Zyprexa/Zyprexa Zydis再普樂

Zyprexa/Zyprexa Zydis Special Precautions



Eli Lilly


Agencia Lei Va Hong
Full Prescribing Info
Special Precautions
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. 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 ischemic 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 Adverse Reactions), 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 judgment.
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.
Hyperglycaemia and diabetes: Hyperglycaemia and/or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma has been reported uncommonly, including some fatal cases (see Adverse Reactions). 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, e.g. measuring of blood glucose at baseline, 12 weeks after starting olanzapine treatment and annually thereafter. Patients treated with any antipsychotic medicines, including ZYPREXA, 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, e.g. at baseline, 4, 8 and 12 weeks after starting olanzapine treatment and quarterly thereafter.
Lipid alterations: Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebo-controlled clinical trials (see Adverse Reactions). Lipid alterations should be managed as clinically appropriate, particularly in dyslipidemic patients and in patients with risk factors for the development of lipid disorders. Patients treated with any antipsychotic agents, including ZYPREXA/Zyprexa Zydis, should be monitored regularly for lipids in accordance with utilised antipsychotic guidelines, e.g. at baseline, 12 weeks after starting olanzapine treatment and every 5 years thereafter.
Anticholinergic activity: While olanzapine demonstrated anticholinergic activity in vitro, experience during oral 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, ALT, 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 medicines. In cases where hepatitis (including hepatocellular, cholestatic or mixed liver injury) has been diagnosed, olanzapine treatment should be discontinued.
Neutropenia: Caution should be exercised in patients with low leukocyte and/or neutrophil counts for any reason, in patients receiving medicines known to cause neutropenia, in patients with a history of drug-induced bone marrow depression/toxicity, in patients with bone marrow depression caused by concomitant illness, radiation therapy or chemotherapy and in patients with hypereosinophilic conditions or with myeloproliferative disease. Neutropenia has been reported commonly when olanzapine and valproate are used concomitantly (see Adverse Reactions).
Discontinuation of treatment: Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting have been reported rarely (≥ 0.01 % and < 0.1 %) when olanzapine is stopped abruptly.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported with olanzapine exposure. DRESS consists of a combination of three or more of the following: cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, lymphadenopathy, and one or more systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and pericarditis. Discontinue olanzapine if DRESS is suspected.
QT interval: In clinical trials with oral administration, clinically meaningful QTc prolongations (Fridericia QT correction [QTcF] ≥ 500 milliseconds [msec] at any time post baseline in patients with baseline QTcF < 500 msec) were uncommon (0.1 % to 1 %) in patients treated with olanzapine, with no significant differences in associated cardiac events compared to placebo. In clinical trials with ZYPREXA powder for solution for injection, olanzapine was not associated with a persistent increase in absolute QT or in QTc intervals. However, caution should be exercised when olanzapine is prescribed with medicines known to increase QTc interval, especially in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalaemia or hypomagnesaemia.
Thromboembolism: Temporal association of olanzapine treatment and venous thromboembolism has been reported uncommonly (<0.01%, Zyprexa Zydis only; ≥ 0.1 % and < 1%, Zyprexa coated tablet and powder for injection only). A causal relationship between the occurrence of venous thromboembolism and treatment with olanzapine has not been established. However, since patients with schizophrenia often present with acquired risk factors for venous thromboembolism, all possible risk factors of VTE e.g. immobilisation of patients, should be identified and preventive measures undertaken.
General CNS activity: Given the primary CNS effects of olanzapine, caution should be used when it is taken in combination with other centrally acting medicines and alcohol. As it exhibits in vitro dopamine antagonism, olanzapine may antagonize the effects of direct and indirect dopamine agonists.
Seizures: Olanzapine should be used cautiously in patients who have a history of seizures or are subject to factors which may lower the seizure threshold. Seizures have been reported to occur uncommonly in patients when treated with olanzapine. In most of these cases, a history of seizures or risk factors for seizures were reported.
Tardive Dyskinesia: In comparator oral studies of one year or less duration, olanzapine was associated with a statistically significant lower incidence of treatment emergent dyskinesia. However the risk of tardive dyskinesia increases with long-term exposure, and therefore if signs or symptoms of tardive dyskinesia appear in a patient on olanzapine, a dose reduction or drug discontinuation should be considered. These symptoms can temporarily deteriorate or even arise after discontinuation of treatment.
Postural hypotension: Postural hypotension was infrequently observed in the elderly in oral olanzapine clinical trials. It is recommended that blood pressure is measured periodically in patients over 65 years.
Sudden cardiac death: In postmarketing reports with olanzapine, the event of sudden cardiac death has been reported in patients with olanzapine. In a retrospective observational cohort study, the risk of presumed sudden cardiac death in patients treated with olanzapine was approximately twice the risk in patients not using antipsychotics. In the study, the risk of olanzapine was comparable to the risk of atypical antipsychotics included in a pooled analysis.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed. Because olanzapine may cause somnolence and dizziness, patients should be cautioned about operating machinery, including motor vehicles.
Zyprexa: Coated tablet: 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.
Lactose: Zyprexa tablets contain lactose. Patients with hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use in Children: Olanzapine is not indicated for use in the treatment of children and adolescents. Studies in patients aged 13-17 years showed various adverse reactions, including weight gain, changes in metabolic parameters and increases in prolactin levels (see Adverse Reactions and Pharmacology: Pharmacodynamics under Actions).
Powder for injection: 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.
Concomitant use of benzodiazepines and other medicinal products: Special caution is necessary in patients who have received treatment with other medicinal products having haemodynamic properties similar to those of intramuscular olanzapine, including other antipsychotics (oral and/or intramuscular) and benzodiazepines (see Interactions). Temporal association of treatment with IM olanzapine with hypotension, bradycardia, respiratory depression and death has been very rarely (< 0.01%) reported particularly in patients who have received benzodiazepines and/or other antipsychotics (see Adverse Reactions).
Simultaneous injection of intramuscular olanzapine and parenteral benzodiazepine is not recommended due to the potential for excessive sedation, cardiorespiratory depression and in very rare cases, death (see Interactions and Incompatibilities under Cautions for Usage). 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.
The safety and efficacy of IM olanzapine has not been evaluated in patients with alcohol or drug intoxication (either with prescribed or illicit drugs) (see Interactions).
Zyprexa Zydis: Phenylalanine: Zyprexa Zydis orodispersible tablet contains aspartame, which is a source of phenylalanine. May be harmful for people with phenylketonuria.
Mannitol: Zyprexa Zydis orodispersible tablet contains mannitol.
Sodium Methyl Parahydroxybenzoate and Sodium Propyl Parahydroxybenzoate: Olanzapine orodispersible tablet contains sodium methyl parahydroxybenzoate and sodium propyl parahydroxybenzoate. These preservatives are known to cause urticaria. Generally, delayed type reactions such as contact dermatitis may occur, but rarely immediate reactions with bronchospasm may occur.
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