Zyprexa

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA 2.5 mg coated tablets 
ZYPREXA 5 mg coated tablets 
ZYPREXA 7.5 mg coated tablets 
ZYPREXA 10 mg coated tablets 
ZYPREXA 15 mg coated tablets 
ZYPREXA 20 mg coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
ZYPREXA 2.5 mg coated tablets 
Each coated tablet contains 2.5 mg olanzapine.  
 
Excipient with known effect: Each coated tablet contains 102 mg lactose monohydrate. 
 
ZYPREXA 5 mg coated tablets 
Each coated tablet contains 5 mg olanzapine.  
 
Excipient with known effect: Each coated tablet contains 156 mg lactose monohydrate. 
 
ZYPREXA 7.5 mg coated tablets 
Each coated tablet contains 7.5 mg olanzapine.  
 
Excipient with known effect: Each coated tablet contains 234 mg lactose monohydrate. 
 
ZYPREXA 10 mg coated tablets 
Each coated tablet contains 10 mg olanzapine.  
 
Excipient with known effect: Each coated tablet contains 312 mg lactose monohydrate. 
 
ZYPREXA 15 mg coated tablets 
Each coated tablet contains 15 mg olanzapine.  
 
Excipient with known effect: Each coated tablet contains 178 mg lactose monohydrate. 
 
ZYPREXA 20 mg coated tablets 
Each coated tablet contains 20 mg olanzapine.  
 
Excipient with known effect: Each coated tablet conatins 238 mg lactose monohydrate. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Coated tablet 
 
ZYPREXA 2.5 mg coated tablets 
Round, white, coated tablets imprinted with “LILLY” and a numeric identicode “4112”. 
 
ZYPREXA 5 mg coated tablets 
Round, white, coated tablets imprinted with “LILLY” and a numeric identicode “4115”. 
 
ZYPREXA 7.5 mg coated tablets 
Round, white, coated tablets imprinted with “LILLY” and a numeric identicode “4116”. 



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ZYPREXA 10 mg coated tablets 
Round, white, coated tablets imprinted with “LILLY” and a numeric identicode “4117”. 
 
ZYPREXA 15 mg coated tablets 
Elliptical, blue, coated tablets debossed with “LILLY” and a numeric identicode “4415”. 
 
ZYPREXA 20 mg coated tablets 
Pink, elliptical, coated tablets debossed with “LILLY” and a numeric identicode, “4420”. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
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). 
 
4.2 Posology and method of administration 
 
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 regards for meals as absorption is not affected by food. Gradual 
tapering of the dose should be considered when discontinuing olanzapine. 
 
Special populations 
 
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. 



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Smokers 
The starting dose and dose range need not be routinely altered for non-smokers relative to smokers. The 
metabolism of olanzapine may be induced by smoking. Clinical monitoring is recommended and an 
increase of olanzapine dose may be considered if necessary (see section 4.5). 
 
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 starting dose. Dose 
escalation, when indicated, should be conservative in such patients. 
 
(See sections 4.5 and 5.2) 
 
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). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.   
Patients with known risk of narrow-angle glaucoma. 
 
4.4 Special warnings and precautions for use 
 
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 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 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 



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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 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 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, 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 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 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. 
 
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, 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 section 4.8).  
 



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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.  
 
QT interval 
In 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 hypomagnesaemia. 
 
Thromboembolism 
Temporal 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 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 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 treatment.  
 
Postural hypotension 
Postural 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. 
 
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. 
 
Paediatric population 
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 sections 4.8 and 5.1). 
 



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Lactose  
ZYPREXA tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the 
Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Interaction studies have only been performed in adults. 
 
Potential interactions affecting olanzapine 
Since olanzapine is metabolised by CYP1A2, substances that can specifically induce or inhibit this 
isoenzyme may affect the pharmacokinetics of olanzapine.  
 
Induction of CYP1A2 
The metabolism of olanzapine may be induced by smoking and carbamazepine, which may lead to 
reduced olanzapine concentrations. Only slight to moderate increase in olanzapine clearance has been 
observed. The clinical consequences are likely to be limited, but clinical monitoring is recommended 
and an increase of olanzapine dose may be considered if necessary (see section 4.2). 
 
Inhibition of CYP1A2 
Fluvoxamine, a specific CYP1A2 inhibitor, has been shown to significantly inhibit the metabolism of 
olanzapine. The mean increase in olanzapine Cmax following fluvoxamine was 54 % in female non-
smokers and 77 % in male smokers. The mean increase in olanzapine AUC was 52 % and 108 % 
respectively. A lower starting dose of olanzapine should be considered in patients who are using 
fluvoxamine or any other CYP1A2 inhibitors, such as ciprofloxacin. A decrease in the dose of 
olanzapine should be considered if treatment with an inhibitor of CYP1A2 is initiated. 
 
Decreased bioavailability 
Activated charcoal reduces the bioavailability of oral olanzapine by 50 to 60 % and should be taken at 
least 2 hours before or after olanzapine. 
 
Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have 
not been found to significantly affect the pharmacokinetics of olanzapine. 
 
Potential for olanzapine to affect other medicinal products 
Olanzapine may antagonise the effects of direct and indirect dopamine agonists. 
 
Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e.g. 1A2, 2D6, 2C9, 2C19, 3A4). 
Thus no particular interaction is expected as verified through in vivo studies where no inhibition of 
metabolism of the following active substances was found: tricyclic antidepressant (representing mostly 
CYP2D6 pathway), warfarin (CYP2C9), theophylline (CYP1A2) or diazepam (CYP3A4 and 2C19).  
 
Olanzapine showed no interaction when co-administered with lithium or biperiden. 
 
Therapeutic monitoring of valproate plasma levels did not indicate that valproate dosage adjustment is 
required after the introduction of concomitant olanzapine. 
 
General CNS activity 
Caution should be exercised in patients who consume alcohol or receive medicinal products that can 
cause central nervous system depression. 
 
The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with 
Parkinson's disease and dementia is not recommended (see section 4.4).  
 
QTc interval 
Caution should be used if olanzapine is being administered concomitantly with medicinal products 
known to increase QTc interval (see section 4.4). 
 



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4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no adequate and well-controlled studies in pregnant women. Patients should be advised to 
notify their physician if they become pregnant or intend to become pregnant during treatment with 
olanzapine. Nevertheless, because human experience is limited, olanzapine should be used in 
pregnancy only if the potential benefit justifies the potential risk to the foetus. 
 
New born infants exposed to antipsychotics (including olanzapine) during the third trimester of 
pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that 
may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, 
hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns 
should be monitored carefully. 
 
Breast-feeding 
In a study in breast-feeding, healthy women, olanzapine was excreted in breast milk. Mean infant 
exposure (mg/kg) at steady state was estimated to be 1.8 % of the maternal olanzapine dose (mg/kg). 
Patients should be advised not to breast feed an infant if they are taking olanzapine. 
 
Fertility 
Effects on fertility are unknown (see section 5.3 for preclinical information). 
 
4.7 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. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Adults 
The most frequently (seen in ≥ 1 % of patients) reported adverse reactions associated with the use of 
olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, 
cholesterol, glucose and triglyceride levels (see section 4.4), glucosuria, increased appetite, dizziness, 
akathisia, parkinsonism, leukopenia, neutropenia (see section 4.4), dyskinesia, orthostatic hypotension, 
anticholinergic effects, transient asymptomatic elevations of hepatic aminotransferases (see section 
4.4), 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 data available). 
 
Very 
common 

Common Uncommon  Rare Not known 

Blood and the lymphatic system disorders  
 Eosinophilia 

Leukopenia10 
Neutropenia10 

 Thrombocytopenia11  

Immune system disorders  
  Hypersensitivity11   



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Metabolism and nutrition disorders  
Weight 
gain1 

Elevated cholesterol 
levels2,3 
Elevated glucose 
levels4 
Elevated triglyceride 
levels2,5 
Glucosuria  
Increased appetite 

Development or 
exacerbation of 
diabetes occasionally 
associated with 
ketoacidosis or coma, 
including some fatal 
cases (see section 
4.4) 11 

Hypothermia12  

Nervous system disorders  
Somnolence Dizziness 

Akathisia6 
Parkinsonism6 
Dyskinesia6 

Seizures where in 
most cases a history 
of seizures or risk 
factors for seizures 
were reported 11 
Dystonia (including 
oculogyration) 11 
Tardive dyskinesia11 
Amnesia 9 
Dysarthria 
Stuttering11 
Restless Legs 
Syndrome11 

Neuroleptic malignant 
syndrome (see section 
4.4)12  
Discontinuation 
symptoms7, 12 
 

 

Cardiac disorders  
  Bradycardia 

QTc prolongation (see 
section 4.4) 

Ventricular 
tachycardia/fibrillation, 
sudden death (see 
section 4.4)11 

 

Vascular disorders  
Orthostatic 
hypotension10 

 Thromboembolism 
(including pulmonary 
embolism and deep 
vein thrombosis) (see 
section 4.4) 

  

Respiratory, thoracic and mediastinal disorders  
  Epistaxis9   
Gastrointestinal disorders  
 Mild, transient 

anticholinergic 
effects including 
constipation and dry 
mouth 

Abdominal 
distension9 
Salivary 
hypersecretion11 

Pancreatitis11  

Hepatobiliary disorders  
 Transient, 

asymptomatic 
elevations of hepatic 
aminotransferases 
(ALT, AST), 
especially in early 
treatment (see section 
4.4) 

 Hepatitis (including 
hepatocellular, 
cholestatic or mixed 
liver injury) 11 

 



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Skin and subcutaneous tissue disorders  
 Rash Photosensitivity 

reaction 
Alopecia 

  

    Drug 
Reaction with 
Eosinophilia 
and Systemic 
Symptoms 
(DRESS)  

Musculoskeletal and connective tissue disorders  
 Arthralgia9  Rhabdomyolysis11  
Renal and urinary disorders  
  Urinary incontinence, 

urinary retention 
Urinary hesitation11 

  

Pregnancy, puerperium and perinatal conditions                                         
    Drug 

withdrawal 
syndrome 
neonatal (see 
section 4.6) 

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. Following short term treatment (median duration 47 days), weight gain ≥ 7 % of baseline 
body weight  was very common (22.2 %), ≥ 15 % was common (4.2 %) and ≥ 25 % was uncommon 
(0.8 %). Patients gaining ≥ 7 %, ≥ 15 % and ≥ 25 % of their baseline body weight with long-term 
exposure (at least 48 weeks) were very common (64.4 %, 31.7 % and 12.3 % 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. 
 
3 Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high 
(≥ 6.2 mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17 - 
< 6.2 mmol/l) to high (≥ 6.2 mmol/l) were very common. 
 



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4 Observed for fasting normal levels at baseline (< 5.56 mmol/l) which increased to high (≥ 7 mmol/l). 
Changes in fasting glucose from borderline at baseline (≥ 5.56 - < 7 mmol/l) to high (≥ 7 mmol/l) were 
very common.  
 
5 Observed for fasting normal levels at baseline (< 1.69 mmol/l) which increased to high 
(≥ 2.26 mmol/l). Changes in fasting triglycerides from borderline at baseline (≥ 1.69 mmol/l - 
< 2.26 mmol/l) to high (≥ 2.26 mmol/l) were very common. 
 
6 In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was 
numerically higher, but not statistically significantly different from placebo. Olanzapine-treated patients 
had a lower incidence of Parkinsonism, akathisia and dystonia compared with titrated doses of 
haloperidol. In the absence of detailed information on the pre-existing history of individual acute and 
tardive extrapyramidal movement disorders, it cannot be concluded at present that olanzapine produces 
less tardive dyskinesia and/or other tardive extrapyramidal syndromes. 
 
7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been 
reported when olanzapine is stopped abruptly. 
 
8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of 
normal range in approximately 30 % of olanzapine treated patients with normal baseline prolactin 
value. In the majority of these patients the elevations were generally mild, and remained below two 
times the upper limit of normal range.  
 
9 Adverse event identified from clinical trials in the Olanzapine Integrated Database. 
 
10 As assessed by measured values from clinical trials in the Olanzapine Integrated Database. 
 
11 Adverse event identified from spontaneous post-marketing reporting with frequency determined 

utilising the Olanzapine Integrated Database. 
 
12 Adverse event identified from spontaneous post-marketing reporting with frequency estimated at the 

upper limit of the 95 % confidence interval utilising the Olanzapine Integrated Database. 

 
Long-term exposure (at least 48 weeks) 
The proportion of patients who had adverse, clinically significant changes in weight gain, glucose, 
total/LDL/HDL cholesterol or triglycerides increased over time. In adult patients who completed 9-
12 months of therapy, the rate of increase in mean blood glucose slowed after approximately 
6 months. 
 
