Marplan - General Information:

An MAO inhibitor that is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in the treatment of panic disorder and the phobic disorders. (From AMA, Drug Evaluations Annual, 1994, p311)

Pharmacology:

Marplan is a non-selective hydrazine monoamine oxidase (MAO) inhibitor used to treat depression. In vivo and in vitro studies demonstrated inhibition of MAO in the brain, heart, and liver. Depression is a complicated disease that is not fully understood. It is thought that depression may be linked to an imbalance of chemicals within the brain. When depression occurs, there may be a decrease in the amount of chemicals released from nerve cells in the brain. These chemicals are called monoamines. Monoamines are broken down by a chemical called monoamine oxidase. Marplan prevents monoamine oxidase from breaking down the monoamines. This results in an increased amount of active monoamines in the brain. By increasing the amount of monoamines in the brain, the imbalance of chemicals thought to be caused by depression is altered. This helps relieve the symptoms of depression.

Marplan for patients

Patients should be instructed to report promptly the occurrence of headache or other unusual symptoms, i. e., palpitation and or tachycardia, a sense of constriction in the throat or chest, sweating, dizziness, neck stiffness, nausea, or vomiting. Patients should be warned against eating the foods listed under CONTRAINDICATIONS while on Marplan therapy and should also be told not to drink alcoholic beverages. The patient should also be warned about the possibility of hypotension and faintness, as well as drowsiness sufficient to impair performance of potentially hazardous tasks, such as driving a car or operating machinery.

Patients should also be cautioned not to take concomitant medications, whether prescription or over-the- counter drugs such as cold, hay fever, or weight-reducing preparations, without the advice of a physician. They should be advised not to consume excessive amounts of caffeine in any form. Likewise, they should inform their physicians and their dentist about the use of Marplan.

Marplan Interactions

Isocarboxazid 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 Isocarboxazid 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 Isocarboxazid may persist for a substantial period after discontinuation of the drug, and this should be borne in mind when another drug is prescribed following Isocarboxazid. To avoid potentiation, the physician wishing to terminate treatment with Isocarboxazid and begin therapy with another agent should allow for an interval of 10 days.

Marplan 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. Patients with Severe/ Frequent Headaches Patients with severe or frequent headaches should not be considered candidates for therapy with Marplan, because headaches during therapy may be the first symptom of a hypertensive reaction to the drug.

Contraindicated MAOI-Other Drug Combinations

Other MAO 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 an MAO inhibitor and bupropion 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 bupropion 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 an 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 at 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.

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 p.d. 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.

