ZYPREXA* 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg coated tablets.

ZYPREXA VELOTAB* 5 mg, 10 mg, 15 mg, and 20 mg orodispersible tablets.

Each coated tablet contains 2.5 mg olanzapine.

Excipient: 102 mg lactose monohydrate.

Each coated tablet contains 5 mg olanzapine.

Excipient: 156 mg lactose monohydrate.

Each coated tablet contains 7.5 mg olanzapine.

Excipient: 234 mg lactose monohydrate.

Each coated tablet contains 10 mg olanzapine.

Excipient: 312 mg lactose monohydrate.

Each coated tablet contains 15 mg olanzapine.

Excipient: 178 mg lactose monohydrate.

Each coated tablet contains 20 mg olanzapine.

Excipient: 238 mg lactose monohydrate.

Each orodispersible tablet contains 5 mg olanzapine.

Excipients: Each orodispersible tablet contains

0.60 mg aspartame

0.1125 mg sodium methyl parahydroxybenzoate

0.0375 mg sodium propyl parahydroxybenzoate

Each orodispersible tablet contains 10 mg olanzapine.

Excipients: Each orodispersible tablet contains

0.80 mg aspartame

0.15 mg sodium methyl parahydroxybenzoate

0.05 mg sodium propyl parahydroxybenzoate

Each orodispersible tablet contains 15 mg olanzapine.

Excipients: Each orodispersible tablet contains

1.20 mg aspartame

0.225 mg sodium methyl parahydroxybenzoate

0.075 mg sodium propyl parahydroxybenzoate

Each orodispersible tablet contains 20 mg olanzapine.

Excipients: Each orodispersible tablet contains

1.60 mg aspartame

0.30 mg sodium methyl parahydroxybenzoate

0.10 mg sodium propyl parahydroxybenzoate

For a full list of excipients, see section 6.1.

Coated Tablets

ZYPREXA 2.5 mg tablets: Round, white, coated tablets imprinted with 'LILLY' and a numeric identicode '4112'.

ZYPREXA 5 mg tablets: Round, white, coated tablets imprinted with 'LILLY' and a numeric identicode '4115'.

ZYPREXA 7.5 mg tablets: Round, white, coated tablets imprinted with 'LILLY' and a numeric identicode '4116'.

ZYPREXA 10 mg tablets: Round, white, coated tablets imprinted with 'LILLY' and a numeric identicode '4117'.

ZYPREXA 15 mg tablets: Elliptical, blue, coated tablets debossed with 'LILLY' and a numeric identicode '4415'.

ZYPREXA 20 mg tablets: Pink, elliptical, coated tablets debossed with 'LILLY' and a numeric identicode '4420'.

Orodispersible Tablets

ZYPREXA VELOTAB 5 mg, 10 mg, 15 mg, and 20 mg orodispersible tablet is a yellow, round, freeze-dried, rapid-dispersing preparation to be placed in the mouth or alternatively to be dispersed in water or other suitable beverage for administration.

Adults

Olanzapine is indicated for the treatment of schizophrenia.

Olanzapine is effective in maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response.

Olanzapine is indicated for the treatment of moderate to severe manic episode.

In patients whose manic episode has responded to olanzapine treatment, olanzapine is indicated for the prevention of recurrence in patients with bipolar disorder (see section 5.1).

Adults

Schizophrenia: The recommended starting dose for olanzapine is 10 mg/day.

Manic episode: The starting dose is 15 mg as a single daily dose in monotherapy or 10 mg daily in combination therapy (see section 5.1).

Preventing recurrence in bipolar disorder: The recommended starting dose is 10 mg/day. For patients who have been receiving olanzapine for treatment of manic episode, continue therapy for preventing recurrence at the same dose. If a new manic, mixed, or depressive episode occurs, olanzapine treatment should be continued (with dose optimisation as needed), with supplementary therapy to treat mood symptoms, as clinically indicated.

During treatment for schizophrenia, manic episode, and recurrence prevention in bipolar disorder, daily dosage may subsequently be adjusted on the basis of individual clinical status within the range 5-20 mg/day. An increase to a dose greater than the recommended starting dose is advised only after appropriate clinical reassessment and should generally occur at intervals of not less than 24 hours.

Olanzapine can be given without regard for meals, as absorption is not affected by food. Gradual tapering of the dose should be considered when discontinuing olanzapine.

ZYPREXA VELOTAB orodispersible tablet should be placed in the mouth, where it will rapidly disperse in saliva, so it can be easily swallowed. Removal of the intact orodispersible tablet from the mouth is difficult. Since the orodispersible tablet is fragile, it should be taken immediately on opening the blister. Alternatively, it may be dispersed in a full glass of water or other suitable beverage (orange juice, apple juice, milk, or coffee) immediately before administration.

Olanzapine orodispersible tablet is bioequivalent to olanzapine coated tablets, with a similar rate and extent of absorption. It has the same dosage and frequency of administration as olanzapine coated tablets. Olanzapine orodispersible tablets may be used as an alternative to olanzapine coated tablets.

