Amitriptyline

PHARMACOLOGIC CATEGORY
Antidepressant, Tricyclic (Tertiary Amine)

DOSING: ADULTS
Depression: Oral: 50-150 mg/day single dose at bedtime or in divided doses; dose may be gradually increased up to 300 mg/day.

Chronic pain management (unlabeled use): Oral: Initial: 25 mg at bedtime; may increase as tolerated to 100 mg/day.

Migraine prophylaxis (unlabeled use): Oral: Initial: 10-25 mg at bedtime; usual dose: 150 mg; reported dosing ranges: 10-400 mg/day

DOSING: PEDIATRIC

(For additional information see "Amitriptyline: Pediatric drug information")
Chronic pain management (unlabeled use): Oral: Initial: 0.1 mg/kg at bedtime, may advance as tolerated over 2-3 weeks to 0.5-2 mg/kg at bedtime

Depressive disorders:
Children (unlabeled use): Oral: Initial doses of 1 mg/kg/day given in 3 divided doses with increases to 1.5 mg/kg/day have been reported in a small number of children (n=9) 9-12 years of age; clinically, doses up to 3 mg/kg/day (5 mg/kg/day if monitored closely) have been proposed
Adolescents: Initial: 25-50 mg/day; may administer in divided doses; increase gradually to 100 mg/day in divided doses.

Migraine prophylaxis (unlabeled use): Oral: Initial: 0.25 mg/kg/day, given at bedtime; increase dose by 0.25 mg/kg/day to maximum 1 mg/kg/day. Reported dosing ranges: 0.1-2 mg/kg/day; maximum suggested dose: 10 mg.

DOSING: ELDERLY — Depression: Oral: Initial: 10-25 mg at bedtime; dose should be increased in 10-25 mg increments every week if tolerated; dose range: 25-150 mg/day. See Renal/Hepatic Impairment.

DOSING: RENAL IMPAIRMENT — Nondialyzable

DOSING: HEPATIC IMPAIRMENT — Use with caution and monitor plasma levels and patient response.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, as hydrochloride: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg

DOSAGE FORMS: CONCISE
Tablet: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg

GENERIC EQUIVALENT AVAILABLE — Yes

USE — Relief of symptoms of depression

USE - UNLABELED / INVESTIGATIONAL — Analgesic for certain chronic and neuropathic pain; prophylaxis against migraine headaches; treatment of depressive disorders in children

ADVERSE REACTIONS SIGNIFICANT — Anticholinergic effects may be pronounced; moderate to marked sedation can occur (tolerance to these effects usually occurs).

Frequency not defined.

Cardiovascular: Orthostatic hypotension, tachycardia, ECG changes (nonspecific), AV conduction changes, cardiomyopathy (rare), MI, stroke, heart block, arrhythmia, syncope, hypertension, palpitation

Central nervous system: Restlessness, dizziness, insomnia, sedation, fatigue, anxiety, cognitive function impaired, seizure, extrapyramidal symptoms, coma, hallucinations, confusion, disorientation, coordination impaired, ataxia, headache, nightmares, hyperpyrexia

Dermatologic: Allergic rash, urticaria, photosensitivity, alopecia

Endocrine & metabolic: Syndrome of inappropriate ADH secretion

Gastrointestinal: Weight gain, xerostomia, constipation, paralytic ileus, nausea, vomiting, anorexia, stomatitis, peculiar taste, diarrhea, black tongue

Genitourinary: Urinary retention

Hematologic: Bone marrow depression, purpura, eosinophilia

Neuromuscular & skeletal: Numbness, paresthesia, peripheral neuropathy, tremor, weakness

Ocular: Blurred vision, mydriasis, ocular pressure increased

Otic: Tinnitus

Miscellaneous: Diaphoresis, withdrawal reactions (nausea, headache, malaise)

Postmarketing and/or case reports: Neuroleptic malignant syndrome (rare), serotonin syndrome (rare)

CONTRAINDICATIONS — Hypersensitivity to amitriptyline or any component of the formulation (cross-sensitivity with other tricyclics may occur); use of MAO inhibitors within past 14 days; acute recovery phase following myocardial infarction; concurrent use of cisapride