Additional information about Marplan

Marplan Indication: Marplan is used to treat depression, especially when the patient is excitable or suffering from phobias (fears).
Mechanism Of Action: Marplan works by irreversibly blocking the action of a chemical substance known as monoamine oxidase (MAO) in the nervous system. MAO subtypes A and B are involved in the metabolism of serotonin and catecholamine neurotransmitters such as epinephrine, norepinephrine, and dopamine. Marplan, as a nonselective MAO inhibitor, binds irreversibly to monoamine oxidase–A (MAO-A) and monoamine oxidase–B (MAO-B). The reduced MAO activity results in an increased concentration of these neurotransmitters in storage sites throughout the central nervous system (CNS) and sympathetic nervous system. This increased availability of one or more monoamines is the basis for the antidepressant activity of MAO inhibitors.
Drug Interactions: Acetohexamide The MAO inhibitor increases the effect of hypoglycemic agent
Chlorpropamide The MAO inhibitor increases the effect of hypoglycemic agent
Ginseng Ginseng increases the effect and toxicity of MAOI
Gliclazide The MAO inhibitor increases the effect of hypoglycemic agent
Glipizide The MAO inhibitor increases the effect of hypoglycemic agent
Glisoxepide The MAO inhibitor increases the effect of hypoglycemic agent
Glibenclamide The MAO inhibitor increases the effect of hypoglycemic agent
Glycodiazine The MAO inhibitor increases the effect of hypoglycemic agent
Insulin The MAO inhibitor increases the effect of hypoglycemic agent
Rizatriptan The MAO inhibitor increases the effect and toxicity of rizatriptan
Tolazamide The MAO inhibitor increases the effect of hypoglycemic agent
Tolbutamide The MAO inhibitor increases the effect of hypoglycemic agent
Zolmitriptan MAO inhibitor increases the effects and toxicity of 5-HT agonist
Almotriptan MAO inhibitor increases the effects and toxicity of 5-HT agonist
Naratriptan MAO inhibitor increases the effects and toxicity of 5-HT agonist
Sumatriptan MAO inhibitor increases the effects and toxicity of 5-HT agonist
Altretamine Risk of severe hypotension
Amitriptyline Possibility of severe adverse effects
Amoxapine Possibility of severe adverse effects
Clomipramine Possibility of severe adverse effects
Desipramine Possibility of severe adverse effects
Doxepin Possibility of severe adverse effects
Imipramine Possibility of severe adverse effects
Guanethidine The agent decreases the effect of guanethidine
Nortriptyline Possibility of severe adverse effects
Protriptyline Possibility of severe adverse effects
Trimipramine Possibility of severe adverse effects
Venlafaxine Possible severe adverse reaction with this combination
L-Tryptophan Possible severe adverse reaction with this combination
Sibutramine Possible serotoninergic syndrome with this combination
Sertraline Possible severe adverse reaction with this combination
Paroxetine Possible severe adverse reaction with this combination
Nefazodone Possible severe adverse reaction with this combination
Mirtazapine Possible severe adverse reaction with this combination
Midodrine Possible hypertensive crisis with this combination
Methylphenidate Possible hypertensive crisis with this combination
Fluvoxamine Possible severe adverse reaction with this combination
Fluoxetine Possible severe adverse reaction with this combination
Escitalopram Possible severe adverse reaction with this combination
Duloxetine Possible severe adverse reaction with this combination
Citalopram Possible severe adverse reaction with this combination
Atomoxetine Possible severe adverse reaction with this combination
Bupropion Possible severe adverse reaction with this combination
Entacapone Possible hypertensive crisis with this combination
Tolcapone Possible hypertensive crisis with this combination
Amphetamine Possible hypertensive crisis
Benzphetamine Possible hypertensive crisis
Buspirone Possible blood pressure elevation
Dexfenfluramine Possible hypertensive crisis
Dextroamphetamine Possible hypertensive crisis
Diethylpropion Possible hypertensive crisis
Fenfluramine Possible hypertensive crisis
Levodopa Possible hypertensive crisis
Mazindol Possible hypertensive crisis
Methamphetamine Possible hypertensive crisis
Phendimetrazine Possible hypertensive crisis
Phenmetrazine Possible hypertensive crisis
Phentermine Possible hypertensive crisis
Tramadol Increased risk of seizures and serotonin syndrome
Dextromethorphan Possible severe adverse reaction
Dobutamine Increased arterial pressure
Dopamine Increased arterial pressure
Donepezil Possible antagonism of action
Ephedra Increased arterial pressure
Ephedrine Increased arterial pressure
Epinephrine Increased arterial pressure
Pseudoephedrine Increased arterial pressure
Fenoterol Increased arterial pressure
Galantamine Possible antagonism of action
Isoproterenol Increased arterial pressure
Methotrimeprazine Possible severe adverse reaction with this combination
Meperidine Potentially fatal adverse effects
Mephentermine Increased arterial pressure
Metaraminol Increased arterial pressure
Methoxamine Increased arterial pressure
Norepinephrine Increased arterial pressure
Orciprenaline Increased arterial pressure
Phenylephrine Increased arterial pressure
Phenylpropanolamine Increased arterial pressure
Pirbuterol Increased arterial pressure
Procaterol Increased arterial pressure
Rivastigmine Possible antagonism of action
Salbutamol Increased arterial pressure
Terbutaline Increased arterial pressure
Tetrabenazine CNS stimulation, hypertensive upsurge with this combination
Food Interactions: Take without regard to meals, avoid tyramine, caffeine and alcohol.
Generic Name: Isocarboxazid
Synonyms: Isocarboxazide [Inn-French]; Isocarboxazide; Isocarboxazida [Inn-Spanish]; Isocarboxazidum [Inn-Latin]; Isocarboxyzid; Isocarbossazide [Dcit]; Isocarbonazid
Drug Category: Antidepressants; Monoamine Oxidase Inhibitors
Drug Type: Small Molecule; Approved
Other Brand Names containing Isocarboxazid: BMIH; Benazide; Enerzer; Maraplan; Marplan; Marplon;
Absorption: Well absorbed from the gastrointestinal tract.
Toxicity (Overdose): Signs of overdose include severe anxiety, confusion, convulsions, cool clammy skin, severe dizziness, severe drowsiness, fast and irregular pulse, fever, hallucinations, severe headache, high or low blood pressure, hyperactive reflexes, muscle stiffness, respiratory depression or failure, slowed reflexes, sweating, severe trouble in sleeping, and unusual irritability.
Protein Binding: Not Available
Biotransformation: Hepatic and rapid (by oxidation).
Half Life: Not Available
Dosage Forms of Marplan: Tablet Oral
Chemical IUPAC Name: 5-methyl-N'-(phenylmethyl)-1,2-oxazole-3-carbohydrazide
Chemical Formula: C12H13N3O2
Isocarboxazid on Wikipedia: http://en.wikipedia.org/wiki/Isocarboxazid
Organisms Affected: Humans and other mammals

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Fri, 20 Jan 2012
Re - Marplan is GREAT - Phillipa - Psycho-Babble
Marplan is GREAT. Ron Hill, posted by Phillipa on January 29, 2012, at 18:27:46. Ron hi how are you doing. Let me know. My bipolar II ultra rapid cycling finally stopped a year-and-a-half ago when I added Valdoxan (agomelatine) to my med combo.
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Marplan is GREAT. In reply to Marplan is GREAT. After two years since your start-up on Marplan, is it still working well for you. I'm finding Marplan to be the most stable, reliable and (in some ways) most effective of the three (and it certainly has the fewest side-effects).
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