AMITRIPTYLINE HYDROCHLORIDE (Page 4 of 5)

Cardiovascular

A maximal limb-lead QRS duration of ≥0.10 seconds may be the best indication of the severity of the overdose. Intravenous sodium bicarbonate should be used to maintain the serum pH in the range of 7.45 to 7.55. If the pH response is inadequate, hyperventilation may also be used. Concomitant use of hyperventilation and sodium bicarbonate should be done with extreme caution, with frequent pH monitoring. A pH >7.60 or a pCO 2 <20 mm Hg is undesirable. Dysrhythmias unresponsive to sodium bicarbonate therapy/hyperventilation may respond to lidocaine, bretylium or phenytoin. Type 1 A and 1 C antiarrhythmics are generally contraindicated (e.g., quinidine, disopyramide, and procainamide).

In rare instances, hemoperfusion may be beneficial in acute refractory cardiovascular instability in patients with acute toxicity. However, hemodialysis, peritoneal dialysis, exchange transfusions, and forced diuresis generally have been reported as ineffective in tricyclic antidepressant poisoning.

CNS

In patients with CNS depression early intubation is advised because of the potential for abrupt deterioration. Seizures should be controlled with benzodiazepines, or if these are ineffective, other anticonvulsants (e.g., phenobarbital, phenytoin).

Physostigmine is not recommended except to treat life-threatening symptoms that have been unresponsive to other therapies, and then only in consultation with a poison control center.

Psychiatric Follow-up

Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Psychiatric referral may be appropriate.

Pediatric Management

The principles of management of pediatric and adult overdosages are similar. It is strongly recommended that the physician contact the local poison control center for specific pediatric treatment.

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. 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. Adjustments in dosage should be made according to the patient’s clinical response and not on the basis of plasma levels. 2


2
Hollister, L.E.; Monitoring Tricyclic Antidepressant Plasma Concentrations. JAMA 1979; 241(23):2530-2533.

HOW SUPPLIED

Amitriptyline hydrochloride tablets, USP for oral administration are available as:

10 mg: Brown coloured, round, biconvex, film coated tablet debossed with “I1” on one side and plain on other side, and supplied as:

NDC 16729-171-10 bottles of 30

NDC 16729-171-01 bottles of 100

NDC 16729-171-17 bottles of 1,000

25 mg: Brown coloured, round, biconvex, film coated tablet debossed with “I2” on one side and plain on other side, and supplied as:

NDC 16729-172-10 bottles of 30

NDC 16729-172-01 bottles of 100

NDC 16729-172-17 bottles of 1,000

50 mg: Brown coloured, round, biconvex, film coated tablet debossed with “I3” on one side and plain on other side, and supplied as:

NDC 16729-173-10 bottles of 30

NDC 16729-173-01 bottles of 100

NDC 16729-173-17 bottles of 1,000

75 mg: Brown coloured, round, biconvex, film coated tablet debossed with “I4” on one side and plain on other side, and supplied as:

NDC 16729-174-10 bottles of 30

NDC 16729-174-01 bottles of 100

NDC 16729-174-17 bottles of 1,000

100 mg: Brown coloured, round, biconvex, film coated tablet debossed with “I5” on one side and plain on other side, and supplied as:

NDC 16729-175-10 bottles of 30

NDC 16729-175-01 bottles of 100

NDC 16729-175-17 bottles of 1,000

150 mg: Brown coloured, capsule shaped, biconvex, film coated tablet debossed with “I6” on one side and plain on other side, and supplied as:

NDC 16729-176-10 bottles of 30

NDC 16729-176-01 bottles of 100

NDC 16729-176-17 bottles of 1,000

Store at 20º to 25ºC (68º to 77ºF) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container.

METABOLISM

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 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, F.J., Jr.: Amitriptyline therapy for depressive reactions, Psychosom. 1: 320-325, Nov.-Dec. 1960.

Diamond, S.: Human metabolization of amitriptyline tagged with carbon 14, Curr. Therap. Res. 7: 170-175, Mar. 1965.

Dorfman, W.: Clinical experiences with amitriptyline (A preliminary report), Psychosom. 1: 153-155, May-June 1960.

Fallette, J.M.; Stasney, C.R.; Mintz, A.A.: Amitriptyline poisoning treated with physostigmine, S. Med. J. 63: 1492-1493, Dec. 1970 (in Soc. Proc.).

Hollister, L.E.; Overall, J.E.; Johnson, M.; Pennington, V.; Katz, G.; Shelton, J.: Controlled comparison of amitriptyline, imipramine and placebo in hospitalized depressed patients, J. Nerv. and Ment. Dis. 139: 370-375, Oct. 1964.

Hordern, A.; Burt, C.G.; Holt, N.F.: Depressive states. A pharmacotherapeutic study, Springfield, Ill., Charles C. Thomas, 1965.

Jenike, M.A.: Treatment of Affective Illness in the Elderly with Drugs and Electroconvulsive Therapy, J. Geriatr. Psychiatry 1989;22(1).77-112.

Klerman, G.L.; Cole, J.O.: Clinical pharmacology of imipramine and related antidepressant compounds, Int. J. Psychiat. 3: 267-304, Apr. 1976.

Liu, B.; Anderson, C.; Mittman, N. et al: Use of selective serotonin-reuptake inhibitors or tricyclic antidepressants and risk of hip fractures in elderly people. Lancet 1998; 351 (91 12):1303-1307.

McConaghy, N.; Joffe, A.D.; Kingston, W.R.; Stevenson, H.G.; Atkinson, I.; Cole, E.; Fennessy, L.A.; Correlation of clinical features of depressed outpatients with response to amitriptyline and protriptyline, Brit. J. Psychiat. 114: 103-106, Jan. 1968.

McDonald, I.M.; Perkins, M.; Marjerrison, G.; Podilsky, M.: A controlled comparison of amitriptyline and electroconvulsive therapy in the treatment of depression, Amer. J. Psychiat. 122: 1427-1431. June 1966 (in Brief Communications).

Slovis, T.; Ott, J.; Teitelbaum, D.; Lipscomb, W.: Physostigmine therapy in acute tricyclic antidepressant poisoning, Clin. Toxicol. 4: 451-459, Sept. 1971.

Symposium on depression with special studies of a new antidepressant, amitriptyline, Dis. Nerv. Syst. 22: 5-56, May 1961 (Sect. 2).

Manufactured For:
Accord Healthcare, Inc.,
1009, Slater Road,
Suite 210-B,
Durham, NC 27703,
USA.

Manufactured By:
Intas Pharmaceuticals Limited,
Ahmedabad- 380 009, India.

10 0374 1 667968

Issued August 2016

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