JANIMINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for JANIMINE (JANIMINE).
Imipramine inhibits the reuptake of norepinephrine and serotonin at nerve terminals, potentiating their neurotransmission. It also has anticholinergic and antihistaminergic effects.
| Metabolism | Primarily metabolized by hepatic cytochrome P450 enzymes, mainly CYP2D6 and CYP1A2, to active metabolite desipramine and other inactive metabolites. |
| Excretion | Primarily renal (70-80% as metabolites, 5% unchanged); biliary/fecal (20-30% as metabolites). |
| Half-life | 5-15 hours (terminal elimination half-life); clinical context: requires twice-daily dosing for steady state. |
| Protein binding | ~80% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 1.5-2.5 L/kg; clinical meaning: extensive tissue distribution, not limited to extracellular fluid. |
| Bioavailability | Subcutaneous: ~80%; oral: 0% (not orally active due to first-pass metabolism). |
| Onset of Action | Subcutaneous: 30-60 minutes; intravenous: 15-30 minutes. |
| Duration of Action | 8-12 hours (subcutaneous); clinical notes: duration may be prolonged in renal impairment. |
| Molecular Weight | 500.6 |
25-50 mg orally 2-4 times daily; maintenance 150 mg/day divided
| Dosage form | TABLET |
| Renal impairment | GFR >50 mL/min: no adjustment; GFR 10-50 mL/min: 50% of dose; GFR <10 mL/min: 25% of dose |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use |
| Pediatric use | 1-3 mg/kg/day in 2-3 divided doses; max 5 mg/kg/day |
| Geriatric use | Initiate at 10-25 mg/day; increase slowly; monitor for sedation and anticholinergic effects |
| 1st trimester | Avoid; associated with cardiovascular malformations and neural tube defects. |
| 2nd trimester | Avoid; risk of spontaneous abortion and fetal growth restriction. |
| 3rd trimester | Avoid; may cause postpartum hemorrhage and neonatal withdrawal. |
Clinical note
Comprehensive clinical and safety monograph for JANIMINE (JANIMINE).
| Placental transfer | Extensive placental transfer; achieves fetal concentrations similar to maternal. |
| Breastfeeding | Excreted into breast milk; insufficient data to document safety in nursing infants. Avoid or use caution. |
| Lactation Rating | L4 - Possibly Hazardous |
■ FDA Black Box Warning
Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies. Closely monitor for clinical worsening, suicidality, or unusual changes in behavior.
| Serious Effects |
Hypersensitivity to JanimineRecent myocardial infarctionConcurrent use with MAOIsGlaucomaUrinary retentionSevere hepatic impairment
| Precautions | Activation of mania/hypomania, Cardiovascular effects including QTc prolongation, arrhythmias, and orthostatic hypotension, Anticholinergic effects (e.g., urinary retention, constipation, blurred vision), Lower seizure threshold, Serotonin syndrome when co-administered with other serotonergic drugs, Ocular effects (angle-closure glaucoma), Hematologic disorders (agranulocytosis), Electroconvulsive therapy (use with caution) |
| Food/Dietary | Avoid alcohol and high-tyramine foods (aged cheese, cured meats, soy sauce) due to risk of hypertensive crisis. Grapefruit juice may increase imipramine levels; limit consumption. |
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| Teratogenic Risk | Pregnancy category D. First trimester: associated with Ebstein's anomaly and other cardiovascular malformations; risk of neural tube defects. Second/third trimester: risk of neonatal cardiac arrhythmias, respiratory depression, hypotonia, withdrawal syndrome. |
| Fetal Monitoring | Maternal: ECG, serum drug levels, electrolytes, hepatic function. Fetal: ultrasound for cardiac structure and growth, fetal echocardiography at 18-22 weeks. |
| Fertility Effects | May impair female fertility due to elevated prolactin levels; male fertility effects not well documented. |
| Clinical Pearls | JANIMINE (imipramine) is a tricyclic antidepressant. Monitor for anticholinergic side effects (dry mouth, constipation, urinary retention). Cardiac toxicity risk: avoid in recent MI, prolonged QT. Taper to avoid withdrawal. Therapeutic drug monitoring: serum levels 150-300 ng/mL for efficacy. |
| Patient Advice | Take exactly as prescribed; do not stop abruptly. · May cause drowsiness; avoid driving until you know how it affects you. · Avoid alcohol. · Notify doctor immediately if you experience chest pain, palpitations, or severe dizziness. · May take 2-4 weeks for full therapeutic effect. · Report worsening depression or suicidal thoughts. |