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AMITRIPTYLINE HYDROCHLORIDE TABLETS, USP
Rx only
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 a 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 a 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 (see Warnings: Clinical Worsening and Suicide Risk, Precautions: Information for Patients, and Precautions: Pediatric Use.)
DESCRIPTION
Amitriptyline HCl is 3-(10,11-dihydro-5H-dibenzo [a,d] cycloheptene-5-ylidene)-N,N-dimethyl-1-propanamine hydrochloride. Its empirical formula is C20H23N∙HCl, and its structural formula is:
Amitriptyline HCl, a dibenzocycloheptadiene derivative, has a molecular weight of 313.87. It 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 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.
ACTIONS
Amitriptyline hydrochloride 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. 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
For the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than are other depressive states.
CONTRAINDICATIONS
Amitriptyline hydrochloride 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 hydrochloride, a minimum of 14 days should be allowed to elapse after the former is discontinued. Amitriptyline hydrochloride should then be initiated cautiously with a gradual increase in dosage until optimum response is achieved.
Amitriptyline hydrochloride should not be given with Cisapride due to the potential for increased QT interval and increased risk for arrhythmia.
This drug is not recommended for use during the acute recovery phase following myocardial infarction.
WARNINGS
Usage In Pregnancy:
PRECAUTIONS
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 manic-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.
The possibility of suicide in depressed patients remains until significant remission occurs. Potentially suicidal patients should not have access to large quantities of this drug. Prescriptions should be written for the smallest amount feasible.
Concurrent administration of amitriptyline hydrochloride and electroshock therapy may increase the hazards associated with such therapy. Such treatment should be limited to patients for whom it is essential.
When possible, the drug should be discontinued several days before elective surgery.
Both elevation and lowering of blood sugar levels have been reported.
Amitriptyline hydrochloride should be used with caution in patients with impaired liver function.
Drug Interactions:
ADVERSE REACTIONS
Within each category the following adverse reactions are uled in order of decreasing severity. Included in the uling are a few adverse reactions which have not been reported with this specific drug. However, pharmacological similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when amitriptyline is administered.
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; delusion; 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; exclient; anxiety; insomnia; restlessness; nightmares; drowsiness; dizziness; weakness; fatigue; headache; syndrome of inappropriate ADH (antidiuretic hormone) secretion; tinnitus; alteration in EEG patterns.
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.
OVERDOSAGE
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 a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose; therefore, hospital monitoring is required as soon as possible.
Management:
DOSAGE AND ADMINISTRATION
Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance.
HOW SUPPLIED
10 mg tablets are blue, round, unscored, film coated tablets, coded "2101" and "V". They are supplied in bottles of 30, 60, 90, 100 and 1000.
25 mg tablets are yellow, round, unscored, film coated tablets, coded "2102" and "V". They are supplied in bottles of 30, 60, 90, 100 and 1000.
50 mg tablets are beige, round, unscored, film coated tablets, coded "2103" and "V". They are supplied in bottles of 30, 60, 90, 100 and 1000.
75 mg tablets are orange, round, unscored, film coated tablets, coded "2104" and "V". They are supplied in bottles of 30, 60, 90, 100 and 1000.
100 mg tablets are mauve, round, unscored, film coated tablets, coded "2105" and "V". They are supplied in bottles of 30, 60, 90, 100 and 1000.
150 mg tablets are blue, capsule shaped, unscored, film coated tablets, coded "2106" on one side and "V" on the other side. They are supplied in bottles of 30, 60, 90, 100 and 1000.
Storage: Store in a well-closed container. Store at 20°–25°C (68°–77°F) [see USP Controlled Room Temperature]. In addition, amitriptyline tablets must be protected from light and stored in a well-closed, light-resistant container.
METABOLISM
Studies in man following oral administration of 14C-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 4 to 6 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.
