Zyprexa Velotab

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



 2 

1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA VELOTAB 5 mg orodispersible tablets 
ZYPREXA VELOTAB 10 mg orodispersible tablets 
ZYPREXA VELOTAB 15 mg orodispersible tablets 
ZYPREXA VELOTAB 20 mg orodispersible tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
ZYPREXA VELOTAB 5 mg orodispersible tablets 
 
Each orodispersible tablet contains 5 mg olanzapine.  
 
Excipients with known effect: Each orodispersible tablet contains 
0.60 mg aspartame, 
0.1125 mg sodium methyl parahydroxybenzoate, 
0.0375 mg sodium propyl parahydroxybenzoate. 
 
ZYPREXA VELOTAB 10 mg orodispersible tablets 
 
Each orodispersible tablet contains 10 mg olanzapine.  
 
Excipients with known effect: Each orodispersible tablet contains 
0.80 mg aspartame, 
0.15 mg sodium methyl parahydroxybenzoate, 
0.05 mg sodium propyl parahydroxybenzoate. 
 
ZYPREXA VELOTAB 15 mg orodispersible tablets 
 
Each orodispersible tablet contains 15 mg olanzapine.  
 
Excipients with known effect: Each orodispersible tablet contains 
1.20 mg aspartame, 
0.225 mg sodium methyl parahydroxybenzoate, 
0.075 mg sodium propyl parahydroxybenzoate. 
 
ZYPREXA VELOTAB 20 mg orodispersible tablets 
 
Each orodispersible tablet contains 20 mg olanzapine.  
 
Excipients with known effect: Each orodispersible tablet contains 
1.60 mg aspartame, 
0.30 mg sodium methyl parahydroxybenzoate, 
0.10 mg sodium propyl parahydroxybenzoate. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Orodispersible tablet 
 
Yellow, round, freeze dried, rapid-dispersing preparation to be placed in the mouth or alternatively to 
be dispersed in water or other suitable beverage for administration. 
 



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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. 
 
ZYPREXA VELOTAB orodispersible tablet should be placed in the mouth, where it will rapidly 
disperse in saliva, so it can be easily swallowed. Removal of the intact orodispersible tablet from the 
mouth is difficult. Since the orodispersible tablet is fragile, it should be taken immediately on opening 
the blister. Alternatively, it may be dispersed in a full glass of water or other suitable beverage (orange 
juice, apple juice, milk or coffee) immediately before administration.  
 
Olanzapine orodispersible tablet is bioequivalent to olanzapine coated tablets, with a similar rate and 
extent of absorption. It has the same dosage and frequency of administration as olanzapine coated 
tablets. Olanzapine orodispersible tablets may be used as an alternative to olanzapine coated tablets. 
 
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). 
 



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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 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. 
 
In cases where dose increments of 2.5 mg are considered necessary, ZYPREXA coated tablets should 
be used. 
 
(See sections 4.5 and 5.2.) 
 
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. 
 



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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. 

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 VELOTAB, 
should be observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, 
polyphagia, and weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus 
should be monitored regularly for worsening of glucose control. Weight should be monitored 
regularly, 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 
VELOTAB, 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. 
 



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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, 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. 



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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). 
 
Phenylalanine 
ZYPREXA VELOTAB orodispersible tablet contains aspartame, which is a source of phenylalanine. 
May be harmful for people with phenylketonuria. 
 
Mannitol 
ZYPREXA VELOTAB orodispersible tablet contains mannitol. 
 
Sodium methyl parahydroxybenzoate and sodium propyl parahydroxybenzoate 
Olanzapine orodispersible tablet contains sodium methyl parahydroxybenzoate and sodium propyl 
parahydroxybenzoate. These preservatives are known to cause urticaria. Generally, delayed type 
reactions such as contact dermatitis may occur, but rarely immediate reactions with bronchospasm 
may occur. 
 
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).  
 



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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). 
 
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. 



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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   
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 
 
 
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) 

  



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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 

 

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 

   



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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. 



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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. 
 
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 

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. 
 
