Isocarboxazid

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Marplan: 10 mg [scored]

Pharmacology

Mechanism of Action

Thought to act by increasing endogenous concentrations of epinephrine, norepinephrine, dopamine, and serotonin through inhibition of the enzyme (monoamine oxidase) responsible for the breakdown of these neurotransmitters

Use: Labeled Indications

Treatment of depression

Contraindications

Hypersensitivity to isocarboxazid or any component of the formulation; cardiovascular disease (including hypertension); cerebrovascular defect (suspected or confirmed); history of headache; history of hepatic disease or abnormal liver function tests; pheochromocytoma; severe renal impairment

Concurrent use of antihistamines, antihypertensives, bupropion, buspirone, caffeine (excessive use), CNS depressants (including ethanol and opioids), dextromethorphan, diuretics, elective surgery requiring general anesthesia (discontinue isocarboxazid ≥10 days prior to elective surgery), local vasoconstrictors, meperidine, MAO inhibitors or dibenzazepine derivatives (eg, amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, protriptyline, doxepin, carbamazepine, cyclobenzaprine, amoxapine, maprotiline, trimipramine), SSRIs or SNRIs, spinal anesthesia (hypotension may be exaggerated), sympathomimetics (including amphetamines, cocaine, phenylephrine, pseudoephedrine) or related compounds (methyldopa, reserpine, levodopa, tryptophan), or foods high in tyramine content

Bupropion: At least 14 days should elapse between MAO inhibitor discontinuation and bupropion initiation.

Buspirone: At least 10 days should elapse between isocarboxazid discontinuation and buspirone initiation.

MAO inhibitors or dibenzazepine derivatives: At least 1 week should elapse between the use of another MAO inhibitor or dibenzazepine derivative and isocarboxazid use.

Meperidine: At least 2-3 weeks should elapse between MAO inhibitor discontinuation and meperidine use.

SSRIs or SNRIs: At least 2 weeks should elapse between the discontinuation of sertraline or paroxetine and the initiation of isocarboxazid. At least 5 weeks should elapse between the discontinuation of fluoxetine and the initiation of isocarboxazid. At least 1 week should elapse between discontinuation of a SNRI and the initiation of isocarboxazid. At least 2 weeks should elapse between the discontinuation of isocarboxazid and the initiation of SSRIs.

Dosage and Administration

Dosing: Adult

Depression: Oral: Initial: 10 mg 2 times/day; may increase by 10 mg/day every 2 to 4 days to 40 mg/day by the end of the first week (divided into 2 to 4 doses). After first week, may increase by up to 20 mg/week to a maximum of 60 mg/day. May take 3 to 6 weeks to see effects. Dose should be reduced once maximum clinical effect is seen. If no response obtained within 6 weeks, additional titration is unlikely to be beneficial. Note: Use caution in patients on >40 mg/day; experience is limited.

Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms. Evidence supporting ideal taper rates is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life and MAO inhibitors may need to be tapered more conservatively. In addition for long-term treated patients, WFSBP guidelines recommend tapering over 4-6 months. If intolerable withdrawal symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (APA 2010; Bauer 2002; Haddad 2001; NCCMH 2010; Schatzberg 2006; Shelton 2001; Warner 2006).

MAO inhibitor recommendations:

Switching to or from an MAO inhibitor intended to treat psychiatric disorders:

Allow 14 days to elapse between discontinuing an alternative antidepressant without long half-life metabolites (eg, TCAs, paroxetine, fluvoxamine, venlafaxine) or MAO inhibitor intended to treat psychiatric disorders and initiation of isocarboxazid.

Allow 5 weeks to elapse between discontinuing fluoxetine (long half-life metabolites) intended to treat psychiatric disorders and initiation of isocarboxazid.

Allow at least 7 to 14 days to elapse between discontinuing isocarboxazid and initiation of an alternative antidepressant or MAO inhibitor intended to treat psychiatric disorders.

Use with other MAO inhibitors (such as linezolid or IV methylene blue):

Do not initiate isocarboxazid in patients receiving linezolid or IV methylene blue; consider other interventions for psychiatric condition.

If urgent treatment with linezolid or IV methylene blue is required in a patient already receiving isocarboxazid and potential benefits outweigh potential risks, discontinue isocarboxazid promptly and administer linezolid or IV methylene blue. Monitor for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or IV methylene blue, whichever comes first. May resume isocarboxazid 24 hours after the last dose of linezolid or IV methylene blue.

Dosing: Geriatric

Refer to adult dosing.

Dietary Considerations

Avoid tyramine-containing foods/beverages. Some examples include aged or matured cheese, air-dried or cured meats (including sausages and salamis), fava or broad bean pods, tap/draft beers, Marmite concentrate, sauerkraut, soy sauce and other soybean condiments. Food’s freshness is also an important concern; improperly stored or spoiled food can create an environment where tyramine concentrations may increase.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.

