Triptil (Protriptyline HCl)

TRIPTIL® Merck Frosst Protriptyline HCl Antidepressant

Indications And Clinical Uses:

In the treatment of depression that is a manifestation of psychosis or neurosis, whether endogenous or reactive in nature. Endogenous depression is more likely to respond than other depressive states. It is especially recommended for apathetic, withdrawn patients because it promptly relieves anergia and lacks sedative activity. These qualities make it useful also in ambulatory depressed patients.

When used in anergic schizophrenic patients, protriptyline has been reported to markedly improve hypoactivity and accessibility, resulting in increased participation in concurrent psychotherapeutic and milieu therapy. However, as with all potent antidepressant agents, the schizophrenic symptomatology may be activated and require a major tranquilizer.

The symptoms of depression that may be helped by this drug include depressed mood, excessive crying, apathy, withdrawal, psychomotor retardation, loss of interest, fatigue, lassitude, feelings of guilt, anorexia, headache, insomnia, and functional somatic complaints, for example gastrointestinal symptoms.

Indications And Clinical Uses:

Cases of known hypersensitivity to tricyclic antidepressants or to any of the nonmedicinal ingredients of the tablets.

Protriptyline should not be given concomitantly with a MAO inhibiting compound. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressant and MAO inhibiting drugs simultaneously.

When it is desired to substitute protriptyline for a MAO inhibitor, a minimum of 14 days should be allowed to elapse after the latter is discontinued. Protriptyline should then be initiated cautiously with gradual increase in dosage until optimum response is achieved.

This drug should not be used during the acute recovery phase following myocardial infarction.

Pregnancy and Lactation: see Precautions.

Warnings in Clinical States:

The drug is to be used with caution in patients with a history of seizures, impaired liver function, urinary retention or increased intraocular pressure.

Tachycardia and postural hypotension may occur more frequently with protriptyline than with other antidepressant drugs. Protriptyline should be used with caution in elderly patients and patients with cardiovascular disorders; such patients should be observed closely because of the tendency of the drug to produce tachycardia, hypotension, arrhythmias, and prolongation of the conduction time.

Myocardial infarction and stroke have 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.

Due to an infrequent risk of arrhythmias, close supervision is required for hyperthyroid patients or those receiving thyroid medication.

Precautions:

When protriptyline is used to treat the depressive component of schizophrenia, psychotic symptoms may be aggravated. Likewise, in manic depressive psychosis, depressed patients may experience a shift toward the manic phase if they are treated with an antidepressant drug. Paranoid delusions, with or without associated hostility, may be exaggerated. In any of these circumstances, it may be advisable to reduce the dose of protriptyline or to use a major tranquilizing drug, such as perphenazine, concurrently.

Symptoms, such as anxiety or agitation, may be aggravated in overactive or agitated patients.

The possibility of suicide in depressed patients remains during treatment. Patients should not have access to large quantities of the drug during treatment. It is advisable to initiate therapy with the concurrent administration of a tranquilizer and preventive supervision in suicidal patients since they usually have a high level of anxiety, and especially as protriptyline may relieve anergia before there is complete recovery from the depressive state.

Discontinue the drug several days before elective surgery if possible.

Occupational Hazards: The drug may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle.

In patients using alcohol excessively, potentiation may increase the inherent danger of suicide attempt or overdosage.

Pregnancy and Lactation: Safe use in pregnancy and lactation has not been established; therefore, use in pregnant women, nursing mothers or women who may become pregnant requires that possible benefits be weighed against possible hazards to mother and child.

Children: This drug is not recommended for use in children (under 12 years of age) because safety and effectiveness in the pediatric age group have not been established.

Drug Interactions:

Protriptyline may block the antihypertensive effect of guanethidine or similarly acting compounds.

When protriptyline is given with anticholinergic agents or sympathomimetic drugs, including epinephrine combined with local anesthetics, close supervision and careful adjustment of dosages are required.

Cimetidine is reported to reduce hepatic metabolism of certain tricyclic antidepressants.

Protriptyline may enhance the response to alcohol and the effects of barbiturates and other CNS depressants.

Concurrent administration of protriptyline and electroshock therapy may increase the hazards of therapy. Such treatment should be limited to patients for whom it is essential.

Patients receiving thyroid medication may develop arrhythmias when protriptyline is given.

Adverse Reactions:

Note: Included in the listing which follows are a few adverse reactions which have not been reported with this specific drug. However, the pharmacological similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when protriptyline is administered. Protriptyline is more likely to aggravate agitation and anxiety and produce cardiovascular reactions such as tachycardia and hypotension.

Cardiovascular: hypotension (particularly orthostatic hypotension), hypertension, tachycardia, palpitation, myocardial infarction, arrhythmias, heart block, stroke.

Psychiatric: confusion states (especially in the elderly) with hallucinations, disorientation, delusions, anxiety, restlessness, agitation; insomnia, panic, and nightmares; hypomania; exacerbation of psychosis.

Neurological: numbness, tingling, and paresthesias of extremities; incoordination; ataxia; tremors; peripheral neuropathy; extrapyramidal symptoms; seizures; alteration in EEG patterns; tinnitus; drowsiness, dizziness, weakness and fatigue; headache.

