Action and Clinical
Trimipramine is a tricyclic antidepressant with sedative properties. It also has anticholinergic properties and potentiates the sympathetic response, presumably by blocking the reuptake of norepinephrine which has been released by the presynaptic neurons. It has a quinidine-like effect on the heart and an EEG activity similar to that of other tricyclic antidepressants.IndicationsIndications:
Indications And Clinical Uses:
The drug treatment of depressive illness. Effective in endogenous depression and may also be useful in some patients with neurotic depression.
Trimipramine should not be given in conjunction with or within 2Â weeks of, treatment with a MAO inhibitor drug; hyperpyretic crises, severe convulsions and death have occurred in patients receiving MAO inhibitors and tricyclic antidepressants. When substituting trimipramine for an MAOI, wait at least 2Â weeks after discontinuing the MAOI, then start trimipramine cautiously and increase gradually.
The drug is contraindicated in the acute recovery period following myocardial infarction. It should not be used in those who have shown prior hypersensitivity to the drug nor in cases of drug induced CNS depression. Cross-sensitivity between this and other dibenzazepines is a possibility.
Extreme caution should be used when this drug is given in the following situations: a. In patients with cardiovascular disease, because of the possibility of conduction defects, arrhythmias, tachycardia, strokes and acute myocardial infarction. In such cases, treatment should be initiated with low doses, with progressive increases only if required and well tolerated. b. In patients with a history of urinary retention or glaucoma because of the anticholinergic properties of the drug. c. In patients with thyroid disease or those on thyroid medication, because of the possibility of cardiovascular toxicity, including arrhythmias. d. In patients with a history of seizure disorder, because this drug has been shown to lower the seizure threshold.
This drug is capable of blocking the antihypertensive effect of guanethidine and similarly acting compounds.
Pregnancy and Lactation: Safe use of trimipramine during pregnancy and lactation has not been established; therefore, if it is to be administered to pregnant patients, nursing mothers, or women of childbearing potential, the possible benefits must be weighed against the possible hazards to mother and child.
Occupational Hazards: This drug may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery; therefore, the patient should be cautioned accordingly.
Reduce dosage, or alter treatment, if serious adverse effects occur.
Trimipramine therapy in patients with manic-depressive illness may induce a hypomanic state after the depressive phase terminates.
The drug may cause exacerbation of psychosis in schizophrenic patients.
Close supervision and careful adjustment of dosage are required when this drug is administered concomitantly with anticholinergic or sympathomimetic drugs.
Patients should be warned that while taking this drug their response to alcoholic beverages may be exaggerated.
Discontinue as soon as possible prior to elective surgery because of the possible cardiovascular effects. Hypertensive episodes have been observed during surgery in patients on tricyclic antidepressants.
The possibility of suicide in seriously depressed patients may remain until significant remission occurs. Such patients should be closely supervised throughout therapy and consideration should be given to the possible need for hospitalization and/or concomitant ECT.
Periodic blood counts and liver function tests should be performed when patients receive trimipramine in large doses or over prolonged periods.
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 trimipramine is administered.
Cardiovascular: orthostatic hypotension, hypertension, tachycardia, palpitation, arrhythmias, heart block, myocardial infarction, stroke. A few instances of unexpected death have been reported in patients with cardiovascular disorders.
Psychiatric: confusional states (especially in the elderly) with hallucinations, disorientation, delusions; anxiety, restlessness, agitation; insomnia and nightmares; hypomania; exacerbation of psychosis.
Neurological: numbness, tingling, paresthesias of extremities; incoordination, ataxia, tremors; peripheral neuropathy; extrapyramidal symptoms; seizures; alteration in EEG patterns; tinnitus.
Anticholinergic: dry mouth, and rarely associated sublingual adenitis; blurred vision, disturbance of accommodation, mydriasis; constipation, paralytic ileus; urinary retention, delayed micturition, dilatation of urinary tract.
Allergic: skin rash, petechiae, urticaria, itching, photosensitization (avoid excessive exposure to sunlight), edema (of face and tongue or general), drug fever, cross-sensitivity with other tricyclic drugs.
Hematologic: bone marrow depressions including agranulocytosis, eosinophilia, purpura, thrombocytopenia.
Gastrointestinal: anorexia, nausea and vomiting, epigastric distress, peculiar taste, abdominal cramps, diarrhea, stomatitis, 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.
Other: jaundice (simulating obstructive), altered liver function; weight gain or loss; perspiration, flushing; urinary frequency, nocturia; parotid swelling; drowsiness, dizziness, weakness and fatigue, headache; alopecia.
Withdrawal Symptoms: Though not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache and malaise.