Additional information on special populations 
In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher 
incidence of death and cerebrovascular adverse reactions compared to placebo (see section 4.4). Very 
common adverse reactions associated with the use of olanzapine in this patient group were abnormal 
gait and falls. Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and 
urinary incontinence were observed commonly.  
 
In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with 
Parkinson’s disease, worsening of Parkinsonian symptomatology and hallucinations were reported 
very commonly and more frequently than with placebo. 
 
In one clinical trial in patients with bipolar mania, valproate combination therapy with olanzapine 
resulted in an incidence of neutropenia of 4.1 %; a potential contributing factor could be high plasma 
valproate levels. Olanzapine administered with lithium or valproate resulted in increased levels 
(≥ 10 %) of tremor, dry mouth, increased appetite, and weight gain. Speech disorder was also reported 
commonly. During treatment with olanzapine in combination with lithium or divalproex, an increase 
of ≥ 7 % from baseline body weight occurred in 17.4 % of patients during acute treatment (up to 



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6 weeks). Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with 
bipolar disorder was associated with an increase of ≥ 7 % from baseline body weight in 39.9 % of 
patients. 
 
Paediatric population 
Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years. 
Although no clinical studies designed to compare adolescents to adults have been conducted, data 
from the adolescent trials were compared to those of the adult trials.  
 
The following table summarises the adverse reactions reported with a greater frequency in adolescent 
patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-term 
clinical trials in adolescent patients. Clinically significant weight gain (≥ 7 %) appears to occur more 
frequently in the adolescent population compared to adults with comparable exposures. The magnitude 
of weight gain and the proportion of adolescent patients who had clinically significant weight gain 
were greater with long-term exposure (at least 24 weeks) than with short-term exposure.  
 
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). 
 
Metabolism and nutrition disorders 
Very common: Weight gain13, elevated triglyceride levels14, increased appetite. 
Common: Elevated cholesterol levels15 
Nervous system disorders 
Very common: Sedation (including: hypersomnia, lethargy, somnolence). 
Gastrointestinal disorders 
Common: Dry mouth 
Hepatobiliary disorders 
Very common: Elevations of hepatic aminotransferases (ALT/AST; see section 4.4). 
Investigations  
Very common: Decreased total bilirubin, increased GGT, elevated plasma prolactin levels16. 
 
13 Following short term treatment (median duration 22 days), weight gain ≥ 7 % of baseline body 
weight (kg) was very common (40.6 %), ≥ 15 % of baseline body weight was common (7.1 %) and 
≥ 25 % was common (2.5 %). With long-term exposure (at least 24 weeks), 89.4 % gained ≥ 7 %, 
55.3 % gained ≥ 15 % and 29.1 % gained ≥ 25 % of their baseline body weight. 
 
14  Observed for fasting normal levels at baseline (< 1.016 mmol/l) which increased to high 
(≥ 1.467 mmol/l) and changes in fasting triglycerides from borderline at baseline (≥ 1.016 mmol/l - 
< 1.467 mmol/l) to high (≥ 1.467 mmol/l). 
 
15 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high 
(≥ 5.17 mmol/l) were observed commonly. Changes in total fasting cholesterol levels from borderline 
at baseline (≥ 4.39 - < 5.17 mmol/l) to high (≥ 5.17 mmol/l) were very common. 
 
16 Elevated plasma prolactin levels were reported in 47.4 % of adolescent patients. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system listed 
in Appendix V. 
 



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4.9 Overdose 
 
Signs and symptoms 
Very common symptoms in overdose (> 10 % incidence) include tachycardia, 
agitation/aggressiveness, dysarthria, various extrapyramidal symptoms, and reduced level of 
consciousness ranging from sedation to coma.  
 
Other medically significant sequelae of overdose include delirium, convulsion, coma, possible 
neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, 
cardiac arrhythmias (< 2 % of overdose cases) and cardiopulmonary arrest. Fatal outcomes have been 
reported for acute overdoses as low as 450 mg but survival has also been reported following acute 
overdose of approximately 2 g of oral olanzapine. 
 
Management  
There is no specific antidote for olanzapine. Induction of emesis is not recommended. Standard 
procedures for management of overdose may be indicated (i.e. gastric lavage, administration of 
activated charcoal). The concomitant administration of activated charcoal was shown to reduce the 
oral bioavailability of olanzapine by 50 to 60 %. 
 
Symptomatic treatment and monitoring of vital organ function should be instituted according to 
clinical presentation, including treatment of hypotension and circulatory collapse and support of 
respiratory function. Do not use epinephrine, dopamine, or other sympathomimetic agents with beta-
agonist activity since beta stimulation may worsen hypotension. Cardiovascular monitoring is 
necessary to detect possible arrhythmias. Close medical supervision and monitoring should continue 
until the patient recovers. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: psycholeptics, diazepines, oxazepines, thiazepines and oxepines, ATC 
code N05A H03. 
 
Pharmacodynamic effects  
Olanzapine is an antipsychotic, antimanic and mood stabilising agent that demonstrates a broad 
pharmacologic profile across a number of receptor systems. 
 
In preclinical studies, olanzapine exhibited a range of receptor affinities (Ki  < 100 nM) for serotonin 
5 HT2A/2C, 5 HT3, 5 HT6; dopamine D1, D2, D3, D4, D5; cholinergic muscarinic receptors M1-M5; α1 
adrenergic; and histamine H1 receptors. Animal behavioural studies with olanzapine indicated 5HT, 
dopamine, and cholinergic antagonism, consistent with the receptor-binding profile. Olanzapine 
demonstrated a greater in vitro affinity for serotonin 5HT2 than dopamine D2 receptors and greater 
5 HT2 than D2 activity in vivo models. Electrophysiological studies demonstrated that olanzapine 
selectively reduced the firing of mesolimbic (A10) dopaminergic neurons, while having little effect on 
the striatal (A9) pathways involved in motor function. Olanzapine reduced a conditioned avoidance 
response, a test indicative of antipsychotic activity, at doses below those producing catalepsy, an effect 
indicative of motor side-effects. Unlike some other antipsychotic agents, olanzapine increases 
responding in an “anxiolytic” test. 
 
In a single oral dose (10 mg) Positron Emission Tomography (PET) study in healthy volunteers, 
olanzapine produced a higher 5 HT2A than dopamine D2 receptor occupancy. In addition, a Single 
Photon Emission Computed Tomography (SPECT) imaging study in schizophrenic patients revealed 
that olanzapine-responsive patients had lower striatal D2 occupancy than some other antipsychotic- 
and risperidone-responsive patients, while being comparable to clozapine-responsive patients. 
 



 14 

Clinical efficacy 
In two of two placebo and two of three comparator controlled trials with over 2,900 schizophrenic 
patients presenting with both positive and negative symptoms, olanzapine was associated with 
statistically significantly greater improvements in negative as well as positive symptoms. 
 
In a multinational, double-blind, comparative study of schizophrenia, schizoaffective, and related 
disorders which included 1,481 patients with varying degrees of associated depressive symptoms 
(baseline mean of 16.6 on the Montgomery-Asberg Depression Rating Scale), a prospective secondary 
analysis of baseline to endpoint mood score change demonstrated a statistically significant 
improvement (p = 0.001) favouring olanzapine (-6.0) versus haloperidol (-3.1). 
 
In patients with a manic or mixed episode of bipolar disorder, olanzapine demonstrated superior 
efficacy to placebo and valproate semisodium (divalproex) in reduction of manic symptoms over 
3 weeks. Olanzapine also demonstrated comparable efficacy results to haloperidol in terms of the 
proportion of patients in symptomatic remission from mania and depression at 6 and 12 weeks. In a 
co-therapy study of patients treated with lithium or valproate for a minimum of 2 weeks, the addition 
of olanzapine 10 mg (co-therapy with lithium or valproate) resulted in a greater reduction in symptoms 
of mania than lithium or valproate monotherapy after 6 weeks. 
 
In a 12 month recurrence prevention study in manic episode patients who achieved remission on 
olanzapine and were then randomised to olanzapine or placebo, olanzapine demonstrated statistically 
significant superiority over placebo on the primary endpoint of bipolar recurrence. Olanzapine also 
showed a statistically significant advantage over placebo in terms of preventing either recurrence into 
mania or recurrence into depression. 
 
In a second 12 month recurrence prevention study in manic episode patients who achieved remission 
with a combination of olanzapine and lithium and were then randomised to olanzapine or lithium 
alone, olanzapine was statistically non-inferior to lithium on the primary endpoint of bipolar 
recurrence (olanzapine 30.0 %, lithium 38.3 %; p = 0.055). 
 
In an 18 month co-therapy study in manic or mixed episode patients stabilised with olanzapine plus a 
mood stabiliser (lithium or valproate), long-term olanzapine co-therapy with lithium or valproate was 
not statistically significantly superior to lithium or valproate alone in delaying bipolar recurrence, 
defined according to syndromic (diagnostic) criteria. 
 
Paediatric population 
Controlled efficacy data in adolescents (ages 13 to 17 years) are limited to short term studies in 
schizophrenia (6 weeks) and mania associated with bipolar I disorder (3 weeks), involving less than 
200 adolescents. Olanzapine was used as a flexible dose starting with 2.5 and ranging up to 
20 mg/day. During treatment with olanzapine, adolescents gained significantly more weight compared 
with adults. The magnitude of changes in fasting total cholesterol, LDL cholesterol, triglycerides, and 
prolactin (see sections 4.4 and 4.8) were greater in adolescents than in adults.  There are no controlled 
data on maintenance of effect or long term safety (see sections 4.4 and 4.8). Information on long term 
safety is primarily limited to open-label, uncontrolled data. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
Olanzapine is well absorbed after oral administration, reaching peak plasma concentrations within 5 to 
8 hours. The absorption is not affected by food. Absolute oral bioavailability relative to intravenous 
administration has not been determined. 
 
Distribution 
The plasma protein binding of olanzapine was about 93 % over the concentration range of about 7 to 
about 1000 ng/ml. Olanzapine is bound predominantly to albumin and α1-acid-glycoprotein. 
 



 15 

Biotransformation 
Olanzapine is metabolized in the liver by conjugative and oxidative pathways. The major circulating 
metabolite is the 10-N-glucuronide, which does not pass the blood brain barrier. Cytochromes P450-
CYP1A2 and P450-CYP2D6 contribute to the formation of the N-desmethyl and 2-hydroxymethyl 
metabolites, both exhibited significantly less in vivo pharmacological activity than olanzapine in 
animal studies. The predominant pharmacologic activity is from the parent olanzapine.  
 
Elimination 
After oral administration, the mean terminal elimination half-life of olanzapine in healthy subjects 
varied on the basis of age and gender. 
 
In healthy elderly (65 and over) versus non-elderly subjects, the mean elimination half-life was 
prolonged (51.8 versus 33.8 hr) and the clearance was reduced (17.5 versus 18.2 l/hr). The 
pharmacokinetic variability observed in the elderly is within the range for the non-elderly. In 
44 patients with schizophrenia > 65 years of age, dosing from 5 to 20 mg/day was not associated with 
any distinguishing profile of adverse events. 
 
In female versus male subjects the mean elimination half life was somewhat prolonged (36.7 versus 
32.3 hr) and the clearance was reduced (18.9 versus 27.3 l/hr). However, olanzapine (5-20 mg) 
demonstrated a comparable safety profile in female (n = 467) as in male patients (n = 869). 
 
Renal impairment 
In renally impaired patients (creatinine clearance < 10 ml/min) versus healthy subjects, there was no 
significant difference in mean elimination half-life (37.7 versus 32.4 hr) or clearance (21.2 versus 
25.0 l/hr). A mass balance study showed that approximately 57 % of radiolabelled olanzapine 
appeared in urine, principally as metabolites. 
 
Hepatic impairment  
A small study of the effect of impaired liver function in 6 subjects with clinically significant (Childs 
Pugh Classification A (n = 5) and B (n = 1)) cirrhosis revealed little effect on the pharmacokinetics of 
orally administered olanzapine (2.5 – 7.5 mg single dose): Subjects with mild to moderate hepatic 
dysfunction had slightly increased systemic clearance and faster elimination half-time compared to 
subjects with no hepatic dysfunction (n = 3). There were more smokers among subjects with cirrhosis 
(4/6; 67 %) than among subjects with no hepatic dysfunction (0/3; 0 %). 
Smoking 
In non-smoking versus smoking subjects (males and females) the mean elimination half-life was 
prolonged (38.6 versus 30.4 hr) and the clearance was reduced (18.6 versus 27.7 l/hr). 
 
The plasma clearance of olanzapine is lower in elderly versus young subjects, in females versus males, 
and in non-smokers versus smokers. However, the magnitude of the impact of age, gender, or smoking 
on olanzapine clearance and half-life is small in comparison to the overall variability between 
individuals. 
 
