ELAVIL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ELAVIL (ELAVIL).

How it works

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.

What the body does with it

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.

Classification & Brands

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

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ELAVIL (ELAVIL).

Breastfeeding	Excreted into breast milk; milk-to-plasma ratio approximately 0.5-1.5. Relative infant dose estimated 0.5-2% of maternal weight-adjusted dose. Limited data suggest low risk; however, monitor infant for drowsiness, poor feeding, and constipation. Decision based on maternal necessity and infant risk.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to amitriptyline or any component; recent myocardial infarction; concurrent use with MAOIs or within 14 days; narrow-angle glaucoma; urinary retention; during acute recovery phase after MI.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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ELAVIL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ELAVIL (ELAVIL).

How it works

What the body does with it

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.

Classification & Brands

Action Class

Tricyclic antidepressants

Brand Substitutes

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ELAVIL (ELAVIL).

Breastfeeding	Excreted into breast milk; milk-to-plasma ratio approximately 0.5-1.5. Relative infant dose estimated 0.5-2% of maternal weight-adjusted dose. Limited data suggest low risk; however, monitor infant for drowsiness, poor feeding, and constipation. Decision based on maternal necessity and infant risk.
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.