(and dosage form):
Each capsule contains trimipramine maleate equivalent to 50 mg of trimipramine.
A 1.2 Psychoanaleptics (Antidepressants).
Trimipramine is a tricyclic antidepressant with antihistaminic and sedative actions. Trimipramine is administered by mouth as the maleate. The mechanism of action is by blockade of the amine transport system of the membrane of the adrenergic nerve terminal. The patient feels sleepy and tends to be quiet, the blood pressure falls slightly and he feels light-headed.
It can have a stimulant action under certain circumstances. The tricyclic antidepressants occasionally have been used as hypnotics because of their sedative property. Although this effect may be useful in the initial therapy of a depressed patient with sleep loss, their general use for hypnosis is not recommended. These medicines do decrease the number of awakenings, increase stage-4 sleep, and markedly decrease REM time.
The main use of trimipramine is for the treatment of depression. It can be of value in the treatment of enuresis in childhood. Some success has been achieved in the treatment of severe obsessive-compulsive neurosis.
Patients recovering from myocardial infarction. A tricyclic antidepressant must not be taken in combination with a monoamine oxidase inhibitor as this can cause severe, even fatal, reactions. Since the tricyclic antidepressants can cause orthostatic hypotension, produce arrhythmias and interact in deleterious ways with other medicines, great caution must be observed in their use in patients with significant cardiac disease. Trimipramine should be avoided in pregnancy and in women who are likely to become pregnant. There are no absolute contra-indications to the use of the tricyclic antidepressants. Administration of the tricyclics is not advised during the first trimester of pregnancy, unless there are compelling reasons for their use.
DOSAGE AND DIRECTIONS FOR USE:
General dosage is the equivalent of 25 mg to 125 mg of trimipramine daily. A therapeutic response is not usually obtained before 2-3 weeks treatment. If the total daily requirement is given at night it can induce sleep and can help the patient to return to a normal sleep pattern and at the same time reduce daytime drowsiness. Patients with recurrent depression may require maintenance therapy for up to one year or longer.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
The main side-effects of imipramine hydrochloride and the other tricyclic antidepressants are due to their anticholinergic actions; these include dry mouth constipation occasionally leading to paralytic ileus, urinary retention, blurred vision and changes in accommodation, palpitations and tachycardia. Other effects include nausea and vomiting, orthostatic hypotension, dizziness, sweating tremor, ataxia, fatigue, excitement, hypomania, epileptiform seizures, eosinophilia and skin reactions. Oestrogenic effects may occur with alterations in libido, impotence, gynaecomastia or breast enlargement, or galactorrhoea. The tricyclic antidepressants have an adverse effect on the myocardium and can cause conduction defects, cardiac arrhythmias, and infarction which have sometimes been fatal.
Large doses have caused hyperpyrexia, convulsions circulatory failure and cardiac arrest, respiratory failure, cyanosis, coma and death; deaths have also occurred from agranulocytosis and jaundice.
Reactions, sometimes fatal, have occurred in patients taking a tricyclic antidepressant with a monoamine oxidase inhibitor. Special precautions should be taken in patients with benign prostatic hypertrophy. Excessive sweating is a fairly common complaint. Headache and muscle tremors are fairly common. Older patients tend to suffer more from dizziness, postural hypotension, constipation, delayed micturition, oedema and muscle tremors. Various types of cardiovascular difficulties may arise. A transition from depression to hypomanic or manic excitement may occur in certain patients. In others, hallucinations and delusions may occur. Hypotension, insomnia and reversal of sleep rhythm may occur. This medicine should be given with care to patients suffering from alcoholism, hepatic diseases, epilepsy, a reduced convulsive threshold and glaucoma. Patients with suicidal tendencies should be carefully observed. Occasionally patients will show physical or psychic dependence on the tricyclic antidepressants. It should be given with care to patients having to commit hazardous tasks such as handling machinery or driving cars.
Administration of tricyclic antidepressants concurrently with or shortly after treatment with MAO inhibitors has resulted in severe reactions, consisting of signs and symptoms resembling those of atropine toxicity. A dose as low as 25 mg of imipramine, taken 3 days after the discontinuation of therapeutic doses of tranylcypromine, has been reported capable of producing a severe reaction characterized by convulsions, coma and hyperpyrexia. Their concurrent use is thus contra-indicated. Ten days to two weeks should elapse between discontinuation of MAO inhibitors and initiation of tricyclic antidepressants therapy. If the situation is desperate, ECT may be employed during the interval.
Other interactions include the potentiation of central depressant drugs, blockade of the antihypertensive effects of guanethidine, and augmentation of the pressor effects of sympathomimetic amines. Interactions with thyroid preparations, methylphenidate, and phenothiazines, all of which may enhance the therapeutic effect of the tricyclic antidepressants, have been reported.
In patients not suffering from endogenous depression it has the effect of producing sedation and dysphoria at the onset of treatment. Deaths can occur from agranulocytosis and jaundice.
