AMITRIPTYLINE HYDROCHLORIDE- amitriptyline hydrochloride tablet, film coated
Suicidality and Antidepressant Drugs
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of amitriptyline hydrochloride tablets or any other antidepressant in child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Amitriptyline hydrochloride tablets are not approved for use in pediatric patients
Amitriptyline HCl is 3-(10,11-dihydro-5H-dibenzo [a,d cycloheptene-5-ylidene)-N,N-dimethyl-1-propanamine hydrochloride. Its empirical formula is C20 H23 N?HCl,
Amitriptyline HCl, dibenzocycloheptadiene derivative, has molecular weight of 313.87. It is 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 or 150 mg tablets. Each tablet contains the following inactive ingredients: colloidal silicon dioxide, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate, sodium starch glycolate and titanium dioxide. The 10 mg tablets also contain FD&C blue #1 lake. The 25 mg tablets also contain D&C yellow #10 lake and FD&C blue #2 lake. The 50 mg tablets also contain synthetic black iron oxide, synthetic red iron oxide and synthetic yellow iron oxide. The 75 mg tablets also contain FD&C yellow #6 lake. The 100 mg tablets also contain D&C red #33 lake and FD&C red #40 lake. The 150 mg tablets also contain FD&C blue #2 lake and FD&C yellow #6 lake.
Amitriptyline hydrochloride is an antidepressant with sedative effects. Its mechanism of action in man is not known. It is not 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. Pharmacologically this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline.
INDICATIONS AND USAGE
For the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than are other depressive states.
Clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic function, concomitant disease and other drug therapy in elderly patients.
Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. As the management is complex and changing, it is recommended that the physician contact poison control center for current info. on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose; therefore, hospital monitoring is required as soon as possible.
DOSAGE AND ADMINISTRATION
Dosage should be initiated at 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 day in divided doses is usually satisfactory. If necessary, this may be increased to total of 150 mg per day. Increases are made preferably in the late afternoon and/or bedtime doses. 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 total of 150 mg per day.
Hospitalized patients may require 100 mg day initially. This can be increased gradually to 200 mg day if necessary. small number of hospitalized patients may need as much as 300 mg day.
Studies in man following oral administration of 14 C-labeled drug indicated that amitriptyline is rapidly absorbed and metabolized. Radioactivity of the plasma was practically negligible, although significant amounts of radioactivity appeared in the urine by to hours and one-half to one-third of the drug was excreted within 24 hours.
Amitriptyline is metabolized by N-demethylation and bridge hydroxylation in man, rabbit and rat. Virtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with little unchanged drug appearing in the urine. Other metabolic pathways may be involved.