APO-OLANZAPINE

What it is

APO-OLANZAPINE is an atypical antipsychotic, antimanic and mood-stabilising agent that demonstrates a broad pharmacological profile across a number of receptor systems. APO-OLANZAPINE uncoated tablets contain olanzapine 2.5 mg, 5 mg, 7.5 mg and 10 mg.

Approved indications

— Treatment of schizophrenia and related psychoses. — Short-term treatment, alone or in combination with lithium or valproate, of acute manic episodes associated with bipolar I disorder. — Preventing recurrence of manic, mixed or depressive episodes in bipolar 1 disorder.

Dosing overview

For schizophrenia and related disorders, the recommended starting dose is 5 to 10 mg per day, administered as a single daily dose without regard to meals, and may subsequently be adjusted within the range of 5 to 20 mg daily. For acute mania associated with bipolar disorder, the recommended starting dose is 10 or 15 mg administered once a day as monotherapy or 10 mg administered once daily in combination therapy with lithium or valproate. For preventing recurrence in bipolar disorder, patients who have been receiving olanzapine for the treatment of acute mania should initially continue therapy at the same dose, while for patients already in remission the suggested starting dose is 10 mg once a day, with subsequent daily dosage adjusted within a range of 5 to 20 mg per day. A low starting dose of 5 mg per day should be considered for patients 65 years of age and over when clinical factors warrant.

Key safety warnings

Hyperglycaemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics including olanzapine, and epidemiological studies suggest an increased risk of treatment-emergent hyperglycaemia-related adverse events in patients treated with atypical antipsychotics. Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebo-controlled trials, with olanzapine-treated patients having a greater mean increase in fasting total cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides compared to placebo-treated patients. Potential consequences of weight gain should be considered prior to starting olanzapine, and as with all antipsychotics, patients receiving olanzapine should receive regular monitoring of weight, with significant weight gain observed across all baseline body mass index categories in olanzapine-treated patients in clinical trials. Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome complex, is associated with antipsychotic drugs including olanzapine, with clinical manifestations including hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability, and additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure, and in such an event all antipsychotic drugs including olanzapine should be discontinued. Olanzapine should be used cautiously in patients who have a history of seizures or are subject to factors which may lower the seizure threshold, as seizures have been reported to occur rarely in such patients when treated with olanzapine. In elderly patients with dementia-related psychosis, the efficacy of olanzapine has not been established, and in placebo-controlled clinical trials of elderly patients with dementia-related psychosis, the incidence of death in olanzapine-treated patients was significantly greater than placebo-treated patients (3.5 versus 1.5%, respectively). Cerebrovascular adverse events (for example stroke, transient ischaemic attack), including fatalities, were reported in trials of olanzapine in elderly patients with dementia-related psychosis, with a higher incidence in patients treated with olanzapine compared to patients treated with placebo (1.3 versus 0.4%, respectively).

Contraindications

Known hypersensitivity to any ingredients of the product.

PBS listing

APO-OLANZAPINE is listed on the PBS in strengths of 5 mg, 10 mg, 15 mg and 20 mg as orally disintegrating tablets, with streamlined restriction status and ex-manufacturer prices of A$4.00, A$6.34, A$9.52 and A$12.69 respectively.

Regulatory history

ARTG registration of APO-OLANZAPINE orally disintegrating tablets (5 mg, 10 mg, 15 mg and 20 mg) was first listed on 26 November 2009. APO-OLANZAPINE uncoated tablets (2.5 mg, 5 mg, 7.5 mg and 10 mg) were first listed on 29 August 2018.