Peripheral anticholinergic side effects; notably dry mouth, constipation, urinary retention and pupillary dilation with blurred vision and changes in visual accommodation. When anticholinergic effects are severe the medicine should be discontinued or reduced. The tricyclic antidepressants may produce drowsiness or excessive sedation in certain patients. On the other hand disorientation and agitation, insomnia and restlessness can also occur with normal doses. The risks of central nervous system depression caused by the tricyclic antidepressant agents are greater than when they are administered together with other central nervous system depressants, eg. alcohol, barbiturates. NOTE: Elderly patients are more prone to all these effects, and therapy should be initiated at lower than standard doses in the elderly.
At the time of initiation of therapy patients should be advised not to drive a motor vehicle, climb potentially dangerous heights or operate dangerous machinery for at least several days. In these situations loss of attention could lead to accidents. Caution should be taken in administering tricyclic antidepressants to patients suffering from a depressive phase of manic depressive psychosis, as occasionally hypomania or mania can be precipitated in such patients.
In elderly male patients suffering from prostatism the administration of the tricyclic antidepressants may cause urinary retention.
In patients suffering from cardiac disease the tricyclic antidepressants should be administered with special caution because of the occasional problems of tachycardia, orthostatic hypotension and other unwanted effects on blood pressure, aggravation of conduction disturbances, and electrocardiographic abnormalities, which may be associated with tricyclic therapy in such patients. Regular cardiological and electrocardiographic examination is advised.
Tricyclic antidepressants should be used with caution in patients suffering from epilepsy.
Drug interactions: tricyclic antidepressant agents should not usually be given to patients receiving other central nervous system depressants, eg. barbiturates, or to patients receiving monoamine oxidase inhibitors (the drugs may be given together if the dosages are carefully controlled preferably in hospital). The pressor effects of the directly acting sympathomimetic agents, adrenaline and noradrenaline are enhanced by tricyclic antidepressants, and the use of local anaesthetics containing these vasoconstrictors should be avoided as hypertensive reactions may occur. The simultaneous administration of other anticholinergic agents with the tricyclic antidepressants may be dangerous.
Tricyclic antidepressants may aggravate narrow-angle glaucoma.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Toxicity due to overdosage is characterized by hyperpyrexia, hypertension, seizures and coma. In some cases of poisoning in children, the medicine has caused cardiac conduction defects and arrhythmias including multifocal ectopic beats. Gastric lavage is useful in acute overdosage. Vital signs and ECG should be monitored continuously and all cases should be treated in an intensive care unit. Convulsions may be controlled with diazepam administered intravenously. Hypertension may be treated with shortacting alpha-adrenergic blocking agents but caution is desirable. Temperature can be reduced and respiration assisted with physical methods. Propranolol and lignocaine are useful in controlling the arrhythmias, however the availability of resuscitative equipment is important. Physostigmine can effectively reverse the anticholinergic CNS manifestations of severe poisoning by the tricyclic antidepressants, including coma, myoclonus, choreoathetosis and delirium. Physostigmine salicylate is given intramuscularly or by slow intravenous injection in an initial dose of 2 mg for adults. This dose is repeated in 20 minutes if there is no response. In cases responding favourably, 1 to 4 mg may have to be given every 30 to 60 minutes over a period of many hours. The tachycardia and tachypnoea may also be counteracted by such therapy.
Overdosage and poisoning may be characterized by central nervous system depression or excitation, severe anticholinergic effects and cardiotoxicity. The following symptoms and signs are characteristic of acute toxicity due to the tricyclic antidepressants: drowsiness, restlessness, ataxia, stupor, coma, pyrexia, palpitations, tachycardia, cardiac arrhythmias, hypotension and in severe cases, respiratory depression. Epileptiform seizures may occur. Mixed poisonings with an overdosage of a tricyclic antidepressant and other central nervous system depressants is not uncommon.
The stomach should be emptied by aspiration and lavage. The administration of activated charcoal in the stomach after lavage is a valuable measure preventing further absorption of the tricyclic antidepressant from the gut. Diazepam may be given intravenously to control convulsions. Ventilatory support is essential. Shock should be treated with fluids or plasma expanders; sympathomimetic agents should be avoided owing to their potentiation by tricyclic antidepressants. Careful cardiac monitoring is recommended for 48 - 72 hours after a serious overdosage as cardiac arrhythmias may be a late manifestation of toxicity. Hyperpyrexia is treated by cooling.
TRICYCLIC ANTIDEPRESSANTS SHOULD AT ALL TIMES BE KEPT OUT OF REACH OF CHILDREN, AS EVEN SMALL DOSES MAY BE FATAL TO THEM.
A No. 2 capsule with an opaque white body and opaque light green cap.
Packs of 30, 50, 100 and 500.
Store below 25°C.
Protect from light and moisture.
KEEP OUT OF REACH OF CHILDREN.
NAME AND BUSINESS ADDRESS OP APPLICANT:
Pharmacare Limited, 7 Fairclough Road, Port Elizabeth 6001
DATE OF PUBLICATION OF THIS PACKAGE INSERT:
Updated on this site: May 2004
Source: Community Pharmacy
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