinically, the interaction has been reported primarily in patients treated with MAOIs (including reversible, irreversible, selective, and nonselective) and tricyclic antidepressants, especially imipramine and clomipramine, which are the most potent serotonin reuptake inhibitors of the class. Other dibenzazepine-type drugs may also interact based on their structural and pharmacologic similarities to the tricyclic antidepressants, although data are limited. An isolated case has been reported for phenelzine and cyclobenzaprine, while no cases have been reported with carbamazepine. On the contrary, there have been published reports citing a lack of interaction as well as successful use of carbamazepine with MAOIs.

MANAGEMENT: In general, dibenzazepine derivatives should not be used concurrently with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, methylene blue, procarbazine). At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with tricyclic antidepressants, and vice versa. Although it remains controversial, some experts have suggested that certain MAOIs and tricyclic antidepressants (except imipramine and clomipramine) may be used together for the treatment of refractory depression under special circumstances and close supervision, with the following empirical guidelines: the current tricyclic or MAOI should be discontinued for 10 to 14 days; both drugs should then be started at low dosages; the drugs should not be administered parenterally; dose changes should be made in small increments; serotonin reuptake inhibitors must not be used concurrently; and patients should be closely monitored for signs of adverse serotonergic effects.

References

  1. Joffe RT, Post RM, Uhde TW "Lack of pharmacokinetic interaction of carbamazepine with tranylcypromine." Arch Gen Psychiatry 42 (1985): 738
  2. de la Fuente JR, Berlanga C, Leon-Andrade C "Mania induced by tricyclic-MAOI combination therapy in bipolar treatment-resistant disorder: case reports." J Clin Psychiatry 47 (1986): 40-1
  3. Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7
  4. Schulz R, Antonin KH, Hoffmann E, et al. "Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline." Clin Pharmacol Ther 46 (1989): 528-36
  5. Kline SS, Mauro LS, Scala-Bennett DM, Zick D "Serotonin syndrome versus neuroleptic malignant death syndrome as a cause of death." Clin Pharm 8 (1989): 510-4
  6. Goldberg LI "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA 190 (1964): 456-62
  7. Wright SP "Hazards with monoamine-oxidase inhibitors: a persistent problem." Lancet 1 (1978): 284-5
  8. Nierenberg DW, Semprebon M "The central nervous system serotonin syndrome." Clin Pharmacol Ther 53 (1993): 84-8
  9. Graham PM, Potter JM, Paterson J "Combination monoamine oxidase inhibitor/tricyclic antidepressants interaction." Lancet 2 (1982): 440
  10. Spiker DG, Pugh DD "Combining tricyclic and monoamine oxidase inhibitor antidepressants." Arch Gen Psychiatry 33 (1976): 828-30
  11. White K, Pistole T, Boyd JL "Combined monoamine oxidase inhibitor-tricyclic antidepressant treatment: a pilot study." Am J Psychiatry 137 (1980): 1422-5
  12. White K, Simpson G "Combined MAOI-tricyclic antidepressant treatment: a reevaluation." J Clin Psychopharmacol 1 (1981): 264-82
  13. Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13
  14. Tackley RM, Tregaskis B "Fatal disseminated intravascular coagulation following a monoamine oxidase inhibitor/tricyclic interaction." Anaesthesia 42 (1987): 760-3
  15. Lader M "Combined use of tricyclic antidepressants and monoamine oxidase inhibitors." J Clin Psychiatry 44 (1983): 20-4
  16. Pascual J, Combarros O, Berciano J "Partial status epilepticus following single low dose of chlorimipramine in a patient on MAO-inhibitor treatment." Clin Neuropharmacol 10 (1987): 565-7
  17. "Product Information. Eldepryl (selegiline)." Somerset Pharmaceuticals Inc PROD (2001):
  18. "Product Information. Flexeril (cyclobenzaprine)." Merck & Co., Inc PROD (2001):
  19. Lefebvre H, Noblet C, Morre N, Wolf LM "Pseudo-phaeochromocytoma after multiple drug interactions involving the selective monoamine oxidase inhibitor selegiline." Clin Endocrinol (Oxf) 42 (1995): 95-8
  20. Limbird LE eds., Gilman AG, Hardman JG "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: McGraw-Hill (1995):
  21. "Product Information. Matulane (procarbazine)." Roche Laboratories PROD (2001):
