Apo-Amitriptyline

Amitriptyline hydrochloride.

Each tablet contains amitriptyline 10 mg or 25 mg, respectively.

Pharmacology: Amitriptyline is structurally and pharmacologically related to imipramine, desipramine and nortriptyline.
In experimental animals, amitripyline exhibits a disruptive action on the electroencephalogram and on operant behavior, a fairly strong anticonvulsant action, a peripheral atropine like action, antihistamine and antiserotonin effects, some adrenergic blockage and a gastric antisecretory effect. Amitriptyline is not a MAO inhibitor. The manner in when it exerts its clinical antidepressant effect is uncertain.
Amitriptyline is well absorbed from the gastrointestinal tract. Antidepressant effects may not be apparent for 2 or more weeks. It is metabolized by the liver to active (nortriptyline) and inactive metabolites. Elimination half-life is 10 to 50 hours. Amitriptyline is excreted in the urine and bile as conjugates of the cis and trans isomers of 10-hydroxynortriptyline.

The treatment of depression including that accompanied by anxiety. Amitriptyline has been found effective in reducing the incidence of enuresis in some cases where organic pathology has been excluded.

Orally Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance.
Initial dose for adults: 25 mg 3 times a day. If necessary, increase dose preferably in the late afternoon and/or bedtime to total of 150 mg a day.
Hospitalized patients may require 100 mg a day initially, increased gradually to 200 mg a day, if necessary. A small number need as much as 300 mg a day.
Adolescent and elderly patients: In general, lower dosages recommended: 10 mg 3 times a day with 20 mg at bedtime may be satisfactory.
Maintenance dose is usually 25 mg 2 to 4 times a day. When satisfactory improvement has been reached, reduce to lowest amount that will maintain relief of symptoms.
Children: Not recommended for treatment of depression in children under 12 years of age.
Enuresis: 10 mg at bedtime for children under 6 years of age. In older children increase dosage as necessary up to 25 mg at bedtime.

Symptoms: High doses may cause temporary confusion, disturbed concentration, transient visual hallucinations, agitation, hyperactive reflexes, muscle rigidity, vomiting or hyperpyrexia, in addition to anything listed under Adverse Reactions. Based on amitriptyline's known pharmacologic actions, overdosage may cause drowsiness, hypothermia, tachycardia and other arrhythmic abnormalities such as bundle branch block. ECG evidence of impaired conduction and congestive heart failure. Other manifestations may be dilated pupils, convulsions, severe hypotension, stupor and coma. All patients suspected of having taken an overdose should be admitted to a hospital as soon as possible.
Treatment: Symptomatic and supportive. Empty the stomach as quickly as possible by emesis or gastric lavage. Follow with activated charcoal (50 to 100 g), plus saline cathartic every 4 to 6 hours during the first 24 hours after ingestion as the drug is enterohepatically recycled.
Monitor cardiac function for any signs of dysrhythmia. Asymptomatic patients should be monitored for 6 hours. Patients with ECG changes should be monitored for 24 to 48 hours after ECG has returned to normal.
Maintain ventilation; regulate body temperature.
Maintain fluid and electrolyte balance. Alkalinize blood to pH 7.4 to 7.5 with i.v. sodium bicarbonate. This may prevent tachycardia and other cardiac arrhythmias. Phenytoin may be used for arrhythmias refractory to sodium bicarbonate. Propranolol is effective but its negative inotropic effect may cause hypotension so it should be used with caution. Avoid quinidine and procainamide.
Diazepam i.v. may be given to control seizures.
Forced diuresis, peritoneal dialysis, hemodialysis or charcoal hemoperfusion are not effective in increasing eliminaton.
Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Deaths by deliberate or accidental overdosage have occured with this class of drugs.
Physostigmine has been useful in treatment of convulsions, cardiac arrhythmias and hallucinations. Not recommended for routine use or to reverse coma. Administer i.v. over 2 minutes to avoid seizures. Adult dose: 2mg; pediatric dose: 0.5 mg. Repeat as required. Have atropine on hand to counteract excessive cholinergic effects

Known hypersensitivity. Concomitant administration with MAO inhibitors has been considered an absolute contraindication; however, patients with refractory depression have received combination therapy without significant adverse effects if used in combination therapy, give the drugs orally, avoid large doses and monitor the patient closely. Not recommended during the acute recovery phase following myocardial infarction, and in the presence of acute congestive heart failure.

