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 |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PRAMINE (PRAMINE).
| Breastfeeding | Pramine is excreted into breast milk with a milk-to-plasma ratio (M/P) of approximately 1.0-1.5. Although the infant dose is low (<10% of maternal weight-adjusted dose), monitor for sedation, irritability, and feeding difficulties in the breastfed infant. Caution is advised, and alternative agents preferred. |
| 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). |
■ 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 tricyclic antidepressants","Recent myocardial infarction","Concomitant use of MAO inhibitors","Concurrent use of cisapride due to QT prolongation risk"]
| 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"] |
Loading safety data…
| 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. |