Drug Interactions

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Alcohol (Ethyl): May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Avoid combination

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Alosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Alpha-/Beta-Agonists (Indirect-Acting): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Alpha-/Beta-Agonists (Indirect-Acting). While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Avoid combination

Alpha1-Agonists: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Alpha1-Agonists. While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Avoid combination

Altretamine: May enhance the orthostatic hypotensive effect of Monoamine Oxidase Inhibitors (Antidepressant). Monitor therapy

Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amphetamines: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Amphetamines. While linezolid and tedizolid may interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: Alosetron; Ondansetron; Ramosetron. Monitor therapy

Antipsychotic Agents: Serotonergic Agents (High Risk) may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Apraclonidine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Apraclonidine. Monoamine Oxidase Inhibitors may increase the serum concentration of Apraclonidine. Avoid combination

AtoMOXetine: Monoamine Oxidase Inhibitors may enhance the neurotoxic (central) effect of AtoMOXetine. Avoid combination

Atropine (Ophthalmic): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Atropine (Ophthalmic). Avoid combination

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benzhydrocodone: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: The use of benzhydrocodone is not recommended for patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. Consider therapy modification

Beta2-Agonists: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

Betahistine: Monoamine Oxidase Inhibitors may increase the serum concentration of Betahistine. Monitor therapy

Bezafibrate: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid combination

Blood Glucose Lowering Agents: Monoamine Oxidase Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Brexanolone: Isocarboxazid may enhance the CNS depressant effect of Brexanolone. Monitor therapy

Brimonidine (Ophthalmic): Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Brimonidine (Ophthalmic). Monoamine Oxidase Inhibitors may increase the serum concentration of Brimonidine (Ophthalmic). Monitor therapy

Brimonidine (Topical): Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Brimonidine (Topical). Monoamine Oxidase Inhibitors may increase the serum concentration of Brimonidine (Topical). Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination

Buprenorphine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Avoid combination

BuPROPion: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of BuPROPion. Avoid combination

BusPIRone: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Avoid combination

Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Exceptions: Cannabidiol. Monitor therapy

CarBAMazepine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Management: Avoid concurrent use of carbamazepine during, or within 14 days of discontinuing, treatment with a monoamine oxidase inhibitor. Avoid combination

Cerebrolysin: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Monitor therapy

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination

Clemastine: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Clemastine. Monitor therapy

Cocaine (Topical): May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Monitor therapy

Codeine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Codeine. Avoid combination

COMT Inhibitors: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Consider therapy modification

Cyclobenzaprine: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Avoid combination

Cyproheptadine: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Cyproheptadine. Cyproheptadine may diminish the serotonergic effect of Monoamine Oxidase Inhibitors. Avoid combination

Dapoxetine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Avoid combination

Deutetrabenazine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Deutetrabenazine. Avoid combination

Dexmethylphenidate: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Dexmethylphenidate. Avoid combination

Dextromethorphan: Monoamine Oxidase Inhibitors may enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Avoid combination

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Diethylpropion: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Diethylpropion. Avoid combination

Dihydrocodeine: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monitor therapy

Diphenoxylate: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Avoid combination

Domperidone: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Domperidone. Monoamine Oxidase Inhibitors may diminish the therapeutic effect of Domperidone. Domperidone may diminish the therapeutic effect of Monoamine Oxidase Inhibitors. Monitor therapy

DOPamine: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of DOPamine. Management: Initiate dopamine at no greater than one-tenth (1/10) of the usual dose in patients who are taking (or have taken within the last 2 to 3 weeks) monoamine oxidase inhibitors. Monitor for an exaggerated hypertensive response to dopamine. Consider therapy modification

Doxapram: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Doxapram. Monitor therapy

Doxylamine: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Doxylamine. Management: The US manufacturer of Diclegis (doxylamine/pyridoxine) and the manufacturers of Canadian doxylamine products specifically lists use with monoamine oxidase inhibitors as contraindicated. Monitor therapy

Droxidopa: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Droxidopa. Avoid combination

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination

EPINEPHrine (Nasal): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of EPINEPHrine (Nasal). Monitor therapy

EPINEPHrine (Oral Inhalation): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Avoid combination

Epinephrine (Racemic): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Epinephrine (Racemic). Monitor therapy

EPINEPHrine (Systemic): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of EPINEPHrine (Systemic). Monitor therapy

Ergot Derivatives: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: Nicergoline. Monitor therapy

Esketamine: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Monitor therapy

FentaNYL: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Avoid combination

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Monitor therapy

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Guanethidine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Avoid combination

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Heroin: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Heroin. Avoid combination

HYDROcodone: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of HYDROcodone. Management: Consider alternatives to this combination when possible. Consider therapy modification

