Amitriptyline HCl is a white, odorless, crystalline compound which is freely soluble in water.
Amitriptyline HCl is supplied as 10 mg, 25 mg, 50 mg, 75 mg, 100 mg and 150 mg tablets and as a sterile solution for intramuscular use.
Each milliliter of the sterile solution contains: Amitriptyline hydrochloride: 10 mg; Dextrose: 44 mg; Water for Injection, q.s.: 1 ml
Amitriptyline HCl is an antidepressant with sedative effects. Its mechanism of action in man is not known. It is not a monoamine oxidase inhibitor and it does not act primarily by stimulation of the central nervous system.
Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons.
Indications and Usage:
For the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than are other depressive states.
Amitriptyline HCl is contraindicated in patients who have shown prior hypersensitivity to it.
It should not be given concomitantly with monoamine oxidase inhibitors. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressant and monoamine oxidase inhibiting drugs simultaneously. When it is desired to replace a monoamine oxidase inhibitor with amitriptyline HCl, a minimum of 14 days should be allowed to elapse after the former is discontinued. Amitriptyline HCl should then be initiated cautiously with gradual increase in dosage until optimum response is achieved.
This drug is not recommended for use during the acute recovery phase following myocardial infarction.
Amitriptyline HCl may block the antihypertensive action of guanethidine or similarly acting compounds.
It should be used with caution in patients with a history of seizures and, because of its atropine-like action, in patients with a history of urinary retention, angle-closure glaucoma or increased intraocular pressure. In patients with angle-closure glaucoma, even average doses may precipitate an attack.
Patients with cardiovascular disorders should be watched closely. Tricyclic antidepressant drugs, including amitriptyline HCl, particularly when given in high doses, have been reported to produce arrhythmias, sinus tachycardia, and prolongation of the conduction time. Myocardial infarction and stroke have been reported with drugs of this class.
Usage in Pregnancy: Teratogenic effects were not observed in mice, rats, or rabbits when amitriptyline was given orally at doses of 2 to 40 mg/kg/day (up to 13 times the maximum recommended human dose).
Nursing Mothers: Amitriptyline is excreted into breast milk.
Because of the potential for serious adverse reactions in nursing infants from amitriptyline, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Usage in Children: In view of the lack of experience with the use of this drug in children, it is not recommended at the present time for patients under 12 years of age.
Schizophrenic patients may develop increased symptoms of psychosis; patients with paranoid symptomatology may have an exaggeration of such symptoms. Depressed patients, particularly those with known maniac-depressive illness, may experience a shift to mania or hypomania. In these circumstances the dose of amitriptyline may be reduced or a major tranquilizer such as perphenazine may be administered concurrently.
Within each category the following adverse reactions are listed in order of decreasing severity:
Cardiovascular: Myocardial infarction; stroke; nonspecific ECG changes and changes in AV conduction; heart block; arrhythmias; hypotension, particularly orthostatic hypotension; syncope; hypertension; tachycardia; palpitation.
CNS and Neuromuscular: Coma; seizures; hallucinations; delusions; confusional states; disorientation; incoordination; ataxia; tremors; peripheral neuropathy; numbness, tingling, and paresthesias of the extremities; extrapyramidal symptoms including abnormal involuntary movements and tardive dyskinesia; dysarthria; disturbed concentration; excitement; anxiety; insomnia; restlessness; nightmares; drowsiness; dizziness; weakness; fatigue.
Anticholinergic: Paralytic ileus; hyperpyrexia; urinary retention; dilatation of the urinary tract; constipation; blurred vision, disturbance of accommodation, increased ocular pressure, mydriasis; dry mouth.
Allergic: Skin rash; urticaria; photosensitization; edema of face and tongue.
Hematologic: Bone marrow depression including agranulocytosis, leukopenia, thrombocytopenia; purpura; eosinophilia.
Gastrointestinal: Rarely hepatitis (including altered liver function and jaundice); nausea; epigastric distress; vomiting; anorexia; stomatitis; peculiar taste; diarrhea; parotid swelling; black tongue.
Endocrine: Testicular swelling and gynecomastia in the male; breast enlargement and galactorrhea in the female; increased or decreased libido; impotence; elevation and lowering of blood sugar levels.
Other: Alopecia; edema; weight gain or loss; urinary frequency; increased perspiration.
Manifestations: High doses may cause temporary confusion, disturbed concentration, or transient visual hallucinations. Overdosage may cause drowsiness; hypothermia; tachycardia and other arrhythmic abnormalities, such as bundle branch block; ECG evidence of impaired conduction; congestive heart failure; dilated pupils; disorders or ocular motility; convulsions; severe hypotension; stupor; coma; and, polyradiculoneuropathy.
Dosage and Administration:
Oral Dosage: Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance.
Initial Dosage for Adults: For outpatients 75 mg of amitriptyline HCl a day in divided doses is usually satisfactory. If necessary, this may be increased to a total of 150 mg per day. Increases are made preferably in the late afternoon and/or bedtime doses. A sedative effect may be apparent before the antidepressant effect is noted, but an adequate therapeutic effect may take as long as 30 days to develop.
An alternate method of initiating therapy in outpatients is to begin with 50 to 100 mg amitriptyline HCl at bedtime. This may be increased by 25 or 50 mg as necessary in the bedtime dose to a total of 150 mg per day.
Hospitalized patients may require 100 mg a day initially. This can be increased gradually to 200 mg a day if necessary. A small number of hospitalized patients may need as much as 300 mg a day.
Adolescent and Elderly Patients: In general, lower dosages are recommended for these patients. Ten mg 3 times a day with 20 mg at bedtime may be satisfactory in adolescent and elderly patients who do not tolerate higher dosages.
Maintenance: The usual maintenance dosage of amitriptyline HCl is 50 to 100 mg per day. In some patients 40 mg per day is sufficient.
Intramuscular Dosage: Initially, 20 to 30 mg (2 to 3 ml) four times a day.
When amitriptyline HCl injection is administered intramuscularly, the effects may appear more rapidly than with oral administration.
When amitriptyline HCl injection is used for initial therapy in patients unable or unwilling to take amitriptyline HCl tablets, the tablets should replace the injection as soon as possible.