AMITRIPTYLINE HYDROCHLORIDE- amitriptyline hydrochloride tablet 
REMEDYREPACK INC.

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BOXED WARNING



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


MM1








CLINICAL PHARMACOLOGY



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.


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

PRECAUTIONS

ADVERSE REACTIONS


Within each category the following adverse reactions are listed in order of decreasing severity. Included in the listing 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; excitement; 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.

Withdrawal Symptoms: After prolonged administration, abrupt cessation of treatment may produce nausea, headache, and malaise. Gradual dosage reductions has been reported to produce, within two weeks, transient symptoms including irritability, restlessness, and dream and sleep disturbance.

These symptoms are not indicative of addiction. Rare instances have been reported of mania or hypomania occurring within 2 to 7 days following cessation of chronic therapy with tricyclic antidepressants.

Causal Relationship Unknown: Other reactions, reported under circumstances where a causal relationship could not be established, are listed to serve as alerting information to physicians.

Body as a Whole:  Lupus-like syndrome (migratory arthritis, positive ANA and rheumatoid factor).

Digestive:  Hepatic failure, ageusia.

Postmarketing Adverse Events: A syndrome resembling neuroleptic malignant syndrome (NMS) has been very rarely reported after starting or increasing the dose of amitriptyline hydrochloride, with and without concomitant medications known to cause NMS. Symptoms have included muscle rigidity, fever, mental status changes, diaphoresis, tachycardia, and tremor.

Very rare cases of serotonin syndrome (SS) have been reported with amitriptyline hydrochloride in combination with other drugs that have a recognized association with SS.

Very rare cases of cardiomyopathy have been reported with amitriptyline.



OVERDOSAGE

DOSAGE & ADMINISTRATION



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. For maintenance therapy the total daily dosage may be given in a single dose preferably at bedtime. When satisfactory improvement has been reached, dosage should be reduced to the lowest amount that will maintain relief of symptoms. It is appropriate to continue maintenance therapy 3 months or longer to lessen the possibility of relapse.

Usage in Pediatric Patients

In view of the lack of experience with the use of this drug in pediatric patients, it is not recommended at the present time for patients under 12 years of age.

Plasma Levels

Because of the wide variation in the absorption and distribution of tricyclic antidepressants in body fluids, it is difficult to directly correlate plasma levels and therapeutic effect. However, determination of plasma levels may be useful in identifying patients who appear to have toxic effects and may have excessively high levels, or those in whom lack of absorption or noncompliance is suspected. Because of increased intestinal transit time and decreased hepatic metabolism in elderly patients, plasma levels are generally higher for a given oral dose of amitriptyline hydrochloride than in younger patients. Elderly patients should be monitored carefully and quantitative serum levels obtained as clinically appropriate. Adjustment in dosage should be made according to the patient's clinical response and not on the basis of plasma levels.


HOW SUPPLIED



10 mg tablets are blue, round, unscored, film coated tablets, debossed “2101” on one side and debossed “V” on the reverse side. They are supplied in bottles of 30, 60, 90, 100 and 1000.

25 mg tablets are yellow, round, unscored, film coated tablets, debossed “2102” on one side and debossed “V” on the reverse side. They are supplied in bottles of 30, 60, 90, 100, 1000 and 2500.

50 mg tablets are beige, round, unscored, film coated tablets, debossed “2103” on one side and debossed “V” on the reverse side. They are supplied in bottles of 30, 60, 90, 100 and 1000.

75 mg tablets are orange, round, unscored, film coated tablets, debossed “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, debossed “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, debossed “2106” on one side and debossed “V” on the reverse 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.


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.

Hollister 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.


MEDICATION GUIDE

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION




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PACKAGE LABEL.PRINCIPAL DISPLAY PANEL


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AMITRIPTYLINE HYDROCHLORIDE 
amitriptyline hydrochloride tablet
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:24236-004
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
AMITRIPTYLINE HYDROCHLORIDE (UNII: 26LUD4JO9K) (AMITRIPTYLINE - UNII:1806D8D52K) AMITRIPTYLINE HYDROCHLORIDE100 mg
Inactive Ingredients
Ingredient NameStrength
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
HYPROMELLOSES (UNII: 3NXW29V3WO)  
LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
POLYETHYLENE GLYCOL (UNII: 3WJQ0SDW1A)  
POLYSORBATE 80 (UNII: 6OZP39ZG8H)  
SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
D&C RED NO. 33 (UNII: 9DBA0SBB0L)  
FD&C RED NO. 40 (UNII: WZB9127XOA)  
Product Characteristics
ColorpinkScoreno score
ShapeROUND (TABLET) Size11mm
FlavorImprint Code 2105;V
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:24236-004-24200 in 1 CANISTER; Type 0: Not a Combination Product12/13/201012/14/2010
2NDC:24236-004-0230 in 1 BLISTER PACK; Type 0: Not a Combination Product12/13/201012/14/2010
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA04021812/13/201012/14/2010
Labeler - REMEDYREPACK INC. (829572556)

Revised: 5/2016
 
REMEDYREPACK INC.