SURMONTIL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SURMONTIL (SURMONTIL).

How it works

Tricyclic antidepressant that inhibits the reuptake of norepinephrine and serotonin, with anticholinergic, antihistaminergic, and alpha-adrenergic blocking properties.

What the body does with it

Metabolism	Hepatic via CYP2D6 and CYP3A4; active metabolite desmethyltrimipramine.
Excretion	Renal excretion of metabolites accounts for approximately 70-80% of elimination, with about 20-30% excreted in feces via biliary elimination. Unchanged drug in urine is less than 5%.
Half-life	11-27 hours (mean approximately 20 hours) for the parent drug; the active metabolite desmethyltrimipramine has a half-life of 15-30 hours. Steady-state is achieved within 5-7 days.
Protein binding	Approximately 95% bound to plasma proteins, mainly albumin and alpha-1-acid glycoprotein.
Volume of Distribution	15-30 L/kg, indicating extensive tissue distribution and accumulation in peripheral compartments.
Bioavailability	Oral: 30-60% due to first-pass metabolism; IM: Not available in the US; not recommended for clinical use.
Onset of Action	Oral: 2-4 weeks for antidepressant effect; sedation occurs within 30-60 minutes. IM: Not routinely used for depression.
Duration of Action	Antidepressant effect persists for several weeks; sedative effects last 6-8 hours after a single dose. Withdrawal symptoms may occur if abruptly discontinued after prolonged therapy.

Classification & Brands

Action Class	Tricyclic antidepressants
Brand Substitutes	Sizonorm Plus Tablet

Dosing & administration

50-75 mg/day orally in divided doses, increase gradually to 150-300 mg/day. Maximum 300 mg/day. Single bedtime dose may be used for maintenance (50-150 mg).

Dosage form	CAPSULE
Renal impairment	No specific guidelines; use with caution in severe renal impairment (GFR <30 mL/min). Consider dose reduction based on tolerability due to potential accumulation of metabolites.
Liver impairment	Child-Pugh A: No adjustment required. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Use contraindicated (consider alternative).
Pediatric use	Not recommended for children under 12 years. For adolescents 12-18 years: 25-50 mg/day initially, increase gradually to 50-100 mg/day in divided doses. Maximum 100 mg/day.
Geriatric use	Initial dose 25-50 mg/day in divided doses, increase slowly. Maintenance often lower: 30-100 mg/day. Monitor for orthostatic hypotension, sedation, 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 SURMONTIL (SURMONTIL).

Breastfeeding	Excreted in breast milk in small amounts (M/P ratio not established). Risk of infant sedation and anticholinergic effects. Caution advised; monitor infant for drowsiness, poor feeding. Consider alternative agents.
Teratogenic Risk	First trimester: Limited human data; animal studies show no consistent teratogenicity. Second and third trimesters: Risk of neonatal withdrawal symptoms (e.g., respiratory distress, jitteriness) and anticholinergic effects if used near term. Avoid in third trimester if possible.

Warnings & precautions

■ FDA Black Box Warning

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.

Side Effect Profile

Serious Effects

Absolute Contraindications

Concurrent MAO inhibitor therapy; recent myocardial infarction; hypersensitivity to tricyclic antidepressants; narrow-angle glaucoma; prostatic hypertrophy; severe liver disease.

Clinical Precautions

Precautions

CNS depression; cardiac toxicity (QT prolongation, arrhythmias); seizures; angle-closure glaucoma; urinary retention; hyponatremia; serotonin syndrome; withdrawal symptoms; impaired cognitive/motor function.

Clinical Tips & Counseling

Drug interactions

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SURMONTIL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SURMONTIL (SURMONTIL).

How it works

Tricyclic antidepressant that inhibits the reuptake of norepinephrine and serotonin, with anticholinergic, antihistaminergic, and alpha-adrenergic blocking properties.

What the body does with it

Metabolism	Hepatic via CYP2D6 and CYP3A4; active metabolite desmethyltrimipramine.
Excretion	Renal excretion of metabolites accounts for approximately 70-80% of elimination, with about 20-30% excreted in feces via biliary elimination. Unchanged drug in urine is less than 5%.
Half-life	11-27 hours (mean approximately 20 hours) for the parent drug; the active metabolite desmethyltrimipramine has a half-life of 15-30 hours. Steady-state is achieved within 5-7 days.
Protein binding	Approximately 95% bound to plasma proteins, mainly albumin and alpha-1-acid glycoprotein.
Volume of Distribution	15-30 L/kg, indicating extensive tissue distribution and accumulation in peripheral compartments.
Bioavailability	Oral: 30-60% due to first-pass metabolism; IM: Not available in the US; not recommended for clinical use.
Onset of Action	Oral: 2-4 weeks for antidepressant effect; sedation occurs within 30-60 minutes. IM: Not routinely used for depression.
Duration of Action	Antidepressant effect persists for several weeks; sedative effects last 6-8 hours after a single dose. Withdrawal symptoms may occur if abruptly discontinued after prolonged therapy.

Classification & Brands

Action Class	Tricyclic antidepressants
Brand Substitutes	Sizonorm Plus Tablet

Dosing & administration

50-75 mg/day orally in divided doses, increase gradually to 150-300 mg/day. Maximum 300 mg/day. Single bedtime dose may be used for maintenance (50-150 mg).

Dosage form	CAPSULE
Renal impairment	No specific guidelines; use with caution in severe renal impairment (GFR <30 mL/min). Consider dose reduction based on tolerability due to potential accumulation of metabolites.
Liver impairment	Child-Pugh A: No adjustment required. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Use contraindicated (consider alternative).
Pediatric use	Not recommended for children under 12 years. For adolescents 12-18 years: 25-50 mg/day initially, increase gradually to 50-100 mg/day in divided doses. Maximum 100 mg/day.
Geriatric use	Initial dose 25-50 mg/day in divided doses, increase slowly. Maintenance often lower: 30-100 mg/day. Monitor for orthostatic hypotension, sedation, 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 SURMONTIL (SURMONTIL).

Breastfeeding	Excreted in breast milk in small amounts (M/P ratio not established). Risk of infant sedation and anticholinergic effects. Caution advised; monitor infant for drowsiness, poor feeding. Consider alternative agents.
Teratogenic Risk	First trimester: Limited human data; animal studies show no consistent teratogenicity. Second and third trimesters: Risk of neonatal withdrawal symptoms (e.g., respiratory distress, jitteriness) and anticholinergic effects if used near term. Avoid in third trimester if possible.

Warnings & precautions

■ FDA Black Box Warning

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.

Side Effect Profile

Serious Effects

Absolute Contraindications

Concurrent MAO inhibitor therapy; recent myocardial infarction; hypersensitivity to tricyclic antidepressants; narrow-angle glaucoma; prostatic hypertrophy; severe liver disease.