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Drug Interactions between Epitol and selegiline

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

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Interactions between your drugs

Major

carBAMazepine selegiline

Applies to: Epitol (carbamazepine) and selegiline

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

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Drug and food interactions

Major

selegiline food

Applies to: selegiline

GENERALLY AVOID: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with monoamine oxidase inhibitors (MAOIs). The mechanism is 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 selegiline is considered a selective inhibitor of MAO-B, the selectivity may not be absolute even at recommended dosages. Rare cases of hypertensive reactions associated with ingestion of tyramine-containing foods have been reported in patients taking the recommended daily oral dose of selegiline. Data for transdermal selegiline indicate that the 6 mg/24 hour dosage may be given safely without dietary restrictions. However, limited data are available for higher dosages.

MANAGEMENT: Patients treated with oral selegiline and transdermal selegiline (greater than 6 mg/24 hour) should preferably avoid consumption of products that contain large amounts of amines and protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, salamis, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, sauerkraut, yogurt, papaya products, meat tenderizers, fava bean pods, protein extracts, yeast extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. At least 14 days should elapse following discontinuation of selegiline therapy before these foods may be consumed. Specially designed reference materials and dietary consultation are recommended so that an appropriate and safe diet can be planned. Patients should also be advised to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, difficulty thinking, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms. The recommended dosages of selegiline should not be exceeded, as it can increase the risk of nonselective MAO inhibition and a hypertensive crisis.

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. (2001) "Product Information. Eldepryl (selegiline)." Somerset Pharmaceuticals Inc
  6. 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
  7. Zetin M, Plon L, DeAntonio M (1987) "MAOI reaction with powdered protein dietary supplement." J Clin Psychiatry, 48, p. 499
  8. Domino EF, Selden EM (1984) "Red wine and reactions." J Clin Psychopharmacol, 4, p. 173-4
  9. 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
  10. Pohl R, Balon R, Berchou R (1988) "Reaction to chicken nuggets in a patient taking an MAOI." Am J Psychiatry, 145, p. 651
  11. 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
  12. (2006) "Product Information. Emsam (selegiline)." Bristol-Myers Squibb
View all 12 references

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Moderate

carBAMazepine food

Applies to: Epitol (carbamazepine)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.

References

  1. (2002) "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals
  2. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77

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Moderate

selegiline food

Applies to: selegiline

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of central nervous system (CNS)-active agents. Use in combination may result in additive CNS depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled against driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  5. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 5 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.

Further information

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