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. 
 



 14 

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. 
 
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. 



 15 

 
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 
 
Olanzapine orodispersible tablet is bioequivalent to olanzapine coated tablets, with a similar rate and 
extent of absorption. Olanzapine orodispersible tablets may be used as an alternative to olanzapine 
coated tablets. 
 
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. 
 
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 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, 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 



 16 

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. 
 
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 [area under the curve] 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. 
 



 17 

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 
 
Gelatin 
Mannitol (E421) 
Aspartame (E951) 
Sodium methyl parahydroxybenzoate (E219) 
Sodium propyl parahydroxybenzoate (E217) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
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 
 
Aluminium blister strips in cartons of 28, 35, 56, 70 or 98 orodispersible 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/1/99/125/001 
EU/1/99/125/002 
EU/1/99/125/003 
EU/1/99/125/004 
EU/1/99/125/005 
EU/1/99/125/006 
EU/1/99/125/007 
EU/1/99/125/008 



 18 

EU/1/99/125/009 
EU/1/99/125/010 
EU/1/99/125/011 
EU/1/99/125/012 
EU/1/99/125/013 
EU/1/99/125/014 
EU/1/99/125/015 
EU/1/99/125/016 
EU/1/99/125/017 
EU/1/99/125/018 
EU/1/99/125/019 
EU/1/99/125/020 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 3 February 2000 
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 

 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 

 
ANNEX II 

 
A. MANUFACTURER 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 



 20 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE  
 
Name and address of the manufacturer responsible for batch release 

 
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 

 
 



 21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



 22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



 23 

 PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON OF ZYPREXA VELOTAB 5 mg ORODISPERSIBLE TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA VELOTAB 5 mg orodispersible tablets 
Olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each orodispersible tablet contains 5 mg olanzapine 
 
 
3. LIST OF EXCIPIENTS 
 
Other ingredients: gelatin, mannitol (E421), aspartame (E951), sodium methyl parahydroxybenzoate 
(E219), sodium propyl parahydroxybenzoate (E217). 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 orodispersible tablets  
35 orodispersible tablets 
56 orodispersible tablets 
70 orodispersible tablets 
98 orodispersible tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
 
Oral use 
 

 
 
1. Separate one blister cell from the strip. 
2. Carefully peel off the backing.  
3. Gently push the tablet out. 
4. Put the tablet in your mouth 
 
 
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 



 24 

 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture. 
 
 
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/1/99/125/001 28 orodispersible tablets 
EU/1/99/125/009 35 orodispersible tablets 
EU/1/99/125/005 56 orodispersible tablets 
EU/1/99/125/013 70 orodispersible tablets 
EU/1/99/125/017 98 orodispersible 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 VELOTAB 5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



 25 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



 26 

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



 27 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON OF ZYPREXA VELOTAB 10 mg ORODISPERSIBLE TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA VELOTAB 10 mg orodispersible tablets 
Olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each orodispersible tablet contains 10 mg olanzapine 
 
 
3. LIST OF EXCIPIENTS 
 
Other ingredients: gelatin, mannitol (E421), aspartame (E951), sodium methyl parahydroxybenzoate 
(E219), sodium propyl parahydroxybenzoate (E217). 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 orodispersible tablets  
35 orodispersible tablets 
56 orodispersible tablets 
70 orodispersible tablets 
98 orodispersible tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
 
Oral use 
 

 
 
1. Separate one blister cell from the strip. 
2. Carefully peel off the backing.  
3. Gently push the tablet out. 
4. Put the tablet in your mouth 
 
 
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 



 28 

 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture. 
 
