APX-QUETIAPINE XR

What it is

APX-QUETIAPINE XR is a modified release tablet containing quetiapine fumarate equivalent to 50 mg, 150 mg, 200 mg, 300 mg or 400 mg of quetiapine free base. The medicine should be administered once daily, without food. 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

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 depressive episodes in bipolar disorder, APX-QUETIAPINE XR should be titrated as follows: 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4), with titration up to 400 mg on Day 5 and up to 600 mg by Day 8. For acute mania, APX-QUETIAPINE XR 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, and doses above 150 mg per day are not recommended.

Key safety warnings

APX-QUETIAPINE XR should be used with caution in patients with known cardiovascular disease, including history of myocardial infarction or ischemic heart disease, heart failure or conduction abnormalities, cerebrovascular disease, or other conditions predisposing to hypotension. Because of the risk of orthostatic hypotension, caution should be observed in cardiac patients. 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 orthostatic hypotension, dizziness and syncope may lead to falls. In clinical trials, quetiapine was not associated with a persistent increase in QTc intervals. However, in post-marketing experience there were cases reported of QT prolongation with overdose, in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase QT interval. Severe cutaneous adverse 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. Discontinue quetiapine if severe cutaneous adverse reactions occur. The risk of suicide attempt is inherent in depression and may persist until significant remission occurs. Patients with depression may experience worsening of their depressive symptoms and emergence of suicidal ideation and behaviour, whether or not they are taking antidepressant medications. 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. Neuroleptic malignant syndrome has been associated with antipsychotic treatment, including quetiapine. Clinical manifestations include hyperthermia, altered mental status, muscular rigidity, autonomic instability, and increased creatine phosphokinase. In such an event, 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. Elderly patients with dementia-related psychosis treated with atypical anti-psychotics are at an increased risk of death compared to placebo. A meta-analysis of seventeen placebo-controlled trials showed a risk of death in the drug-treated patients of approximately 1.6 to 1.7 times that seen in placebo-treated patients.

Contraindications

APX-QUETIAPINE XR is contraindicated in patients who are hypersensitive to any component of this product.

Regulatory history

APX-QUETIAPINE XR was first registered on the Australian Register of Therapeutic Goods on 17 January 2014, with registrations across five strengths: 50 mg, 150 mg, 200 mg, 300 mg and 400 mg modified release tablets.