Symptoms And Treatment Of Overdose:
OverdoseSymptoms: drowsiness, mydriasis, dysarthria, excitement, muscle spasms, convulsions, disturbances of cardiac conduction, arrhythmia, circulatory collapse, respiratory depression and coma. Cardiac arrhythmias and CNS involvement pose the greatest threat and may occur suddenly even when initial symptoms appear mild.Treatment
Treatment: There is no specific antidote and treatment must be symptomatic. Gastric lavage or, in the absence of coma, induction of emesis may be beneficial.
Administration of activated charcoal may help reduce absorption of trimipramine. In cases of severe intoxication dialysis may be undertaken, although the efficacy of such a procedure in tricyclic poisoning is doubtful due to low plasma concentrations of these drugs.
ECG monitoring in an intensive care unit is recommended in all patients, particularly in the presence of ECG abnormalities, and should be maintained for several days after the cardiac rhythm has returned to normal. Because of its effect on cardiac conduction, digitalis should be used only with caution. If rapid digitalization is required for the treatment of congestive heart failure, special care should be exercised in using the drug.
External stimulation should be minimized to reduce the tendency to convulsions. If an anticonvulsant is necessary, administer i.v. diazepam; barbiturates should be avoided since they intensify respiratory depression, particularly in children, and aggravate hypotension and coma.
Shock should be treated with supportive measures such as i.v. fluids, oxygen and corticosteroids. Pressor agents, such as levarterenol (but not epinephrine), are rarely indicated and should be given only after careful consideration and under continuous monitoring.
The slow i.v. administration of physostigmine salicylate has been reported to reverse most of the cardiovascular and CNS anticholinergic manifestations of tricyclic overdosage. The recommended dosage in adults has been 1 to 2 mg in very slow i.v. injection. In children, the initial dosage should not exceed 500 g and should be adjusted to age and response. Since physostigmine has a short duration of action, administration may have to be repeated at 30 to 60 minute intervals.
Dosage And Administration:
Treatment should be initiated at the lowest recommended dose and increased gradually, noting carefully the clinical response and any evidence of intolerance. It should be kept in mind that a lag in therapeutic response usually occurs at the onset of therapy, lasting from several days to a few weeks. Increasing the dosage does not normally shorten this latent period and may increase the incidence of side effects. All doses are expressed in terms of trimipramine base.
Initial Dosage: Adults: The recommended initial dose is 75 mg daily in two or three divided doses. Initial tolerance may be tested by giving the patient 25 mg on the evening of the first day. The initial dose should be increased by 25 mg increments, usually up to 150 mg daily, preferably by adding to the late afternoon and/or bedtime doses. In the case of severely depressed patients, a higher initial dose of 100 mg daily in two or three divided doses may be indicated. The usual optimal dose is 150 mg to 200 mg daily, but some patients may require up to 300 mg daily, depending on tolerance and response of each individual patient.
Elderly or Debilitated Patients: In these patients it is advisable to give a test dose ofÂ 12.5 to 25 mg and after 45 minutes examine the patient sitting and standing to check for orthostatic hypotension. Initial doses should usually be no more than 50 mg a day in divided doses, with weekly increments of no more than 25 mg a week, leading to a usual therapeutic dose range ofÂ 50Â to 150 mg a day. Blood pressure and cardiac rhythm must be checked frequently, particularly in patients who have unstable cardiovascular function.
Maintenance Dosage: Once a satisfactory response has been obtained, the dosage should be adjusted to the lowest level required to maintain symptomatic relief. Medication should be continued for the expected duration of the depressive episode in order to minimize the possibility of relapse following clinical improvement.
When a maintenance dosage has been established as described above, trimipramine may be administered in a single dose before bedtime, provided such a dosage regimen is well tolerated.
Availability And Storage:
Capsules: Each capsule contains: trimipramine base 75 mg (as the maleate). Nonmedicinal ingredients: calcium phosphate dibasic, D&C Yellow No 10, FD&C Blue No 1, FD&C Red No 3, gelatin, magnesium stearate, polacrilin potassium and titanium dioxide. Tartrazine-free. Bottles of 100.
Tablets: Each tablet contains: trimipramine base 12.5 mg, 25 mg, 50 mg and 100 mg (as the maleate). Nonmedicinal ingredients: acetic anhydride, carnauba wax, cellulose, colloidal silicon dioxide, diethyl phthalate, erythrosine, FD&C Red No 3, lactose, magnesium stearate, sodium croscarmellose, talc, titanium dioxide and zein. Tartrazine-free. Bottles of 100 and 500.
SURMONTIL® Rh-ne-Poulenc Rorer Trimipramine Maleate Antidepressant
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