Yes

Antidepressant, Tricyclic (Tertiary Amine)

Relief of symptoms of depression

D

Hypersensitivity to amitriptyline (cross-sensitivity with other tricyclics may occur); use of monoamine oxidase inhibitors within past 14 days; recovery from acute myocardial infarction

Often causes drowsiness/sedation, resulting in impaired performance of tasks requiring alertness (ie, operating machinery or driving). Sedative effects may be additive with other CNS depressants and/or ethanol. The degree of sedation is very high relative to other antidepressants. May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disease. May cause hyponatremia/SIADH. May increase the risks associated with electroconvulsive therapy. This agent should be discontinued, when possible, prior to elective surgery. Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods.

Use caution in patients with depression, particularly if suicidal risk may be present. Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities). The risk of conduction abnormalities with this agent is high relative to other antidepressants. May lower seizure threshold - use caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage, alcoholism, or concurrent therapy with other drugs which lower the seizure threshold. Use with caution in hyperthyroid patients or those receiving thyroid supplementation. Use with caution in patients with hepatic or renal dysfunction and in elderly patients. Not for use in patients <12 years of age.

Anticholinergic effects may be pronounced; moderate to marked sedation can occur (tolerance to these effects usually occurs)

Central nervous system: Restlessness, dizziness, insomnia, sedation, fatigue, anxiety, impaired cognitive function, seizures, extrapyramidal symptoms

Dermatologic: Allergic rash, urticaria, photosensitivity

Gastrointestinal: Weight gain, xerostomia, constipation

Genitourinary: Urinary retention

Ocular: Blurred vision, mydriasis

Miscellaneous: Diaphoresis

Symptoms of overdose include agitation, confusion, hallucinations, urinary retention, hypothermia, hypotension, ventricular tachycardia, seizures

Following initiation of essential overdose management, toxic symptoms should be treated. Sodium bicarbonate is indicated when QRS interval is >0.10 seconds or QT_c >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 I.V. slowly for adults or 0.5 mg I.V. slowly 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.

CYP1A2, 2C9, 2C19, 2D6, and 3A3/4 enzyme substrate

Amitriptyline inhibits the antihypertensive response to bethanidine, clonidine, debrisoquin, guanadrel, guanethidine, guanabenz, guanfacine; monitor BP; consider alternate antihypertensive agent

Abrupt discontinuation of clonidine may cause hypertensive crisis, amitriptyline may enhance the response

Use with altretamine may cause orthostatic hypertension

Amitriptyline may be additive with or may potentiate the action of other CNS depressants (sedatives, hypnotics, or ethanol)

With MAO inhibitors, hyperpyrexia, hypertension, tachycardia, confusion, seizures, and deaths have been reported (serotonin syndrome); this combination should be avoided

Amitriptyline may increase the prothrombin time in patients stabilized on warfarin

Cimetidine and methylphenidate may decrease the metabolism of amitriptyline

Additive anticholinergic effects seen with other anticholinergic agents

The SSRIs, to varying degrees, inhibit the metabolism of TCAs and clinical toxicity may result

Use of lithium with a TCA may increase the risk for neurotoxicity

Phenothiazines may increase concentration of some TCAs and TCAs may increase concentration of phenothiazines; monitor for altered clinical response

TCAs may enhance the hypoglycemic effects of tolazamide, chlorpropamide, or insulin; monitor for changes in blood glucose levels

Cholestyramine and colestipol may bind TCAs and reduce their absorption; monitor for altered response

TCAs may enhance the effect of amphetamines; monitor for adverse CV effects

Diltiazem and verapamil appear to decrease the metabolism of imipramine and potentially other TCAs; monitor for increased TCA concentrations

The pressor response to I.V. epinephrine, norepinephrine, and phenylephrine may be enhanced in patients receiving TCAs; this combination is best avoided

Grapefruit juice, amprenavir, indinavir, ritonavir may inhibit the metabolism of clomipramine and potentially other TCAs; monitor for altered effects; a decrease in TCA dosage may be required

Quinidine may inhibit the metabolism of TCAs; monitor for altered effect

Combined use of anticholinergics with TCAs may produce additive anticholinergic effects

Combined use of beta-agonists with TCAs may predispose patients to cardiac arrhythmias

Protect injection and Elavil® 10 mg tablets from light

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

Onset of therapeutic effect: 7-21 days

Desired therapeutic effect (for depression) may take as long as 3-4 weeks, at that point dosage should be reduced to lowest effective level

When used for migraine headache prophylaxis, therapeutic effect may take as long as 6 weeks; a higher dosage may be required in a heavy smoker, because of increased metabolism

Distribution: Crosses placenta; enters breast milk

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

Half-life: Adults: 9-25 hours (15-hour average)

Time to peak serum concentration: Within 4 hours

Elimination: Renal excretion of 18% as unchanged drug; small amounts eliminated in feces by bile

Children: Pain management: Oral: Initial: 0.1 mg/kg at bedtime, may advance as tolerated over 2-3 weeks to 0.5-2 mg/day at bedtime

Adolescents: Oral: Initial: 25-50 mg/day; may administer in divided doses; increase gradually to 100 mg/day in divided doses

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

I.M.: 20-30 mg 4 times/day

Pain management: Oral: Initial: 25 mg at bedtime; may increase as tolerated to 100 mg/day

Dosing interval in hepatic impairment: Use with caution and monitor plasma levels and patient response

Hemodialysis: Nondialyzable

Alcohol: Additive CNS effects, avoid use

Not recommended for I.V.

