DOTHEP

What it is

DOTHEP contains dosulepin (dothiepin) hydrochloride as the active ingredient . It is available as capsules containing 25 mg and tablets containing 75 mg of dosulepin (dothiepin) hydrochloride . Dosulepin (dothiepin) hydrochloride is a thioanalogue of amitriptyline . The therapeutic site of action is thought to be in the CNS, and dosulepin (dothiepin) hydrochloride possesses anticholinergic, antihistamine and central sedative properties .

Approved indications

— Treatment of major depression

Dosing overview

For adults, treatment begins with 25 mg three times daily for one to two weeks, with daily dosage increased by 25 to 50 mg at intervals of one to two weeks if the response is inadequate. The daily dose should not exceed 200 mg, and up to 150 mg of the daily dose may be given as a single night time dose once an effective dose has been established . The main dose should be taken at night as it may produce drowsiness . DOTHEP should not be used in children and adolescents aged less than 18 years for the treatment of depression .

Key safety warnings

Dosulepin (dothiepin) hydrochloride is associated with high mortality in overdose, with a low margin of safety between the maximum therapeutic dose and potentially fatal doses . Onset of toxicity occurs within 4–6 hours, and a limited number of tablets should be prescribed to reduce the risk from overdose for all patients and especially for patients at risk of suicide . Patients with depression may experience worsening of their depressive symptoms and/or the emergence of suicidal ideation and behaviour whether or not they are taking antidepressant medications, and patients should be closely monitored for clinical worsening and suicidality, especially at the beginning of a course of treatment or at the time of dose changes . DOTHEP may increase the risk of cardiovascular toxicity including cardiac arrhythmias, conduction disorders, cardiac failure and circulatory collapse, especially in the elderly, and caution should be exercised in using DOTHEP in the elderly and in patients with suspected cardiovascular disease . Alertness is decreased, and hence ability to drive or operate machinery may be impaired .

Contraindications

Epilepsy, as seizure thresholds may be lowered by the drug . Tricyclic antidepressants should not be used concomitantly or within 14 days of treatment with monoamine oxidase inhibitors since cerebral excitation followed by coma and dangerous hyperthermia may occur . Acute recovery phase following myocardial infarction, as tricyclic antidepressants may produce conduction defects and arrhythmias . Hepatic failure . Hypersensitivity to dosulepin (dothiepin) hydrochloride .

Regulatory history

DOTHEP 25 was first listed on the Australian Register of Therapeutic Goods on 24 December 1991 . DOTHEP 75 was first listed on 23 January 1998 .