PAMELOR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PAMELOR (PAMELOR).
Nortriptyline, the active ingredient, is a tricyclic antidepressant that inhibits the reuptake of norepinephrine and serotonin at the presynaptic neuronal membrane, increasing their availability in the synaptic cleft.
| Metabolism | Primarily hepatic via CYP2D6 and CYP3A4; also undergoes glucuronidation. Active metabolite: 10-hydroxynortriptyline. |
| Excretion | Primarily renal (approximately 70% as metabolites, 40-50% as glucuronide conjugates, 20-30% as free or conjugated nortriptyline; <5% unchanged), with 20-30% biliary/fecal elimination. |
| Half-life | Mean terminal elimination half-life is 18-24 hours (range 13-40 hours) in adults; prolonged in elderly and hepatic impairment (up to 60 hours). Steady-state achieved in 4-5 days. |
| Protein binding | 93-95% bound, primarily to alpha-1-acid glycoprotein (AAG) and albumin. |
| Volume of Distribution | Approximately 15-25 L/kg, indicating extensive tissue distribution and high lipophilicity. |
| Bioavailability | Oral: 40-60% (due to extensive first-pass metabolism). |
| Onset of Action | Oral: 2-4 weeks for antidepressant effect; rapid onset of sedation within 1-2 hours. IM (not typical): 1-2 hours for sedation. |
| Duration of Action | Antidepressant effect: sustained with chronic dosing; sedation lasts 6-8 hours after a single dose. Analgesic effect in neuropathic pain: 12-24 hours. |
25-150 mg orally per day, typically as a single daily dose at bedtime or in divided doses; start at 25 mg 1-3 times daily and titrate gradually. Maximum 150 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-59 mL/min: reduce dose by 25-50%; GFR 15-29 mL/min: reduce dose by 50% and use with caution; GFR <15 mL/min: avoid use (limited data; risk of accumulation). |
| Liver impairment | Child-Pugh A: caution, consider 50% dose reduction; Child-Pugh B: reduce dose by 50-75% and monitor closely; Child-Pugh C: contraindicated. |
| Pediatric use | Not approved for children <12 years; for adolescent depression: 1-3 mg/kg/day orally in divided doses, max 100 mg/day. |
| Geriatric use | Start at 10-25 mg/day orally, increase by 10-25 mg every 3-7 days as tolerated; usual range 25-75 mg/day; monitor for anticholinergic effects, sedation, orthostatic hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PAMELOR (PAMELOR).
| Breastfeeding | Nortriptyline is excreted into breast milk in small amounts; M/P ratio is approximately 1.3. Relative infant dose is about 1-3% of maternal weight-adjusted dose. No adverse effects commonly reported in nursing infants, but monitor for sedation and poor feeding. Benefits likely outweigh risks in most cases. |
| Teratogenic Risk | Pamelor (nortriptyline) is a tricyclic antidepressant. First trimester: Limited human data show no consistent association with major malformations; however, animal studies have shown adverse effects at high doses. Second and third trimesters: Use may be associated with transient neonatal withdrawal symptoms (irritability, tachycardia, respiratory distress) and anticholinergic effects. Risk may be dose-dependent. |
■ FDA Black Box Warning
WARNING: Suicidality and Antidepressant Drugs. Antidepressants increased the risk of suicidal thinking and behavior in short-term studies in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. Monitor closely for worsening and emergence of suicidal thoughts and behaviors.
| Serious Effects |
["Hypersensitivity to nortriptyline or any component","Concomitant use with MAOIs (risk of hypertensive crisis, serotonin syndrome)","Recent myocardial infarction (within 6 weeks)","Concurrent use with cisapride, pimozide, or other QT-prolonging drugs","Severe hepatic impairment","Narrow-angle glaucoma","Severe renal impairment","Lactation (use with caution if breastfeeding)"]
| Precautions | ["Risk of suicidality","Activation of mania/hypomania","QT prolongation and cardiac arrhythmias","Orthostatic hypotension","Serotonin syndrome","Angle-closure glaucoma","Urinary retention","Seizure threshold lowering","Bone marrow suppression (agranulocytosis)","Anticholinergic effects","Discontinuation syndrome"] |
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| Fetal Monitoring | Monitor maternal mood and side effects (anticholinergic, cardiac). Fetal monitoring: serial ultrasounds for growth and amniotic fluid volume if third-trimester exposure. Neonatal monitoring after delivery for withdrawal symptoms (irritability, abnormal tone, respiratory distress) for at least 48 hours. |
| Fertility Effects | Limited data. Tricyclic antidepressants may cause sexual dysfunction (libido, ejaculation) potentially affecting fertility in males. In females, no established impact on ovulation or conception risk. |