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) |
| Molecular Weight | 510.7 |
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 | Risk of fetal cardiovascular malformations with first-trimester exposure. |
| 2nd trimester | Neonatal withdrawal symptoms and respiratory distress possible. |
| 3rd trimester | Neonatal withdrawal including irritability, hypertonia, and seizures. |
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 |
| Placental transfer | Crosses placenta readily with fetal serum concentrations reaching 50-100% of maternal levels. |
| Breastfeeding | Excreted into breast milk in small amounts. Monitor infant for drowsiness, irritability, and weight gain. American Academy of Pediatrics considers use compatible with breastfeeding, but caution advised. |
■ 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 tricyclic antidepressantConcurrent use of MAO inhibitors (within 14 days)Recent myocardial infarction (acute recovery phase)Narrow-angle glaucomaUrinary retentionPropensity for tachycardia or arrhythmias
| 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. |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | 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. |
| Grapefruit and grapefruit juice may inhibit the metabolism of imipramine, leading to increased plasma concentrations and risk of toxicity; patients should avoid concurrent consumption. High-fiber foods may reduce absorption; take consistent amounts of fiber in the diet. Alcohol and foods containing tyramine (e.g., aged cheeses, cured meats, fermented products) should be avoided due to potential hypertensive crisis, especially in patients also on MAOIs, as imipramine has some MAOI activity at high doses. Caffeine may increase the risk of arrhythmias and should be used in moderation. Patients should maintain a consistent diet and discuss any dietary changes with their healthcare provider. |
| Clinical Pearls | Imipramine pamoate is a tricyclic antidepressant (TCA) with a long half-life, allowing for once-daily dosing, typically at bedtime to capitalize on sedative effects. It is metabolized to desipramine, an active metabolite with significant norepinephrine reuptake inhibition. Therapeutic drug monitoring is recommended for doses >200 mg/day in adults or >5 mg/kg in children to avoid toxicity. Baseline and periodic ECGs are essential due to risk of QT prolongation and arrhythmias, especially in patients with cardiac disease, electrolyte imbalances, or concurrent use of other QT-prolonging agents. Anticholinergic side effects (dry mouth, constipation, blurred vision) are common and may require dose adjustment or adjunctive therapy. Avoid abrupt discontinuation to prevent withdrawal symptoms (nausea, headache, malaise). Use cautiously in patients with angle-closure glaucoma, urinary retention, or hyperthyroidism. Imipramine pamoate is FDA-approved for depression and childhood enuresis (age ≥6). |
| Patient Advice | Take this medication exactly as prescribed, usually once daily at bedtime to help with sleep and reduce daytime drowsiness. · Do not stop taking this medication suddenly, as this may cause nausea, headache, or worsening of your condition; follow your doctor's instructions for tapering. · Avoid alcohol and other CNS depressants (e.g., sedatives, anxiolytics) as they can enhance drowsiness and dizziness. · This medication may cause dry mouth; suck on ice chips or sugarless candy, or practice good oral hygiene. · Report any signs of allergic reaction (rash, hives, difficulty breathing) or cardiac symptoms (fast or irregular heartbeat, fainting) immediately. · Avoid activities requiring mental alertness until you know how this drug affects you, as it may cause drowsiness or blurred vision. · Do not take this medication if you have taken a monoamine oxidase inhibitor (MAOI) within the past 14 days. · Keep this medication out of reach of children, as overdose can be fatal. · Attend all scheduled appointments for blood tests and ECGs to monitor drug levels and heart function. · If you miss a dose, take it as soon as you remember unless it is close to the next dose; do not double doses. |