MARPLAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MARPLAN (MARPLAN).

How it works

Irreversible, non-selective monoamine oxidase inhibitor (MAOI) that increases synaptic concentrations of monoamine neurotransmitters (serotonin, norepinephrine, dopamine, tyramine) by inhibiting their oxidative deamination.

What the body does with it

Metabolism	Hepatic metabolism primarily via acetylation (N-acetyltransferase) to inactive metabolites; undergoes first-pass metabolism.
Excretion	Primarily renal excretion of metabolites, with less than 1% excreted unchanged; approximately 60-70% of a dose is recovered in urine within 24 hours, mainly as isocarboxazide metabolites; minor biliary/fecal elimination accounts for the remainder.
Half-life	Terminal elimination half-life ranges from 2.5 to 4 hours, but due to irreversible inhibition of monoamine oxidase (MAO), the pharmacodynamic effect persists for up to 2-3 weeks after discontinuation until new enzyme synthesis occurs.
Protein binding	Approximately 90-95% bound to plasma proteins, particularly albumin.
Volume of Distribution	Estimated volume of distribution is approximately 1.5-2 L/kg, indicating extensive tissue distribution and penetration into the central nervous system.
Bioavailability	Oral bioavailability is essentially complete due to high absorption, but first-pass metabolism reduces systemic availability to approximately 50-60% of an oral dose.
Onset of Action	Oral: Clinical antidepressant effect typically begins after 7-14 days of daily dosing, though some improvement may be noted within 1 week; full therapeutic benefit may require 4-6 weeks.
Duration of Action	Pharmacodynamic effect (MAO inhibition) persists for 2-3 weeks after cessation of therapy due to irreversible enzyme inhibition; pharmacokinetic half-life is short, but clinical duration is prolonged. Dosing is typically once or twice daily.

Classification & Brands

Dosing & administration

10 mg orally 3 times daily initially, increased to 20 mg 3 times daily; maintenance 10-20 mg 3 times daily.

Dosage form	TABLET
Renal impairment	No specific recommendations; use with caution in severe renal impairment (GFR <30 mL/min) due to potential accumulation.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh class C). In mild-moderate impairment (Child-Pugh A/B), reduce dose by 50% or increase dosing interval.
Pediatric use	Not recommended for use in pediatric patients.
Geriatric use	Initiate at 10 mg per day orally, increase slowly to lowest effective dose; monitor for hypotension and anticholinergic effects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MARPLAN (MARPLAN).

Breastfeeding	Excreted into breast milk; M/P ratio unknown. Potential for serious adverse reactions in nursing infants (e.g., MAOI effects). Decision to discontinue nursing or drug based on importance to mother.
Teratogenic Risk	Pregnancy Category C. Animal studies have shown adverse effects, but no adequate human studies in first trimester. Potential risk of fetal malformations; use only if benefit outweighs risk. In late pregnancy, may cause neonatal withdrawal or respiratory depression.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants. Also risk of hypertensive crisis with tyramine-rich foods or concomitant sympathomimetic drugs.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to isocarboxazid or any MAOI","Pheochromocytoma","Concurrent use of other MAOIs, SSRIs, SNRIs, tricyclic antidepressants, bupropion, or meperidine","Concurrent use of sympathomimetics (e.g., amphetamines, methylphenidate, decongestants)","Uncontrolled hypertension","Elective surgery requiring general anesthesia (relative)","Tyramine-rich diet (absolute during treatment and for 2 weeks after discontinuation)"]

Clinical Precautions

Precautions

["Hypertensive crisis with tyramine-rich foods or pressor amines","Serotonin syndrome with other serotonergic drugs","Suicidal ideation and behavior","Activation of mania/hypomania in bipolar disorder","Seizure threshold lowering","Dietary restrictions required (avoid aged cheeses, cured meats, fermented foods, alcoholic beverages)","Avoid concurrent MAOIs or within 14 days of discontinuing other MAOIs"]

Clinical Tips & Counseling

Drug interactions

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MARPLAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MARPLAN (MARPLAN).

How it works

What the body does with it

Metabolism	Hepatic metabolism primarily via acetylation (N-acetyltransferase) to inactive metabolites; undergoes first-pass metabolism.
Excretion	Primarily renal excretion of metabolites, with less than 1% excreted unchanged; approximately 60-70% of a dose is recovered in urine within 24 hours, mainly as isocarboxazide metabolites; minor biliary/fecal elimination accounts for the remainder.
Half-life	Terminal elimination half-life ranges from 2.5 to 4 hours, but due to irreversible inhibition of monoamine oxidase (MAO), the pharmacodynamic effect persists for up to 2-3 weeks after discontinuation until new enzyme synthesis occurs.
Protein binding	Approximately 90-95% bound to plasma proteins, particularly albumin.
Volume of Distribution	Estimated volume of distribution is approximately 1.5-2 L/kg, indicating extensive tissue distribution and penetration into the central nervous system.
Bioavailability	Oral bioavailability is essentially complete due to high absorption, but first-pass metabolism reduces systemic availability to approximately 50-60% of an oral dose.
Onset of Action	Oral: Clinical antidepressant effect typically begins after 7-14 days of daily dosing, though some improvement may be noted within 1 week; full therapeutic benefit may require 4-6 weeks.
Duration of Action	Pharmacodynamic effect (MAO inhibition) persists for 2-3 weeks after cessation of therapy due to irreversible enzyme inhibition; pharmacokinetic half-life is short, but clinical duration is prolonged. Dosing is typically once or twice daily.

Classification & Brands

Dosing & administration

10 mg orally 3 times daily initially, increased to 20 mg 3 times daily; maintenance 10-20 mg 3 times daily.

Dosage form	TABLET
Renal impairment	No specific recommendations; use with caution in severe renal impairment (GFR <30 mL/min) due to potential accumulation.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh class C). In mild-moderate impairment (Child-Pugh A/B), reduce dose by 50% or increase dosing interval.
Pediatric use	Not recommended for use in pediatric patients.
Geriatric use	Initiate at 10 mg per day orally, increase slowly to lowest effective dose; monitor for hypotension and anticholinergic effects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MARPLAN (MARPLAN).

Breastfeeding	Excreted into breast milk; M/P ratio unknown. Potential for serious adverse reactions in nursing infants (e.g., MAOI effects). Decision to discontinue nursing or drug based on importance to mother.
Teratogenic Risk	Pregnancy Category C. Animal studies have shown adverse effects, but no adequate human studies in first trimester. Potential risk of fetal malformations; use only if benefit outweighs risk. In late pregnancy, may cause neonatal withdrawal or respiratory depression.
Fetal Monitoring