CEYXA

Adults For intramuscular use. Do not administer intravenously or subcutaneously. Ceyxa powder for solution for injection is intended for short term use only, for up to a maximum of three consecutive days. The maximum daily dose of olanzapine (including all formulations of olanzapine) is 20 mg.

The recommended initial dose for olanzapine injection is 10 mg, administered as a single intramuscular injection. 4). A second injection, 5-10 mg, may be administered 2 hours after the first injection on the basis of individual clinical status.

Not more than three injections should be given in any 24-hour period and the maximum daily dose of olanzapine of 20 mg (including all formulations) should not be exceeded. 6. For further information on continued treatment with oral olanzapine (5 to 20 mg daily), refer to the Summary of Product Characteristics for the relevant product Olanzapine film-coated tablets or Olanzapine orodispersible tablets.

5 - 5 mg. 5 - 5 mg, may be administered 2 hours after the first injection. Not more than 3 injections should be given in any 24-hour period and the maximum daily dose of 20 mg (including all formulations) of olanzapine should not be exceeded.

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.

Smokers The dose and dose range need not be routinely altered for non-smokers relative to smokers. The metabolism of olanzapine may be induced by smoking. 5). 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 dose.

Additional injections, when indicated, should be conservative in such patients. ) Paediatric population There is no experience in children. Ceyxa powder for solution for injection is not recommended for use in children and adolescents due to a lack of data on safety and efficacy.

Summary of the safety profile A common (≥ 1/100 to < 1/10) undesirable effect associated with the use of intramuscular olanzapine in clinical trials was somnolence. 5). The following table is based on the undesirable effects and laboratory investigations from clinical trials with olanzapine powder for solution for injection rather than oral olanzapine.

Cardiac disorders Common (≥1/100 to <1/10):

Bradycardia with or without hypotension or syncope, tachycardia.

Uncommon (≥1/1,000 to <1/100):

Sinus pause.

Vascular Disorders Common (≥1/100 to <1/10):

Postural hypotension, hypotension.

Respiratory , thoracic and mediastinal disorders Uncommon (≥1/1,000 to <1/100):

Hypoventilation.

General disorders and administration site conditions Common (≥1/100 to <1/10):

Injection site discomfort. The undesirable effects listed below have been observed following administration of oral and prolonged release intramuscular injection olanzapine, but may also occur following administration of Ceyxa 10 mg powder for solution for injection.

4), rash, asthenia, fatigue, pyrexia, arthralgia, increased alkaline phosphatase, high gamma glutamyltransferase, high uric acid, high creatine phosphokinase and oedema. Tabulated list of adverse reactions The following table lists the adverse reactions and laboratory investigations observed from spontaneous reporting and in clinical trials.

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

The frequency terms listed are defined as follows:

Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). 6) Reproductive system and breast disorders Erectile dysfunction in males Decreased libido in males and females Amenorrhea Breast enlargement Galactorrhea in females Gynaecomastia/breast enlargement in males Priapism12 General disorders and administration site conditions Asthenia Fatigue Oedema Pyrexia10 Investigations Elevated plasma prolactin levels8 Increased alkaline phosphatase10 High creatine phosphokinase11 High Gamma Glutamyltransferase10 High Uric acid 10 Increased total bilirubin 1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories.

8 %). 3 % respectively). 2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline. 2 mmol/l). 2 mmol/l) were very common.

4 Observed […]

The efficacy of IM olanzapine has not been established in patients with agitation and disturbed behaviours related to conditions other than schizophrenia or manic episode. Unstable medical conditions IM olanzapine should not be administered to patients with unstable medical conditions, such as acute myocardial infarction, unstable angina pectoris, severe hypotension and/or bradycardia, sick sinus syndrome, or following heart surgery.

If the patient’s medical history with regard to these unstable medical conditions cannot be determined, the risks and benefits of IM olanzapine should be considered in relation to other alternative treatments. 5). 8). 2). If the patient is considered to need parenteral benzodiazepine treatment, this should not be given until at least one hour after IM olanzapine administration.

If the patient has received parenteral benzodiazepine, IM olanzapine administration should only be considered after careful evaluation of clinical status and the patient should be closely monitored for excessive sedation and cardiorespiratory depression.

Hypotension It is extremely important that patients receiving intramuscular olanzapine should be closely observed for hypotension including postural hypotension, bradyarrhythmia and/or hypoventilation, particularly for the first 4 hours following injection and close observation should be continued after this period if clinically indicated.

Blood pressure, pulse, respiratory rate and level of consciousness should be observed regularly and remedial treatment provided if required. Patients should remain recumbent if dizzy or drowsy after injection until examination indicates that they are not experiencing hypotension including postural hypotension, bradyarrhythmia and/or hypoventilation.

5). Dementia-related psychosis and/or behavioural disturbances Olanzapine is not recommended for use in patients with dementia-related psychosis and/or behavioural disturbances because of an increase in mortality and the risk of cerebrovascular accident.

5% vs. 5%, respectively). 4 mg) or duration of treatment. , 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.

, stroke, transient ischemic attack), including fatalities, were reported. 3% vs. 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. 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.

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 products. 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. […]

1. Patients with known risk of narrow-angle glaucoma.