 
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/1/99/125/002 28 orodispersible tablets 
EU/1/99/125/010 35 orodispersible tablets 
EU/1/99/125/006 56 orodispersible tablets 
EU/1/99/125/014 70 orodispersible tablets 
EU/1/99/125/018 98 orodispersible 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 VELOTAB 10 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



 29 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 30 

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



 31 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON OF ZYPREXA VELOTAB 15 mg ORODISPERSIBLE TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA VELOTAB 15 mg orodispersible tablets 
Olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each orodispersible tablet contains 15 mg olanzapine 
 
 
3. LIST OF EXCIPIENTS 
 
Other ingredients: gelatin, mannitol (E421), aspartame (E951), sodium methyl parahydroxybenzoate 
(E219), sodium propyl parahydroxybenzoate (E217). 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 orodispersible tablets  
35 orodispersible tablets 
56 orodispersible tablets 
70 orodispersible tablets 
98 orodispersible tablets 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
 
Oral use 
 

 
 
1. Separate one blister cell from the strip. 
2. Carefully peel off the backing.  
3. Gently push the tablet out. 
4. Put the tablet in your mouth 
 
 
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 
 



 32 

 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture. 
 
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/1/99/125/003 28 orodispersible tablets 
EU/1/99/125/011 35 orodispersible tablets 
EU/1/99/125/007 56 orodispersible tablets 
EU/1/99/125/015 70 orodispersible tablets 
EU/1/99/125/019 98 orodispersible 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 VELOTAB 15 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



 33 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 34 

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



 35 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON OF ZYPREXA VELOTAB 20 mg ORODISPERSIBLE TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ZYPREXA VELOTAB 20 mg orodispersible tablets 
Olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each orodispersible tablet contains 20 mg olanzapine  
 
 
3. LIST OF EXCIPIENTS 
 
Other ingredients: gelatin, mannitol (E421), aspartame (E951), sodium methyl parahydroxybenzoate 
(E219), sodium propyl parahydroxybenzoate (E217). 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 orodispersible tablets  
35 orodispersible tablets 
56 orodispersible tablets 
70 orodispersible tablets 
98 orodispersible tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use 
 

 
 
1. Separate one blister cell from the strip. 
2. Carefully peel off the backing.  
3. Gently push the tablet out. 
4. Put the tablet in your mouth 
 
 
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 



 36 

 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture 
 
 
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/1/99/125/004 28 orodispersible tablets 
EU/1/99/125/012 35 orodispersible tablets 
EU/1/99/125/008 56 orodispersible tablets 
EU/1/99/125/016 70 orodispersible tablets 
EU/1/99/125/020 98 orodispersible 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 VELOTAB 20 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



 37 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 38 

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



 39 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



 40 

Package leaflet: Information for the user 
 

ZYPREXA VELOTAB 5 mg orodispersible tablets 
ZYPREXA VELOTAB 10 mg orodispersible tablets 
ZYPREXA VELOTAB 15 mg orodispersible tablets 
ZYPREXA VELOTAB 20 mg orodispersible 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 VELOTAB is and what it is used for 
2. What you need to know before you take ZYPREXA VELOTAB 
3. How to take ZYPREXA VELOTAB 
4. Possible side effects 
5. How to store ZYPREXA VELOTAB 
6. Contents of the pack and other information 
 
 
1. What ZYPREXA VELOTAB is and what it is used for 
 
ZYPREXA VELOTAB contains the active substance olanzapine. ZYPREXA VELOTAB 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 VELOTAB 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 VELOTAB  
 
Do not take ZYPREXA VELOTAB 
• 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 VELOTAB 
• The use of ZYPREXA VELOTAB in elderly patients with dementia 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 VELOTAB tell your doctor. 



 41 

• 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 VELOTAB. 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 VELOTAB. Your doctor should do blood tests to check blood sugar and certain 
fat levels before you start taking ZYPREXA VELOTAB 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 VELOTAB is not for patients who are under 18 years. 
 
Other medicines and ZYPREXA VELOTAB 
Only take other medicines while you are on ZYPREXA VELOTAB if your doctor tells you that you 
can. You might feel drowsy if ZYPREXA VELOTAB 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 VELOTAB dose. 
 
ZYPREXA VELOTAB with alcohol 
Do not drink any alcohol if you have been given ZYPREXA VELOTAB 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 
VELOTAB can pass into breast milk. 
 



