Olanzapine is now available in four different formulations: tablets, orally disintegrating tablets (and wafers), immediate release injection, and long acting injection. It is listed on the Pharmaceutical Benefits Scheme (PBS) for treatment of schizophrenia and bipolar 1 disorder. The immediate release injection is the only preparation not included on the PBS. The tablets and orally disintegrating tablets are also available in a number of generic brands.
Most brands are formulated as sugar coated tablets, and are available in strengths of 2.5mg, 5mg, 7.5mg and 10mg, which should not be broken. The 5mg and 10mg Olanzapine Sandoz® tablets offer the flexibility of being scored, which enables them to be broken in half, but not crushed. Other brands are not scored and should be swallowed whole.
Some brands contain lactose as an excipient, which would need to be considered before prescribing to patients who are confirmed to be lactose intolerant.
Orally Disintegrating Tablets (and Wafers)
The generic brands of olanzapine orally disintegrating tablets (ODTs) are considered to be bio-equivalent to the Zyprexa® Zydis® wafers, according to the Therapeutic Goods Administration (TGA). ODTs rapidly dissolve in the saliva of the mouth; alternatively they can be dissolved in water or other beverages, but not cola-based drinks. The product information for all olanzapine brands states that wafers and ODTs are bio-equivalent to the standard release tablets “with a similar rate and extent of absorption”, and that they can be used as an alternative to the tablets, i.e. for regular use but not for acute use.
Both tablets and ODTs are intended for long term regular use with once daily dosage, determined according to response. The question then is – which should be used? As with all long term illnesses, the success of treatment for schizophrenia and other psychoses depends to a large extent on compliance. Since the ODTs dissolve rapidly in the mouth they would be suitable if non-compliance or diversion is suspected. In patients who are agitated or difficult to treat ODTs may be easier to administer. In older patients swallowing could be a problem that is easily overcome with the use of ODTs. Patient preference should also be taken into account. Tablets may be packed in dose administration aids, such as mediSACHe, however ODTs should not be removed from their foil packaging as they will absorb moisture from the air and disintegrate. If compliance, administering, or swallowing are not problematic and the patient does not have a preference for ODTs; then tablets would generally be the first preference.
ODTs are available in strengths of 5mg, 10mg, 15mg and 20mg. ODTs should not be broken in half.
Some brands contain lactose as an excipient – this would need to be considered in patients who are confirmed lactose intolerant. Also, some brands contain aspartame which should be considered for patients with phenylketonuria.
Olanzapine Intramuscular Injection
Olanzapine intramuscular (IM) injection is used for the rapid control of agitation and disturbed behaviours in schizophrenia and related psychoses, and for acute mania in bi-polar disorder. It should be used when oral therapy is not suitable. Initiate with a dose of 5-10mg; followed by a second injection of up to 10mg after two hours if required; and a third injection of up to 10mg may be given four or more hours after the second, up to a maximum of 30mg in 24 hours. The patient should transfer to oral therapy as soon as appropriate.
Olanzapine Long Acting Injection
Long acting olanzapine (Zyprexa® Relprevv®) injection is used for maintenance dosing in schizophrenic patients already stabilised on oral therapy with olanzapine and who agree to have injections for convenience or to improve compliance. It is available in three strengths: 210mg, 300mg and 405mg. Initial dose is 210 or 300mg every two weeks or 405mg every four weeks and adjusted after two months depending on response.
The manufacturer gives the following black box warning in the product information:
WARNING: The potential for signs and symptoms of sedation and/or delirium consistent with olanzapine overdose exists after every injection of Zyprexa® Relprevv®. Zyprexa® Relprevv® should be administered by appropriately qualified health professionals in a healthcare facility with access to emergency services for management of olanzapine overdose. Healthcare professionals who prescribe or administer Zyprexa® Relprevv® should be aware of this potential risk and the consequent need to monitor patients for at least two hours after each injection. The two hour period should be extended as clinically appropriate for patients who exhibit any potential signs or symptoms of a post-injection syndrome event.
As smoking induces the metabolism of olanzapine, the clearance of olanzapine from the body is, on average, higher for smokers than for non-smokers, therefore the dose of olanzapine may need to be adjusted if a patient either stops or starts smoking.
For the majority of patients olanzapine tablets are the preferred preparation. ODTs would be used for patients where compliance is a problem due to behaviours, diversion, or swallowing difficulties. Use of olanzapine IM is recommended for rapid control of agitated or disturbed behaviours. Olanzapine long acting injections could be used as maintenance therapy provided that suitable facilities are available.
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- Psychotropic drugs – olanzapine. In: Australian Medicines Handbook 2014 [online]. Adelaide: Australian Medicines Handbook Pty Ltd; 2014 January. Available from: http://www.amh.net.au.