In a study of Caucasians, Japanese, and Chinese subjects, there were no differences in the 
pharmacokinetic parameters among the three populations. 
 
Paediatric population 
Adolescents (ages 13 to 17 years): The pharmacokinetics of olanzapine are similar between 
adolescents and adults. In clinical studies, the average olanzapine exposure was approximately 27 % 
higher in adolescents. Demographic differences between the adolescents and adults include a lower 
average body weight and fewer adolescents were smokers. Such factors possibly contribute to the 
higher average exposure observed in adolescents. 
 



 16 

5.3 Preclinical safety data 
 
Acute (single-dose) toxicity 
Signs of oral toxicity in rodents were characteristic of potent neuroleptic compounds: hypoactivity, 
coma, tremors, clonic convulsions, salivation, and depressed weight gain. The median lethal doses 
were approximately 210 mg/kg (mice) and 175 mg/kg (rats). Dogs tolerated single oral doses up to 
100 mg/kg without mortality. Clinical signs included sedation, ataxia, tremors, increased heart rate, 
labored respiration, miosis, and anorexia. In monkeys, single oral doses up to 100 mg/kg resulted in 
prostration and, at higher doses, semi-consciousness. 
 
Repeated-dose toxicity  
In studies up to 3 months duration in mice and up to 1 year in rats and dogs, the predominant effects 
were CNS depression, anticholinergic effects, and peripheral haematological disorders. Tolerance 
developed to the CNS depression. Growth parameters were decreased at high doses. Reversible effects 
consistent with elevated prolactin in rats included decreased weights of ovaries and uterus and 
morphologic changes in vaginal epithelium and in mammary gland. 
 
Haematologic toxicity 
Effects on haematology parameters were found in each species, including dose-related reductions in 
circulating leukocytes in mice and non-specific reductions of circulating leukocytes in rats; however, 
no evidence of bone marrow cytotoxicity was found. Reversible neutropenia, thrombocytopenia, or 
anaemia developed in a few dogs treated with 8 or 10 mg/kg/day (total olanzapine exposure [AUC] is 
12- to 15-fold greater than that of a man given a 12-mg dose). In cytopenic dogs, there were no 
adverse effects on progenitor and proliferating cells in the bone marrow.  
 
Reproductive toxicity 
Olanzapine had no teratogenic effects. Sedation affected mating performance of male rats. Estrous 
cycles were affected at doses of 1.1 mg/kg (3 times the maximum human dose) and reproduction 
parameters were influenced in rats given 3 mg/kg (9 times the maximum human dose). In the offspring 
of rats given olanzapine, delays in foetal development and transient decreases in offspring activity 
levels were seen. 
 
Mutagenicity 
Olanzapine was not mutagenic or clastogenic in a full range of standard tests, which included bacterial 
mutation tests and in vitro and in vivo mammalian tests. 
 
Carcinogenicity 
Based on the results of studies in mice and rats, it was concluded that olanzapine is not carcinogenic. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
 
Lactose monohydrate 
Hyprolose 
Crospovidone  
Microcrystalline cellulose  
Magnesium stearate 
 
Tablet coat 
 
ZYPREXA 2.5 mg , 5 mg, 7.5 mg and 10 mg coated tablets 
Hypromellose 
Colour mixture white (hypromellose, titanium dioxide E171, macrogol, polysorbate 80) 



 17 

Carnauba wax 
Edible blue ink (shellac, ethanol anhydrous, isopropyl alcohol, butyl alcohol, propylene glycol, 
ammonium hydroxide, indigo carmine E132) 
 
ZYPREXA 15 mg coated tablets 
Hypromellose 
Colour mixture light blue (titanium dioxide E171, lactose monohydrate, hypromellose, triacetin, 
indigo carmine colour (E132)) 
Carnauba wax 
 
ZYPREXA 20 mg coated tablets 
Hypromellose 
Colour mixture pink (titanium dioxide E171, macrogol, lactose monohydrate, hypromellose, synthetic 
red iron oxide) 
Carnauba wax 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
ZYPREXA 2.5 mg coated tablets 
2 years. 
 
ZYPREXA 5 mg, 7.5 mg, 10 mg, 15 mg  and 20 mg coated tablets 
3 years. 
 
6.4 Special precautions for storage 
 
Store in the original package in order to protect from light and moisture. 
 
6.5 Nature and contents of container 
 
Cold-formed aluminium blister strips in cartons of 28, 35, 56, 70 or 98 tablets per carton. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands. 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/96/022/002 - ZYPREXA - 2.5 mg - coated tablets - 28 tablets, per box.  
EU/1/96/022/019 - ZYPREXA - 2.5 mg - coated tablets - 56 tablets, per box. 
EU/1/96/022/023 - ZYPREXA - 2.5 mg - coated tablets - 35 tablets, per box.  
EU/1/96/022/029 - ZYPREXA - 2.5 mg - coated tablets - 70 tablets, per box.  
EU/1/96/022/035 - ZYPREXA - 2.5 mg - coated tablets - 98 tablets, per box. 
EU/1/96/022/004 - ZYPREXA - 5 mg - coated tablets - 28 tablets, per box.  
EU/1/96/022/020 - ZYPREXA - 5 mg - coated tablets - 56 tablets, per box. 



 18 

EU/1/96/022/024 - ZYPREXA - 5 mg - coated tablets - 35 tablets, per box.  
EU/1/96/022/030 - ZYPREXA - 5 mg - coated tablets - 70 tablets, per box.  
EU/1/96/022/036 - ZYPREXA - 5 mg - coated tablets - 98 tablets, per box. 
EU/1/96/022/011 - ZYPREXA - 7.5 mg - coated tablets - 28 tablets, per box.  
EU/1/96/022/006 - ZYPREXA - 7.5 mg - coated tablets - 56 tablets, per box.  
EU/1/96/022/025 - ZYPREXA – 7.5 mg - coated tablets - 35 tablets, per box.  
EU/1/96/022/031 - ZYPREXA – 7.5 mg - coated tablets - 70 tablets, per box.  
EU/1/96/022/037 - ZYPREXA - 7.5 mg - coated tablets - 98 tablets, per box. 
EU/1/96/022/009 - ZYPREXA - 10 mg - coated tablets - 28 tablets, per box. 
EU/1/96/022/010 - ZYPREXA - 10 mg - coated tablets - 56 tablets, per box. 
EU/1/96/022/026 - ZYPREXA - 10 mg - coated tablets - 35 tablets, per box.  
EU/1/96/022/032 - ZYPREXA - 10 mg - coated tablets - 70 tablets, per box.  
EU/1/96/022/038 - ZYPREXA - 10 mg - coated tablets - 98 tablets, per box.  
EU/1/96/022/012 - ZYPREXA - 15 mg - coated tablets - 28 tablets, per box.  
EU/1/96/022/021 - ZYPREXA - 15 mg - coated tablets - 56 tablets, per box. 
EU/1/96/022/027 - ZYPREXA - 15 mg - coated tablets - 35 tablets, per box.  
EU/1/96/022/033 - ZYPREXA - 15 mg - coated tablets - 70 tablets, per box.  
EU/1/96/022/039 - ZYPREXA - 15 mg - coated tablets - 98 tablets, per box.  
EU/1/96/022/014 - ZYPREXA - 20 mg - coated tablets - 28 tablets, per box.  
EU/1/96/022/022 - ZYPREXA - 20 mg - coated tablets - 56 tablets, per box. 
EU/1/96/022/028 - ZYPREXA - 20 mg - coated tablets - 35 tablets, per box.  
EU/1/96/022/034 - ZYPREXA - 20 mg - coated tablets - 70 tablets, per box.  
EU/1/96/022/040 - ZYPREXA - 20 mg - coated tablets - 98 tablets, per box.  
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 27 September 1996  
Date of latest renewal: 12 September 2006 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 



 19 

1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA 10 mg powder for solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial contains 10 mg olanzapine. After reconstitution each ml of the solution contains 5 mg 
olanzapine. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder for solution for injection 
Yellow lyophilised powder. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Adults  
ZYPREXA powder for solution for injection is indicated for the rapid control of agitation and 
disturbed behaviours in patients with schizophrenia or manic episode, when oral therapy is not 
appropriate. Treatment with ZYPREXA powder for solution for injection should be discontinued and 
the use of oral olanzapine should be initiated as soon as clinically appropriate. 
 
4.2 Posology and method of administration 
 
Adults 
For intramuscular use. Do not administer intravenously or subcutaneously. ZYPREXA 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. A lower dose (5 mg or 7.5 mg) may be given, on the basis of individual 
clinical status, which should also include consideration of medicinal products already administered 
either for maintenance or acute treatment (see section 4.4). 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. 
 
ZYPREXA powder for solution for injection should be reconstituted in accordance with the 
recommendation in section 6.6. 
 
For further information on continued treatment with oral olanzapine (5 to 20 mg daily), see the 
Summary of Product Characteristics for ZYPREXA coated tablets or ZYPREXA VELOTAB 
orodispersible tablets. 
 



 20 

Special populations 
 
Elderly 
The recommended starting dose in elderly patients (> 60 years) is 2.5 - 5 mg. Depending on the 
patient's clinical status (see section 4.4), a second injection, 2.5 - 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. Clinical monitoring is recommended and an 
increase of olanzapine dose may be considered if necessary (see section 4.5). 
 
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. 
 
(See sections 4.5 and 5.2) 
 
Paediatric population 
There is no experience in children. ZYPREXA powder for solution for injection is not recommended 
for use in children and adolescents due to a lack of data on safety and efficacy. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.   
Patients with known risk of narrow-angle glaucoma. 
 
4.4 Special warnings and precautions for use 
 
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 section 4.5). 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 section 4.8). 
 
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 sections 4.5 and 6.2). 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 



 21 

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 section 4.5).  
 
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. 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 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 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. 
 



 22 

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 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, 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 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 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. 
 
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 section 4.8).  
 
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.  
 
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. 
 



 23 

Thromboembolism 
Temporal 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 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 discontinuation should be considered. These symptoms 
can temporally 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. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Interaction studies have only been performed in adults. 
 
IM olanzapine has not been studied in patients with alcohol or drug intoxication (see section 4.4). 
 
Caution should be exercised in patients who consume alcohol or receive medicinal products that can 
induce hypotension, bradycardia, respiratory or central nervous system depression (see section 4.4). 
 
Potential for interaction following intramuscular injection 
In a single dose intramuscular study of olanzapine 5 mg, administered 1 hour before intramuscular 
lorazepam 2 mg (metabolised by glucuronidation), the pharmacokinetics of both medicines were 
unchanged. However, the combination added to the somnolence observed with either medicines alone. 
Concomitant injection of olanzapine and parenteral benzodiazepine is not recommended (see sections 
4.4 and 6.2). 
 
Potential interactions affecting olanzapine 
Since olanzapine is metabolised by CYP1A2, substances that can specifically induce or inhibit this 
isoenzyme may affect the pharmacokinetics of olanzapine.  
 



 24 

Induction of CYP1A2 
The metabolism of olanzapine may be induced by smoking and carbamazepine, which may lead to 
reduced olanzapine concentrations. Only slight to moderate increase in olanzapine clearance has been 
observed. The clinical consequences are likely to be limited, but clinical monitoring is recommended 
and an increase of olanzapine dose may be considered if necessary (see section 4.2). 
 
Inhibition of CYP1A2 
Fluvoxamine, a specific CYP1A2 inhibitor, has been shown to significantly inhibit the metabolism of 
olanzapine. The mean increase in olanzapine Cmax following fluvoxamine was 54 % in female non-
smokers and 77 % in male smokers. The mean increase in olanzapine AUC was 52 % and 108 % 
respectively. A lower starting dose of olanzapine should be considered in patients who are using 
fluvoxamine or any other CYP1A2 inhibitors, such as ciprofloxacin. A decrease in the dose of 
olanzapine should be considered if treatment with an inhibitor of CYP1A2 is initiated. 
 
Decreased bioavailability 
Activated charcoal reduces the bioavailability of oral olanzapine by 50 to 60 % and should be taken at 
least 2 hours before or after olanzapine. 
 
Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have 
not been found to significantly affect the pharmacokinetics of olanzapine. 
 
Potential for olanzapine to affect other medicinal products 
Olanzapine may antagonise the effects of direct and indirect dopamine agonists (see section 6.2). 
 
Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e.g. 1A2, 2D6, 2C9, 2C19, 3A4). 
Thus no particular interaction is expected as verified through in vivo studies where no inhibition of 
metabolism of the following active substances was found: tricyclic antidepressant (representing mostly 
CYP2D6 pathway), warfarin (CYP2C9), theophylline (CYP1A2) or diazepam (CYP3A4 and 2C19).  
 
