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Drug Interactions between Etrafon Forte and procarbazine

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

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Major

amitriptyline procarbazine

Applies to: Etrafon Forte (amitriptyline / perphenazine) and procarbazine

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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Moderate

amitriptyline perphenazine

Applies to: Etrafon Forte (amitriptyline / perphenazine) and Etrafon Forte (amitriptyline / perphenazine)

MONITOR: Coadministration of a phenothiazine with a tricyclic antidepressant (TCA) may result in elevated plasma concentrations of one or both drugs as well as additive adverse effects. Most phenothiazines and TCAs have been found to undergo metabolism by CYP450 2D6, thus competitive inhibition of the enzyme may occur when more than one of these agents are administered. Although these drugs have been used together clinically, the possibility of increased risk of serious adverse effects such as central nervous system depression, tardive dyskinesia, hypotension, and prolongation of the QT interval should be considered, as many of these agents alone can and have produced these effects. In addition, excessive anticholinergic effects may occur in combination use, which can result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of anticholinergic intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures.

MANAGEMENT: Concurrent use of phenothiazines and TCAs should be approached with caution, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication (e.g., abdominal pain, fever, heat intolerance, blurred vision, confusion, hallucinations) or cardiovascular toxicity (e.g., dizziness, palpitations, arrhythmias, syncope). Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A dosage reduction in one or both drugs may be necessary if excessive adverse effects develop.

References

  1. Loga S, Curry S, Lader M (1981) "Interaction of chlorpromazine and nortriptyline in patients with schizophrenia." Clin Pharmacokinet, 6, p. 454-62
  2. Stadnyk AN, Glezos JD (1983) "Drug-induced heat stroke." Can Med Assoc J, 128, p. 957-9
  3. Bock JL, Nelson JC, Gray S, Jatlow PI (1983) "Desipramine hydroxylation: variability and effect of antipsychotic drugs." Clin Pharmacol Ther, 33, p. 322-8
  4. Gram LF, Overo KF (1972) "Drug interaction: inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man." Br Med J, 1, p. 463-5
  5. El-Yousef MK, Manier DH (1974) "Tricyclic antidepressants and phenothiazines." JAMA, 229, p. 1419
  6. Hirschowitz J, Bennett JA, Zemlan FP, Garver DL (1983) "Thioridazine effect on desipramine plasma levels." J Clin Psychopharmacol, 3, p. 376-9
  7. Vandel S, Sandoz M, Vandel B, Bonin B, Allers G, Volmat R (1986) "Biotransformation of amitriptyline in man: interaction with phenothiazines." Neuropsychobiology, 15, p. 15-9
  8. Zelman S, Guillan R (1970) "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry, 126, p. 1787-90
  9. Mann SC, Boger WP (1978) "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry, 135, p. 1097-100
  10. Warnes H, Lehmann HE, Ban TA (1967) "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J, 96, p. 1112-3
  11. Siris SG, Cooper TB, Rifkin AE, Brenner R, Lieberman JA (1982) "Plasma imipramine concentrations in patients receiving concomitant fluphenazine decanoate." Am J Psychiatry, 139, p. 104-6
  12. Johnson AL, Hollister LE, Berger PA (1981) "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry, 42, p. 313-7
  13. Lee BS (1986) "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry, 47, p. 571
  14. Moreau A, Jones BD, Banno V (1986) "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry, 31, p. 339-41
  15. Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA (1983) "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm, 2, p. 174-8
  16. Maynard GL, Soni P (1996) "Thioridazine interferences with imipramine metabolism and measurement." Ther Drug Monit, 18, p. 729-31
View all 16 references

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Moderate

procarbazine perphenazine

Applies to: procarbazine and Etrafon Forte (amitriptyline / perphenazine)

MONITOR: Coadministration of monoamine oxidase inhibitors (MAOIs) and phenothiazines may result in additive hypotensive effects and central nervous system effects such as dizziness, drowsiness, confusion, disorientation, memory loss, and seizures. MAOIs alone quite commonly produce orthostatic hypotension. This effect may stem from a gradual MAOI-induced accumulation of false neurotransmitters in peripheral adrenergic neurons that have minimal activity at alpha- and beta-adrenergic receptors, resulting in a functional block of sympathetic neurotransmission. Phenothiazines can also cause hypotension (including orthostatic hypotension), reflex tachycardia, increased pulse rate, syncope, and dizziness, particularly during initiation of treatment with parenteral doses. Low-potency agents such as chlorpromazine and thioridazine are more likely to induce these effects, which usually subside within the first couple of hours following administration. Tolerance to the hypotensive effects often develops after a few doses.

MONITOR: An increased incidence of extrapyramidal effects has been reported when some MAOIs and phenothiazines are used concomitantly. Data are limited, and the mechanism of interaction has not been established. There have also been rare reports of suspected neuroleptic malignant syndrome (NMS) in patients treated with irreversible, nonselective MAOIs and certain phenothiazines, although the role of MAOIs is uncertain. Since NMS is thought to be triggered by a sudden decrease of activity at central dopamine receptors, neuroleptics such as phenothiazines alone can cause the syndrome. In one report, a 70-year-old female inpatient of a psychiatric ward developed dyspnea, tachycardia, diffuse muscular rigidity, pyrexia, hypotension, cyanosis, hyperreflexia, coma, and a grand mal seizure while being treated with isocarboxazid and chlorpromazine. Laboratory findings included a mild neutrophil leucocytosis and elevated serum potassium and creatine phosphokinase. The patient improved within 24 hours after discontinuation of psychotropic medications and initiation of supportive measures and anticonvulsants, but she subsequently died from acute renal failure secondary to rhabdomyolysis. Another patient developed symptoms of NMS one week after initiating treatment with a tranylcypromine-trifluoperazine combination, immediately after the dose was doubled. The case was complicated by rhabdomyolysis and disseminated intravascular coagulation, but was treated successfully with dantrolene sodium and generous fluid therapy. In other reports, rare cases of fatal hyperthermia occurred during treatment with methotrimeprazine and pargyline or tranylcypromine. Again, the relationship to MAOIs is unknown, since phenothiazines alone have been associated with hyperpyrexia.

