treatment, improvement in the patient's clinical condition may take
several days to some weeks. Patients should be closely monitored
during this period.
psychosis and/or behavioural disturbances
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.
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
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, 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.
Malignant Syndrome (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.
and/or development or exacerbation of diabetes occasionally
associated with ketoacidosis or coma has been reported uncommonly,
including some fatal cases. 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
alterations in lipids have been observed in olanzapine-treated
patients in placebo- controlled clinical trials. 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 medicines, including ZYPREXA, 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.
olanzapine demonstrated anticholinergic activity in
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.
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
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.
symptoms such as sweating, insomnia, tremor, anxiety, nausea, or
vomiting have been reported rarely (≥ 0.01 % and < 0.1 %) when
olanzapine is stopped abruptly.
clinical trials, 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. 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
association of olanzapine treatment and venous thromboembolism has
been reported uncommonly (≥ 0.1 % and < 1 %). 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
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
antagonism, olanzapine may antagonize the effects of direct and
indirect dopamine agonists.
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.
comparator 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 discontinuation should be considered. These symptoms can
temporally deteriorate or even arise after discontinuation of
hypotension was infrequently observed in the elderly in olanzapine
clinical trials. It is recommended that blood pressure is measured
periodically in patients over 65 years.
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.
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.
tablets contain lactose. Patients with rare hereditary problems of
galactose intolerance, the Lapp lactase deficiency or
glucose-galactose malabsorption should not take this medicine.
VELOTAB orodispersible tablet contains up to 1.6 mg aspartame in each
tablet. Aspartame is a source of phenylalanine. It may be harmful for
people who have phenylketonuria (PKU), a rare genetic disorder in
which phenylalanine builds up because the body cannot remove it
methyl parahydroxybenzoate and sodium propyl parahydroxybenzoate
orodispersible tablet contains sodium methyl parahydroxybenzoate and
sodium propyl parahydroxybenzoate, which may cause allergic reactions
medicine contains less than 1 mmol sodium (23 mg) per tablet, that is
to say essentially ‘sodium-free’.
[Summary of Product Characteristics]. Utrecht, The Netherlands: Eli
Lilly Nederland B.V.