Olazax Disperzi

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

 



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1. NAME OF THE MEDICINAL PRODUCT 

 

Olazax Disperzi 5 mg orodispersible tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each orodispersible tablet contains 5 mg olanzapine. 

 

Excipient with known effect: Each orodispersible tablet contains 0.23 mg aspartame 

 

For the full list of excipients see section 6.1 

 

 

3. PHARMACEUTICAL FORM 

 

Orodispersible tablet 

 

Yellow coloured circular flat bevelled edge orodispersible tablets with ‘B’ debossed on one side. 

 

 

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. 



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Olazax Disperzi orodispersible tablets should be placed in the mouth, where it will rapidly disperse in 

saliva, so it can be easily swallowed. Alternatively, it may be dispersed in a full glass of water or 

other suitable beverage (orange juice, apple juice, milk or coffee) immediately before the 

administration. 

 

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. 

 

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 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 % verses 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 



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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 % verses 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. 

 

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 olanzapine, 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 olanzapine, 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. 

 



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Hepatic function 

Transient, asymptomatic elevations of hepatic aminotransferases , alanine transferase (ALT), 

aspartatetransferase (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, 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. 

 



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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. Long-term outcomes associated with these 

events have not been studied and remain unknown (see sections 4.8 and 5.1). 

 

Phenylalanine 

Olazax Disperzi orodispersible tablet contains aspartame, which is a source of phenylalanine. May be 

harmful for people with phenylketonuria. 

 

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 nonsmokers and 

77 % 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. 



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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). 

 

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). 

 



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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 (< 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 

 Thrombocytopenia1

1 

 

Immune system disorders 

  Hypersensitivity11   

Metabolism and nutrition disorders 

Weight gain 1 Elevated 

cholesterol levels 
2,3 

Elevated glucose 

levels 4 

Elevated 

triglyceride levels 
2,5 

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 

 

Akathisia 6 

 

Parkinsonism 6 

 

Dyskinesia 6 

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 

Neuroleptic 

malignant 

syndrome (see 

section 4.4)12 

 

Discontinuation 

Symptoms 7,12 

 



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Stuttering11 

Restless legs 

syndrome11 

Cardiac disorders 

  Bradycardia 

QTc prolongation (see 

section 4.4) 

Ventricular 

tachycardia/fibrillat

ion 

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 

 

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 Amenorrhea Priapism12  



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dysfunction in 

males 

Decreased libido in 

males and females 

Breast enlargement 

Galactorrhea in 

females 

Gynaecomastia/breast 

enlargement in males 

General disorders 

and 

administration 

site conditions 

    

 Asthenia 

Fatigue 

Oedema 

Pyrexia10 

   

Investigations 

Elevated plasma 

prolactin levels 8 

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. 

 
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 can not 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. 

 



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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 

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. 



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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 levels 14, increased appetite. 
Common: Elevated cholesterol levels 15 

Nervous system disorders 

Very common: Sedation (including: hypersomnia, lethargy, somnolence). 

Gastrointestinal disorders 
Common: Dry mouth 

Hepato-biliary disorders 

Very common: Elevations of hepatic aminotransferases  (ALT/AST; see section 4.4). 

Investigations 
Very common: Decreased total bilirubin, increased GGT, elevated plasma prolactin levels 16 

 
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.  

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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 betaagonist 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; α 

1 adrenergic; and histamine H1 receptors.  

 

Animal behavioral 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 5HT2A 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 



14 

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 1-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.  

 



15 

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 

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. 



16 

 

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 

 

Mannitol (E 421) 

Microcrystalline cellulose 

Aspartame (E 951) 

Crospovidone 

Magnesium stearate 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

30 months 

 

6.4 Special precautions for storage 

 

Store below 30 C. 

 



17 

6.5 Nature and contents of container 
 

Aluminium/aluminium blisters in cartons of 28, 56 tablets per carton. 

 

Not all pack sizes may be marketed 

 

6.6 Special precautions for disposal  

 

No special requirements 

 

7. MARKETING AUTHORISATION HOLDER 

 

Glenmark Pharmaceuticals s.r.o. 

Hvězdova 1716/2b, 140 78 Praha 4 

Czech Republic  

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/09/592/001 

EU/1/09/592/006 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 10.12.2009 

Date of renewal of authorisation: 06.08.2014 

 

 

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 (EMA) http://www.ema.europa.eu 

http://www.emea.europa.eu/


18 

1. NAME OF THE MEDICINAL PRODUCT 

 

Olazax Disperzi 10 mg orodispersible tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each orodispersible tablet contains 10 mg olanzapine. 

 

Excipient with known effect: Each orodispersible tablet contains 0.46 mg aspartame 

 

For the full list of excipients see section 6.1 

 

 

3. PHARMACEUTICAL FORM 

 

Orodispersible tablet 

Yellow coloured circular flat bevelled edge tablets with ‘OL’ debossed on one side and ‘D’ debossed 

on other side. 

 

 

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. 



19 

 

Olazax Disperzi orodispersible tablets should be placed in the mouth, where it will rapidly 

disperse in saliva, so it can be easily swallowed. 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. 

 

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. 

 

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, Olanzapine 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 % vrs 1.5 %, 



20 

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 % vrs 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. 

 

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 olanzapine, 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. 

 



21 

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 olanzapine, 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, alanine transferase (ALT), aspartate 

transferase (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, 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. 

 



22 

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). 

 

Phenylalanine 

Olazax Disperzi orodispersible tablet contains aspartame, which is a source of phenylalanine. May be 

harmful for people with phenylketonuria. 

 

 

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). 

 



23 

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 nonsmokers 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). 