MANAGEMENT: Although often safe and effective, caution is advised during coadministration of MAOIs and phenothiazines, especially during the first few weeks of treatment. Close monitoring for development of hypotension is recommended. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Ambulatory patients should also be counseled to avoid 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. Alcohol should be avoided, since it may increase hypotensive and CNS effects.

References

  1. Pettinger WA, Soyangco FG, Oates JA (1968) "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther, 9, p. 442-7
  2. Goldberg LI (1964) "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA, 190, p. 456-62
  3. (2001) "Product Information. Phenergan (promethazine)." Wyeth-Ayerst Laboratories
  4. Ban TA (1975) "Drug interactions with psychoactive drugs." Dis Nerv Syst, 36, p. 164-6
  5. Poster DS (1978) "Procarbazine-prochlorperazine interaction: an underreported phenomenon." J Med, 9, p. 519-24
  6. (2001) "Product Information. Matulane (procarbazine)." Roche Laboratories
  7. 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
  8. Kronig MH, Roose SP, Walsh BT, Woodring S, Glassman AH (1983) "Blood pressure effects of phenelzine." J Clin Psychopharmacol, 3, p. 307-10
  9. Golwyn DH, Sevlie CP (1993) "Monoamine oxidase inhibitor hypertensive crisis headache and orthostatic hypotension." J Clin Psychopharmacol, 13, p. 77-8
  10. (2001) "Product Information. Nardil (phenelzine)." Parke-Davis
  11. (2001) "Product Information. Parnate (tranylcypromine)." SmithKline Beecham
  12. (2001) "Product Information. Marplan (isocarboxazid)." Roche Laboratories
  13. (2001) "Product Information. Tacaryl (methdilazine)." Westwood Squibb Pharmaceutical Corporation
  14. Barsa JA, Saunders JC (1964) "A comparative study of tranylcypromine and paragyline." Psychopharmacologia, 6, p. 295-8
  15. Jones EM, Dawson A (1989) "Neuroleptic malignant syndrome: a case report with post-mortem brain and muscle pathology." J Neurol Neurosurg Psychiatry, 52, p. 1006-9
View all 15 references

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Drug and food interactions

Major

procarbazine food

Applies to: procarbazine

CONTRAINDICATED: 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.

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

MANAGEMENT: In general, patients treated with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, procarbazine) should 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 MAOI 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 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. Patients should also be counseled not to use MAOIs with alcohol, and to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them.

References

  1. Pettinger WA, Soyangco FG, Oates JA (1968) "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther, 9, p. 442-7
  2. Goldberg LI (1964) "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA, 190, p. 456-62
  3. Nuessle WF, Norman FC, Miller HE (1965) "Pickled herring and tranylcypromine reaction." JAMA, 192, p. 142-3
  4. 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
  5. Walker JI, Davidson J, Zung WWK (1984) "Patient compliance with MAO Inhibitor therapy." J Clin Psychiatry, 45, p. 78-80
  6. Ban TA (1975) "Drug interactions with psychoactive drugs." Dis Nerv Syst, 36, p. 164-6
  7. Darcy PF, Griffin JP (1995) "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev, 14, p. 211-31
  8. Maxwell MB (1980) "Reexamining the dietary restrictions with procarbazine (an MAOI)." Cancer Nurs, 3, p. 451-7
  9. (2001) "Product Information. Matulane (procarbazine)." Roche Laboratories
  10. 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
  11. Zetin M, Plon L, DeAntonio M (1987) "MAOI reaction with powdered protein dietary supplement." J Clin Psychiatry, 48, p. 499
  12. Domino EF, Selden EM (1984) "Red wine and reactions." J Clin Psychopharmacol, 4, p. 173-4
  13. 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
  14. Pohl R, Balon R, Berchou R (1988) "Reaction to chicken nuggets in a patient taking an MAOI." Am J Psychiatry, 145, p. 651
  15. (2001) "Product Information. Furoxone (furazolidone)." Roberts Pharmaceutical Corporation
  16. (2001) "Product Information. Nardil (phenelzine)." Parke-Davis
  17. (2001) "Product Information. Marplan (isocarboxazid)." Roche Laboratories
  18. (2001) "Product Information. Zyvox (linezolid)." Pharmacia and Upjohn
  19. Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
View all 19 references

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Moderate

amitriptyline food

Applies to: Etrafon Forte (amitriptyline / perphenazine)

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

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Moderate

perphenazine food

Applies to: Etrafon Forte (amitriptyline / perphenazine)

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.

References

  1. Lutz EG (1976) "Neuroleptic-induced akathisia and dystonia triggered by alcohol." JAMA, 236, p. 2422-3
  2. Freed E (1981) "Alcohol-triggered-neuroleptic-induced tremor, rigidity and dystonia." Med J Aust, 2, p. 44-5

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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.