REFERENCES
Ayd FJ Jr: Amitriptyline therapy for depressive reactions. Psychosomatics
1960;1:320-325.
Diamond S: Human metabolizer of amitriptyline tagged with carbon 14.
Curr Ther Res, Mar 1965, pp 170-175.
Dorfman W: Clinical experiences with amitriptyline: A preliminary report.
Psychosomatics 1960;1:153-155.
Fallette JM, Stasney CR, Mintz AA: Amitriptyline poisoning treated with
physostigmine. South Med J 1970;63:1492-1493.
Holuler LE, Overall JE, Johnson M, et al: Controlled comparison of
amitriptyline, imipramine and placebo in hospitalized depressed
patients. J Nerv Ment Dis 1964;139:370-375.
Hordern A, Burt CG, Holt NF: Depressive states: A pharmacotherapeutic
study, Springfield study. Springfield, Ill, Charles C. Thomas, 1965.
Jenike MA: Treatment of Affective Illness in the Elderly with Drugs and
Electroconvulsive Therapy. J Geriatr Psychiatry 1989; 22(1):77-112.
Klerman GL, Cole JO: Clinical pharmacology of imipramine and related
antidepressant compounds. Int J Psychiatry 1976;3:267-304.
Liu B, Anderson G, Mittman N, et al: Use of selective serotonin-reuptake
inhibitors or tricyclic antidepressants and risk of hip fractures in elderly
people. Lancet 1998; 351(9112):1303-1307.
McConaghy N, Joffe AD, Kingston WA, et al: Correlation of clinical features
of depressed out-patients with response to amitriptyline and
protriptyline. Br J Psychiatry 1968;114:103-106.
McDonald IM, Perkins M, Marjerrison G, et al: A controlled comparison of
amitriptyline and electroconvulsive therapy in the treatment of
depression. Am J Psychiatry 1966;122:1427-1431.
Slovis T, Ott J, Teitelbaum D, et al: Physostigmine therapy in acute tricyclic
antidepressant poisoning. Clin Toxicol 1971;4:451-459.
Symposium on depression with special studies of a new antidepressant,
amitriptyline. Dis Nerv Syst, (Sect 2) May 1961, pp 5-56.
*Based on a maximum recommended amitriptyline dose of 150 mg/day or 3 mg/kg/day for a 50 kg patient.
**Holuler LE: Monitoring Tricyclic Antidepressant Plasma Concentrations. JAMA 1979; 241(23):2530-2533.
Manufactured by:
VINTAGE PHARMACEUTICALS, LLC
Huntsville, AL 35811
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A SUPPLY OF MEDICATION GUIDES AS PRINTED AT THE END OF THIS INSERT IS AVAILABLE, FREE OF CHARGE, BY CALLING (800) 444-4011.
Medication Guide
Antidepressant Medicines, Depression and
other Serious Mental Illnesses, and Suicidal
Thoughts or Actions
Read the Medication Guide that comes with you or your family member’s antidepressant medicine. This Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines. Talk to your, or your family member’s, healthcare provider about:
- all risks and benefits of treatment with antidepressant medicines
- all treatment choices for depression or other serious mental illness
What is the most important information I should know about antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions?
- Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults when the medicine is first started.
- Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These include people who have (or have a family history of) bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions.
- How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?
- Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is first started or when the dose is changed.
- Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.
- Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.
Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:
- thoughts about suicide or dying
- attempts to commit suicide
- new or worse depression
- new or worse anxiety
- feeling very agitated or restless
- panic attacks
- trouble sleeping (insomnia)
- new or worse irritability
- acting aggressive, being angry, or violent
- acting on dangerous impulses
- an extreme increase in activity and talking (mania)
- other unusual changes in behavior or mood
What else do I need to know about antidepressant medicines?
- Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
- Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.
- Antidepressant medicines have other side effects. Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member.
- Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a ul of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider.
- Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk to your child’s healthcare provider for more information.
This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.
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