MARPLAN- isocarboxazid tablet
Validus Pharmaceuticals LLC
brand of isocarboxazid t ablets
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Marplan or any other antidepressant in a child, adolescent or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Marplan is not approved for use in pediatric patients (see Warnings: Clinical Worsening and Suicide Risk , Precautions: Information for Patients , and Precautions: Pediatric Use ) .
Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials.
Marplan (isocarboxazid), a monoamine oxidase inhibitor, is available for oral administration in 10-mg tablets. Each tablet also contains lactose, corn starch, povidone, D&C Red No. 27, FD&C Yellow No. 6, and magnesium stearate. Chemically, isocarboxazid is 5-methyl-3-isoxazolecarboxylic acid 2-benzylhydrazide. The structural formula is:
Isocarboxazid is a colorless, crystalline substance with very little taste.
Isocarboxazid is a non-selective hydrazine monoamine oxidase (MAO) inhibitor. In vivo and in vitro studies demonstrated inhibition of MAO in the brain, heart, and liver. The mechanism by which MAO inhibitors act as antidepressants is not fully understood, but it is thought to involve the elevation of brain levels of biogenic amines. However, MAO is a complex enzyme system, widely distributed throughout the body, and drugs that inhibit MAO in the laboratory are associated with a number of clinical effects. Thus, it is unknown whether MAO inhibition per se, other pharmacologic actions, or an interaction of both is responsible for the antidepressant effects observed.
Marplan pharmacokinetic information is not available.
Clinical Efficacy Data
The effectiveness of Marplan was demonstrated in two 6-week placebo-controlled studies conducted in adult outpatients with depressive symptoms that corresponded to the DSM-IV category of major depressive disorder. The patients often also had signs and symptoms of anxiety (anxious mood, panic, and/or phobic symptoms). Patients were initiated with a dose of 10 mg bid, with increases every 2 to 4 days, as tolerated, until a therapeutic effect was achieved, up to a maximum dose of 80 mg/day. Doses were administered on a divided schedule ranging from 2 to 4 times a day. The mean dose overall for both studies was approximately 40 mg/day, with very few patients receiving doses greater than 60 mg/day. In both studies at the end of 6 weeks, patients receiving Marplan had significantly greater reduction in signs and symptoms of depression evaluated by the Hamilton Depression Scale, for both the Total Score and the Depressed Mood Score, than patients who received placebo.
Marplan Indications and Usage
Marplan is indicated for the treatment of depression. Because of its potentially serious side effects, Marplan is not an antidepressant of first choice in the treatment of newly diagnosed depressed patients.
The efficacy of Marplan in the treatment of depression was established in 6-week controlled trials of depressed outpatients. These patients had symptoms that corresponded to the DSM-IV category of major depressive disorder; however, they often also had signs and symptoms of anxiety (anxious mood, panic, and/or phobic symptoms) ( see CLINICAL PHARMACOLOGY).
A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation.
The antidepressant effectiveness of Marplan in hospitalized depressed patients, or in endogenomorphically retarded and delusionally depressed patients, has not been adequately studied.
The effectiveness of Marplan in long-term use, that is, for more than 6 weeks, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use Marplan for extended periods should periodically evaluate the long-term usefulness of the drug for the individual patient.
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
Marplan should not be used in patients with known hypersensitivity to isocarboxazid.
Marplan should not be administered to any patient with a confirmed or suspected cerebrovascular defect or to any patient with cardiovascular disease or hypertension.
Marplan should not be used in the presence of pheochromocytoma, as such tumors secrete pressor substances whose metabolism may be inhibited by Marplan.
Marplan should not be used in patients with a history of liver disease, or in those with abnormal liver function tests.
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)|
|Nortriptyline HCL||Aventyl® (Eli Lilly & Co.)|
|Protripyline HCL||Vivactil® (Merck Sharp & Dohme)|
|Doxepin HCL||Adapin® (Fisons)|
|Cyclobenzaprine HCL||Flexeril® (Merck Sharp & Dohme)|
|Maprotiline HCL||Ludiomil® (Novartis)|
|Trimipramine maleate||Surmontil® (Wyeth-Ayerst Laboratories)|
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.
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.
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