JANIMINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for JANIMINE (JANIMINE).

How it works

Imipramine inhibits the reuptake of norepinephrine and serotonin at nerve terminals, potentiating their neurotransmission. It also has anticholinergic and antihistaminergic effects.

What the body does with it

Metabolism	Primarily metabolized by hepatic cytochrome P450 enzymes, mainly CYP2D6 and CYP1A2, to active metabolite desipramine and other inactive metabolites.
Excretion	Primarily renal (70-80% as metabolites, 5% unchanged); biliary/fecal (20-30% as metabolites).
Half-life	5-15 hours (terminal elimination half-life); clinical context: requires twice-daily dosing for steady state.
Protein binding	~80% bound to plasma proteins (primarily albumin).
Volume of Distribution	1.5-2.5 L/kg; clinical meaning: extensive tissue distribution, not limited to extracellular fluid.
Bioavailability	Subcutaneous: ~80%; oral: 0% (not orally active due to first-pass metabolism).
Onset of Action	Subcutaneous: 30-60 minutes; intravenous: 15-30 minutes.
Duration of Action	8-12 hours (subcutaneous); clinical notes: duration may be prolonged in renal impairment.

Classification & Brands

Dosing & administration

25-50 mg orally 2-4 times daily; maintenance 150 mg/day divided

Dosage form	TABLET
Renal impairment	GFR >50 mL/min: no adjustment; GFR 10-50 mL/min: 50% of dose; GFR <10 mL/min: 25% of dose
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use
Pediatric use	1-3 mg/kg/day in 2-3 divided doses; max 5 mg/kg/day
Geriatric use	Initiate at 10-25 mg/day; increase slowly; monitor for 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 JANIMINE (JANIMINE).

Breastfeeding	Contraindicated; excreted into breast milk with M/P ratio approximately 0.5. Potential for neonatal adverse effects (cardiac, respiratory, neurological).
Teratogenic Risk	Pregnancy category D. First trimester: associated with Ebstein's anomaly and other cardiovascular malformations; risk of neural tube defects. Second/third trimester: risk of neonatal cardiac arrhythmias, respiratory depression, hypotonia, withdrawal syndrome.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies. Closely monitor for clinical worsening, suicidality, or unusual changes in behavior.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to imipramine or any component","Within 14 days of monoamine oxidase inhibitor use","Acute recovery phase after myocardial infarction","Concurrent use of MAOIs, linezolid, or intravenous methylene blue"]

Clinical Precautions

Precautions

["Activation of mania/hypomania","Cardiovascular effects including QTc prolongation, arrhythmias, and orthostatic hypotension","Anticholinergic effects (e.g., urinary retention, constipation, blurred vision)","Lower seizure threshold","Serotonin syndrome when co-administered with other serotonergic drugs","Ocular effects (angle-closure glaucoma)","Hematologic disorders (agranulocytosis)","Electroconvulsive therapy (use with caution)"]

Clinical Tips & Counseling

Drug interactions

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JANIMINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for JANIMINE (JANIMINE).

How it works

Imipramine inhibits the reuptake of norepinephrine and serotonin at nerve terminals, potentiating their neurotransmission. It also has anticholinergic and antihistaminergic effects.

What the body does with it

Metabolism	Primarily metabolized by hepatic cytochrome P450 enzymes, mainly CYP2D6 and CYP1A2, to active metabolite desipramine and other inactive metabolites.
Excretion	Primarily renal (70-80% as metabolites, 5% unchanged); biliary/fecal (20-30% as metabolites).
Half-life	5-15 hours (terminal elimination half-life); clinical context: requires twice-daily dosing for steady state.
Protein binding	~80% bound to plasma proteins (primarily albumin).
Volume of Distribution	1.5-2.5 L/kg; clinical meaning: extensive tissue distribution, not limited to extracellular fluid.
Bioavailability	Subcutaneous: ~80%; oral: 0% (not orally active due to first-pass metabolism).
Onset of Action	Subcutaneous: 30-60 minutes; intravenous: 15-30 minutes.
Duration of Action	8-12 hours (subcutaneous); clinical notes: duration may be prolonged in renal impairment.

Classification & Brands

Dosing & administration

25-50 mg orally 2-4 times daily; maintenance 150 mg/day divided

Dosage form	TABLET
Renal impairment	GFR >50 mL/min: no adjustment; GFR 10-50 mL/min: 50% of dose; GFR <10 mL/min: 25% of dose
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use
Pediatric use	1-3 mg/kg/day in 2-3 divided doses; max 5 mg/kg/day
Geriatric use	Initiate at 10-25 mg/day; increase slowly; monitor for 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 JANIMINE (JANIMINE).

Breastfeeding	Contraindicated; excreted into breast milk with M/P ratio approximately 0.5. Potential for neonatal adverse effects (cardiac, respiratory, neurological).
Teratogenic Risk	Pregnancy category D. First trimester: associated with Ebstein's anomaly and other cardiovascular malformations; risk of neural tube defects. Second/third trimester: risk of neonatal cardiac arrhythmias, respiratory depression, hypotonia, withdrawal syndrome.
Fetal Monitoring