Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Zyprexa (Eli Lilly)
5 mg, 7.5 mg and 10 mg tablets
Indication: schizophrenia
The long-term outcome of treatment for schizophrenia is often unsatisfactory. For example, the disease can often relapse. To try to improve outcomes, atypical antipsychotics such as clozapine have been studied. Olanzapine is a new drug with a structure similar to clozapine.
Patients begin with a dose of 10 mg once a day. This is then adjusted according to the response. The absorption of olanzapine is not affected by food and the peak plasma concentration is reached within 5-8 hours. In-vitro olanzapine binds with
dopamine, serotonin, cholinergic and histamine receptors. The drug reduces the activity of dopaminergic neurones. Olanzapine is metabolised by the liver, but its half-life depends on the sex and age of the patient. The half-life is longer in women and can exceed 50 hours in the elderly.
In studies lasting for 6 weeks, olanzapine was more effective than placebo and at least as effective as haloperidol. These trends have persisted when treatment has continued beyond 6 weeks. There appear to be no data comparing olanzapine with clozapine.
The adverse effects of olanzapine resemble those of other antipsychotic drugs. However, unlike clozapine, agranulocytosis does not currently appear to be a problem. The most common adverse effects are somnolence and weight gain. Patients may also complain of constipation, dry mouth, dizziness and oedema. Olanzapine may affect the concentrations of prolactin and liver enzymes.
Although olanzapine is metabolised by cytochrome P450, it does not have a significant effect on the metabolism of warfarin, theophylline, imipramine or diazepam. The clearance of olanzapine is affected by smoking and carbamazepine.
There is a need to establish if olanzapine is as effective as clozapine. If it is, then it seems to offer a safer alternative in the treatment of schizophrenia.
