ELAVIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ELAVIL (ELAVIL).
Amitriptyline inhibits the reuptake of serotonin and norepinephrine in the central nervous system, increasing their synaptic concentrations. It also exhibits anticholinergic, antihistaminergic, and alpha-adrenergic blocking effects.
| Metabolism | Extensively metabolized in the liver via CYP2C19 and CYP2D6 isoenzymes, as well as other pathways. Major metabolites include nortriptyline and hydroxylated derivatives. Amitriptyline undergoes first-pass metabolism, with variable bioavailability. |
| Excretion | Renal (approximately 40% as metabolites, <5% unchanged); biliary/fecal (approximately 60% as metabolites, including glucuronide conjugates). |
| Half-life | 10–50 hours (mean ~20 hours); terminal elimination half-life is prolonged in elderly and patients with hepatic impairment; steady-state achieved in 7–21 days. |
| Protein binding | 90–95% bound to plasma proteins (albumin, alpha-1 acid glycoprotein). |
| Volume of Distribution | 13–30 L/kg; large Vd indicates extensive tissue binding (e.g., brain, heart, lung). |
| Bioavailability | Oral: 30–60% due to extensive first-pass hepatic metabolism; IM: 100%. |
| Onset of Action | Oral: 2–4 weeks for antidepressant effect; IM: 30–60 minutes for sedation; IV: not clinically used. |
| Duration of Action | 24–48 hours for steady-state; clinical antidepressant effect requires continuous dosing for weeks; sedative effects may persist for 12–24 hours after single dose. |
| Molecular Weight | 313.86 |
| Action Class | Tricyclic antidepressants |
| Brand Substitutes | Neurotrip 10mg Tablet, Triptop 10mg Tablet, Relidep 10mg Tablet, Amitone 10mg Tablet, Tryp 10mg Tablet, Amidep 25mg Tablet, Amitar 25mg Tablet, Latilin 25mg Tablet, Amiford 25mg Tablet, Tryptomer 25mg Tablet, Dep 50mg Tablet, Tryp 50mg Tablet, Latilin 50mg Tablet, Odep 50mg Tablet, Amitril DS Tablet, Mytrip 75mg Tablet, Triplex 75mg Tablet, Amypres 75mg Tablet, Latilin 75mg Tablet, Shine 75mg Tablet |
Oral: Initial 75 mg/day in divided doses or 50-100 mg at bedtime; increase to 150 mg/day; maximum 300 mg/day. IM: 20-30 mg q6h, switch to oral as soon as possible.
| Dosage form | INJECTABLE |
| Renal impairment | GFR <10 mL/min: Administer 50% of normal dose. Not dialyzable; no supplemental dose needed. |
| Liver impairment | Child-Pugh Class A: No adjustment. Class B: Reduce dose by 50%. Class C: Avoid use or reduce by 75%. |
| Pediatric use | Children 6-12 years: 1-1.5 mg/kg/day in divided doses; maximum 3 mg/kg/day. Adolescents: 50-100 mg/day initially, increase to 150-200 mg/day. |
| Geriatric use | Initial 10-25 mg at bedtime; increase slowly to 50-100 mg/day; maximum 150 mg/day. Monitor for anticholinergic effects and sedation. |
| 1st trimester | Limited human data; risk of fetal malformations not established. Animal studies show adverse effects at high doses. Use only if benefit outweighs risk. |
| 2nd trimester | Avoid use, especially near term, due to risk of neonatal withdrawal and anticholinergic effects. Not recommended unless no alternative. |
| 3rd trimester | Avoid use in third trimester; may cause neonatal irritability, hypertonia, tremors, respiratory depression, and urinary retention. Discontinue prior to delivery if possible. |
Clinical note
Comprehensive clinical and safety monograph for ELAVIL (ELAVIL).
| Placental transfer | Amitriptyline crosses the placenta with fetal plasma levels approximately 50-60% of maternal levels. Drug accumulation in fetal tissues may occur. |
| Breastfeeding | Amitriptyline and its metabolite nortriptyline are excreted into breast milk in low concentrations. Relative infant dose is estimated at 1-2% of maternal weight-adjusted dose. Monitor infant for sedation, poor feeding, and anticholinergic effects. Generally considered compatible with breastfeeding; however, caution in preterm or compromised infants. |
■ FDA Black Box Warning
Amitriptyline increases the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. It should not be used within 14 days of MAO inhibitors due to the risk of serotonin syndrome.
| Serious Effects |
Concomitant use with MAO inhibitors (risk of serotonin syndrome)Recent myocardial infarctionHypersensitivity to amitriptyline or any componentConcurrent use with linezolid or intravenous methylene blue
| Precautions | Risk of suicidal thoughts and behaviors; caution in patients with cardiovascular disease (arrhythmias, MI, heart block); anticholinergic effects (urinary retention, narrow-angle glaucoma, constipation); activation of mania/hypomania; seizures; QT prolongation; drug interactions with MAOIs, CNS depressants, anticholinergics; thyroid medication interactions; hyponatremia; withdrawal symptoms upon abrupt discontinuation. |
| Food/Dietary | Avoid grapefruit juice as it may increase amitriptyline levels. High-tyramine foods (aged cheese, cured meats, fermented products) may cause hypertensive crisis if used with MAOIs, but risk is lower with amitriptyline alone; still advise moderation. Alcohol should be avoided due to additive CNS depression. |
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| Lactation Rating | L2 (Possibly Safe, probably compatible) |
| Teratogenic Risk | First trimester: Case reports of limb malformations but no consistent pattern in epidemiological studies; risk appears low but cannot exclude. Second/third trimester: Late gestational exposure may cause transient neonatal withdrawal symptoms (irritability, feeding difficulties) and anticholinergic effects (tachycardia, poor feeding). Neonatal respiratory distress and urinary retention reported. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, ECG for QT prolongation. Assess for anticholinergic side effects. Fetal ultrasound for growth and anatomy if first-trimester exposure. Neonatal monitoring for withdrawal and anticholinergic effects for 48 hours after birth. |
| Fertility Effects | May cause minor transient menstrual irregularities and suppress libido. No significant impairment of fertility reported in human studies. Hyperprolactinemia possible but rare. |
| Clinical Pearls | Amitriptyline (Elavil) is a tricyclic antidepressant with significant anticholinergic and sedative properties. Start low (e.g., 10-25 mg at bedtime) and titrate slowly. Monitor ECG for QTc prolongation, especially in elderly or those with cardiac disease. Avoid abrupt discontinuation to prevent withdrawal symptoms. Use with caution in patients with seizure disorder, narrow-angle glaucoma, or urinary retention. Effective for neuropathic pain and migraine prophylaxis at lower doses. |
| Patient Advice | Take this medication at bedtime to minimize daytime drowsiness. · Avoid alcohol; it can increase sedation and impair coordination. · Do not stop taking abruptly; taper under doctor's guidance. · Report any fast or irregular heartbeat, vision changes, or difficulty urinating. · May cause dry mouth, constipation, or blurred vision; use sugar-free gum or candy for dry mouth. |