WARNINGS / PRECAUTIONS — [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children and adolescents with major depressive disorder (MDD) and other depressive disorders; consider risk prior to prescribing. Closely monitor for clinical worsening, suicidality, or unusual changes in behavior; the child's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. Such observation would generally include at least weekly face-to-face contact with patients or their family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks. Additional contact by telephone may be appropriate between face-to-face visits. Adults treated with antidepressants should be observed similarly for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. A medication guide should be dispensed with each prescription. Amitriptyline is not FDA-approved for use in children <12>0.5 mcg/mL; plasma levels do not always correlate with clinical effectiveness

TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include agitation, confusion, hallucinations, urinary retention, hypothermia, hypotension, ventricular tachycardia, and seizures. Following initiation of essential overdose management, toxic symptoms should be treated. Sodium bicarbonate is indicated when the QRS interval is >0.10 seconds or the QTc is >0.42 seconds. Ventricular arrhythmias often respond to phenytoin 15-20 mg/kg (adults) with concurrent systemic alkalinization (sodium bicarbonate 0.5-2 mEq/kg I.V.). Arrhythmias unresponsive to this therapy may respond to lidocaine 1 mg/kg I.V. followed by a titrated infusion. Physostigmine (1-2 mg slow I.V. for adults or 0.5 mg slow I.V. for children) may be indicated in reversing cardiac arrhythmias that are due to vagal blockade, or for anticholinergic effects, but should only be used as a last measure in life-threatening situations. Seizures usually respond to diazepam I.V. boluses (5-10 mg for adults up to 30 mg or 0.25-0.4 mg/kg/dose for children up to 10 mg/dose). If seizures are unresponsive or recur, phenytoin or phenobarbital may be required.

CANADIAN BRAND NAMES — Apo-Amitriptyline®; Levate®; Novo-Triptyn; PMS-Amitriptyline

INTERNATIONAL BRAND NAMES — Adepril (IT); Amilit (IT); Amineurin (DE); Amiplin (TW); Amiprin (JP); Amitrip (NZ); Amitriptylinum (PL); Amytril (BR); Anapsique (MX); Antalin (CL); Apo-Amitriptyline (CA); Domical (GB); Elatrol (IL); Elatrolet (IL); Elavil (FR); Enafon (KR); Endep (AU); Lantron (JP); Laroxyl (BF, BJ, CI, ET, FR, GH, GM, GN, IT, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Levate (CA); Miketorin (JP); Neurotol (PY); Novo-Triptyn (CA); Novoprotect (DE); Pinsaun (TW); PMS-Amitriptyline (CA); Protanol (BR); Qualitriptine (HK); Redomex (BE); Sarotard (KR); Saroten (BF, BJ, CH, CI, CY, DE, DK, EE, ET, FI, GH, GM, GN, GR, IR, KE, LR, MA, ML, MR, MU, MW, NE, NG, PT, SC, SD, SE, SL, SN, TZ, UG, ZA, ZM, ZW); Saroten Retard (MY); Sarotena (IN); Sarotex (NL, NO, UY); Syneudon (DE); Teperin (HU, IQ, JO); Trepiline (ZA); Tridep (BG); Tripta (MY, TH); Triptizol (IT); Trynol (TW); Tryptal (IL); Tryptanol (AR, BR, EC, JP, MX, PE, TH, ZA); Tryptizol (AT, BE, CH, DK, EG, ES, GB, NL, NO, PT, SE); Trytomer (IN); Uxen (AR)

MECHANISM OF ACTION — Increases the synaptic concentration of serotonin and/or norepinephrine in the central nervous system by inhibition of their reuptake by the presynaptic neuronal membrane

PHARMACODYNAMICS / KINETICS
Onset of action: Migraine prophylaxis: 6 weeks, higher dosage may be required in heavy smokers because of increased metabolism; Depression: 4-6 weeks, reduce dosage to lowest effective level

Distribution: Crosses placenta; enters breast milk

Metabolism: Hepatic to nortriptyline (active), hydroxy and conjugated derivatives; may be impaired in the elderly

Half-life elimination: Adults: 9-27 hours (average: 15 hours)

Time to peak, serum: ~4 hours

Excretion: Urine (18% as unchanged drug); feces (small amounts)

PATIENT INFORMATION — Do not discontinue medication abruptly. Full effect may not occur for 3-6 weeks. Avoid alcohol. May cause urine to turn blue-green. May cause drowsiness. Dry mouth may be helped by sips of water, sugarless gum, or hard candy.