Olanzapine showed no interaction when co-administered with lithium or biperiden. 
 
Therapeutic monitoring of valproate plasma levels did not indicate that valproate dosage adjustment is 
required after the introduction of concomitant olanzapine. 
 
The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with 
Parkinson's disease and dementia is not recommended (see section 4.4).  
 
QTc interval 
Caution should be used if olanzapine is being administered concomitantly with medicinal products 
known to increase QTc interval (see section 4.4). 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no adequate and well-controlled studies in pregnant women. Patients should be advised to 
notify their physician if they become pregnant or intend to become pregnant during treatment with 
olanzapine. Nevertheless, because human experience is limited, olanzapine should be used in 
pregnancy only if the potential benefit justifies the potential risk to the foetus. 
 
New born infant exposed to antipsychotics (including olanzapine) during the third trimester of 
pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that 
may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, 
hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns 
should be monitored carefully. 
 



 25 

Breast-feeding 
In a study in breast-feeding, healthy women, olanzapine was excreted in breast milk. Mean infant 
exposure (mg/kg) at steady state was estimated to be 1.8 % of the maternal olanzapine dose (mg/kg). 
Patients should be advised not to breast feed an infant if they are taking olanzapine. 
 
Fertility 
Effects on fertility are unknown (see section 5.3 for preclinical information). 
 
4.7 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. 
 
4.8 Undesirable effects 
 
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.  
 
In post marketing reports, temporal association of treatment with IM olanzapine with cases of 
respiratory depression, hypotension or bradycardia and death have been very rarely reported, mostly in 
patients who concomitantly received benzodiazepines, and/or other antipsychotic medicinal products 
or who were treated in excess of olanzapine recommended daily doses (see sections 4.4 and 4.5). 
 
The following table is based on the undesirable effects and laboratory investigations from clinical 
trials with ZYPREXA 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 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 
ZYPREXA powder for solution for injection. 
 
Adults 
The most frequently (seen in ≥ 1% of patients) reported adverse reactions associated with the use of 
olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, 
cholesterol, glucose and triglyceride levels (see section 4.4), glucosuria, increased appetite, dizziness, 
akathisia, parkinsonism, leukopenia, neutropenia (see section 4.4), dyskinesia, orthostatic hypotension, 
anticholinergic effects, transient asymptomatic elevations of hepatic aminotransferases (see section 
4.4), 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 data available). 



 26 

 
Very common Common Uncommon  Rare Not 

known 
Blood and the lymphatic system disorders  
 Eosinophilia 

Leukopenia10 
Neutropenia10 

 Thrombocytopenia11  

Immune system disorders  
  Hypersensitivity11   
Metabolism and nutrition disorders  
Weight gain1 Elevated 

cholesterol levels2,3 
Elevated glucose 
levels4 
Elevated 
triglyceride levels2,5 
Glucosuria  
Increased appetite 

Development or 
exacerbation of 
diabetes occasionally 
associated with 
ketoacidosis or coma, 
including some fatal 
cases (see section 
4.4) 11 

Hypothermia12  

Nervous system disorders  
Somnolence Dizziness 

Akathisia6 
Parkinsonism6 
Dyskinesia6 

Seizures where in 
most cases a history 
of seizures or risk 
factors for seizures 
were reported11 
 
 
 
Dystonia (including 
oculogyration)11 
Tardive dyskinesia11 
 
 
Amnesia9 
 
Dysarthria 
Stuttering11, 13 
Restless Legs 
Syndrome11 

Neuroleptic malignant 
syndrome (see section 
4.4)12  
Discontinuation 
symptoms7,12 

 

Cardiac disorders  
  Bradycardia 

QTc prolongation (see 
section 4.4) 

Ventricular 
tachycardia/fibrillation, 
sudden death (see 
section 4.4)11 

 

Vascular disorders  
Orthostatic 
hypotension10 

 Thromboembolism 
(including pulmonary 
embolism and deep 
vein thrombosis) (see 
section 4.4) 

  

Respiratory, thoracic and mediastinal disorders  
  Epistaxis9   



 27 

Gastrointestinal disorders  
 Mild, transient 

anticholinergic 
effects including 
constipation and 
dry mouth 

Abdominal 
distension9 
Salivary 
hypersecretion11 

Pancreatitis11  

Hepatobiliary disorders  
 Transient, 

asymptomatic 
elevations of 
hepatic 
aminotransferases 
(ALT, AST), 
especially in early 
treatment (see 
section 4.4) 

 Hepatitis (including 
hepatocellular, 
cholestatic or mixed 
liver injury)11 

 

Skin and subcutaneous tissue disorders  
 Rash Photosensitivity 

reaction 
Alopecia 

 Drug 
Reaction 
with 
Eosinophilia 
and 
Systemic 
Symptoms 
(DRESS)  
 

Musculoskeletal and connective tissue disorders  
 Arthralgia9  Rhabdomyolysis11  
Renal and urinary disorders  
  Urinary incontinence, 

urinary retention 
Urinary hesitation11 

  

Pregnancy, puerperium and perinatal conditions  
    Drug 

withdrawal 
syndrome 
neonatal 
(see 
section 
4.6) 

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 

   



 28 

Investigations  
Elevated 
plasma 
prolactin 
levels8 

Increased alkaline 
phosphatase10 
High creatine 
phosphokinase11 
High Gamma 
Glutamyltransferase  
10 

High Uric acid 10 

Increased total 
bilirubin 

  

 
1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) 
categories. Following short term treatment (median duration 47 days), weight gain ≥ 7% of baseline 
body weight  was very common (22.2 %), ≥ 15 % was common (4.2 %) and ≥ 25 % was uncommon 
(0.8 %). Patients gaining ≥ 7 %, ≥ 15 % and ≥ 25 % of their baseline body weight with long-term 
exposure (at least 48 weeks) were very common (64.4 %, 31.7 % and 12.3 % 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. 
 
3 Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high 
(≥ 6.2 mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17 - 
< 6.2 mmol/l) to high (≥ 6.2 mmol/l) were very common. 
 
4 Observed for fasting normal levels at baseline (< 5.56 mmol/l) which increased to high (≥ 7 mmol/l). 
Changes in fasting glucose from borderline at baseline (≥ 5.56 - < 7 mmol/l) to high (≥ 7 mmol/l) were 
very common.  
 
5 Observed for fasting normal levels at baseline (< 1.69 mmol/l) which increased to high 
(≥ 2.26 mmol/l). Changes in fasting triglycerides from borderline at baseline (≥ 1.69 mmol/l - 
< 2.26 mmol/l) to high (≥ 2.26 mmol/l) were very common. 
 
6 In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was 
numerically higher, but not statistically significantly different from placebo. Olanzapine-treated patients 
had a lower incidence of Parkinsonism, akathisia and dystonia compared with titrated doses of 
haloperidol. In the absence of detailed information on the pre-existing history of individual acute and 
tardive extrapyramidal movement disorders, it cannot be concluded at present that olanzapine produces 
less tardive dyskinesia and/or other tardive extrapyramidal syndromes. 
 
7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been 
reported when olanzapine is stopped abruptly. 
 
8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of 
normal range in approximately 30% of olanzapine treated patients with normal baseline prolactin 
value. In the majority of these patients the elevations were generally mild, and remained below two 
times the upper limit of normal range.  
 
9 Adverse event identified from clinical trials in the Olanzapine Integrated Database. 
 
10 As assessed by measured values from clinical trials in the Olanzapine Integrated Database. 
 
11 Adverse event identified from spontaneous post-marketing reporting with frequency determined 

utilising the Olanzapine Integrated Database.   
 
12 Adverse event identified from spontaneous post-marketing reporting with frequency estimated at the 

upper limit of the 95% confidence interval utilising the Olanzapine Integrated Database. 
 



 29 

13Undesirable effects listed and observed following administration of oral and LAIM olanzapine, 
which may also occur following administration of RAIM olanzapine. 

 
Long-term exposure (at least 48 weeks) 
The proportion of patients who had adverse, clinically significant changes in weight gain, glucose, 
total/LDL/HDL cholesterol or triglycerides increased over time. In adult patients who completed 9-12 
months of therapy, the rate of increase in mean blood glucose slowed after approximately 6 months. 
 
Additional information on special populations 
In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher 
incidence of death and cerebrovascular adverse reactions compared to placebo (see section 4.4). Very 
common adverse reactions associated with the use of olanzapine in this patient group were abnormal 
gait and falls. Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and 
urinary incontinence were observed commonly.  
 
In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with 
Parkinson’s disease, worsening of Parkinsonian symptomatology and hallucinations were reported 
very commonly and more frequently than with placebo. 
 
In one clinical trial in patients with bipolar mania, valproate combination therapy with olanzapine 
resulted in an incidence of neutropenia of 4.1%; a potential contributing factor could be high plasma 
valproate levels. Olanzapine administered with lithium or valproate resulted in increased levels 
(≥ 10%) of tremor, dry mouth, increased appetite, and weight gain. Speech disorder was also reported 
commonly. During treatment with olanzapine in combination with lithium or divalproex, an increase 
of ≥ 7% from baseline body weight occurred in 17.4% of patients during acute treatment (up to 6 
weeks). Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with 
bipolar disorder was associated with an increase of ≥ 7% from baseline body weight in 39.9% of 
patients. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system listed 
in Appendix V. 
 
4.9 Overdose 
 
Signs and symptoms 
Very common symptoms in overdose (> 10% incidence) include tachycardia, agitation/aggressiveness, 
dysarthria, various extrapyramidal symptoms, and reduced level of consciousness ranging from 
sedation to coma.  
 
Other medically significant sequelae of overdose include delirium, convulsion, coma, possible 
neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, 
cardiac arrhythmias (< 2% of overdose cases) and cardiopulmonary arrest. Fatal outcomes have been 
reported for acute overdoses as low as 450 mg but survival has also been reported following acute 
overdose of approximately 2 g of oral olanzapine. 
 
Management 
There is no specific antidote for olanzapine.  
 
Symptomatic treatment and monitoring of vital organ function should be instituted according to 
clinical presentation, including treatment of hypotension and circulatory collapse and support of 
respiratory function. Do not use epinephrine, dopamine, or other sympathomimetic agents with beta-
agonist activity since beta stimulation may worsen hypotension. Cardiovascular monitoring is 
necessary to detect possible arrhythmias. Close medical supervision and monitoring should continue 
until the patient recovers. 



 30 

 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: psycholeptics, diazepines, oxazepines, thiazepines and oxepines, ATC 
code N05A H03. 
 
Pharmacodynamic effects  
Olanzapine is an antipsychotic, antimanic and mood stabilising agent that demonstrates a broad 
pharmacologic profile across a number of receptor systems. 
 
In preclinical studies, olanzapine exhibited a range of receptor affinities (Ki < 100 nM) for serotonin 5 
HT2A/2C, 5 HT3, 5 HT6; dopamine D1, D2, D3, D4, D5; cholinergic muscarinic receptors M1-M5; α1 
adrenergic; and histamine H1 receptors. Animal behavioural studies with olanzapine indicated 5HT, 
dopamine, and cholinergic antagonism, consistent with the receptor-binding profile. Olanzapine 
demonstrated a greater in vitro affinity for serotonin 5HT2 than dopamine D2 receptors and greater 5 
HT2 than D2 activity in vivo models. Electrophysiological studies demonstrated that olanzapine 
selectively reduced the firing of mesolimbic (A10) dopaminergic neurons, while having little effect on 
the striatal (A9) pathways involved in motor function. Olanzapine reduced a conditioned avoidance 
response, a test indicative of antipsychotic activity, at doses below those producing catalepsy, an effect 
indicative of motor side-effects. Unlike some other antipsychotic agents, olanzapine increases 
responding in an “anxiolytic” test. 
 
In a single oral dose (10 mg) Positron Emission Tomography (PET) study in healthy volunteers, 
olanzapine produced a higher 5 HT2A than dopamine D2 receptor occupancy. In addition, a Single 
Photon Emission Computed Tomography (SPECT) imaging study in schizophrenic patients revealed 
that olanzapine-responsive patients had lower striatal D2 occupancy than some other antipsychotic- 
and risperidone-responsive patients, while being comparable to clozapine-responsive patients. 
 
Clinical efficacy 
In two of two placebo and two of three comparator controlled trials with over 2,900 schizophrenic 
patients presenting with both positive and negative symptoms, olanzapine was associated with 
statistically significantly greater improvements in negative as well as positive symptoms. 
 
In a multinational, double-blind, comparative study of schizophrenia, schizoaffective, and related 
disorders which included 1,481 patients with varying degrees of associated depressive symptoms 
(baseline mean of 16.6 on the Montgomery-Asberg Depression Rating Scale), a prospective secondary 
analysis of baseline to endpoint mood score change demonstrated a statistically significant 
improvement (p= 0.001) favouring olanzapine (-6.0) versus haloperidol (-3.1). 
 
