PRAMINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PRAMINE (PRAMINE).
Tricyclic antidepressant; inhibits reuptake of norepinephrine and serotonin at presynaptic neuronal membrane, increasing their concentration in the synaptic cleft.
| Metabolism | Hepatic via CYP2D6 and other cytochrome P450 enzymes; active metabolite desipramine. |
| Excretion | Renal: 70% (as metabolites); Fecal: 30% (as metabolites and unchanged drug) |
| Half-life | 10-12 hours (terminal elimination half-life; may be prolonged in elderly and hepatic impairment) |
| Protein binding | 85-90% (bound to alpha-1-acid glycoprotein and albumin) |
| Volume of Distribution | 8-12 L/kg (indicates extensive tissue distribution) |
| Bioavailability | Oral: 40-50% (first-pass metabolism); IM: 70-80% |
| Onset of Action | Oral: 2-4 hours; IV: 15-30 minutes; IM: 1-2 hours |
| Duration of Action | Oral: 6-8 hours; IV: 4-6 hours; IM: 4-6 hours; clinical effects may persist longer with chronic dosing |
| Molecular Weight | 280.4 |
Imipramine (PRAMINE) 75-150 mg orally once daily at bedtime, titrated from 25-50 mg, max 300 mg/day.
| Dosage form | TABLET |
| Renal impairment | No specific GFR-based adjustments; use with caution in severe renal impairment (GFR < 30 mL/min) with dose reduction by 25-50%. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated or use with extreme caution at 25% of normal dose. |
| Pediatric use | Not recommended for children <12 years; for adolescents (12-18 years): 1.5-3 mg/kg/day orally, max 100 mg/day. |
| Geriatric use | Start at 25-50 mg orally at bedtime, increase slowly to 75-100 mg/day; monitor for orthostatic hypotension, sedation, and anticholinergic effects. |
| 1st trimester | Avoid: evidence of teratogenicity in animal studies; use only if benefit outweighs risk. |
| 2nd trimester | Use with caution: may cause fetal tachycardia; monitor closely. |
| 3rd trimester | Avoid near term: may cause neonatal withdrawal or respiratory depression. |
Clinical note
Comprehensive clinical and safety monograph for PRAMINE (PRAMINE).
| Placental transfer | Crosses placenta readily; measurable fetal concentrations. |
| Breastfeeding | Small amounts excreted into breast milk; monitor infant for drowsiness, poor feeding, and respiratory depression. |
| Lactation Rating | L3 (Moderately Safe) |
■ FDA Black Box Warning
Suicidality and antidepressant drugs: Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Serious Effects |
Hypersensitivity to PRAMINE or any tricyclic antidepressantConcurrent use of MAO inhibitors (within 14 days)Recent myocardial infarctionAcute angle-closure glaucomaUrinary retention (e.g., from prostatic hypertrophy)
| Precautions | Serotonin syndrome with concurrent serotonergic drugs, QT prolongation, Seizures, Angle-closure glaucoma, Urinary retention, Cardiovascular disease including myocardial infarction, Electroconvulsive therapy, Hyperthyroidism, Hepatic impairment, Suicidal ideation |
| Food/Dietary | Avoid tyramine-rich foods (e.g., aged cheeses, cured meats, fermented products) only if patient is also taking an MAOI. PRAMINE alone does not require tyramine restriction. However, limit grapefruit juice as it may increase imipramine levels. Avoid alcohol. |
Loading safety data…
| Teratogenic Risk | FDA Pregnancy Category D. First trimester: Epidemiologic studies suggest a small increased risk of congenital cardiac malformations (e.g., ventricular septal defect) with first-trimester exposure. Second/third trimester: Exposure may increase risk of neonatal withdrawal (jitteriness, respiratory distress, feeding difficulties) and anticholinergic effects (e.g., urinary retention, constipation). |
| Fetal Monitoring | Monitor maternal heart rate, blood pressure, and ECG due to risk of QT prolongation. Assess for anticholinergic side effects (dry mouth, blurred vision, urinary retention). In fetus/newborn: evaluate for signs of withdrawal, respiratory depression, and anticholinergic toxicity (e.g., tachycardia, poor feeding). Consider fetal echocardiography if first-trimester exposure. |
| Fertility Effects | May cause hyperprolactinemia leading to galactorrhea, amenorrhea, and reduced fertility due to dopamine blockade. Reversible upon discontinuation. Limited data on male fertility; rare reports of erectile dysfunction or decreased libido. |
| Clinical Pearls | PRAMINE (imipramine) is a tricyclic antidepressant. Monitor ECG for QTc prolongation, especially in elderly. Avoid abrupt discontinuation to prevent withdrawal symptoms. Therapeutic drug monitoring recommended (target plasma level 150-250 ng/mL). Onset of antidepressant effect may take 2-4 weeks. Use with caution in patients with seizure disorder or closed-angle glaucoma. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly without consulting your doctor. · May cause drowsiness; avoid driving or operating machinery until you know how this medication affects you. · Do not consume alcohol or other CNS depressants while taking PRAMINE. · Report any signs of allergic reaction, chest pain, or changes in mood or behavior. · It may take several weeks to feel the full benefit of this medication. |