May block the antihypertensive action of guanethidine or similarly acting compounds.
Should be used with caution in patients with a history of seizures or urinary retention or with narrow-angle glaucoma or increased intraocular pressure.
Arrhythmias, sinus tachycardia and prolongation of the conduction time have been reported, particularly with high doses. A few instances of unexpected death have been reported in patients with cardiovascular disorders. Myocardial infarction and stroke have also been reported with drugs of this class. Therefore, these drugs should be used with caution in patients with a history of cardiovascular diseases such as myocardial infarction and congestive heart failure.
Close supervision is require for hyperthyroid patients or those receiving thyroid medication.
Occupational hazards: May impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle.
Schizophrenic patients and those with paranoid symptomatology may have increased symptoms, manic-depressives may experience a shift to the manic phase. In these circumstances amitriptyline dosage may be reduce or a phenothiazine antipsychotic agent may be administered concurrently.
When given with anticholinergic agents or sympathomimetic drugs, close supervision and careful adjustment of dosages are required. May enhance the response to alcohol and the effects of barbiturates and other CNS depressants.
The possibility of suicide in depressed patients remains during treatment and until significant remission occurs, this type of patients should not have easy access to large quantities of the drug.
Concurrent electroshock therapy may increase the hazards of therapy; such treatment should be limited to patients for whom it is essential.
Discontinue the drug several days before elective surgery if possible.
Use in pregnancy and lactation: Safe use during pregnancy and lactation has not been established in pregnant patients, nursing mothers or women who may become pregnant, weigh possible benefits against possible hazards to mother and child. Amitriptyline and nortriptyline are excreted in low concentrations in breast milk.

Pregnancy and lactation: Safe use during pregnancy and lactation has not been established in pregnant patients, nursing mothers, or women who may become pregnant, weigh possible benefits against possible hazards to mother and child. Amitriptyline and notriptyline are excreted in low concentrations in breast milk.

Note: Included in this listing are a few adverse reactions not reported with this specific drug. However, pharmacological similarities among the tricyclic antidepressant drugs require that each reaction be considered when amitriptyline is administered.
Behavioural: Activation of latent schizoprenia, high doses may cause temporary confusion or disturbed concentration, or rarely, transient visual hallucination, hypomanic reactions, drowsiness which usually disappears with continuance of therapy; insomnia, giddiness, restlessness, agitation, fatigue, nightmares, disorientation, delusions, excitement, anxiety and jitteriness.
Neurological: epileptiform seizures, numbness, tingling, paresthesias of the limbs, including peripheral neuropathy; dizziness, fine tremor, headache, ataxia, seizures, alteration in EEG patterns, extrapyramidal symptoms, tinnitus and incoordination; severe tremor only observed with high doses.
Autonomic: evidence of anticholinergic activity, such as urinary retention, reversible dilatation of the urinary tract, constipation and more rarely paralytic ileus of particular concern in the elderly, dry mouth, blurred vision and disturbance of accomodation.
Cardiovascular: a quinidine like effect and other reversible EEG changes such as flattening or inversion of T waves and bundle branch block, orthostatic hypotension, hypertension, palpitaion, arrhythmias, heart block and with toxic doses, ventricular tachycardia and fibrillation, myocardial infarction and stroke. A few instances of unexpected death have been reported in patients with cardiovascular disorders.
Toxic and allergic effects: bone marrow depression including agranulocytosis, eosinophilia, purpura and thrombocytopenia, jaundice rarely. Allergic type reactions manifested by skin rash, urticaria, photosensitization or swelling of the face and tongue and itching occurred rarely.
Gastrointestinal: nausea, epigastric distress, heartburn, 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, elevation and lowering of blood sugar levels.
Metabolic: increased appetite, weight gain or weight loss in some patients.
Ophthalmologic: Precipitaion of latent glaucoma or aggravation of existing glaucoma; blurred vision and mydriasis.
Miscellaneous: other side effects that may occur include fainting, weakness, urinary frequency, increased perspiration and alopecia.
Withdrawal symptoms: Abrupt cessation of treatment after prolonged administration may produce nausea, headache and malaise, these are not indicative of addiction.

Antidepressants

N06AA09 - amitriptyline ; Belongs to the class of non-selective monoamine reuptake inhibitors. Used in the management of depression.

POM