HYDROmorphone: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of HYDROmorphone. Avoid combination

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Indoramin: Monoamine Oxidase Inhibitors may enhance the hypotensive effect of Indoramin. Avoid combination

Iobenguane Radiopharmaceutical Products: Monoamine Oxidase Inhibitors may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Avoid combination

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Isometheptene: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Isometheptene. Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy

Lasmiditan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Levodopa-Containing Products: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Of particular concern is the development of hypertensive reactions when levodopa is used with nonselective MAOI. Avoid combination

Levomethadone: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Avoid combination

Levonordefrin: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Levonordefrin. Avoid combination

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Linezolid: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Avoid combination

Lithium: Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect of Lithium. This could result in serotonin syndrome. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes). Consider therapy modification

Lorcaserin: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Maprotiline: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Avoid combination

Meperidine: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Avoid combination

Meptazinol: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Meptazinol. Avoid combination

Mequitazine: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Mequitazine. Avoid combination

Metaraminol: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Metaraminol. Monitor therapy

Metaxalone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Methadone: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Avoid combination

Methyldopa: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Methyldopa. Avoid combination

Methylene Blue: Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Avoid combination

Methylphenidate: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Methylphenidate. Avoid combination

Metoclopramide: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Avoid combination

Mianserin: Monoamine Oxidase Inhibitors may enhance the neurotoxic effect of Mianserin. Avoid combination

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Monoamine Oxidase Inhibitors (Antidepressant): May enhance the hypertensive effect of other Monoamine Oxidase Inhibitors (Antidepressant). Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect of other Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Avoid combination

Monoamine Oxidase Inhibitors (Type B): Monoamine Oxidase Inhibitors (Antidepressant) may enhance the hypertensive effect of Monoamine Oxidase Inhibitors (Type B). Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Avoid combination

Morphine (Systemic): Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Morphine (Systemic). Avoid combination

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nefazodone: Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Avoid combination

Nefopam: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Nefopam. Avoid combination

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Norepinephrine: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Norepinephrine. Monitor therapy

Normethadone: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Normethadone. Avoid combination

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Ondansetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Opioid Agonists: Anticholinergic Agents may enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Opioid Agonists: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: FentaNYL; Meperidine; TraMADol. Monitor therapy

Opium: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Opium. Avoid combination

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

OxyCODONE: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Avoid combination

OxyMORphone: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Avoid combination

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pheniramine: May enhance the anticholinergic effect of Monoamine Oxidase Inhibitors. Avoid combination

Pholcodine: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Avoid combination

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pizotifen: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Pizotifen. Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy

Ramosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Reboxetine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Reboxetine. Avoid combination

Remifentanil: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Remifentanil. Specifically, the risk for opioid toxicity (eg, respiratory depression) may be increased. Remifentanil may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: The use of remifentanil is not recommended for patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. Consider therapy modification

Reserpine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Reserpine. Existing MAOI therapy can result in paradoxical effects of added reserpine (e.g., excitation, hypertension). Management: Monoamine oxidase inhibitors (MAOIs) should be avoided or used with great caution in patients who are also receiving reserpine. Consider therapy modification

Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Avoid combination

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Consider therapy modification

Selective Serotonin Reuptake Inhibitors: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Exceptions: Dapoxetine. Avoid combination

Serotonergic Non-Opioid CNS Depressants: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Avoid combination

Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase the serum concentration of Serotonin 5-HT1D Receptor Agonists (Triptans). Avoid combination

Serotonin/Norepinephrine Reuptake Inhibitors: Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Avoid combination

Solriamfetol: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Solriamfetol. Avoid combination

St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

SUFentanil: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Specifically, the risk for serotonin syndrome or opioid toxicities (eg, respiratory depression, coma) may be increased. Management: Sufentanil should not be used with monoamine oxidase (MAO) inhibitors (or within 14 days of stopping an MAO inhibitor) due to the potential for serotonin syndrome and/or excessive CNS depression. Avoid combination

Syrian Rue: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Tapentadol: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Specifically, the additive effects of norepinephrine may lead to adverse cardiovascular effects. Tapentadol may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Avoid combination

Tetrabenazine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Avoid combination

Tetrahydrozoline (Nasal): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Tetrahydrozoline (Nasal). Avoid combination

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tianeptine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Avoid combination

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy

TraMADol: Monoamine Oxidase Inhibitors (Antidepressant) may enhance the adverse/toxic effect of TraMADol. Specifically, the risk for serotonin syndrome/serotonin toxicity and seizures may be increased.. Avoid combination

Tricyclic Antidepressants: Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Avoid combination

Tryptophan: Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect of Tryptophan. This could result in serotonin syndrome. Avoid combination

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Valbenazine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Avoid combination

