Isocarboxazid: uses, dosing, side effects & brands

Adverse Findings Observed in Short-Term, Placebo-Controlled Trials Systematically collected data are available from only 86 patients exposed to Marplan, of whom only 52 received doses of ≥50 mg/day, including only 11 who were dosed at ≥60 mg/day. Because of the limited experience with systematically monitored patients receiving Marplan at the higher end of the currently recommended dose range of up to 60 mg/day, caution is indicated in patients for whom a dose of 40 mg/day is exceeded ( see WARNINGS ). The table that follows enumerates the incidence, rounded to the nearest percent, of treatment emergent adverse events that occurred among 86 depressed patients who received Marplan at doses ranging from 20 to 80 mg/day in placebo-controlled trials of 6 weeks in duration. Events included are those occurring in 1% or more of patients treated with Marplan and for which the incidence in patients treated with Marplan was greater than the incidence in placebo-treated patients. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators.…

Marplan (isocarboxazid) should not be administered in combination with any of the following: MAO inhibitors or dibenzazepine derivatives; sympathomimetics (including amphetamines); some central nervous system depressants (including narcotics and alcohol); antihypertensive, diuretic, antihistaminic, sedative or anesthetic drugs, buproprion HCL, buspirone HCL, dextromethorphan, cheese or other foods with a high tyramine content; or excessive quantities of caffeine. Marplan (isocarboxazid) should not be administered to any patient with a confirmed or suspected cerebrovascular defect or to any patient with cardiovascular disease, hypertension, or history of headache. Contraindicated Patient Populations Hypersensitivity Marplan should not be used in patients with known hypersensitivity to isocarboxazid. Cerebrovascular Disorders Marplan should not be administered to any patient with a confirmed or suspected cerebrovascular defect or to any patient with cardiovascular disease or hypertension. Pheochromocytoma Marplan should not be used in the presence of pheochromocytoma, as such tumors secrete pressor substances whose metabolism may be inhibited by Marplan. Liver Disease Marplan should not be used in patients with a history of liver disease, or in those with abnormal liver function tests. Renal Impairment Marplan should not be used in patients with severe impairment of renal function. Contraindicated MAOI-Other Drug Combinations Other MAOI Inhibitors or With Dibenzazepine-Related Entities Marplan should not be administered together with, or in close proximity to, other MAO inhibitors or dibenzazepine-related entities. Hypertensive crises, severe convulsive seizures, coma, or circulatory collapse may occur in patients receiving such combinations. In patients being transferred to Marplan from another MAO inhibitor or from a dibenzazepine-related entity, a medication-free interval of at least 1 week should be allowed, after which Marplan therapy should be started using half the normal starting dosage for at least the first week of therapy. Similarly, at least 1 week should elapse between the discontinuation of Marplan and initiation of another MAO inhibitor or dibenzazepine-related entity, or the readministration of Marplan. The following list includes some other MAO inhibitors, dibenzazepine-related entities, and tricyclic antidepressants. Generic Name Trademark (Manufacturer) Other MAO Inhibitors Furazolidone Furoxone ® (Roberts Laboratories) Pargyline HCL Eutonyl ® (Abbott Laboratories) Pargyline HCL and methyclothiazide Eutron ® (Abbott Laboratories) Phenelzine sulfate Nardil ® (Parke-Davis) Procarbazine Matulane ® (Roche Laboratories) Tranylcypromine sulfate Parnate ® (SmithKline Beecham Pharmaceuticals) Dibenzazepine-Related and Other Tricyclics Amitriptyline HCL Elavil ® (Zeneca) Endep ® (Roche Products) Perphenazine and amitriptyline HCL Etrafon ® (Schering) Triavil ® (Merck Sharp & Dohme) Clomipramine hydrochloride Anafranil ® (Novartis) Desipramine HCL Norpramin ® (Hoechst Marion Roussel) Pertofrane ® (Rhône-Poulenc Rorer Pharmaceuticals) Imipramine HCL Janimine ® (Abbott Laboratories) Tofranil ® (Novartis) Nortriptyline HCL Aventyl ® (Eli Lilly & Co.) Pamelor ® (Novartis) Protripyline HCL Vivactil ® (Merck Sharp & Dohme) Doxepin HCL Adapin ® (Fisons) Sinequan ® (Pfizer) Carbamazepine Tegretol ® (Novartis) Cyclobenzaprine HCL Flexeril ® (Merck Sharp & Dohme) Amoxapine Asendin ® (Lederle) Maprotiline HCL Ludiomil ® (Novartis) Trimipramine maleate Surmontil ® (Wyeth-Ayerst Laboratories) Bupropion The concurrent administration of a MAO inhibitor and buproprion hydrochloride (Wellbutrin ® , and Zyban ® , Glaxo Wellcome) is contraindicated. