QUETIN

What it is

QUETIN is a medicine containing quetiapine fumarate. QUETIN is available as a modified release tablet in five strengths containing quetiapine fumarate equivalent to 50 mg, 150 mg, 200 mg, 300 mg and 400 mg of quetiapine free base. QUETIN should be administered once daily, without food, and the tablets should be swallowed whole and not split, chewed or crushed.

Approved indications —

Maintenance treatment of bipolar I disorder, as monotherapy or in combination with lithium or sodium valproate, for the prevention of relapse or recurrence of manic, depressive or mixed episodes. — Treatment of depressive episodes associated with bipolar disorder. — Treatment of acute mania associated with bipolar I disorder as monotherapy or in combination with lithium or sodium valproate. — Treatment of schizophrenia, prevention of relapse and maintenance of clinical improvement during continuation therapy. — Treatment of recurrent major depressive disorder in patients who are intolerant of, or who have an inadequate response to alternative therapies. — Treatment of generalised anxiety disorder.

Dosing overview

Dosing varies by indication. For prevention of relapse or recurrence of manic, depressive and mixed episodes in bipolar disorder, the usual effective dose is within the range of 300 to 800 mg per day. For bipolar depression, QUETIN should be titrated as follows: 50 mg on Day 1, 100 mg on Day 2, 200 mg on Day 3 and 300 mg on Day 4, with further titration to 400 mg on Day 5 and up to 600 mg by Day 8. For acute mania, QUETIN should be titrated as follows: 300 mg on Day 1, 600 mg on Day 2 and up to 800 mg after Day 2, with the dose adjusted within the usual effective dose range of 400 to 800 mg per day. For schizophrenia, the daily dose at the start of therapy is 300 mg on Day 1, 600 mg on Day 2 and up to 800 mg after Day 2, with the dose adjusted within the usual effective dose range of 400 to 800 mg per day. For recurrent major depressive disorder, initial dosing should begin at 50 mg on Day 1 and 2, increased to 150 mg on Day 3 and 4, with the usual effective dose being 150 mg. For generalised anxiety disorder, initial dosing should begin at 50 mg on Day 1 and 2, increased to 150 mg on Day 3 and 4, with further adjustments within the recommended dose range of 50 mg to 150 mg. In elderly patients, QUETIN should be used with caution, with a slower rate of dose titration and lower daily therapeutic dose than in younger patients; elderly patients should be started on 50 mg per day with the dose increased in increments of 50 mg per day to an effective dose.

Key safety warnings

Quetiapine should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions predisposing to hypotension. Quetiapine may induce orthostatic hypotension associated with dizziness, tachycardia and, in some patients, syncope especially during the initial dose-titration period; syncope has been commonly reported and may lead to falls. In clinical trials, quetiapine was not associated with a persistent increase in QT intervals; however, in post-marketing experience there were cases of QT prolongation with overdose, in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase QT interval. Cardiomyopathy and myocarditis have been reported in clinical trials and during post-marketing experience; in patients with suspected cardiomyopathy or myocarditis, discontinuation of quetiapine should be considered. Severe cutaneous reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms are potentially life threatening adverse drug reactions that have been reported during quetiapine exposure. The risk of suicide attempt is inherent in depression; patients with depression may experience worsening of depressive symptoms and emergence of suicidal ideation and behaviour, and should be closely monitored for clinical worsening and suicidality, especially at the beginning of treatment or at the time of dose changes. Neuroleptic malignant syndrome has been associated with antipsychotic treatment including quetiapine, with clinical manifestations including hyperthermia, altered mental status, muscular rigidity, autonomic instability and increased creatine phosphokinase; quetiapine should be discontinued and appropriate medical treatment given. Hyperglycaemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics including quetiapine. Agranulocytosis has been reported among patients treated with quetiapine during clinical trials and post-marketing reports including fatal cases; most cases of severe neutropenia have occurred within the first two months of starting therapy. Elderly patients with dementia-related psychosis treated with atypical antipsychotics are at an increased risk of death; a meta-analysis showed a risk of death in drug-treated patients of approximately 1.6 to 1.7 times that seen in placebo-treated patients, with the rate of death in drug-treated patients about 4.5% compared to about 2.6% in the placebo group, and most deaths appearing to be cardiovascular or infectious in nature.

Contraindications

QUETIN is contraindicated in patients who are hypersensitive to any component of the product.

Regulatory history

QUETIN was first listed on the ARTG on 13 February 2014, with five strengths registered: 25 mg, 100 mg, 150 mg, 200 mg and 300 mg film-coated tablets, each as a blister pack.