AMITID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AMITID (AMITID).
Amitriptyline inhibits the reuptake of serotonin and norepinephrine, increasing their levels in the synaptic cleft. It also blocks histamine H1, alpha-adrenergic, and muscarinic receptors.
| Metabolism | Hepatic via CYP2D6, CYP2C19, CYP3A4; active metabolite nortriptyline. |
| Excretion | Renal: 60-80% as metabolites, <5% unchanged; Biliary/Fecal: 20-30% as metabolites. |
| Half-life | Terminal elimination half-life is 7-10 hours; clinically, steady-state is reached within 2-3 days. |
| Protein binding | 90-95% bound primarily to albumin and α1-acid glycoprotein. |
| Volume of Distribution | 3-5 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: 60-70%; Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 2-5 minutes. |
| Duration of Action | Oral: 6-8 hours; Intravenous: 2-4 hours; note: analgesic effect may outlast plasma levels. |
75–150 mg orally once daily at bedtime; maximum 200 mg daily. For depression, initial dose 25–75 mg/day, titrate up to 150 mg/day. For neuropathic pain, start 10–25 mg at bedtime, increase to 25–100 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR ≥30 mL/min: no adjustment. GFR 15–29 mL/min: reduce dose by 50%. GFR <15 mL/min: contraindicated or use with extreme caution, maximum 25 mg/day. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid use. |
| Pediatric use | Not FDA-approved for use in children <12 years. For adolescent depression (off-label): start 25 mg/day, titrate up to 50–100 mg/day. Weight-based: 1–3 mg/kg/day, not to exceed 150 mg/day. |
| Geriatric use | Start at 10–25 mg orally at bedtime; increase by 10–25 mg every 3–7 days to effective dose, typically 50–75 mg/day. Maximum 100 mg/day due to increased risk of anticholinergic effects, sedation, and orthostatic hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AMITID (AMITID).
| Breastfeeding | Amitriptyline and its active metabolite nortriptyline are excreted into breast milk with a milk-to-plasma (M/P) ratio of approximately 0.5–1.5. Relative infant dose is low (estimated <2% of weight-adjusted maternal dose). No adverse effects reported in infants followed prospectively. The American Academy of Pediatrics considers amitriptyline compatible with breastfeeding. However, monitor infant for sedation, poor feeding, and growth. |
| Teratogenic Risk | First trimester: Amitriptyline (likely the active ingredient in AMITID) is associated with a small increased risk of congenital malformations, particularly cardiovascular defects, based on observational studies. Absolute risk is low. Second and third trimesters: Chronic use may lead to neonatal adaptation syndrome (irritability, respiratory distress) and anticholinergic effects (e.g., constipation, urinary retention). Late third trimester exposure may increase risk of persistent pulmonary hypertension of the newborn (PPHN). |
■ FDA Black Box Warning
Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Serious Effects |
["Hypersensitivity to amitriptyline","Concomitant use with MAOIs (within 14 days)","Acute recovery phase after myocardial infarction","Concurrent use of cisapride or other QT-prolonging drugs"]
| Precautions | ["Clinical worsening and suicide risk","Serotonin syndrome","Cardiovascular effects (QT prolongation, arrhythmia)","Anticholinergic effects","Seizures","Angle-closure glaucoma","Urinary retention","Hepatic impairment","Hyponatremia"] |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase drug levels. Tyramine-rich foods (aged cheese, cured meats, fermented products) should be limited due to risk of hypertensive crisis. Maintain adequate fluid intake to prevent constipation. |
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| Fetal Monitoring | For mother: Liver function tests, blood counts, ECG in those with cardiac risk factors. For fetus/neonate: Ultrasound for structural anomalies if first-trimester exposure; during third trimester, monitor fetal growth and amniotic fluid volume; postpartum observe for neonatal adaptation syndrome (e.g., jitteriness, respiratory distress, feeding difficulty) for 48 hours. |
| Fertility Effects | Available data limited. Amitriptyline may cause hyperprolactinemia via dopamine receptor blockade, potentially leading to menstrual irregularities, galactorrhea, and impaired fertility. Effects are generally reversible upon discontinuation. |
| Clinical Pearls | Amitriptyline is a tricyclic antidepressant with strong anticholinergic effects; monitor for QT prolongation, especially in elderly or those with cardiac disease. Start low (10-25 mg at bedtime) and titrate slowly. Avoid in recent MI, narrow-angle glaucoma, and urinary retention. Use with caution in seizure disorders. |
| Patient Advice | Take this medication at bedtime as it may cause drowsiness. · Avoid alcohol and other CNS depressants. · Do not stop abruptly; taper under medical supervision to avoid withdrawal symptoms. · May cause dry mouth, constipation, blurred vision; report severe side effects like fainting or irregular heartbeat. · Full therapeutic effect may take 2-4 weeks. |