Paediatric population

Olanzapine is not recommended for use in children and adolescents below 18 years of age due to a lack of data on safety and efficacy. A greater magnitude of weight gain, lipid and prolactin alterations has been reported in short-term studies of adolescent patients than in studies of adult patients (see sections 4.4, 4.8, 5.1 and 5.2).

Elderly

A lower starting dose (5 mg/day) is not routinely indicated but should be considered for those 65 and over when clinical factors warrant (see section 4.4).

Renal and/or hepatic impairment

A lower starting dose (5 mg) should be considered for such patients. In cases of moderate hepatic insufficiency (cirrhosis, Child-Pugh class A or B), the starting dose should be 5 mg and only increased with caution.

Gender

The starting dose and dose range need not be routinely altered for female patients relative to male patients.

Smokers

The starting dose and dose range need not be routinely altered for non-smokers relative to smokers.

When more than one factor is present which might result in slower metabolism (female gender, geriatric age, non-smoking status), consideration should be given to decreasing the starting dose. Dose escalation, when indicated, should be conservative in such patients.

In cases where dose increments of 2.5 mg are considered necessary, ZYPREXA coated tablets should be used.

(See sections 4.5 and 5.2.)

Hypersensitivity to the active substance or to any of the excipients. Patients with known risk of narrow-angle glaucoma.

During antipsychotic treatment, improvement in the patient's clinical condition may take several days to some weeks. Patients should be closely monitored during this period.

Dementia-related psychosis and/or behavioural disturbances

Olanzapine is not approved for the treatment of dementia-related psychosis and/or behavioural disturbances and is not recommended for use in this particular group of patients because of an increase in mortality and the risk of cerebrovascular accident. In placebo-controlled clinical trials (6-12 weeks duration) of elderly patients (mean age 78 years) with dementia-related psychosis and/or disturbed behaviours, there was a 2-fold increase in the incidence of death in olanzapine-treated patients compared to patients treated with placebo (3.5% vs. 1.5%, respectively). The higher incidence of death was not associated with olanzapine dose (mean daily dose 4.4 mg) or duration of treatment. Risk factors that may predispose this patient population to increased mortality include age > 65 years, dysphagia, sedation, malnutrition and dehydration, pulmonary conditions (e.g., pneumonia, with or without aspiration), or concomitant use of benzodiazepines. However, the incidence of death was higher in olanzapine-treated than in placebo-treated patients independent of these risk factors.

In the same clinical trials, cerebrovascular adverse events (CVAE e.g., stroke, transient ischaemic attack), including fatalities, were reported. There was a 3-fold increase in CVAE in patients treated with olanzapine compared to patients treated with placebo (1.3% vs. 0.4%, respectively). All olanzapine- and placebo-treated patients who experienced a cerebrovascular event had pre-existing risk factors. Age > 75 years and vascular/mixed type dementia were identified as risk factors for CVAE in association with olanzapine treatment. The efficacy of olanzapine was not established in these trials.

Parkinson's disease

The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with Parkinson's disease is not recommended. In clinical trials, worsening of Parkinsonian symptomatology and hallucinations were reported very commonly and more frequently than with placebo (see section 4.8), and olanzapine was not more effective than placebo in the treatment of psychotic symptoms. In these trials, patients were initially required to be stable on the lowest effective dose of anti-Parkinsonian medicinal products (dopamine agonist) and to remain on the same anti-Parkinsonian medicinal products and dosages throughout the study. Olanzapine was started at 2.5 mg/day and titrated to a maximum of 15 mg/day based on investigator judgement.

Neuroleptic Malignant Syndrome (NMS)

NMS is a potentially life-threatening condition associated with antipsychotic medicinal product. Rare cases reported as NMS have also been received in association with olanzapine. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all antipsychotic medicines, including olanzapine must be discontinued.

Hyperglycaemia and diabetes

Hyperglycaemia and/or development or exacerbation of diabetes, occasionally associated with ketoacidosis or coma, has been reported rarely, including some fatal cases (see section 4.8). In some cases, a prior increase in body weight has been reported, which may be a predisposing factor. Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines. Patients treated with any antipsychotic agents, including ZYPREXA/ZYPREXA VELOTAB, should be observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia, and weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be monitored regularly.

Lipid alterations

Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebo-controlled clinical trials (see section 4.8). Lipid alterations should be managed as clinically appropriate, particularly in dyslipidemic patients and in patients with risk factors for the development of lipids disorders. Patients treated with any antipsychotic agents, including ZYPREXA/ZYPREXA VELOTAB, should be monitored regularly for lipids in accordance with utilised antipsychotic guidelines.

Anticholinergic activity

While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials revealed a low incidence of related events. However, as clinical experience with olanzapine in patients with concomitant illness is limited, caution is advised when prescribing for patients with prostatic hypertrophy, or paralytic ileus and related conditions.

Hepatic function

Transient, asymptomatic elevations of hepatic aminotransferases, alanine transferase (ALT), aspartate transferase (AST) have been seen commonly, especially in early treatment. Caution should be exercised and follow-up organised in patients with elevated ALT and/or AST, in patients with signs and symptoms of hepatic impairment, in patients with pre-existing conditions associated with limited hepatic functional reserve, and in patients who are being treated with potentially hepatotoxic medici