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Marplan (Isocarboxazid) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Drug Interactions

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.

OVERDOSAGE

The lethal dose of Marplan in humans is not known. There has been one report of a fatality in a patient who ingested 400 mg of Marplan together with an unspecified amount of another drug. Symptoms: Major overdosage may be evidenced by tachycardia, hypotension, coma, convulsions, respiratory depression, sluggish reflexes, pyrexia, and diaphoresis; these signs may persist for 8 to 14 days. Treatment: General supportive measures should be used, along with immediate gastric lavage or emetics. If the latter are given, the danger of aspiration must be borne in mind. An adequate airway should be maintained, with supplemental oxygen if necessary. The mechanism by which amine-oxidase inhibitors produce hypotension is not fully understood, but there is evidence that these agents block the vascular bed response. Thus it is suggested that plasma may be of value in the management of this hypotension. Administration of pressor amines such as Levophed® (levarterenol bitartrate) may be of limited value (note that their effects may be potentiated by Marplan). Continue treatment for several days until homeostasis is restored. Liver function studies are recommended during the 4 to 6 weeks after recovery, as well as the time of overdosage.

In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center on the treatment of any overdose.

CONTRAINDICATIONS

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 Reuptake 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 or 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 extracts, meat prepared with tenderizers, or dry sausage.

Anesthetic Agents

Patients taking Marplan should not undergo elective surgery requiring general anesthesia. Also, they should not be given cocaine or local anesthesia containing sympathomimetic vasoconstrictors. The possible combined hypotensive effects of Marplan and spinal anesthesia should be kept in mind. Marplan should be discontinued at least 10 days before elective surgery.

CNS Depressants

Marplan should not be used in combination with some central nervous system depressants, such as narcotics, barbiturates, or alcohol.

Antihypertensives

Marplan should not be used in combination with antihypertensive agents, including thiazide diuretics. A marked potentiating effect on these drugs has been reported, resulting in hypotension.

Caffeine

Excessive use of caffeine in any form should be avoided in patients receiving Marplan.

DRUG ABUSE AND DEPENDENCE

Controlled Substance Class

Marplan is not a controlled substance.

Physical and Psychological Dependence

Marplan has not been systematically studied in animals or humans for its potential for abuse, tolerance, or physical dependence. There have been reports of drug dependency in patients using doses of Marplan significantly in excess of the therapeutic range. Some of these patients had a history of previous substance abuse. The following withdrawal symptoms have been reported: restlessness, anxiety, depression, confusion, hallucinations, headache, weakness, and diarrhea. Consequently, physicians should carefully evaluate Marplan patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse (eg, development of tolerance, incrementations of dose, drug-seeking behavior).

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