CLOMIPRAMINE

Before initiating treatment with clomipramine, hypokalemia should be treated (see

, for a description of the risks of discontinuation of clomipramine). 3 Contraindications Clomipramine is contra-indicated in patients with known hypersensitivity to clomipramine, any of the excipients, or cross-sensitivity tricyclic antidepressants of the dibenzazepine group, severe liver disease, recent myocardial infarction, cardiac failure or any degree of heart block or cardiac arrhythmias, narrow angle glaucoma, urine retention and mania.

5 Interactions with other Medicinal Products and other forms of Interaction). 5). The concomitant treatment with selective, reversible MAO-A inhibitors such as moclobemide, is also contraindicated. 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 clomipramine 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.

1 Therapeutic indications). Antidepressants increase the risk of suicide-related behaviours (suicide attempt and suicidal thoughts), and hostility (predominately aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo.

If based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long term safety data in children and adolescents concerning growth, maturation and cognitive behavioural development are lacking.

8 Undesirable effects), as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Prescriptions for clomipramine should be written for the smallest quantity of tablets and capsules consistent with good patient management, in order to reduce the risk of overdose.

Modifying the therapeutic regimen, including possibly discontinuing the medication, should be considered in these patients, especially if these changes are severe, abrupt in onset, or were not part of the patient's presenting symptoms.

Other Psychiatric Effects Many patients with panic disorders may experience a paradoxical increase in anxiety particularly at the start of treatment but this usually subsides within the first 2 weeks. Activation of psychosis has occasionally been observed in schizophrenic patients receiving tricyclic antidepressants.

Hypomanic or manic episodes have also been reported during a depressive phase in patients with cyclic affective disorders receiving treatment with a tricyclic antidepressant. In such cases it may be necessary to reduce the dosage of clomipramine or to withdraw it and administer an antipsychotic agent.

After such episodes have subsided, low dose therapy with clomipramine may be resumed if required. In predisposed and elderly patients, tricyclic antidepressants may provoke pharmacogenic (delirious) psychoses, particularly at night.

These disappear within a few days of withdrawing the drug. As improvement in depression may not occur for the first two to four weeks treatment, patients should be closely monitored during this period. The elderly are particularly liable to experience adverse effects, especially confusion, agitation and postural hypotension.

Before initiating treatment it is advisable to check the patient's blood pressure, because individuals with hypotension or a labile circulation may react to the drug with a fall in blood pressure. g. […]

). 4. Special Warnings and Precautions for use). 4 Special Warnings and Precautions for use and

Clomipramine is contra-indicated in patients with known hypersensitivity to clomipramine, any of the excipients, or cross-sensitivity tricyclic antidepressants of the dibenzazepine group, severe liver disease, recent myocardial infarction, cardiac failure or any degree of heart block or cardiac arrhythmias, narrow angle glaucoma, urine retention and mania.

Clomipramine should not be administered concurrently with monoamine oxidase inhibitors, or within 3 weeks before or after treatment with a MAO inhibitor (see section