 42 

The following symptoms may occur in newborn babies, of mothers that have used ZYPREXA 
VELOTAB 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 VELOTAB. If this happens do not 
drive or operate any tools or machines. Tell your doctor. 
 
ZYPREXA VELOTAB contains aspartame, mannitol and sodium methyl parahydroxybenzoate 
and sodium propyl parahydroxybenzoate 
Patients who cannot take phenylalanine should note that ZYPREXA VELOTAB contains aspartame, 
which is a source of phenylalanine. May be harmful for people with phenylketonuria. 
 
Patients who cannot take mannitol should note that ZYPREXA VELOTAB contains mannitol. 
 
ZYPREXA VELOTAB contains sodium methyl parahydroxybenzoate and sodium propyl 
parahydroxybenzoate, which may cause an allergic reaction in some people. An allergic reaction may 
be recognised as a rash, itching or shortness of breath. This may occur immediately or some time after 
you take ZYPREXA VELOTAB. 
 
 
3. How to take ZYPREXA VELOTAB  
 
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 VELOTAB tablets to take and how long you should 
continue to take them. The daily dose of ZYPREXA VELOTAB is between 5 mg and 20 mg. Consult 
your doctor if your symptoms return but do not stop taking ZYPREXA VELOTAB unless your doctor 
tells you to. 
 
You should take your ZYPREXA VELOTAB 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 VELOTAB orodispersible tablets are for oral use. 
 
ZYPREXA VELOTAB tablets break easily, so you should handle the tablets carefully. Do not handle 
the tablets with wet hands as the tablets may break up. 
 
1. Hold the blister strip at the edges and separate one blister cell from the rest of the strip by gently 

tearing along the perforations around it. 
2. Carefully peel off the backing.  
3. Gently push the tablet out. 
4. Put the tablet in your mouth. It will dissolve directly in your mouth, so that it can be easily 

swallowed. 
 
You can also place the tablet in a full glass or cup of water, orange juice, apple juice, milk or coffee, 
and stir. With some drinks, the mixture may change colour and possibly become cloudy. Drink it 
straight away. 

 
 
If you take more ZYPREXA VELOTAB than you should 
Patients who have taken more ZYPREXA VELOTAB than they should have experienced the 
following symptoms: rapid beating of the heart, agitation/aggressiveness, problems with speech, 



 43 

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 VELOTAB  
Take your tablets as soon as you remember. Do not take two doses in one day. 
 
If you stop taking ZYPREXA VELOTAB 
Do not stop taking your tablets just because you feel better. It is important that you carry on taking 
ZYPREXA VELOTAB for as long as your doctor tells you. 
 
If you suddenly stop taking ZYPREXA VELOTAB, 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. 
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. 



 44 

 
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 VELOTAB 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. 
 
 
5. How to store ZYPREXA VELOTAB  
 
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 VELOTAB 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 VELOTAB contains 
• The active substance is olanzapine. Each ZYPREXA VELOTAB orodispersible tablet contains 

either 5 mg, 10 mg, 15 mg or 20 mg of the active substance. The exact amount is shown on your 
ZYPREXA VELOTAB pack.  

• The other ingredients are  
- gelatin, mannitol (E421), aspartame (E951), sodium methyl parahydroxybenzoate (E219) and 

sodium propyl parahydroxybenzoate (E217). 
 
What ZYPREXA VELOTAB looks like and contents of the pack 
ZYPREXA VELOTAB 5 mg, 10 mg, 15 mg and 20 mg are yellow orodispersible tablets. 
Orodispersible tablet is the technical name for a tablet which dissolves directly in your mouth, so that 
it can be easily swallowed. 
 
ZYPREXA VELOTAB is available in packs containing 28, 35, 56, 70 or 98 tablets. Not all pack sizes 
may be marketed. 
 



 45 

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 

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 

 
 



 46 

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 

http://www.ema.europa.eu/
http://www.ema.europa.eu/


 47 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 

 
 
 
 
 

Annex IV 

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

 
 
 
 
 

 



 48 

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. MANUFACTURER 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)