In patients with a manic or mixed episode of bipolar disorder, olanzapine demonstrated superior 
efficacy to placebo and valproate semisodium (divalproex) in reduction of manic symptoms over 3 
weeks. Olanzapine also demonstrated comparable efficacy results to haloperidol in terms of the 
proportion of patients in symptomatic remission from mania and depression at 6 and 12 weeks. In a 
co-therapy study of patients treated with lithium or valproate for a minimum of 2 weeks, the addition 
of olanzapine 10 mg (co-therapy with lithium or valproate) resulted in a greater reduction in symptoms 
of mania than lithium or valproate monotherapy after 6 weeks. 
 
In a 12-month recurrence prevention study in manic episode patients who achieved remission on 
olanzapine and were then randomised to olanzapine or placebo, olanzapine demonstrated statistically 
significant superiority over placebo on the primary endpoint of bipolar recurrence. Olanzapine also 
showed a statistically significant advantage over placebo in terms of preventing either recurrence into 
mania or recurrence into depression. 
 



 31 

In a second 12-month recurrence prevention study in manic episode patients who achieved remission 
with a combination of olanzapine and lithium and were then randomised to olanzapine or lithium 
alone, olanzapine was statistically non-inferior to lithium on the primary endpoint of bipolar 
recurrence (olanzapine 30.0%, lithium 38.3%; p = 0.055). 
 
In an 18-month co-therapy study in manic or mixed episode patients stabilised with olanzapine plus a 
mood stabiliser (lithium or valproate), long-term olanzapine co-therapy with lithium or valproate was 
not statistically significantly superior to lithium or valproate alone in delaying bipolar recurrence, 
defined according to syndromic (diagnostic) criteria. 
 
5.2 Pharmacokinetic properties 
 
In a pharmacokinetic study in healthy volunteers, a dose of 5 mg of ZYPREXA powder for solution 
for injection produced a maximum plasma concentration (Cmax) approximately 5 times higher than 
that seen with the same dose of olanzapine administered orally. The Cmax occurs earlier after 
intramuscular compared to oral use (15 to 45 minutes versus 5 to 8 hours). As with oral use, Cmax and 
area under the curve after intramuscular use are directly proportional to the dose administered. For the 
same dose of olanzapine administered intramuscularly and orally, the associated area under the curve, 
half-life, clearance and volume of distribution are similar. The metabolic profiles following 
intramuscular and oral use are similar. 
 
In non-smoking versus smoking subjects (males and females) administered olanzapine intramuscularly 
the mean elimination half-life was prolonged (38.6 versus 30.4 hr) and the clearance was reduced 
(18.6 versus 27.7 l/hr). 
 
Additional pharmacokinetic data following administration of oral olanzapine are described below. 
 
Distribution 
The plasma protein binding of olanzapine was about 93 % over the concentration range of about 7 to 
about 1,000 ng/ml. Olanzapine is bound predominantly to albumin and α1-acid-glycoprotein. 
 
Biotransformation 
Olanzapine is metabolised in the liver by conjugative and oxidative pathways. The major circulating 
metabolite is the 10-N-glucuronide, which does not pass the blood brain barrier. Cytochromes P450- 
CYP1A2 and P450-CYP2D6 contribute to the formation of the N-desmethyl and 2-hydroxymethyl 
metabolites, both exhibited significantly less in vivo pharmacological activity than olanzapine in 
animal studies. The predominant pharmacologic activity is from the parent olanzapine.  
 
Elimination 
After oral administration, the mean terminal elimination half-life of olanzapine in healthy subjects 
varied on the basis of age and gender. 
 
In healthy elderly (65 and over) versus non-elderly subjects administered oral olanzapine, the mean 
elimination half-life was prolonged (51.8 versus 33.8 hr) and the clearance was reduced (17.5 versus 
18.2 l/hr). The pharmacokinetic variability observed in the elderly is within the range for the non-
elderly. In 44 patients with schizophrenia > 65 years of age, dosing from 5 to 20 mg/day was not 
associated with any distinguishing profile of adverse events. 
 
In female versus male subjects administered oral olanzapine the mean elimination half life was 
somewhat prolonged (36.7 versus 32.3 hrs) and the clearance was reduced (18.9 versus 27.3 l/hr). 
However, olanzapine (5-20 mg) demonstrated a comparable safety profile in female (n=467) as in 
male patients (n=869). 
 
Renal impairment 
In renally impaired patients (creatinine clearance < 10 ml/min) versus healthy subjects administered 
oral olanzapine, there was no significant difference in mean elimination half-life (37.7 versus 32.4 hr) 



 32 

or clearance (21.2 versus 25.0 l/hr). A mass balance study showed that approximately 57 % of 
radiolabelled olanzapine appeared in urine, principally as metabolites. 
 
Hepatic impairment  
A small study of the effect of impaired liver function in 6 subjects with clinically significant (Childs 
Pugh Classification A (n = 5) and B (n = 1)) cirrhosis revealed little effect on the pharmacokinetics of 
orally administered olanzapine (2.5 – 7.5 mg single dose): Subjects with mild to moderate hepatic 
dysfunction had slightly increased systemic clearance and faster elimination half-time compared to 
subjects with no hepatic dysfunction (n = 3). There were more smokers among subjects with cirrhosis 
(4/6; 67 %) than among subjects with no hepatic dysfunction (0/3; 0 %). 
 
Smoking 
The plasma clearance of olanzapine is lower in elderly versus young subjects, in females versus males, 
and in non-smokers versus smokers. However, the magnitude of the impact of age, gender, or smoking 
on olanzapine clearance and half-life is small in comparison to the overall variability between 
individuals. 
 
In a study of Caucasians, Japanese, and Chinese subjects, there were no differences in the 
pharmacokinetic parameters among the three populations. 
 
5.3 Preclinical safety data 
 
Acute (single-dose) toxicity 
Signs of oral toxicity in rodents were characteristic of potent antipsychotic compounds: hypoactivity, 
coma, tremors, clonic convulsions, salivation, and depressed weight gain. The median lethal doses 
were approximately 210 mg/kg (mice) and 175 mg/kg (rats). Dogs tolerated single oral doses up to 
100 mg/kg without mortality. Clinical signs included sedation, ataxia, tremors, increased heart rate, 
laboured respiration, miosis, and anorexia. In monkeys, single oral doses up to 100 mg/kg resulted in 
prostration and, at higher doses, semi-consciousness. 
 
Repeated-dose toxicity 
In studies up to 3 months duration in mice and up to 1 year in rats and dogs, the predominant effects 
were CNS depression, anticholinergic effects, and peripheral haematological disorders. Tolerance 
developed to the CNS depression. Growth parameters were decreased at high doses. Reversible effects 
consistent with elevated prolactin in rats included decreased weights of ovaries and uterus and 
morphologic changes in vaginal epithelium and in mammary gland. 
 
Haematologic toxicity 
Effects on haematology parameters were found in each species, including dose-related reductions in 
circulating leukocytes in mice and non-specific reductions of circulating leukocytes in rats; however, 
no evidence of bone marrow cytotoxicity was found. Reversible neutropenia, thrombocytopenia, or 
anaemia developed in a few dogs treated with 8 or 10 mg/kg/day (total olanzapine exposure [AUC] is 
12- to 15-fold greater than that of a man given a 12-mg dose). In cytopenic dogs, there were no 
undesirable effects on progenitor and proliferating cells in the bone marrow. 
 
Reproductive toxicity 
Olanzapine had no teratogenic effects. Sedation affected mating performance of male rats. Oestrous 
cycles were affected at doses of 1.1 mg/kg (3 times the maximum human dose) and reproduction 
parameters were influenced in rats given 3 mg/kg (9 times the maximum human dose). In the offspring 
of rats given olanzapine, delays in foetal development and transient decreases in offspring activity 
levels were seen. 
 
Mutagenicity 
Olanzapine was not mutagenic or clastogenic in a full range of standard tests, which included bacterial 
mutation tests and in vitro and oral in vivo mammalian tests. 
 



 33 

Carcinogenicity 
Based on the results of oral studies in mice and rats, it was concluded that olanzapine is not 
carcinogenic. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Lactose monohydrate 
Tartaric acid, E334 
Hydrochloric acid.  
Sodium hydroxide. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
Olanzapine for injection should not be combined in a syringe with diazepam injection because 
precipitation occurs when these products are mixed. 
 
Lorazepam injection should not be used to reconstitute olanzapine for injection as this combination 
results in a delayed reconstitution time. 
 
Olanzapine for injection should not be combined in a syringe with haloperidol injection because the 
resulting low pH has been shown to degrade olanzapine over time. 
 
6.3 Shelf life 
 
Powder: 3 years. 
Solution (after reconstitution): 1 hour. Do not freeze. 
 
6.4 Special precautions for storage 
 
Do not store above 25º C. Store in the original package in order to protect from light. For storage 
conditions of the reconstituted medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Type I, 5 ml glass vial.  
One carton contains 1 or 10 vial(s). 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Reconstitute ZYPREXA only with water for injections using standard aseptic techniques for 
reconstitution of parenteral products. No other solutions should be used for reconstitution (see section 
6.2). 
 
1. Withdraw 2.1 ml of water for injection into a sterile syringe. Inject into a vial of ZYPREXA. 
 
2. Rotate the vial until the contents have completely dissolved, giving a yellow coloured solution. 

The vial contains 11.0 mg olanzapine as a solution of 5 mg/ml (1 mg olanzapine is retained in 
the vial and syringe, thus allowing delivery of 10 mg olanzapine). 

 



 34 

3. The following table provides injection volumes for delivering various doses of olanzapine: 
 

Dose (mg) Volume of injection (ml) 
10 2.0 
7.5 1.5 
5 1.0 
2.5 0.5 

 
4. Administer the solution intramuscularly. Do not administer intravenously or subcutaneously. 
 
5. Discard the syringe and any unused solution in accordance with appropriate clinical procedures. 
 
6. Use the solution immediately within 1 hour of reconstitution.  
 
Parenteral medicines should be inspected visually for particulate matter prior to administration. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands. 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/96/022/016 – ZYPREXA - Powder for solution for injection. 1 vial 
EU/1/96/022/017 – ZYPREXA - Powder for solution for injection. 10 vials 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 27 September 1996  
Date of latest renewal: 12 September 2006 
 
 
10. DATE OF REVISION OF THE TEXT 

 
{MM/YYYY} 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 



 35 

 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 



 36 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Coated Tablets 
Lilly S.A., Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain. 
 
Powder for solution for injection 
Lilly S.A., Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription.  
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 
 

•  Periodic safety update reports (PSURs)  
 
The requirements for submission of PSURs for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D.  CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
  

•  Risk management plan (RMP)  
 
The marketing authorization holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2. of the Marketing 
Authorisation and any agreed subsequent updates of the RMP.  
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency. 
 

• Whenever the risk management system is modified,especially as the result of  new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached 



 37 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



 38 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



 39 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON OF COATED TABLETS IN BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA 2.5 mg coated tablets 
olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each coated tablet contains 2.5 mg olanzapine 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate see package leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 coated tablets 
35 coated tablets 
56 coated tablets 
70 coated tablets 
98 coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture. 



