AMITRIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AMITRIL (AMITRIL).
Amitriptyline inhibits the reuptake of serotonin and norepinephrine, thereby increasing their synaptic concentrations. It also blocks histamine H1, alpha-1 adrenergic, and muscarinic receptors.
| Metabolism | Hepatic, primarily via CYP2D6 and CYP3A4, with contributions from CYP1A2 and CYP2C19. Amitriptyline is metabolized to nortriptyline (active) and other metabolites. |
| Excretion | Renal: ~70% as metabolites, <5% unchanged; fecal: ~30% via bile. |
| Half-life | Terminal elimination half-life: 15–25 hours (mean 20 h); may extend to >40 h in elderly or hepatic impairment. |
| Protein binding | 90–95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 15–30 L/kg; extensive tissue distribution, including CNS. |
| Bioavailability | Oral: 30–60% due to first-pass metabolism. |
| Onset of Action | Oral: 2–4 hours for sedative effect; antidepressant effect requires 2–4 weeks. |
| Duration of Action | Antidepressant effect: sustained with chronic dosing; sedative effect: 6–8 hours after single dose. |
| Molecular Weight | 277.4 |
| Action Class | Tricyclic antidepressants |
| Brand Substitutes | Triptop 10mg Tablet, Relidep 10mg Tablet, Amitone 10mg Tablet, Tryp 10mg Tablet, Odep 10mg Tablet, Amidep 25mg Tablet, Amitar 25mg Tablet, Trilin 25mg Tablet, Latilin 25mg Tablet, Amiford 25mg Tablet, Dep 50mg Tablet, Tryp 50mg Tablet, Latilin 50mg Tablet, Odep 50mg Tablet, Amifull 50 Tablet, Mytrip 75mg Tablet, Triplex 75mg Tablet, Amypres 75mg Tablet, Tryp 75mg Tablet, Latilin 75mg Tablet |
Adults: Initial 25 mg PO once daily at bedtime, increase by 25 mg every 3-7 days as tolerated to typical maintenance 75-150 mg/day PO divided doses or single dose at bedtime. Maximum 300 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-59 mL/min: Reduce dose by 50%. GFR 15-29 mL/min: Reduce dose by 75%. GFR <15 mL/min: Contraindicated. Hemodialysis: Not dialyzable; avoid use. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Use contraindicated or reduce dose by 75% with extreme caution. |
| Pediatric use | Children ≥12 years: Initial 25-50 mg/day PO, increase gradually to 100 mg/day in divided doses. Children 6-11 years: 1-3 mg/kg/day PO in divided doses, not to exceed 100 mg/day. Not recommended under 6 years. |
| Geriatric use | Initial 10-25 mg PO at bedtime, with gradual titration. Maintenance often 50-100 mg/day. Monitor for orthostatic hypotension, falls, and anticholinergic effects. |
| 1st trimester | Amitriptyline crosses the placenta. Data on malformations are limited but some studies suggest a small increased risk of cardiovascular malformations. Use only if benefit outweighs risk. |
| 2nd trimester | Amitriptyline may cause fetal tachycardia and withdrawal symptoms in the neonate. Use with caution and at the lowest effective dose. |
| 3rd trimester | Use in the third trimester may result in neonatal withdrawal (jitteriness, respiratory distress, feeding difficulties) and persistent pulmonary hypertension. Consider tapering prior to delivery. |
Clinical note
Comprehensive clinical and safety monograph for AMITRIL (AMITRIL).
| Placental transfer | Amitriptyline crosses the placenta; fetal exposure is approximately 60-70% of maternal serum concentrations. |
| Breastfeeding | Amitriptyline is excreted into breast milk in low levels. The infant dose is estimated at 1-2% of maternal weight-adjusted dose. Monitor infant for drowsiness, irritability, and feeding issues. With long-term use, consider monitoring infant serum levels if symptoms arise. |
■ FDA Black Box Warning
Amitriptyline is not approved for use in pediatric patients. Clinical worsening and suicide risk: Monitor for clinical worsening, suicidality, or unusual changes in behavior during initial therapy. Serotonin syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs.
| Serious Effects |
Recent myocardial infarctionConcomitant use with MAOIs or within 14 days of MAOI therapySevere hepatic impairmentHypersensitivity to tricyclic antidepressantsNarrow-angle glaucomaUrinary retention (e.g., from prostatic hypertrophy)
| Precautions | Suicidality in children, adolescents, and young adults; serotonin syndrome; activation of mania/hypomania; seizures; angle-closure glaucoma; urinary retention; cardiovascular effects (QT prolongation, arrhythmias); impaired cognitive/motor performance. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase serum levels of amitriptyline. Limit tyramine-rich foods (aged cheeses, cured meats, fermented products) if taking MAOIs concurrently (contraindicated). Alcohol consumption may enhance sedative effects and is not recommended. High-fat meals may delay absorption but do not significantly alter overall exposure. |
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| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | First trimester: Possible increased risk of cardiovascular malformations (OR ~1.2-1.5). Second/third trimester: Risk of neonatal withdrawal syndrome (irritability, feeding difficulties) and direct toxic effects (tachycardia, urinary retention). Late third trimester: Possible persistent pulmonary hypertension of the newborn (PPHN) with SSRI-like effects, though data limited for tricyclics. |
| Fetal Monitoring | Maternal: Monitor for anticholinergic effects (dry mouth, constipation, blurred vision), sedation, cardiac arrhythmias (ECG at baseline and periodically), and orthostatic hypotension. Fetal/neonatal: Growth ultrasound in third trimester; neonatal assessment for withdrawal syndrome, hypotonia, respiratory distress, and poor feeding postpartum. |
| Fertility Effects | Amitriptyline may cause menstrual irregularities, anorgasmia, and decreased libido, potentially impairing fertility. In males, may cause erectile dysfunction, delayed ejaculation. Effects are reversible upon discontinuation. |
| Clinical Pearls | For neuropathic pain, start at 10-25 mg at bedtime; titrate slowly to reduce sedative effects. Monitor QTc interval at baseline and with dose increases, especially in patients with cardiac risk factors. Anticholinergic effects (dry mouth, constipation) are common; consider prophylactic stool softeners. Avoid abrupt discontinuation; taper over 2-4 weeks to prevent withdrawal symptoms. |
| Patient Advice | Take exactly as prescribed, usually once daily at bedtime due to drowsiness. · Do not stop suddenly; taper under doctor's guidance to avoid nausea, headache, or insomnia. · Avoid alcohol and other CNS depressants (e.g., sedatives, opioids) as they increase sedation risk. · Report any signs of serotonin syndrome (e.g., agitation, hallucinations, rapid heart rate) or cardiac symptoms (e.g., palpitations, fainting). · May cause dry mouth, constipation, blurred vision; use sugar-free gum, hydrate, and consider fiber supplements. |