Monitor blood pressure and pulse rate prior to and during initial therapy; evaluate mental status; monitor weight

Therapeutic: Amitriptyline and nortriptyline 100-250 ng/mL (SI: 360-900 nmol/L); nortriptyline 50-150 ng/mL (SI: 190-570 nmol/L); Toxic: >0.5 mg/mL; plasma levels do not always correlate with clinical effectiveness

glucose

Use with caution; epinephrine, norepinephrine and levonordefrin have been shown to have an increased pressor response in combination with TCAs

>10% of patients experience dry mouth; amitriptyline is the most anticholinergic and sedating of the antidepressants; pronounced effects on the cardiovascular system; long-term treatment with TCAs such as amitriptyline increases the risk of caries by reducing salivation and salivary buffer capacity. In a study by Rundergren, et al, pathological alterations were observed in the oral mucosa of 72% of 58 patients; 55% had new carious lesions after taking TCAs for a median of 51/2 years. Current research is investigating the use of the salivary stimulant pilocarpine (Salagen®) to overcome the xerostomia from amitriptyline.

Take exactly as directed (do not increase dose or frequency); may take several weeks to achieve desired results; may cause physical and/or psychological dependence. Do not use alcohol, excess caffeine, and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). May turn urine blue-green (normal). You may experience drowsiness, lightheadedness, impaired coordination, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); constipation (increased exercise, fluids, or dietary fruit and fiber may help); urinary retention (void before taking medication); postural hypotension (use caution climbing stairs or when changing position from lying or sitting to standing); altered sexual drive or ability (reversible); or photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). Report persistent CNS effects (eg, nervousness, restlessness, insomnia, anxiety, excitation, headache, agitation, impaired coordination, changes in cognition); muscle cramping, weakness, tremors, or rigidity; ringing in ears or visual disturbances; chest pain, palpitations, or irregular heartbeat; blurred vision; or worsening of condition. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures. Breast-feeding is not recommended.

May increase appetite and possibly a craving for sweets

Injection, as hydrochloride: 10 mg/mL (10 mL)

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

Boakes AJ, Laurence DR, Teoh PC, et al, "Interactions Between Sympathomimetic Amines and Antidepressant Agents in Man," Br Med J, 1973, 1(849):311-5.

Bosse GM, Barefoot JA, Pfeifer MP, et al, "Comparison of Three Methods of Gut Decontamination in Tricyclic Antidepressant Overdose," J Emerg Med, 1995, 13(2):203-9.

Ellison DW and Pentel PR, "Clinical Features and Consequences of Seizures Due to Cyclic Antidepressant Overdose," Am J Emerg Med, 1989, 7(1):5-10.

Elser JM and Woody RC, "Migraine Headache in the Infant and Young Child," Headache, 1990, 30(6):366-8.

Foulke GE, "Identifying Toxicity Risk Early After Antidepressant Overdose," Am J Emerg Med, 1995, 13(2):123-6.

Guharoy SR, "Adult Respiratory Distress Syndrome Associated With Amitriptyline Overdose," Vet Hum Toxicol, 1994, 36(4):316-7.

Jastak JT and Yagiela JA, "Vasoconstrictors and Local Anesthesia: A Review and Rationale for Use," J Am Dent Assoc, 1983, 107(4):623-30.

Kashani JH, Shekim WO, and Reid JC, "Amitriptyline in Children With Major Depressive Disorder: A Double-Blind Crossover Pilot Study," J Am Acad Child Psychiatry, 1984, 23(3):348-51.

Knudsen K and Abrahamsson K, "Effects of Epinephrine, Norepinephrine, Magnesium Sulfate, and Milrinone on Survival and the Occurrence of Arrhythmias in Amitriptyline Poisoning in the Rat," Crit Care Med, 1994, 22(11):1851-5.

Larochelle P, Hamet P, and Enjalbert M, "Responses to Tyramine and Norepinephrine After Imipramine and Trazodone," Clin Pharmacol Ther, 1979, 26(1):24-30.

Levy HB, Harper CR, and Weinberg WA, "A Practical Approach to Children Failing in School," Pediatr Clin North Am, 1992, 39(4):895-928.

Mitchell JR, "Guanethidine and Related Agents. III Antagonism by Drugs Which Inhibit the Norepinephrine Pump in Man," J Clin Invest, 1970, 49(8):1596-604.

Nies A, Robinson DS, Friedman MJ, et al, "Relationship Between Age and Tricyclic Antidepressant Plasma Levels," Am J Psychiatry, 1977, 134:790-3.

Perrot LJ, "Amitriptyline Overdose Versus Sudden Infant Death Syndrome in a Two Month Old White Female," J Forensic Sci, 1988, 33(1):272-5.

Rundegren J, van Dijken J, Mörnstad H, et al, "Oral Conditions in Patients Receiving Long-Term Treatment With Cyclic Antidepressant Drugs," Swed Dent J, 1985, 9(2):55-64.

Sasyniuk BI, Jhamandas V, Valois M, et al, "Experimental Amitriptyline Intoxication: Treatment of Cardiac Toxicity With Sodium Bicarbonate," Ann Emerg Med, 1986, 15(9):1052-9.

Schulz P, Turner-Tamiyasu K, Smith G, et al, "Amitriptyline Disposition in Young and Elderly Normal Men," Clin Pharmacol Ther, 1983, 33(3):360-6.

Stone CK, Kraemer CM, Carroll R, et al, "Does a Sodium-Free Buffer Affect QRS Width in Experimental Amitriptyline Overdose?" Ann Emerg Med, 1995, 26(1):58-64.

Svedmyr N, "The Influence of a Tricyclic Antidepressive Agent (Protriptyline) on Some of the Circulatory Effects of Noradrenaline and Adrenalin® in Man," Life Sci, 1968, 7(1):77-84.