 40 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands. 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/96/022/002 28 coated tablets 
EU/1/96/022/023 35 coated tablets 
EU/1/96/022/019 56 coated tablets 
EU/1/96/022/029 70 coated tablets 
EU/1/96/022/035 98 coated tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
ZYPREXA 2.5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



 41 

  
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
ZYPREXA 2.5 mg COATED TABLETS: BLISTER FOIL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA 2.5 mg coated tablets 
Olanzapine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Lilly 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
5. OTHER 
 
 



 42 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON OF COATED TABLETS IN BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA 5 mg coated tablets 
olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each coated tablet contains 5 mg olanzapine 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate see package leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 coated tablets 
35 coated tablets 
56 coated tablets 
70 coated tablets 
98 coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture 



 43 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/96/022/004 28 coated tablets 
EU/1/96/022/024 35 coated tablets 
EU/1/96/022/020 56 coated tablets 
EU/1/96/022/030 70 coated tablets 
EU/1/96/022/036 98 coated tablets 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
ZYPREXA 5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 44 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
ZYPREXA 5 mg COATED TABLETS: BLISTER FOIL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA 5 mg coated tablets 
Olanzapine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Lilly 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. OTHER 
 
 



 45 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON OF COATED TABLETS IN BLISTERS  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA 7.5 mg coated tablets 
olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each coated tablet contains 7.5 mg olanzapine 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate see package leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 coated tablets 
35 coated tablets 
56 coated tablets 
70 coated tablets 
98 coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture 



 46 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/96/022/011 28 coated tablets 
EU/1/96/022/025 35 coated tablets 
EU/1/96/022/006 56 coated tablets 
EU/1/96/022/031 70 coated tablets 
EU/1/96/022/037 98 coated tablets 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
ZYPREXA 7.5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 47 

  
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
ZYPREXA 7.5 mg COATED TABLETS: BLISTER FOIL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA 7.5 mg coated tablets 
Olanzapine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Lilly 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



 48 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON OF COATED TABLETS IN BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA 10 mg coated tablets 
olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each coated tablet contains 10 mg olanzapine 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate see package leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
 
28 coated tablets 
35 coated tablets 
56 coated tablets 
70 coated tablets 
98 coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture 



 49 

 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/96/022/009 28 coated tablets 
EU/1/96/022/026 35 coated tablets 
EU/1/96/022/010 56 coated tablets 
EU/1/96/022/032 70 coated tablets 
EU/1/96/022/038 98 coated tablets 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
ZYPREXA 10 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



 50 

 MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
ZYPREXA 10 mg COATED TABLETS: BLISTER FOIL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA 10 mg coated tablets 
Olanzapine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Lilly 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



 51 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON OF COATED TABLETS IN BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA 15 mg coated tablets 
olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each coated tablet contains 15 mg olanzapine 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate see package leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 coated tablets 
35 coated tablets 
56 coated tablets 
70 coated tablets 
98 coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture 



 52 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/96/022/012 28 coated tablets 
EU/1/96/022/027 35 coated tablets 
EU/1/96/022/021 56 coated tablets 
EU/1/96/022/033 70 coated tablets 
EU/1/96/022/039 98 coated tablets 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15.  INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
ZYPREXA 15 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



 53 

 MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
ZYPREXA 15 mg COATED TABLETS: BLISTER FOIL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA 15 mg coated tablets 
Olanzapine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Lilly 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
5. OTHER 
 
 



 54 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON OF COATED TABLETS IN BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA 20 mg coated tablets 
olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each coated tablet contains 20 mg olanzapine 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate see package leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 coated tablets 
35 coated tablets 
56 coated tablets 
70 coated tablets 
98 coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture 



 55 

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/96/022/014 28 coated tablets 
EU/1/96/022/028 35 coated tablets 
EU/1/96/022/022 56 coated tablets 
EU/1/96/022/034 70 coated tablets 
EU/1/96/022/040 98 coated tablets 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
ZYPREXA 20 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



 56 

 MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
ZYPREXA 20 mg COATED TABLETS: BLISTER FOIL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA 20 mg coated tablets 
Olanzapine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Lilly 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



 57 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON OF VIAL OF POWDER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA 10 mg powder for solution for injection 
olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 10 mg olanzapine. After reconstitution each ml of the solution contains 5 mg 
olanzapine 
 
 
3. LIST OF EXCIPIENTS 
 
Lactose monohydrate, tartaric acid, hydrochloric acid, sodium hydroxide 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for injection. 1 vial 
Powder for solution for injection. 10 vials 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intramuscular use. Single use vial. Read the package leaflet before use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP 
Use solution within 1 hour 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25º C. Store in original package in order to protect from light 
 
 



 58 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
Discard syringe and unused solution appropriately 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER (S) 
 
EU/1/96/022/016 Powder for solution for injection. 1 vial 
EU/1/96/022/017 Powder for solution for injection. 10 vials 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



 59 

 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL ON VIAL OF 10 mg POWDER 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
ZYPREXA 10 mg olanzapine powder for solution for injection 
IM use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use 
 
 
3. EXPIRY DATE 
 
EXP 
Use solution within 1 hour 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
10 mg olanzapine per vial 
 



 60 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



 61 

Package leaflet: Information for the user 
 

ZYPREXA 2.5 mg coated tablets 
ZYPREXA 5 mg coated tablets 

ZYPREXA 7.5 mg coated tablets 
ZYPREXA 10 mg coated tablets 
ZYPREXA 15 mg coated tablets 
ZYPREXA 20 mg coated tablets 

Olanzapine 
 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
• Keep this leaflet. You may need to read it again. 
• If you have any further questions, ask your doctor or pharmacist. 
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
• If you get any side effects talk to your doctor or pharmacist.  This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What ZYPREXA is and what it is used for 
2. What you need to know before you take ZYPREXA 
3. How to take ZYPREXA 
4. Possible side effects 
5. How to store ZYPREXA 
6. Contents of the pack and other information 
 
 
1. What ZYPREXA is and what it is used for 
 
ZYPREXA contains the active substance olanzapine. ZYPREXA belongs to a group of medicines 
called antipsychotics and is used to treat the following conditions: 

• Schizophrenia, a disease with symptoms such as hearing, seeing or sensing things which are not 
there, mistaken beliefs, unusual suspiciousness, and becoming withdrawn. People with this 
disease may also feel depressed, anxious or tense. 

• Moderate to severe manic episodes, a condition with symptoms of excitement or euphoria. 
 

ZYPREXA has been shown to prevent recurrence of these symptoms in patients with bipolar disorder 
whose manic episode has responded to olanzapine treatment. 
 
 
2. What you need to know before you take ZYPREXA 
 
Do not take ZYPREXA 
• If you are allergic (hypersensitive) to olanzapine or any of the other ingredients of this medicine 

(listed in section 6). An allergic reaction may be recognised as a rash, itching, a swollen face, 
swollen lips or shortness of breath. If this has happened to you, tell your doctor.  

• If you have been previously diagnosed with eye problems such as certain kinds of glaucoma 
(increased pressure in the eye). 

 
Warnings and precautions 
Talk to your doctor or pharmacist before you take ZYPREXA. 
• The use of ZYPREXA in elderly patients with dementia is not recommended as it may have 

serious side effects. 



 62 

• Medicines of this type may cause unusual movements mainly of the face or tongue. If this happens 
after you have been given ZYPREXA tell your doctor. 

• Very rarely, medicines of this type cause a combination of fever, faster breathing, sweating, 
muscle stiffness and drowsiness or sleepiness. If this happens, contact your doctor at once.  

• Weight gain has been seen in patients taking ZYPREXA. You and your doctor should check your 
weight regularly. Consider referral to a dietician or help with a diet plan if necessary. 

• High blood sugar and high levels of fat (triglycerides and cholesterol) have been seen in patients 
taking ZYPREXA. Your doctor should do blood tests to check blood sugar and certain fat levels 
before you start taking ZYPREXA and regularly during treatment.  

• Tell the doctor if you or someone else in your family has a history of blood clots, as medicines 
like these have been associated with the formation of blood clots.  

 
If you suffer from any of the following illnesses tell your doctor as soon as possible: 
 
• Stroke or “mini” stroke (temporary symptoms of stroke) 
• Parkinson’s disease 
• Prostate problems 
• A blocked intestine (Paralytic ileus) 
• Liver or kidney disease 
• Blood disorders 
• Heart disease 
• Diabetes 
• Seizures 
• If you know that you may have salt depletion as a result of prolonged severe diarrhoea and vomiting 

(being sick) or usage of diuretics (water tablets) 
 
If you suffer from dementia, you or your carer/relative should tell your doctor if you have ever had a 
stroke or “mini” stroke. 
 
As a routine precaution, if you are over 65 years your blood pressure may be monitored by your 
doctor. 
 
Children and adolescents 
ZYPREXA is not for patients who are under 18 years. 
 
Other medicines and ZYPREXA 
Only take other medicines while you are on ZYPREXA if your doctor tells you that you can. You 
might feel drowsy if ZYPREXA is taken in combination with antidepressants or medicines taken for 
anxiety or to help you sleep (tranquillisers).  
 
Tell your doctor if you are taking, have recently taken or might take any other medicines.  
 
In particular, tell your doctor if you are taking: 
• medicines for Parkinson’s disease. 
• carbamazepine (an anti-epileptic and mood stabiliser), fluvoxamine (an antidepressant) or 

ciprofloxacin (an antibiotic) - it may be necessary to change your ZYPREXA dose. 
 
ZYPREXA with alcohol 
Do not drink any alcohol if you have been given ZYPREXA as together with alcohol it may make you 
feel drowsy. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. You should not be given this medicine when 
breast-feeding, as small amounts of ZYPREXA can pass into breast milk. 
 



 63 

The following symptoms may occur in newborn babies, of mothers that have used ZYPREXA in the 
last trimester (last three months of their pregnancy): shaking, muscle stiffness and/or weakness, 
sleepiness, agitation, breathing problems, and difficulty in feeding. If your baby develops any of these 
symptoms you may need to contact your doctor. 
 
Driving and using machines 
There is a risk of feeling drowsy when you are given ZYPREXA. If this happens do not drive or 
operate any tools or machines. Tell your doctor. 
 
ZYPREXA contains lactose 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicinal product. 
 
 
3. How to take ZYPREXA 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure.  
 
Your doctor will tell you how many ZYPREXA tablets to take and how long you should continue to 
take them. The daily dose of ZYPREXA is between 5 mg and 20 mg. Consult your doctor if your 
symptoms return but do not stop taking ZYPREXA unless your doctor tells you to.  
 
You should take your ZYPREXA tablets once a day following the advice of your doctor. Try to take 
your tablets at the same time each day. It does not matter whether you take them with or without food. 
ZYPREXA coated tablets are for oral use. You should swallow the ZYPREXA tablets whole with 
water. 
 
If you take more ZYPREXA than you should 
Patients who have taken more ZYPREXA than they should have experienced the following symptoms: 
rapid beating of the heart, agitation/aggressiveness, problems with speech, unusual movements 
(especially of the face or tongue) and reduced level of consciousness. Other symptoms may be: acute 
confusion, seizures (epilepsy), coma, a combination of fever, faster breathing, sweating, muscle 
stiffness and drowsiness or sleepiness, slowing of the breathing rate, aspiration, high blood pressure or 
low blood pressure, abnormal rhythms of the heart. Contact your doctor or hospital straight away if 
you experience any of the above symptoms. Show the doctor your pack of tablets. 
 
If you forget to take ZYPREXA 
Take your tablets as soon as you remember. Do not take two doses in one day. 
 
If you stop taking ZYPREXA 
Do not stop taking your tablets just because you feel better. It is important that you carry on taking 
ZYPREXA for as long as your doctor tells you. 
 
If you suddenly stop taking ZYPREXA, symptoms such as sweating, unable to sleep, tremor, anxiety 
or nausea and vomiting might occur. Your doctor may suggest you to reduce the dose gradually before 
stopping treatment. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 



 64 

Tell your doctor immediately if you have:  
• unusual movement (a common side effect that may affect up to 1 in 10 people) mainly of the 

face or tongue; 
• blood clots in the veins (an uncommon side effect that may affect up to 1 in 100 people) 

especially in the legs (symptoms include swelling, pain, and redness in the leg), which may travel 
through blood vessels to the lungs causing chest pain and difficulty in breathing. If you notice any 
of these symptoms seek medical advice immediately; 

• a combination of fever, faster breathing, sweating, muscle stiffness and drowsiness or sleepiness 
(the frequency of this side effect cannot be estimated from the available data). 

 
Very common side effects (may affect more than 1 in 10 people) include weight gain; sleepiness; and 
increases in levels of prolactin in the blood. In the early stages of treatment, some people may feel 
dizzy or faint (with a slow heart rate), especially when getting up from a lying or sitting position. This 
will usually pass on its own but if it does not, tell your doctor. 
 
Common side effects (may affect up to 1 in 10 people) include changes in the levels of some blood 
cells, circulating fats and early in treatment, temporary increases in liver enzymes; increases in the level 
of sugars in the blood and urine; increases in levels of uric acid and creatine phosphokinase in the blood; 
feeling more hungry; dizziness; restlessness; tremor; unusual movements(dyskinesias); constipation; dry 
mouth; rash; loss of strength; extreme tiredness; water retention leading to swelling of the hands, ankles 
or feet; fever; joint pain; and sexual dysfunctions such as decreased libido in males and females or 
erectile dysfunction in males.  
 
Uncommon side effects (may affect up to 1 in 100 people) include hypersensitivity (e.g. swelling in the 
mouth and throat, itching, rash); diabetes or the worsening of diabetes, occasionally associated with 
ketoacidosis (ketones in the blood and urine) or coma; seizures, usually associated with a history of 
seizures (epilepsy); muscle stiffness or spasms (including eye movements); restless legs syndrome; 
problems with speech; stuttering; slow heart rate; sensitivity to sunlight; bleeding from the nose; 
abdominal distension; drooling; memory loss or forgetfulness; urinary incontinence; lack of ability to 
urinate; hair loss; absence or decrease in menstrual periods; and changes in breasts in males and females 
such as an abnormal production of breast milk or abnormal growth. 
 
