APO-CLOMIPRAMINE

What it is

APO-CLOMIPRAMINE is a tricyclic antidepressant. Each tablet contains 25 mg of clomipramine hydrochloride. It inhibits the neuronal reuptake of noradrenaline and serotonin released in the synaptic cleft, with the dominant component being inhibition of serotonin uptake.

Approved indications

— Major depression. — Obsessive-compulsive disorders and phobias in adults. — Cataplexy associated with narcolepsy.

Dosing overview

For elderly patients, start with 25 mg daily and gradually increase over about ten days to an optimum level of 50–75 mg daily, then adhere to this dose until the end of treatment. Plasma concentrations do not stabilise for 7 to 14 days after commencing treatment or after a dosage change.

Key safety warnings

The risk of suicide attempt is inherent in depression and may persist until significant remission occurs. Patients with depression may experience worsening of depressive symptoms and emergence of suicidal ideation and behaviours, and patients should be closely monitored for clinical worsening and suicidality, especially at the beginning of treatment or at times of dose changes. Pooled analyses of antidepressant trials in children and adolescents revealed a greater risk of suicidal behaviour or thinking during the first few months of treatment, with an average risk of 4% in those receiving antidepressants compared with 2% given placebo. An increased risk of suicidal thinking and behaviour has also been shown in young adults aged 18 to 24 during initial treatment. Caution is required in patients with cardiovascular disorders, particularly those with a history of conduction disorders. Cardiovascular insufficiency, atrioventricular block and arrhythmias require cardiovascular function monitoring and ECG assessment, especially in elderly patients, as myocardial infarction, congestive cardiac failure, stroke and sudden death have been associated with this class of medicines. There may be a risk of QTc prolongation and torsades de pointes, particularly at supra-therapeutic doses or plasma concentrations, and concomitant administration of medicines that can cause clomipramine accumulation or prolong the QTc interval should be avoided. Hypokalaemia is a risk factor for QTc prolongation and torsades de pointes, and should be treated before initiating treatment. Serotonin syndrome, with symptoms such as hyperpyrexia, myoclonus, agitation, seizures, delirium and coma, can possibly occur when clomipramine is co-administered with serotonergic medications such as selective serotonin reuptake inhibitors, serotonin and noradrenergic reuptake inhibitors, tricyclic antidepressants or lithium. Clinical trials have shown a clear relationship between dose size and seizure occurrence, and the recommended daily dose should not be exceeded.

Contraindications

Known hypersensitivity to clomipramine or any of the excipients. Cross sensitivity to tricyclic antidepressants of the dibenzazepine group. Concomitant use with a monoamine oxidase inhibitor, or within 14 days before or after treatment with an irreversible MAO inhibitor, or within 14 days before moclobemide. Acute and recovery stages of myocardial infarction. Congenital long QT syndrome.

PBS listing

APO-CLOMIPRAMINE 25 mg tablet is listed on the PBS with restricted access, ex-manufacturer price A$4.65.

Regulatory history

APO-CLOMIPRAMINE was first registered on the ARTG on 7 June 2000 as a 25 mg tablet blister pack.