  22. De Vita VT, Hahn MA, Oliverio VT "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med 120 (1965): 561-5
  23. Fischer P "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol 15 (1995): 440-2
  24. Yatham LN, Barry S, Mobayed M, Dinan TG "Is the carbamazepine-phenelzine combination safe?." Am J Psychiatry 147 (1990): 367
  25. Feighner JP, Herbstein J, Damlouji N "Combined MAOI, TCA, and direct stimulant therapy of treatment- resistant depression." J Clin Psychiatry 46 (1985): 206-9
  26. Zetin M "Combined use of trimipramine and phenelzine in depression." J Nerv Ment Dis 170 (1982): 246-7
  27. Waghray SN, Francis K "Epilepsy as an adverse reaction to combined therapy of MAOIs and tricyclics." J R Soc Med 77 (1984): 346
  28. Kay DW, Garside RF, Fahy TJ "A double-blind trial of phenelzine and amitriptyline in depressed out- patients. A possible differential effect of the drugs on symptoms." Br J Psychiatry 123 (1973): 63-7
  29. Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763
  30. "Product Information. Furoxone (furazolidone)." Roberts Pharmaceutical Corporation PROD (2001):
  31. Dardennes RM, Even C, Ballon N, Bange F "Serotonin syndrome caused by a clomipramine-moclobemide interaction." J Clin Psychiatry 59 (1998): 382-3
  32. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG "Serotonin syndrome resulting from drug interactions." Med J Aust 169 (1998): 523-5
  33. "Product Information. Nardil (phenelzine)." Parke-Davis PROD (2001):
  34. "Product Information. Parnate (tranylcypromine)." SmithKline Beecham PROD (2001):
  35. "Product Information. Marplan (isocarboxazid)." Roche Laboratories PROD (2001):
  36. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
  37. Otte W, Birkenhager TK, van den Broek WW "Fatal interaction between tranylcypromine and imipramine." Eur Psychiatry 18 (2003): 264-5
  38. Boyer EW, Shannon M "The serotonin syndrome." N Engl J Med 352 (2005): 1112-20
  39. "Product Information. Emsam (selegiline)." Bristol-Myers Squibb (2006):
  40. Ketter TA, Post RM, Parekh PI, Worthington K "Addition of monoamine oxidase inhibitors to carbamazepine: preliminary evidence of safety and antidepressant efficacy in treatment-resistant depression." J Clin Psychiatry 56 (1995): 471-5
  41. Lydiard RB, White D, Harvey B, Taylor A "Lack of pharmacokinetic interaction between tranylcypromine and carbamazepine." J Clin Psychopharmacol 7 (1987): 360
  42. "Product Information. Azilect (rasagiline)." Teva Pharmaceuticals USA (2006):
  43. Keegan MT, Brown DR, Rabinstein AA "Serotonin syndrome from the interaction of cyclobenzaprine with other serotoninergic drugs." Anesth Analg 103 (2006): 1466-8
  44. "Product Information. Methylene Blue (methylene blue)." American Regent Laboratories Inc (2012):
View all 44 references

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Drug and food interactions

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

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Moderate

amitriptyline food

Applies to: amitriptyline

GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.

References

  1. Dorian P, Sellers EM, Reed KL, et al. "Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction." Eur J Clin Pharmacol 25 (1983): 325-31
  2. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  3. Sandoz M, Vandel S, Vandel B, Bonin B, Allers G, Volmat R "Biotransformation of amitriptyline in alcoholic depressive patients." Eur J Clin Pharmacol 24 (1983): 615-21
  4. Ciraulo DA, Barnhill JG, Jaffe JH "Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers." Clin Pharmacol Ther 43 (1988): 509-18
  5. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M "Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving." Clin Pharmacol Ther 17 (1975): 515-22
  6. Ciraulo DA, Barnhill JG, Jaffe JH, Ciraulo AM, Tarmey MF "Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls." J Stud Alcohol 51 (1990): 366-72
  7. Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA "Imipramine disposition in alcoholics." J Clin Psychopharmacol 2 (1982): 2-7
View all 7 references

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Therapeutic duplication warnings

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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.

Further information

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