Rare side effects (may affect up to 1 in 1000 people) include lowering of normal body temperature; 
abnormal rhythms of the heart; sudden unexplained death; inflammation of the pancreas causing severe 
stomach pain, fever and sickness; liver disease appearing as yellowing of the skin and white parts of the 
eyes; muscle disease presenting as unexplained aches and pains; and prolonged and/or painful erection. 
 
Very rare side effects include serious allergic reactions such as Drug Reaction with Eosinophilia and 
Systemic Symptoms (DRESS).  DRESS appears initially as flu-like symptoms with a rash on the face 
and then with an extended rash, high temperature, enlarged lymph nodes, increased levels of liver 
enzymes seen on blood tests and an increase in a type of white blood cells (eosinophilia). 
 
While taking olanzapine, elderly patients with dementia may suffer from stroke, pneumonia, urinary 
incontinence, falls, extreme tiredness, visual hallucinations, a rise in body temperature, redness of the 
skin and have trouble walking. Some fatal cases have been reported in this particular group of patients. 
 
In patients with Parkinson's disease ZYPREXA may worsen the symptoms. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects you can help provide more information on the safety of this 
medicine. 
 
 



 65 

5. How to store ZYPREXA 
 
Keep this medicine out of sight and reach of children. 
 
Do not use this medicine after the expiry date, which is stated on the carton. 
 
ZYPREXA should be stored in its original pack in order to protect from light and moisture. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What ZYPREXA contains 
• The active substance is olanzapine. Each ZYPREXA tablet contains either 2.5 mg, 5 mg, 7.5 mg, 

10 mg, 15 mg or 20 mg of the active substance. The exact amount is shown on your ZYPREXA 
tablet pack. 

• The other ingredients are  
- (tablet core) lactose monohydrate, hyprolose, crospovidone, microcrystalline cellulose, 

magnesium stearate and 
- (tablet coating) hypromellose, titanium dioxide (E171), carnauba wax. 

• In addition the different ZYPREXA tablet strengths also contain the following ingredients: 
 
TABLET STRENGTH  OTHER INGREDIENTS 

 
ZYPREXA 2.5 mg, 5 mg, 7.5 mg and 10 mg 
tablets 

(tablet coating) shellac, macrogol, propylene 
glycol, polysorbate 80 and indigo carmine 
colour (E132), ethanol anhydrous, isopropyl 
alcohol, butyl alcohol, ammonium hydroxide 
 

ZYPREXA 15 mg tablets (tablet coating) triacetin and indigo carmine 
colour (E132) 
 

ZYPREXA 20 mg tablets (tablet coating) macrogol and synthetic red iron 
oxide (E172) 
 

 
What ZYPREXA looks like and contents of the pack 
ZYPREXA 2.5 mg coated tablets are white imprinted with “LILLY” and a numeric identicode “4112”.  
ZYPREXA 5 mg coated tablets are white imprinted with “LILLY” and a numeric identicode “4115”.  
ZYPREXA 7.5 mg coated tablets are white imprinted with “LILLY” and a numeric identicode “4116”.  
ZYPREXA 10 mg coated tablets are white imprinted with “LILLY” and a numeric identicode “4117”. 
ZYPREXA 15 mg coated tablets are blue.  
ZYPREXA 20 mg coated tablets are pink.  
 
ZYPREXA is available in packs containing 28, 35, 56, 70 or 98 tablets. Not all pack sizes may be 
marketed. 
 
Marketing Authorisation Holder  
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands. 
 
Manufacturer 
Lilly S.A., Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain. 
 



 66 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Eli Lilly Benelux S.A./N.V. 
Tél/Tel: + 32 (0)2 548 84 84 

Lietuva 
Eli Lilly Lietuva 
Tel: + 370 (5) 2649600 

България 
ТП "Ели Лили Недерланд" Б.В. - България 
Тел: + 359 2 491 41 40 

Luxembourg/Luxemburg 
Eli Lilly Benelux S.A./N.V. 
Tél/Tel: + 32 (0)2 548 84 84  

Česká republika 
Eli Lilly ČR, s.r.o. 
Tel: + 420 234 664 111 

 Magyarország 
Lilly Hungária Kft. 
Tel: + 36 1 328 5100 

Danmark 
Eli Lilly Danmark A/S 
Tlf.: + 45 45 26 60 00 

Malta 
Charles de Giorgio Ltd. 
Tel: + 356 25600 500 

Deutschland 
Lilly Deutschland GmbH 
Tel: + 49 (0) 6172 273 2222 

Nederland 
Eli Lilly Nederland B.V. 
Tel: + 31(0)30 6025800 

Eesti 
Eli Lilly Nederland B.V. 
Tel: + 372 6817 280 

Norge 
Eli Lilly Norge A.S 
Tlf: + 47 22 88 18 00 

Ελλάδa 
ΦΑΡΜΑΣΕΡΒ-ΛΙΛΛΥ Α.Ε.Β.Ε. 
Τηλ: + 30 210 629 4600 

Österreich 
Eli Lilly Ges. m.b.H.  
Tel: + 43 (0) 1 711 780 

España 
Lilly S.A. 
Tel: + 34 91 663 50 00 

Polska 
Eli Lilly Polska Sp. z o.o. 
Tel: + 48 22 440 33 00 

France 
Lilly France SAS 
Tél: + 33 (0) 1 55 49 34 34 

Portugal 
Lilly Portugal Produtos Farmacêuticos, Lda 
Tel: + 351 21 412 66 00 

Hrvatska 
Eli Lilly Hrvatska d.o.o. 
Tel: +385 1 2350 999 

România 
Eli Lilly România S.R.L. 
Tel: + 40 21 4023000 

Ireland 
Eli Lilly and Company (Ireland) Limited 
Tel: + 353 (0) 1 661 4377 

Slovenija 
Eli Lilly farmacevtska družba, d.o.o. 
Tel: + 386 (0)1 580 00 10 

Ísland 
Icepharma hf. 
Sími: + 354 540 8000 

Slovenská republika 
Eli Lilly Slovakia s.r.o. 
Tel: + 421 220 663 111 

Italia 
Eli Lilly Italia S.p.A. 
Tel: + 39 055 42571 

Suomi/Finland 
Oy Eli Lilly Finland Ab 
Puh/Tel: + 358 (0)9 8545 250 

Κύπρος 
Phadisco Ltd  
Τηλ: + 357 22 715000 

Sverige 
Eli Lilly Sweden AB 
Tel: + 46 (0)8 7378800 

Latvija 
Eli Lilly (Suisse) S.A Pārstāvniecība Latvijā  
 
Tel: + 371 67364000 

United Kingdom 
Eli Lilly and Company Limited 
Tel: + 44 (0) 1256 315000 

 
 
This leaflet was last revised in {month XXXX} 
 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 



 67 

Package leaflet: Information for the user 
 

ZYPREXA 10 mg powder for solution for injection 
Olanzapine 

 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor. 
- If you get any side effects talk to your doctor or nurse.  This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet: 
 
1. What ZYPREXA is and what it is used for 
2. What you need to know before you are given ZYPREXA 
3. How ZYPREXA is given 
4. Possible side effects 
5. How to store ZYPREXA 
6. Contents of the pack and other information 
 
 
1. What ZYPREXA is and what it is used for 
 
ZYPREXA contains the active substance olanzapine. ZYPREXA Injection belongs to a group of 
medicines called antipsychotics and is used to treat symptoms of agitation and distressing behaviour 
that may occur in the following conditions: 
 
• Schizophrenia, a disease with symptoms such as hearing, seeing or sensing things which are not 

there, mistaken beliefs, unusual suspiciousness, and becoming withdrawn. People with this disease 
may also feel depressed, anxious or tense. 

• Mania, a condition with symptoms of excitement or euphoria. 
 
ZYPREXA Injection is given when rapid control of agitation and distressing behaviour is needed and 
treatment with ZYPREXA tablets is not appropriate. Your doctor will change your treatment to 
ZYPREXA tablets, as soon as appropriate. 
 
 
2. What you need to know before you are given ZYPREXA 
 
You should not be given ZYPREXA 
• If you are allergic (hypersensitive) to olanzapine or any of the other ingredients of this medicine 

(listed in section 6). An allergic reaction may be recognised as a rash, itching, a swollen face, 
swollen lips or shortness of breath. If this has happened to you, tell your doctor.  

• If you have been previously diagnosed with eye problems such as certain kinds of glaucoma 
(increased pressure in the eye). 

 
Warnings and precautions 
Talk to your doctor or nurse before you are given ZYPREXA Injection 
• Tell the doctor or nurse if you feel dizzy or faint after the injection. You will probably need to lie 

down until you feel better. The doctor or nurse may also want to measure your blood pressure and 
pulse. 

• The use of ZYPREXA in elderly patients with dementia (confusion and memory loss) is not 
recommended as it may have serious side effects. 

• Medicines of this type may cause unusual movements mainly of the face or tongue. If this happens 
after you have been given ZYPREXA, talk to your doctor. 



 68 

• Very rarely, medicines of this type cause a combination of fever, faster breathing, sweating, 
muscle stiffness and drowsiness or sleepiness. If this happens, contact your doctor at once. No 
more injections will be given to you. 

• Weight gain has been seen in patients taking ZYPREXA. You and your doctor should check your 
weight regularly. Consider referral to a dietician or help with a diet plan if necessary. 

• High blood sugar and high levels of fat (triglycerides and cholesterol) have been seen in patients 
taking ZYPREXA. Your doctor should do blood tests to check blood sugar and certain fat levels 
before you start taking ZYPREXA and regularly during treatment.   

• Tell the doctor if you or someone else in your family has a history of blood clots, as medicines like 
these have been associated with formation of blood clots. 

 
If you suffer from any of the following illnesses tell your doctor as soon as possible: 
• Stroke or “mini” stroke (temporary symptoms of stroke) 
• Parkinson’s disease 
• Prostate problems 
• A blocked intestine (Paralytic ileus) 
• Liver or kidney disease 
• Blood disorders  
• If you have had a recent heart attack, or have heart disease, including sick sinus syndrome, 

unstable angina or suffer from low blood pressure. 
• Diabetes 
• Seizures 
• If you know that you may have salt depletion as a result of prolonged severe diarrhoea and vomiting 

(being sick) or usage of diuretics (water tablets) 
 
If you suffer from dementia, you or your carer/relative should tell your doctor if you have ever had a 
stroke or “mini” stroke. 
 
As a routine precaution, if you are over 65 years your doctor may monitor your blood pressure. 
 
Children and adolescents 
ZYPREXA is not for patients who are under 18 years. 
 
Other medicines and ZYPREXA 
A combination of ZYPREXA with the following medicines might make you feel drowsy: medicines 
taken for anxiety or to help you sleep (tranquillisers, including benzodiazepines), and antidepressants. 
Only take other medicines while you are on ZYPREXA if your doctor tells you that you can. 
 
If you receive ZYPREXA injection, a benzodiazepine injection is not recommended at the same time 
as this may result in excessive sleepiness, may have serious effects on your heart rate or your 
breathing, and, in very rare cases, may result in death. If your doctor has to give a benzodiazepine 
injection to treat your condition, there should be at least a one hour time period after the ZYPREXA 
injection and you are to be monitored closely after the benzodiazepine injection is given. 
 
Tell your doctor if you are taking or have recently taken any other medicines, including medicines 
obtained without a prescription. Especially tell your doctor if you are taking medicines for Parkinson’s 
disease. 
 
ZYPREXA with alcohol 
Do not drink any alcohol if you have been given ZYPREXA as together with alcohol it may make you 
feel drowsy. 
 



 69 

Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before being given this medicine. You should not be given this medicine when 
breast-feeding, as small amounts of ZYPREXA can pass into breast milk. 
 
The following symptoms may occur in newborn babies, of mothers that have used ZYPREXA in the 
last trimester (last three months of their pregnancy): shaking, muscle stiffness and/or weakness, 
sleepiness, agitation, breathing problems, and difficulty in feeding. If your baby develops any of these 
symptoms you may need to contact your doctor. 
 
Driving and using machines 
There is a risk of feeling drowsy when you are given ZYPREXA. If this happens do not drive or 
operate any tools or machines. Tell your doctor. 
 
 
3. How ZYPREXA is given 
 
Information on reconstitution and administration is provided in a detachable section at the end of this 
leaflet. 
 
Your doctor will decide how much ZYPREXA you need and how long you need it for. The dose is 
usually 10 mg for the first injection, but it may be less than this. Up to 20 mg in 24 hours may be 
given. The dose for patients aged over 65 years is 2.5 mg or 5 mg. 
 