Adverse Reactions

>10%: Central nervous system: Dizziness (29%), headache (15%)

1% to 10%:

Cardiovascular: Orthostatic hypotension (4%), palpitations (2%), syncope (2%)

Central nervous system: Disturbed sleep (5%), drowsiness (4%), anxiety (2%), chills (2%), feeling of heaviness (2%), forgetfulness (2%), hyperactivity (2%), lethargy (2%), myoclonus (2%), paresthesia (2%), sedation (2%)

Dermatologic: Diaphoresis (2%)

Gastrointestinal: Xerostomia (9%), constipation (7%), nausea (6%), diarrhea (2%)

Genitourinary: Urinary frequency (2%), impotence (2%), urinary hesitancy (1%)

Neuromuscular & skeletal: Tremor (4%)

<1%, postmarketing, and/or case reports: Akathisia, ataxia, coma, dysuria, euphoria, hallucination, hematologic abnormality, melanoglossia, neuritis, sexual disorder, SIADH (syndrome of inappropriate antidiuretic hormone secretion), skin photosensitivity, spider telangiectasia, toxic amblyopia, urinary incontinence, urinary retention

Warnings/Precautions

Major psychiatric warnings:

• Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient’s family or caregiver should be instructed to closely observe the patient and communicate condition with health care provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Isocarboxazid is FDA approved for the treatment of depression in children ≥16 years of age.

The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.

Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.

Concerns related to adverse effects:

• Hypertensive crisis: Cases of hypertensive crisis (sometimes fatal) have occurred; symptoms include severe headache, nausea/vomiting, neck stiffness/soreness, photophobia, and sweating. Monitor blood pressure closely in all patients. May occur with foods/supplements high in tyramine, tryptophan, phenylalanine, or tyrosine content; treatment with phentolamine is recommended for hypertensive crisis.
• Orthostatic hypotension: May cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).

Disease-related concerns:

• Angina: MAO inhibitors may mask anginal pain.
• Diabetes: Use with caution in patients with diabetes mellitus; sensitization to the effects of insulin may occur, monitor blood glucose closely.
• Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists, especially in patients using excessive doses.
• Mania/hypomania: May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Isocarboxazid is not FDA approved for the treatment of bipolar depression.
• Renal impairment: Use with caution in patients with renal impairment; contraindicated in patients with severe impairment.
• Seizure disorder: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold.
• Thyroid dysfunction: Use with caution in patients with hyperthyroidism.

Concurrent drug therapy issues:

• High potential for interactions: Do not use with other MAO inhibitors or antidepressants. Do not use within 5 weeks of fluoxetine discontinuation or 1 week of other antidepressant discontinuation. Avoid products containing sympathomimetic stimulants, dextromethorphan, disulfiram, and meperidine. Concurrent use with antihypertensive agents may lead to exaggeration of hypotensive effects.
• Sedatives: CNS effects may be potentiated when used with other sedative drugs or ethanol.

Special populations:

• Elderly: The MAO inhibitors are effective and generally well tolerated by older patients. It is the potential interactions with tyramine-containing foods and other drugs, and their effects on blood pressure that have limited their use.
• Hyperactive or agitated patients: Use with caution in patients who are hyperactive and/or hyperexcitable.
• Surgical patients: According to the manufacturer isocarboxazid use within 10 days prior elective surgery is contraindicated. The decision to continue or withhold MAO inhibitors must be done in collaboration with the patient's psychiatrist. Currently, an MAO-safe anesthetic technique which excludes the use of meperidine and indirect-acting adrenergic agonists is recommended for patients requiring continued MAO inhibitor therapy (Huyse 2006).

Other warnings/precautions:

• Appropriate use: Isocarboxazid is not generally considered a first-line agent for the treatment of depression; it is typically used in patients who have failed to respond to other treatments.
• Discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, lightheadedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. More severe symptoms have also been associated with MAO inhibitors. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2 to 5 days after treatment discontinuation and last 7 to 14 days (APA 2010; Fav, 2006; Haddad 2001; Shelton 2001; Warner 2006).
• Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.
• Myelography: Discontinue at least 48 hours prior to myelography.

Monitoring Parameters

Renal function (baseline, periodic); liver function (baseline, periodic); blood pressure, heart rate; mood, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased)

Pregnancy

Pregnancy Considerations

Animal reproduction studies have not been conducted.

Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience dry mouth, fatigue, constipation, or trouble sleeping. Have patient report immediately to prescriber signs of depression (thoughts of suicide, anxiety, emotional instability, or confusion), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), irritability, panic attacks, mood changes, agitation, chest pain, fast heartbeat, slow heartbeat, passing out, severe nausea, vomiting, headache, abnormal heartbeat, neck rigidity, sweating a lot, enlarged pupils, sensitivity to light, seizures, or severe dizziness (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.