ZACTIN

What it is

ZACTIN is fluoxetine hydrochloride. Each capsule contains 20 mg fluoxetine (as hydrochloride). It is presented as a green/off-white hard gelatin, self-locked, size 2 capsule imprinted with 'FLX' and 'MIL' on cap/body in black edible ink, containing white powder. The antidepressant and anti-obsessional action of fluoxetine is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin.

Approved indications ZACTIN is indicated for treatment of:

— Major depression — Obsessive Compulsive Disorder (OCD) — Premenstrual Dysphoric Disorder (PMDD) as defined by DSM-IV criteria

Dosing overview

For depression, a dose of 20 mg/day, administered in the morning, is the usual recommended initial dose. If no clinical improvement is observed, a dose increase may be considered after several weeks. Doses above 20 mg/day should not exceed a maximum dose of 80 mg/day. For Obsessive-Compulsive Disorder, a dose of 20 mg/day, administered in the morning, is recommended as the initial dose. If insufficient clinical improvement is observed, a dose increase may be considered after several weeks. A dose range of 20–60 mg/day is recommended, however, doses of up to 80 mg/day have been well tolerated in open studies of OCD. For Premenstrual Dysphoric Disorder, the recommended dose of fluoxetine is 20 mg/day given continuously (every day of the menstrual cycle) or intermittently (defined as starting a daily dose 14 days prior to the anticipated onset of menstruation through the first full day of menses and repeating with each new cycle).

Key safety warnings

The risk of suicide attempt is inherent in depression and other psychiatric disorders and may persist until significant remission occurs. As with other drugs with similar pharmacological action, isolated cases of suicidal ideation and suicidal behaviours have been reported during fluoxetine therapy or early after treatment discontinuation. This risk must be considered in all depressed patients. 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. Patients (and caregivers of patients) should be alerted about the need to closely monitor for any worsening of their condition and/or the emergence of suicidal ideation/behaviour or thoughts of harming themselves and to seek medical advice immediately if these symptoms present. Development of serotonin syndrome may occur in association with treatment with SSRIs and SNRIs, particularly when given in combination with MAOIs or other serotonergic agents. Symptoms and signs of serotonin syndrome include rapid onset of neuromuscular excitation (hyperreflexia, incoordination, myoclonus, tremor), altered mental status (confusion, agitation, hypomania) and autonomic dysfunction (diaphoresis, diarrhoea, fever, shivering and rapidly fluctuating vital signs). Treatment with fluoxetine should be discontinued if such events occur and supportive symptomatic treatment initiated. QT prolongation can occur with fluoxetine treatment. Fluoxetine should be used with caution in patients with conditions such as congenital long QT syndrome; acquired long QT syndrome (e.g. due to concomitant use of a drug that prolongs the QT); a family history of QT prolongation; or other clinical conditions that predispose to arrhythmias (e.g. hypokalemia or hypomagnesemia) or increased exposure to fluoxetine (e.g., hepatic impairment). SSRIs may cause symptoms of sexual dysfunction. There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite discontinuation of SSRIs. SSRIs and serotonin-noradrenaline reuptake inhibitors (SNRIs), including fluoxetine, may increase the risk of bleeding events, including gastrointestinal bleeding and postpartum haemorrhage.

Contraindications

ZACTIN is contraindicated in patients known to be hypersensitive to fluoxetine or any of the other ingredients in the formulation. Fluoxetine should not be used in combination with a MAOI (selective, reversible or irreversible), or within a minimum of 14 days of discontinuing therapy with a MAOI. Since fluoxetine and its major metabolite have very long elimination half-lives, at least 5 weeks (perhaps longer, especially if fluoxetine has been prescribed chronically and/or at higher doses) should be allowed after stopping fluoxetine before starting a MAOI. Concomitant use in patients taking pimozide is contraindicated. Fluoxetine is contraindicated in combination with metoprolol used in cardiac failure.

PBS listing

ZACTIN is listed on the PBS as a 20 mg (as hydrochloride) dispersible tablet. There are 2 PBS items with restricted access. The ex-manufacturer price is A$3.50.

Regulatory history

ZACTIN was first registered on the ARTG on 1995-11-13 as fluoxetine 20 mg (as hydrochloride) capsules, sponsored by Alphapharm. A dispersible tablet formulation (ZACTIN TABS) was subsequently registered on 2002-09-12.