Anticholinergic: dry mouth and rarely associated sublingual adenitis; blurred vision, disturbance of accommodation, mydriasis; constipation; paralytic ileus; hyperpyrexia; urinary retention, delayed micturition, dilation of the urinary tract.

Allergic: skin rash, petechiae, urticaria, itching, photosensitization (avoid excessive exposure to sunlight), edema (general, or of face and tongue), drug fever.

Hematologic: bone marrow depression; agranulocytosis; leukopenia; eosinophilia; purpura; thrombocytopenia.

Gastrointestinal: nausea and vomiting; anorexia; epigastric distress; diarrhea; peculiar taste; stomatitis; abdominal cramps; black tongue.

Endocrine: gynecomastia in the male, breast enlargement and galactorrhea in the female; increased or decreased libido, impotence; testicular swelling; elevation or depression of blood sugar levels; syndrome of inappropriate ADH secretion.

Other: jaundice (stimulating obstructive); altered liver function; weight gain or loss; perspiration; flushing; urinary frequency, nocturia; parotid swelling; alopecia.

Abrupt cessation of treatment after prolonged administration may produce nausea, headache, and malaise. Gradual dosage reduction has been reported to produce, within 2 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.

Symptoms And Treatment Of Overdose:

Symptoms: High doses may cause temporary confusion, disturbed concentration, or transient visual hallucinations. Overdosage may cause drowsiness; hypothermia; tachycardia and other arrhythmic abnormalities, for example, bundle branch block; ECG evidence of impaired conduction; congestive heart failure; dilated pupils; convulsions; severe hypotension; stupor; and coma. Other symptoms may be agitation, hyperactive reflexes, muscle rigidity, vomiting, hyperpyrexia, or any of those listed under Adverse Effects.

Treatment: Experience in the management of overdosage with protriptyline is limited. The following recommendations are based on the management of overdosage with other tricyclic antidepressants.

All patients suspected of having taken an overdosage should be admitted to a hospital. Treatment is symptomatic and supportive. If ingestion is recent, empty the stomach as quickly as possible by emesis followed by gastric lavage. Following gastric lavage, activated charcoal may be administered. Twenty to 30 g of activated charcoal may be given every 4 to 6 hours during the first 24 to 48 hours after ingestion. An ECG should be taken and close monitoring of cardiac function instituted if there is any sign of abnormality. Maintain an open airway and adequate fluid intake; regulate body temperature.

The i.v. administration of 1 to 3 mg of physostigmine salicylate is reported to reverse the symptoms of other tricyclic antidepressant poisoning in humans. Because physostigmine is rapidly metabolized, the dosage of physostigmine should be repeated as required particularly if life-threatening signs such as arrhythmias, convulsions, and deep coma recur or persist after the initial dosage of physostigmine. Because physostigmine itself may be toxic, it is not recommended for routine use.

Standard measures should be used to manage circulatory shock and metabolic acidosis. Close monitoring of cardiac function for not less than 5 days is advisable.

Anticonvulsants may be given to control convulsions.

Dialysis is of no value because of low plasma concentrations of the drug.

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

Deaths by deliberate or accidental overdosage have occurred with this class of drugs.

Dosage & Administration:

Depression tends to be cyclical in nature and varying in severity. Therefore, dosage must be individualized, bearing in mind the possibility of spontaneous remission in certain instances, regardless of therapy, as well as the danger of relapse.

The natural course of depression is often many months in duration. Accordingly, it is suggested that maintenance therapy should be continued for at least 3 months after there is satisfactory improvement. This will reduce the chance of relapse, which may occur if the depressive cycle is not complete. If relapse does occur after discontinuation of protriptyline, therapy with the drug may be reinstituted.

Daily dosage ranges between 20 and 60 mg orally depending on the severity of the condition and should preferably be divided into 2 or 4 doses a day. If insomnia is present, the last dose of the day should be given no later than midafternoon. Required increases in dosage should be added to the morning dose. When a satisfactory response is obtained, dosage should be reduced to the smallest amount required for maintenance therapy.

If dosage required to maintain adequate response produces overstimulation, concomitant use of a tranquilizer will usually provide effective control. If dosage can be kept below 20 mg daily, overstimulation may not occur.

Outpatients: An initial dosage of 20 to 30 mg a day, orally, is recommended.

Hospitalized Patients: A dosage of 30 to 60 mg a day, orally, may be necessary to obtain adequate initial dosage.

Elderly Patients and Adolescents: These patients often respond to lower doses, and may not tolerate higher doses as well as other patients. Ten mg twice a day may be given to them as initial therapy. In the elderly patients, the cardiovascular system should be closely monitored if the daily dose exceeds 20 mg.

Availability & Storage:

Each white, round, film-coated tablet, with MSD 47 printed on one side, contains: protriptyline HCl 10 mg. Nonmedicinal ingredients: calcium phosphate, carnauba wax, cellulose derivatives, guar gum, magnesium stearate, silica, starch, talc and titanium dioxide. Gluten-, lactose- and tartrazine-free. High density polyethylene bottles of 100. Store at controlled room temperature (between 15 and 30°C).

TRIPTIL® Merck Frosst Protriptyline HCl Antidepressant