ZYPREXA comes as a powder. Your doctor or nurse will make it up into a solution. ZYPREXA 
Injection is for intramuscular use. The correct amount of solution will be injected into your muscle. 
 
If you are given more ZYPREXA than you think you should be 
Patients who have been given more ZYPREXA than they should, have experienced the following 
symptoms: rapid beating of the heart, agitation/aggressiveness, problems with speech, unusual 
movements (especially of the face or tongue) and reduced level of consciousness. Other symptoms 
may include: acute confusion, seizures (epilepsy), coma, a combination of fever, faster breathing, 
sweating, muscle stiffness and drowsiness or sleepiness, slowing of the breathing rate, aspiration, high 
or low blood pressure, abnormal rhythms of the heart. Tell your doctor or nurse of your concern. 
 
Only a few doses of ZYPREXA Injection are needed. Your doctor will decide when you need a dose 
of ZYPREXA Injection. 
 
If you have any further questions on the use of this medicine, ask your doctor or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, ZYPREXA injection can cause side effects, although not everybody gets them. 
 
Tell your doctor immediately if you have:  

• unusual movement (a common side effect that may affect up to 1 in 10 people) mainly of the 
face or tongue; 

• blood clots in the veins (an uncommon side effect that may affect up to 1 in 100 people) 
especially in the legs (symptoms include swelling, pain, and redness in the leg), which may travel 
through blood vessels to the lungs causing chest pain and difficulty in breathing. If you notice any 
of these symptoms seek medical advice immediately; 

• a combination of fever, faster breathing, sweating, muscle stiffness and drowsiness or sleepiness 
(the frequency of this side effect cannot be estimated from the available data). 

 
Common side effects (may affect up to 1 in 10 people) with ZYPREXA Injection include slower or 
faster heart rate; sleepiness; low blood pressure; discomfort at the site of injection.  



 70 

 
Some people may feel dizzy or faint (with a slow heart rate) after injection, especially when getting up 
from a lying or sitting position. This will usually pass on its own but if it does not, tell your doctor or a 
nurse as soon as possible.  
 
Uncommon side effects (may affect up to 1 in 100 people) include breathing more slowly; and 
abnormal rhythms of the heart, which can be serious. 
 
In addition, the following side effects have been seen after patients have taken ZYPREXA orally. 
 
Other very common side effects (may affect more than 1 in 10 people) include weight gain; and 
increases in levels of prolactin in the blood. In the early stages of treatment, some people may feel 
dizzy or faint (with a slow heart rate), especially when getting up from a lying or sitting position. This 
will usually pass on its own but if it does not, tell your doctor. 
 
Other common side effects(may affect up to 1 in 10 people) include changes in the levels of some blood 
cells, circulating fats and early in treatment, temporary increases in liver enzymes; increases in the level 
of sugars in the blood and urine; increases in levels of uric acid and creatine phosphokinase in the blood; 
feeling more hungry; dizziness; restlessness; tremor; unusual movements (dyskinesias); constipation; 
dry mouth; rash; loss of strength; extreme tiredness; water retention leading to swelling of the hands, 
ankles or feet; fever; joint pain; and sexual dysfunctions such as decreased libido in males and females 
or erectile dysfunction in males.  
 
Other uncommon side effects (may affect up to 1 in 100 people) include hypersensitivity (e.g. swelling 
in the mouth and throat, itching, rash): diabetes or the worsening of diabetes, occasionally associated 
with ketoacidosis (ketones in the blood and urine) or coma; seizures, usually associated with a history of 
seizures (epilepsy); muscle stiffness or spasms (including eye movements); restless legs syndrome; 
problems with speech; stuttering; slow heart rate; sensitivity to sunlight; bleeding from nose; abdominal 
distension; drooling; memory loss or forgetfulness; urinary incontinence; lack of ability to urinate; hair 
loss; absence or decrease in menstrual periods; and changes in breasts in males and females such as an 
abnormal production of breast milk or abnormal growth. 
 
Rare side effects (may affect up to 1 in 1000 people) include lowering of normal body temperature;  
abnormal rhythms of the heart; sudden unexplained death; inflammation of the pancreas causing severe 
stomach pain, fever and sickness; liver disease appearing as yellowing of the skin and white parts of the 
eyes; muscle disease presenting as unexplained aches and pains; and prolonged and/or painful erection. 
 
Very rare side effects include serious allergic reactions such as Drug Reaction with Eosinophilia and 
Systemic Symptoms (DRESS).  DRESS appears initially as flu-like symptoms with a rash on the face 
and then with an extended rash, high temperature, enlarged lymph nodes, increased levels of liver 
enzymes seen on blood tests and an increase in a type of white blood cells (eosinophilia). 
 
While taking olanzapine, elderly patients with dementia may suffer from stroke, pneumonia, urinary 
incontinence, falls, extreme tiredness, visual hallucinations, a rise in body temperature, redness of the 
skin and have trouble walking. Some fatal cases have been reported in this particular group of patients. 
 
In patients with Parkinson's disease ZYPREXA may worsen the symptoms. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects you can help provide more information on the safety of this 
medicine. 
 
 



 71 

5. How to store ZYPREXA 
 
Keep this medicine out of the sight and reach of children.  
 
Do not use this medicine after the expiry date, which is stated on the carton. 
 
Do not store above 25°C. Store in original package in order to protect from light. 
 
After ZYPREXA Injection is made into a solution, use within one hour. Do not freeze after 
reconstitution.  
 
Discard any unused contents. 
 
 
6. FURTHER INFORMATION 
 
What ZYPREXA Injection contains 
• The active substance is olanzapine. Each vial contains 10 mg of the active substance.  
• The other ingredients are lactose monohydrate, tartaric acid, hydrochloric acid and sodium 

hydroxide. 
 
What ZYPREXA Injection looks like and contents of the pack 
ZYPREXA comes as a yellow powder in a vial. A vial of ZYPREXA can provide you with 10 mg of 
olanzapine. Your doctor or nurse will make it up into a solution that will be given as an injection. 
 
ZYPREXA Injection is available in a pack containing 1 or 10 vial(s). Not all pack sizes may be 
marketed. 
 
Marketing Authorisation Holder  
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands. 
 
Manufacturer 
 
Lilly S.A., Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain. 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Eli Lilly Benelux S.A./N.V. 
Tél/Tel: + 32 (0)2 548 84 84 

Lietuva 
Eli Lilly Lietuva 
Tel: + 370 (5) 2649600 

България 
ТП "Ели Лили Недерланд" Б.В. - България 
Тел ; + 359 2 491 41 40 

Luxembourg/Luxemburg 
Eli Lilly Benelux S.A./N.V. 
Tél/Tel: + 32 (0)2 548 84 84  

Česká republika 
Eli Lilly ČR, s.r.o. 
Tel: + 420 234 664 111 

Magyarország 
Lilly Hungária Kft. 
Tel: + 36 1 328 5100 

Danmark 
Eli Lilly Danmark A/S 
Tlf: + 45 45 26 60 00 

Malta 
Charles de Giorgio Ltd. 
Tel: + 356 25600 500 

Deutschland 
Lilly Deutschland GmbH 
Tel: + 49 (0) 6172 273 2222 

Nederland 
Eli Lilly Nederland B.V. 
Tel: + 31 (0)30 6025800 

Eesti 
Eli Lilly Nederland B.V. 
Tel: + 372 6817 280 

Norge 
Eli Lilly Norge A.S 
Tlf: + 47 22 88 18 00 



 72 

Ελλάδa 
ΦΑΡΜΑΣΕΡΒ-ΛΙΛΛΥ Α.Ε.Β.Ε. 
Τηλ: + 30 210 629 4600 

Österreich 
Eli Lilly Ges. m.b.H.  
Tel: + 43 (0) 1 711 780 

España 
  Spaly Bioquímica S.A. 
Tel: + 34 91 663 50 00 

Polska 
Eli Lilly Polska Sp. z o.o. 
Tel: + 48 22 440 33 00 

France 
Lilly France SAS 
Tél: + 33 (0) 1 55 49 34 34 

Portugal 
Lilly Portugal Produtos Farmacêuticos, Lda 
Tel: + 351 21 412 66 00 

Hrvatska 
Eli Lilly Hrvatska d.o.o. 
Tel: +385 1 2350 999 

România 
Eli Lilly România S.R.L. 
Tel: + 40 21 4023000 

Ireland 
Eli Lilly and Company (Ireland) Limited 
Tel: + 353 (0) 1 661 4377 

Slovenija 
Eli Lilly farmacevtska družba, d.o.o. 
Tel: + 386 (0)1 580 00 10 

Ísland 
Icepharma hf. 
Sími: + 354 540 8000 

Slovenská republika 
Eli Lilly Slovakia s.r.o. 
Tel: + 421 220 663 111 

Italia 
Eli Lilly Italia S.p.A. 
Tel: + 39 055 42571 

Suomi/Finland 
Oy Eli Lilly Finland Ab 
Puh/Tel: + 358 (0)9 8545 250 

Κύπρος 
Phadisco Ltd  
Τηλ: + 357 22 715000 

Sverige 
Eli Lilly Sweden AB 
Tel: + 46 (0)8 7378800 

Latvija 
Eli Lilly (Suisse) S.A Pārstāvniecība Latvijā  
Tel: + 371 67364000 

United Kingdom 
Eli Lilly and Company Limited 
Tel: + 44 (0) 1256 315000 

 
This leaflet was last revised in {month XXXX} 
 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 



 73 

--------------------------------------------------------------------------------------------------------------------------- 
(Perforation to allow health care provider information to be detached)  
 
INSTRUCTIONS FOR HEALTH CARE PROFESSIONALS 
 
Reconstitution and administration of ZYPREXA 
 
Reconstitute ZYPREXA Powder for Solution for Injection only with water for injections. 
 
ZYPREXA Powder for Solution for Injection must not be combined in the syringe with any 
commercially available medicinal products because of incompatibilities. See examples below. 
 
Olanzapine for injection should not be combined in a syringe with haloperidol injection because the 
resulting low pH has been shown to degrade olanzapine over time. 
 
Olanzapine for injection may not be combined in a syringe nor should it be used concomitantly with 
benzodiazepines. 
 
Powder for Solution for Injection 
 
Reconstitute ZYPREXA Powder for Solution for Injection using standard aseptic techniques for 
reconstitution of parenteral products. 
 
1. Withdraw 2.1 ml of water for injections into a sterile syringe. Inject into a vial of ZYPREXA 

Powder for Solution for Injection. 
 
2. Rotate the vial until the contents have completely dissolved, giving a yellow coloured solution. 

The vial contains 11.0 mg olanzapine as a solution of 5 mg/ml. If 2.0 ml solution is withdrawn, 
1 mg olanzapine is retained in the vial and syringe, thus allowing delivery of 10mg  olanzapine. 

 
3. The following table provides injection volumes for delivering various doses of olanzapine: 

 
Dose (mg) Volume of injection (ml) 

10 2.0 
7.5 1.5 
5 1.0 

2.5 0.5 
 
4. Administer the solution intramuscularly. Do not administer intravenously or subcutaneously. 
 
5. Discard the syringe and any unused solution in accordance with appropriate clinical procedures. 
 
6. Use the solution immediately within 1 hour of reconstitution. Do not store above 25º C. Do not 

freeze. 
 
Parenteral medicines should be inspected visually for particulate matter prior to administration. 



 74 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 

 

 

 

Annex IV 
 

Scientific conclusions and grounds for the variation to the terms of the marketing 
authorisation(s) 

 
 
 
 
 

 



 75 

Scientific conclusions 

Taking into account the PRAC Assessment Report on the PSUR(s) for olanzapine, the scientific 
conclusions of CHMP are as follows:  

Following the review of case reports in the UK Sentinel database, the EudraVigilance database, and 
the literature, a signal for salivary hypersecretion with olanzapine was identified on 14 February 
2019 by the Medicines and Healthcare products Regulatory Agency (MHRA) and validated by the 
PRAC. 

Based on signal analysis presented by the MAH including mechanistic plausibility, number of 
dechallenge/rechallenge cases and strong temporal relationship, the PRAC agrees that salivary 
hypersecretion may be associated with olanzapine and the adverse reaction salivary hypersecretion 
should be added to the product information. 

The CHMP agrees with the scientific conclusions made by the PRAC. 

 

Grounds for the variation to the terms of the marketing authorisation(s) 

On the basis of the scientific conclusions for olanzapine the CHMP is of the opinion that the 
benefit-risk balance of the medicinal product(s) containing olanzapine is unchanged subject to the 
proposed changes to the product information 

The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D.  CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
	Scientific conclusions and grounds for the variation to the terms of the marketing authorisation(s)