NORPRAMIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NORPRAMIN (NORPRAMIN).

How it works

Norpramin (desipramine) is a tricyclic antidepressant (TCA) that primarily inhibits the reuptake of norepinephrine, and to a lesser extent serotonin, at the presynaptic neuronal membrane, thereby increasing their concentrations in the synaptic cleft. It also has anticholinergic, antihistaminergic, and alpha1-adrenergic blocking properties.

What the body does with it

Metabolism	Hepatic via CYP2D6 (major) and CYP1A2, CYP2C19 (minor). Active metabolite: 2-hydroxydesipramine.
Excretion	Primarily renal (70%) as metabolites and unchanged drug; biliary/fecal (30%) as metabolites.
Half-life	Terminal half-life: 18-34 hours (mean ~27 hours); clinical context: supports once-daily dosing, but steady-state requires 5-7 days.
Protein binding	90-95% bound primarily to alpha1-acid glycoprotein and albumin.
Volume of Distribution	Vd: 15-30 L/kg; indicates extensive tissue distribution and high tissue binding.
Bioavailability	Oral: 50-70% due to first-pass metabolism; IM: not clinically used; IV: 100% but not available.
Onset of Action	Oral: 2-4 weeks for antidepressant effect; IM: no significant advantage; therapeutic lag of 2-4 weeks.
Duration of Action	After single dose: therapeutic effect persists 24-48 hours; chronic use: sustained antidepressant effect with daily dosing.

Classification & Brands

Dosing & administration

25 mg orally three times daily; may increase gradually to 150 mg/day in divided doses. Maximum 200 mg/day.

Dosage form	TABLET
Renal impairment	GFR 10-50 mL/min: use 50% of normal dose. GFR <10 mL/min: use 25% of normal dose.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: use with caution; reduce dose by 75%.
Pediatric use	Not recommended for children under 12 years. For adolescents 12-18 years: 25-50 mg/day initially, increase to 100 mg/day in divided doses.
Geriatric use	Initiate at 10-25 mg/day, increase slowly to a maximum of 100 mg/day in divided doses. Monitor for orthostatic hypotension, urinary retention, and confusion.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for NORPRAMIN (NORPRAMIN).

Breastfeeding	Present in breast milk in small amounts (milk-to-plasma ratio ~0.5–1.0). American Academy of Pediatrics considers compatible with breastfeeding; monitor infant for sedation, poor feeding, and weight gain.
Teratogenic Risk	First trimester: Limited human data; animal studies show fetal anomalies at high doses. Second/third trimester: Neonatal withdrawal (tachycardia, irritability, respiratory distress) and anticholinergic effects (ileus, urinary retention). Avoid use in pregnancy unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Suicidality and Antidepressant Drugs: Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies. Monitor closely for clinical worsening, suicidality, or unusual changes in behavior. Family and caregivers should be advised of the need for close observation.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Recent myocardial infarction","Concurrent use of MAOIs (risk of serotonin syndrome; allow 2-week washout)","Known hypersensitivity to desipramine or other TCAs","Use in children (safety and efficacy not established for depression)","Severe hepatic impairment"]

Clinical Precautions

Precautions

["Risk of suicide","Activation of mania/hypomania","Cardiovascular effects (prolonged QT interval, arrhythmias, tachycardia)","Seizure threshold lowering","Anticholinergic effects","Orthostatic hypotension","Serotonin syndrome (with MAOIs or other serotonergic drugs)","Bone marrow suppression (rare)","Use in cardiac disease: caution; ECGs recommended"]

Clinical Tips & Counseling

Drug interactions

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NORPRAMIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NORPRAMIN (NORPRAMIN).

How it works

What the body does with it

Metabolism	Hepatic via CYP2D6 (major) and CYP1A2, CYP2C19 (minor). Active metabolite: 2-hydroxydesipramine.
Excretion	Primarily renal (70%) as metabolites and unchanged drug; biliary/fecal (30%) as metabolites.
Half-life	Terminal half-life: 18-34 hours (mean ~27 hours); clinical context: supports once-daily dosing, but steady-state requires 5-7 days.
Protein binding	90-95% bound primarily to alpha1-acid glycoprotein and albumin.
Volume of Distribution	Vd: 15-30 L/kg; indicates extensive tissue distribution and high tissue binding.
Bioavailability	Oral: 50-70% due to first-pass metabolism; IM: not clinically used; IV: 100% but not available.
Onset of Action	Oral: 2-4 weeks for antidepressant effect; IM: no significant advantage; therapeutic lag of 2-4 weeks.
Duration of Action	After single dose: therapeutic effect persists 24-48 hours; chronic use: sustained antidepressant effect with daily dosing.

Classification & Brands

Dosing & administration

25 mg orally three times daily; may increase gradually to 150 mg/day in divided doses. Maximum 200 mg/day.

Dosage form	TABLET
Renal impairment	GFR 10-50 mL/min: use 50% of normal dose. GFR <10 mL/min: use 25% of normal dose.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: use with caution; reduce dose by 75%.
Pediatric use	Not recommended for children under 12 years. For adolescents 12-18 years: 25-50 mg/day initially, increase to 100 mg/day in divided doses.
Geriatric use	Initiate at 10-25 mg/day, increase slowly to a maximum of 100 mg/day in divided doses. Monitor for orthostatic hypotension, urinary retention, and confusion.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for NORPRAMIN (NORPRAMIN).

Breastfeeding	Present in breast milk in small amounts (milk-to-plasma ratio ~0.5–1.0). American Academy of Pediatrics considers compatible with breastfeeding; monitor infant for sedation, poor feeding, and weight gain.
Teratogenic Risk	First trimester: Limited human data; animal studies show fetal anomalies at high doses. Second/third trimester: Neonatal withdrawal (tachycardia, irritability, respiratory distress) and anticholinergic effects (ileus, urinary retention). Avoid use in pregnancy unless benefit outweighs risk.