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with buproprion hydrochloride. Selective Serotonin Re - uptake Inhibitors (SSRIs) Marplan should not be administered in combination with any SSRI. There have been reports of serious, sometimes fatal, reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation and confusion progressing to delirium and coma) in patients receiving fluoxetine (Prozac ® , Lilly) in combination with a monoamine oxidase inhibitor (MAOI), and in patients who have recently discontinued fluoxetine and are then started on a MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Fluoxetine and other SSRIs should therefore not be used in combination with Marplan, or within 14 days of discontinuing therapy with Marplan. As fluoxetine and its major metabolite have very long elimination half-lives, at least 5 weeks should be allowed after stopping fluoxetine before starting Marplan. At least 2 weeks should be allowed after stopping sertraline (Zoloft ® , Pfizer) or paroxetine (Paxil ® , SmithKline Beecham Pharmaceuticals) before starting Marplan. In addition, there should be an interval of least 10 days between discontinuation of Marplan and initiation of fluoxetine or other SSRIs. Buspirone Marplan should not be used in combination with buspirone HCL (Buspar ® , Bristol Myers Squibb); several cases of elevated blood pressure have been reported in patients taking MAO inhibitors who were then given buspirone HCL. At least 10 days should elapse between the discontinuation of Marplan and the institution of buspirone HCL. Serious reactions may also occur when MAO inhibitors are given with serotoninergic drugs (e.g., dexfenfluramine, fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, venlafaxine). Sympathomimetics Marplan should not be administered in combination with sympathomimetics, including amphetamines, or with over-the-counter drugs such as cold, hay fever, or weight-reducing preparations that contain vasoconstrictors. During Marplan therapy, it appears that some patients are particularly vulnerable to the effects of sympathomimetics when the activity of metabolizing enzymes is inhibited. Use of sympathomimetics and compounds such as guanethidine, methyldopa, methylphenidate, reserpine, epinephrine, norepinephrine, phenylalanine, dopamine, levodopa, tyrosine, and tryptophan with Marplan may precipitate hypertension, headache, and related symptoms. The combination of MAO inhibitors and tryptophan has been reported to cause behavioral and neurologic symptoms, including disorientation, confusion, amnesia, delirium, agitation, hypomanic signs, ataxia, myoclonus, hyperreflexia, shivering, ocular oscillations, and Babinski signs. Meperidine Meperidine should not be used concomitantly with MAO inhibitors or within 2- or 3-weeks following MAO therapy. Serious reactions have been precipitated with concomitant use, including coma, severe hypertension or hypotension, severe respiratory depression, convulsions, malignant hyperpyrexia, excitation, peripheral vascular collapse, and death. It is thought that these reactions may be mediated by accumulation of 5-HT (serotonin) consequent to MAO inhibition. Dextromethorphan Marplan should not be used in combination with dextromethorphan. The combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behavior. Cheese or Other Foods With a High Tyramine Content Hypertensive crises have sometimes occurred during Marplan therapy after ingestion of foods with a high tyramine content. In general, patients should avoid protein foods in which aging or protein breakdown is used to increase flavor. In particular, patients should be instructed not to take foods such as cheese (particularly strong or aged varieties), sour cream, Chianti wine, sherry, beer (including non-alcoholic beer), liqueurs, pickled herring, anchovies, caviar, liver, canned figs, raisins, bananas or avocados (particularly if overripe), chocolate, soy sauce, sauerkraut, the pods of broad beans (fava beans), yeast extracts, yogurt, meat…

See CONTRAINDICATIONS , WARNINGS , and PRECAUTIONS sections for information on drug interactions. Marplan should be administered with caution to patients receiving Antabuse ® (disulfiram, Wyeth-Ayerst Laboratories). In a single study, rats given high intraperitoneal doses of an MAO inhibitor plus disulfiram experienced severe toxicity, including convulsions and death. Concomitant use of Marplan and other psychotropic agents is generally not recommended because of possible potentiating effects. This is especially true in patients who may subject themselves to an overdosage of drugs. If combination therapy is needed, careful consideration should be given to the pharmacology of all agents to be used. The monoamine oxidase inhibitory effects of Marplan may persist for a substantial period after discontinuation of the drug, and this should be borne in mind when another drug is prescribed following Marplan. To avoid potentiation, the physician wishing to terminate treatment with Marplan and begin therapy with another agent should allow for an interval of 10 days.