Basic Information
ID DDInter2064 and DDInter1189
Interaction Centrally-acting sympathomimetic agents (i.e., CNS stimulants), particularly the amphetamines and amphetamine derivatives, may precipitate severe hypertensive reactions and hyperpyrexia in patients treated with monoamine oxidase inhibitors (MAOIs). Death has occurred in some reported cases. The mechanism involves a synergistic sympathomimetic effect due to enhanced norepinephrine storage in adrenergic neurons (MAOI activity) and increased liberation or decreased reuptake of catecholamines (central sympathomimetic activity). MAOIs also slow amphetamine metabolism, which may potentiate amphetamine effect on the release of norepinephrine and other monoamines from adrenergic nerve endings.
Management In general, CNS stimulants should not be used concurrently with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, methylene blue, procarbazine). At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with CNS stimulants.
References [1] Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7 [2] 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 [3] Krisko I, Lewis E, Johnson JE "Severe hyperpyrexia due to tranylcypromine-amphetamine toxicity." Ann Intern Med 70 (1969): 559-64 [4] Elis J, Laurence DR, Mattie H, Prichard BN "Modification by monoamine oxidase inhibitors of the effect of some sympathomimetics on blood pressure." Br Med J 2 (1967): 75-8 [5] Goldberg LI "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA 190 (1964): 456-62 [6] Sjoqvist F "Psychotropic drugs (2) interaction between monoamine oxidase (MAO) inhibitors and other substances." Proc R Soc Med 58 (1965): 967-78 [7] Harrison WM, McGrath PJ, Stewart JW, Quitkin F "MAOIs and hypertensive crises: the role of OTC drugs." J Clin Psychiatry 50 (1989): 64-5 [8] Wright SP "Hazards with monoamine-oxidase inhibitors: a persistent problem." Lancet 1 (1978): 284-5 [9] Boakes AJ, Laurence DR, Teoh PC, Barar FS, Benedikter LT, Pritchard BN "Interactions between sympathomimetic amines and antidepressant agents in man." Br Med J 1 (1973): 311-5 [10] Dally PJ "Fatal reaction associated with tranylcypromine and methylamphetamine." Lancet 1 (1962): 1235-6 [11] Schildkraut JJ, Klerman GL, Friend DG, Greenblatt M "Biochemical and pressor effects of oral d,l-dihydroxyphenylalanine in patients pretreated with antidepressant drugs." Ann N Y Acad Sci 107 (1963): 1005-15 [12] Smookler S, Bermudez AJ "Hypertensive crisis resulting from an MAO inhibitor and an over-the-counter appetite suppressant." Ann Intern Med 11 (1982): 482-4 [13] Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6 [14] Darcy PF, Griffin JP "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev 14 (1995): 211-31 [15] 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 [16] "Product Information. Ritalin (methylphenidate)." Novartis Pharmaceuticals (2001): [17] "Product Information. Dexedrine (dextroamphetamine)." SmithKline Beecham (2001): [18] "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc (2001): [19] Markowitz JS, Patrick KS "Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder." Clin Pharmacokinet 40 (2001): 753-72 [20] "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001): [21] "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002): [22] "Product Information. Vyvanse (lisdexamfetamine)." Shire US Inc (2007):
Alternative for Furazolidone G01A
Econazole Bumetanide Ascorbic acid Clindamycin Amphotericin B Torasemide
Tioconazole Povidone-iodine Probenecid Diiodohydroxyquinoline Lactic acid
More
Alternative for Methylphenidate N06B
Caffeine Citicoline Armodafinil Modafinil Pemoline
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.