IMIPRAMINE PAMOATE
Clinical safety rating: caution
MAOIs can cause serotonin syndrome and hyperpyrexia Strong anticholinergic effects may occur with other drugs Increased risk of suicide in children and young adults.
Imipramine is a tricyclic antidepressant that inhibits the reuptake of norepinephrine and serotonin at presynaptic neuronal membranes, increasing their concentrations in the synaptic cleft. It also has anticholinergic, antihistaminergic, and alpha-adrenergic blocking effects.
| Metabolism | Primarily hepatic via CYP1A2, CYP2C19, CYP2D6, and CYP3A4. Active metabolite desipramine is formed via N-demethylation. |
| Excretion | Primarily renal (70% as metabolites, <5% unchanged); 20-30% fecal via biliary excretion |
| Half-life | 11-25 hours (mean 19 h); extended in elderly (up to 30 h) and hepatic impairment; clinical context: steady-state reached in 7-14 days |
| Protein binding | 90-95% bound to alpha1-acid glycoprotein, albumin, and lipoproteins |
| Volume of Distribution | 11-15 L/kg; large Vd indicates extensive tissue distribution (lung, brain, heart), with clinical significance for loading dose requirements |
| Bioavailability | Oral: 22-77% (extensive first-pass metabolism); IM: 100% (not available in US); interindividual variability due to CYP2D6 polymorphisms |
| Onset of Action | Oral: antidepressant effect 2-4 weeks; IM: no advantage; analgesic effect in neuropathic pain: 1-7 days |
| Duration of Action | 24-48 hours for single dose; clinical effects persist days after discontinuation due to active metabolite desipramine (half-life 22-30 h) |
150-300 mg orally once daily at bedtime for depression; 75-150 mg/day for panic disorder.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment typically required; use with caution if GFR <30 mL/min. |
| Liver impairment | Reduce dose by 50-75% in Child-Pugh class B or C; monitor closely. |
| Pediatric use | 1.5-5 mg/kg/day orally in divided doses; maximum 200 mg/day for adolescents. |
| Geriatric use | Start with 25-50 mg/day; increase by 25 mg every 3-4 days; maximum 100 mg/day in divided doses. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs can cause serotonin syndrome and hyperpyrexia Strong anticholinergic effects may occur with other drugs Increased risk of suicide in children and young adults.
| FDA category | Animal |
| Breastfeeding | Imipramine and its active metabolite desipramine are excreted into breast milk. M/P ratio approximately 0.5-1.5. Infant serum levels may reach up to 10% of maternal therapeutic levels. Monitor infant for sedation, poor feeding, and weight gain. Generally considered compatible with caution. |
| Teratogenic Risk |
■ FDA Black Box Warning
Suicidality and Antidepressant Drugs: Imipramine may increase the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. Close monitoring is required.
| Common Effects | enuresis |
| Serious Effects |
Hypersensitivity to imipramine or any component; recent myocardial infarction; concomitant use of MAOIs (within 14 days); concurrent use of linezolid or intravenous methylene blue; history of seizure disorder; narrow-angle glaucoma; urinary retention; prostate hypertrophy; concurrent use of cisapride, thioridazine, or pimozide due to QT prolongation risk.
| Precautions | Activation of mania/hypomania; cardiovascular effects (QT prolongation, arrhythmias); seizure threshold lowering; angle-closure glaucoma; urinary retention; serotonin syndrome; withdrawal symptoms; use in pregnancy (Category D); use in breastfeeding; bone marrow suppression. |
Loading safety data…
| First trimester: Limited human data, possible cardiovascular malformations (case reports). Second and third trimesters: Risk of neonatal withdrawal syndrome (tachycardia, irritability, poor feeding) and anticholinergic effects. Avoid if possible. |
| Fetal Monitoring | Maternal: ECG if cardiac history, liver function tests, blood pressure, and mental status. Fetal/neonatal: Ultrasound for growth and anatomy (especially cardiac) in second trimester; monitor neonate for withdrawal syndrome for 48-72 hours after delivery. |
| Fertility Effects | May cause hyperprolactinemia and galactorrhea in women, potentially impairing ovulation. In men, may cause sexual dysfunction (libido, erectile, ejaculatory). Effects reversible upon discontinuation. |