NORPRAMIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NORPRAMIN (NORPRAMIN).
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.
| 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. |
| Molecular Weight | 266.38 |
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. |
| 1st trimester | Avoid due to risk of teratogenicity; associated with cardiovascular malformations if used in first trimester. |
| 2nd trimester | Use only if clearly needed; may cause neonatal withdrawal symptoms. |
| 3rd trimester | Avoid near term due to risk of neonatal withdrawal, respiratory distress, and persistent pulmonary hypertension. |
Clinical note
Comprehensive clinical and safety monograph for NORPRAMIN (NORPRAMIN).
| Placental transfer | Crosses placenta; detectable in fetal serum at levels approximately 50% of maternal concentration. |
| Breastfeeding | Excreted into breast milk in low concentrations; monitor infant for sedation, poor feeding, and irritability. Generally considered compatible but caution advised, especially in premature infants or those with impaired metabolism. |
■ 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.
| Serious Effects |
Hypersensitivity to desipramine or other tricyclic antidepressantsConcomitant use with MAO inhibitors within 14 daysRecent myocardial infarctionConcurrent use with cisaprideConcurrent use with linezolid or methylene blue intravenous
| 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 |
| Food/Dietary | Avoid tyramine-rich foods (aged cheeses, cured meats, yeast extracts, sauerkraut, beer, wine) as desipramine may have weak MAOI activity at high doses, potentially causing hypertensive crisis. Also avoid large amounts of caffeine or other stimulants due to potential additive cardiovascular effects. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| 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. |
| Fetal Monitoring | Monitor maternal blood pressure, ECG (QTc prolongation), and signs of toxicity. Fetal: ultrasound for growth restriction, neonatal assessment for withdrawal symptoms after delivery. |
| Fertility Effects | May cause menstrual irregularities, anovulation, and decreased libido in women; reversible upon discontinuation. In men, reports of erectile dysfunction and impaired spermatogenesis. |
| Clinical Pearls | NORPRAMIN (desipramine) is a secondary amine tricyclic antidepressant (TCA) with strong norepinephrine reuptake inhibition. It has less anticholinergic, sedative, and orthostatic effects compared to tertiary amines like amitriptyline. Useful for patients sensitive to sedation or anticholinergic side effects. Caution: QTc prolongation risk, especially with electrolyte disturbances or concurrent QTc-prolonging drugs. Therapeutic drug monitoring recommended: serum levels 100-300 ng/mL for efficacy; toxicity >300 ng/mL. Use with MAOIs requires a 14-day washout. Discontinue gradually to avoid withdrawal symptoms. |
| Patient Advice | Take this medication exactly as prescribed. Do not increase or stop abruptly without consulting your doctor. · It may take 2-4 weeks to feel the full antidepressant effect. Continue taking it even if you don't notice immediate improvement. · Avoid alcohol and other central nervous system depressants (e.g., benzodiazepines, opioids) as they can increase sedation and dizziness. · This drug may cause drowsiness, dizziness, or blurred vision. Avoid driving or operating heavy machinery until you know how this medication affects you. · Notify your doctor immediately if you experience fast or irregular heartbeat, fainting, difficulty urinating, or seizure. · Store at room temperature away from moisture and heat. Keep out of reach of children. · Take missed dose as soon as remembered unless near next dose. Do not double dose. · Use sunscreen and protective clothing when outdoors, as this medication may increase sensitivity to sunlight. |