Document: spc-doc_PL 20046-0294 change

• spc-doc_PL 17780-0638
• spc-doc_PL 20046-0294

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Trimpramine 50mg Capsules

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Trimipramine Maleate 69.74mg equivalent to 50mg trimipramine per capsule. For full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Capsule, hard

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Trimipramine has a potent antidepressant action similar to that of other tricyclic antidepressants. It also possesses pronounced sedative action. It is, therefore, indicated in the treatment of depressive illness, especially where sleep disturbance, anxiety or agitation are presenting symptoms. Sleep disturbance is controlled within 24 hours and true antidepressant action follows within 7 to 10 days.

4.2 Posology and method of administration

For oral use.

Adults: For depression 50-75 mg/day initially increasing to 150-300 mg/day in divided doses or one dose at night. The maintenance dose is 75-150 mg/day.

Elderly: 10-25 mg three times a day initially. The initial dose should be increased with caution under close supervision. Half the normal maintenance dose may be sufficient to produce a satisfactory clinical response.

Children: Not recommended.

4.3 Contraindications

Recent myocardial infarction.

Any degree of heart block or other cardiac arrhythmias. Mania.

Severe liver disease.

During breast feeding.

4.4 Special warnings and precautions for use

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Other psychiatric conditions for which Trimipramine is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than    25 years    old.

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

The elderly are particularly liable to experience adverse reactions, especially agitation, confusion and postural hypotension.

Avoid if possible in the patients with narrow angle glaucoma, symptoms suggestive of prostatic hypertrophy and a history of epilepsy.

Tricyclic antidepressants potentiate the central nervous depressant action of alcohol.

Anaesthetics given during tri/tetracyclic antidepressant therapy may increase the risk of arrhythmias and hypotension. If surgery is necessary, the anaesthetist should be informed that a patient is being so treated.

It may be advisable to monitor liver function in the patients on long term treatment with Trimipramine.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Trimipramine should not be given concurrently with, or within 2 weeks of cessation of, therapy with monoamine oxidase inhibitors. Trimipramine may decrease the antihypertensive effect of guanethidine, debrisoquine, bethanidine and possibly clonidine. It would be advisable to review all antihypertensive therapy during treatment with tricyclic antidepressants.

Trimipramine should not be given with sympathomimetic agents such as adrenaline, ephedrine, isoprenaline, noradrenaline, phenylephrine and phenylpropanolamine.

Barbiturates may increase the rate of metabolism.

Trimipramine should be administered with care in the patients receiving therapy for hyperthyroidism.

4.6 Fertility, Pregnancy and lactation

Do not use in pregnancy especially during the first and last trimesters unless there are compelling reasons. There is no evidence from animal work that it is free from hazard. Trimipramine is contra-indicated during lactation.

4.7 Effects on ability to drive and use machines

Trimipramine may initially impair alertness. Patients should be warned of the possible hazard when driving or operating machinery.

4.8 Undesirable effects

Cardiac arrhythmias and severe hypotension are likely to occur with high dosage or in deliberate overdosage. They may also occur in patients with pre-existing heart disease taking normal dosage.

The following adverse effects, although not necessarily all reported with trimipramine, have occurred with other tricyclic antidepressants:-

Atropine-like side effects including dry mouth, disturbance of accommodation, tachycardia, constipation and hesitancy of micturition are common early in treatment but usually lessen. Other common adverse effects include drowsiness, sweating, postural hypotension, tremor and skin rashes. Interference with sexual function may occur.

Serious adverse effects are rare; the following have been reported: depression of bone marrow, including agranulocytosis, cholestatic jaundice, hypomania, convulsions and peripheral neuropathy. Psychotic manifestations including mania and paranoid delusions, may be exacerbated during treatment with tricyclic antidepressants.

Withdrawal symptoms may occur on abrupt cessation of therapy and include insomnia, irritability and excessive perspiration. Adverse effects such as withdrawal symptoms, respiratory depression and agitation have been reported in neonates whose mothers had taken trimipramine during the last trimester of pregnancy.

Cases of suicidal ideation and suicidal behaviours have been reported during trimipramine therapy or early after treatment discontinuation (see section 4.4).

Class effects

Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to this risk is unknown.

Reporting of suspected adverse reactions:

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

4.9 Overdose

Acute overdosage may be accompanied by hypotensive collapse, convulsions and coma. Provided coma is not present, gastric lavage should be carried out without delay even though some time may have passed since the drug was ingested. Patients in coma should have an endotracheal tube passed before gastric lavage is started. Absorption of trimipramine is slow but, as cardiac effects may appear soon after the drug is absorbed, a saline purge should be given. Electrocardiography monitoring is essential.

It is important to treat acidosis as soon as it appears with, for example, 20 ml per kg of M/6 sodium lactate injection by slow intravenous injection. Intubation is necessary and the patient should be ventilated before convulsions develop. Convulsions should be treated with diazepam administered intravenously.

Ventricular tachycardia or fibrillation should be treated by electrical defibrillation. If supraventricular tachycardia develops, pyridostigmine bromide 1 mg (adults) intravenously or propranolol 1 mg (adults) should be administered at intervals as required.

Treatment should be continued for at least three days even if the patient appears to have recovered.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Trimipramine is a tricyclic antidepressant. It has marked sedative properties.

5.2 Pharmacokinetic properties

Trimipramine undergoes high first-pass hepatic clearance, with a mean value for bioavailability of about 41% after oral administration.

The absolute volume of distribution is 31 litres/kg and total metabolic clearance is 16 ml/min/kg.

Plasma protein binding of trimipramine is about 95%. The plasma elimination halflife is around 23 hours. Trimipramine is largely metabolised by demethylation prior to conjugation yielding a glucuronide.

5.3 Preclinical safety data

There are no preclinical data of relevance to the prescriber additional to those already included in other section of SPC.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Lactose monohydrate Sodium lauryl sulphate Maize starch

Calcium hydrogen phosphate dihydrate

Magnesium stearate

Gelatin

Titanium dioxide (E171)

Indigo carmine (E132)

Yellow iron oxide (E172)

6.2 Incompatibilities

None known.

6.3 Shelf life

36 months

6.4 Special precautions for storage

Do not store above 25°C. Store in the original packaging.