PRESAMINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PRESAMINE (PRESAMINE).
Predominantly inhibits serotonin reuptake in the presynaptic neuron, increasing serotonin availability in the synaptic cleft. Also inhibits norepinephrine reuptake to a lesser extent.
| Metabolism | Hepatic via CYP2D6, CYP2C19, CYP3A4; active metabolite N-desmethylcitalopram |
| Excretion | Primarily renal (70% as metabolites, <5% unchanged); biliary/fecal (30%). |
| Half-life | 21 hours (range 16-28 h) for imipramine; active metabolite desipramine ~24 h; clinically, steady-state reached in 5-7 days. |
| Protein binding | 90% bound primarily to alpha1-acid glycoprotein and albumin. |
| Volume of Distribution | 15 L/kg (range 10-20 L/kg), indicating extensive tissue distribution, particularly to brain and heart. |
| Bioavailability | Oral: 30-50% due to first-pass metabolism; IM: ~100%. |
| Onset of Action | Oral: 2-4 weeks for antidepressant effect; IM: 30-60 min for sedation (not for depression). |
| Duration of Action | Oral: prolonged antidepressant effect sustained with regular dosing; half-life supports once-daily dosing; clinical duration weeks. |
| Molecular Weight | 280.41 |
100-300 mg/day orally in divided doses, typically starting at 75 mg/day and titrating upward. Maximum dose 300 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR >30 mL/min: no adjustment. GFR 10-30 mL/min: reduce dose by 50%. GFR <10 mL/min: avoid or use with extreme caution, monitor closely. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: contraindicated. |
| Pediatric use | Not recommended for children under 12 years. For adolescents: 1-2 mg/kg/day orally, up to 100 mg/day in divided doses. |
| Geriatric use | Start at 25-50 mg/day, increase by 25 mg every 3-4 days. Maximum 150 mg/day. Monitor for orthostasis, sedation, anticholinergic effects. |
| 1st trimester | Teratogenic effects in animal studies; avoid unless benefit outweighs risk. May be associated with cardiovascular malformations. |
| 2nd trimester | Consider risk of maternal toxicity and neonatal withdrawal; use only if clearly needed. |
| 3rd trimester | Use in third trimester may cause neonatal withdrawal, respiratory depression, and anticholinergic effects; avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for PRESAMINE (PRESAMINE).
| Placental transfer | Crosses placenta; measurable fetal serum levels approximately 50-100% of maternal levels. |
| Breastfeeding | Small amounts excreted into breast milk; monitor infant for drowsiness, irritability, and weight gain; generally considered compatible with caution. |
■ FDA Black Box Warning
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 antidepressantsConcomitant use with MAOIsRecent myocardial infarctionSevere liver diseaseAngle-closure glaucomaUrinary retention
| Precautions | QT interval prolongation, serotonin syndrome, activation of mania/hypomania, seizure risk, angle-closure glaucoma, hyponatremia, and increased bleeding risk. |
| Food/Dietary | Avoid tyramine-rich foods (aged cheese, cured meats, fermented products) if taking MAOIs concurrently. Grapefruit juice may increase imipramine levels. High-fat meals can delay absorption. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Studies suggest a small increased risk of cardiovascular malformations, particularly septal defects. Second trimester: No specific major risks identified but fetal growth monitoring recommended. Third trimester: Risk of neonatal adaptation syndrome including respiratory distress, feeding difficulties, and irritability. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and ECG for arrhythmias. Assess for serotonin syndrome if combined with other serotonergic drugs. Fetal ultrasound for growth and anatomy in second trimester, and neonatal monitoring for adaptation syndrome after delivery. |
| Fertility Effects | Imipramine may cause reversible infertility in males via decreased libido, erectile dysfunction, or ejaculatory disturbances. In females, it may disrupt menstrual cycle or reduce libido. Effects are dose-dependent and reversible upon discontinuation. |
| Clinical Pearls | PRESAMINE (imipramine) requires baseline ECG in patients over 40 due to risk of arrhythmias. Caution with MAOIs: allow 14-day washout. Anticholinergic effects (constipation, dry mouth) are dose-limiting. Monitor for orthostatic hypotension, especially in elderly. |
| Patient Advice | Take exactly as prescribed; do not stop abruptly. · Avoid driving until you know how this medicine affects you. · Report suicidal thoughts or worsening depression immediately. · May cause dry mouth, constipation, blurred vision. · Avoid alcohol and over-the-counter cold remedies. |