 

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 



24 

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 (< 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 

 Thrombocyto

penia11 

 

Immune system disorders  

  Hypersensitivity
11 

  

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 

Hypothermia
12 

 



25 

(see section 4.4) 11 

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 

 

Discontinuati

on 

symptoms7, 12 

 

Cardiac disorders  

  Bradycardia 

QTc 
prolongation 

(see section 4.4) 

Ventricular 

tachycardia/fib

rillation, 

sudden death 

(see section 

4.4)11 

 

Vascular disorders  

Orthostatic 

hypotension10 

 Thromboemboli

sm (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 

hypersecretion
11 

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 Photosensitivit

y reaction 

Alopecia 

 Drug Reaction 

with Eosinophilia 

and Systemic 

Symptoms 



26 

(DRESS) 

Musculoskeletal and connective tissue disorders  

 Arthralgia9  Rhabdomyolys

is11 

 

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 

Gynaecomasti

a/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 

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. 

 



27 

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 



28 

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 gain 13, elevated triglyceride levels 14, increased appetite. 
Common: Elevated cholesterol levels 15 

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 levels 16 

 
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 



29 

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 

betaagonist 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 

5HT2A/2C, 5HT3, 5HT6; dopamine D1, D2, D3, D4, D5; cholinergic muscarinic receptors M1-M5; 

α1 adrenergic; and histamine H1 receptors.  

 

Animal behavioral 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 5HT2 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. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


30 

 

In a single oral dose (10 mg) Positron Emission Tomography (PET) study in healthy volunteers, 

olanzapine produced a higher 5HT2A 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. 

 

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 

 



31 

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 1-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 

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. 

 



32 

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 [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 

 

Mannitol (E 421) 

Microcrystalline cellulose 

Aspartame (E 951) 

Crospovidone 



33 

Magnesium stearate 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

30 months 

 

6.4 Special precautions for storage 

 

Store below 30 C. 

 

6.5 Nature and contents of container 

 

Aluminium/aluminium blisters in cartons of 28, 56 tablets per carton. 

 

Not all pack sizes may be marketed 

 

6.6 Special precautions for disposal  

 

No special requirements 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Glenmark Pharmaceuticals s.r.o. 

Hvězdova 1716/2b, 140 78 Praha 4 

Czech Republic  

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/09/592/003 

EU/1/09/592/008 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 10.12.2009 

Date of renewal of authorisation: 06.08.2014 

 

 

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 (EMA) http://www.ema.europa.eu 

http://www.emea.europa.eu/


34 

1. NAME OF THE MEDICINAL PRODUCT 

 

 

Olazax Disperzi 15 mg orodispersible tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each orodispersible tablet contains 15 mg olanzapine. 

 

Excipient with known effect: Each orodispersible tablet contains 0.69 mg aspartame 

 

For the full list of excipients see section 6.1 

 

 

3. PHARMACEUTICAL FORM 

 

Orodispersible tablet 

 

Yellow coloured circular flat bevelled edge orodispersible tablets with ‘OL’ debossed on one side and 

‘E’ debossed on other side. 

 

 

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. 



35 

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. 

 

Olazax Disperzi orodispersible tablets should be placed in the mouth, where it will rapidly disperse in 

saliva, so it can be easily swallowed. 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. 

 

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. 

 

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 week’s 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 % 

versus 1.5 %, respectively). The higher incidence of death was not associated with olanzapine dose 

(mean daily dose 4.4 mg) or duration of treatment.  

 



36 

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 % versus 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. 

 

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 olanzapine, 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 olanzapine, 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 



37 

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, alanine transferase (ALT), aspartate 

transferase (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, 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 



38 

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). 

 

Phenylalanine 

Olazax Disperzi orodispersible tablet contains aspartame, which is a source of phenylalanine. May be 

harmful for people with phenylketonuria. 

 

 

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 nonsmokers and 

77 % in male smokers.  

 



39 

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). 

 

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). 



40 

 

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 (< 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 

 Thrombocytope

nia11 

 

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 

Neuroleptic 

malignant 

syndrome (see 

section 4.4)12  

Discontinuation 

 



41 

reported11 

Dystonia (including 

oculogyration)11 

Tardive 

dyskinesia11 

Amnesia9 

Dysarthria 

Stuttering11 

Restless legs 

syndrome11
 

symptoms7, 12 

Cardiac disorders  

  Bradycardia 

QTc prolongation 

(see section 4.4) 

Ventricular 

tachycardia/fibri

llation, 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 

 

Skin and subcutaneous tissue disorders  

 Rash Photosensitivity 

reaction 

Alopecia 

 Drug 

Reaction 

with 

Eosinophili

a and 

Systemic 

Symptoms 

(DRESS) 

Musculoskeletal and connective tissue disorders  

 Arthralgia9  Rhabdomyolys

is11 

 

Renal and urinary disorders  

  Urinary 

incontinence, 

urinary retention 

Urinary hesitation11 

  

Pregnancy, puerperium and perinatal conditions 



42 

    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/bre

ast 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 

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 



43 

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 

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. 

 



44 

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 gain 13, elevated triglyceride levels 14, increased appetite. 
Common: Elevated cholesterol levels 15 

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 levels 16 

 
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.  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


45 

 

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 

betaagonist 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, 5HT3, 5HT6; dopamine D1, D2, D3, D4, D5; cholinergic muscarinic receptors M1-M5; 

α1 adrenergic; and histamine H1 receptors.  

 

Animal behavioral 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 5HT2 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 Ttomography (PET) study in healthy volunteers, 

olanzapine produced a higher 5HT2A 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 



46 

(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 1-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.  

 



47 

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 

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. 



48 

 

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 

 

Mannitol (E 421) 

Microcrystalline cellulose 

Aspartame (E 951) 

Crospovidone 

Magnesium stearate 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

30 months 

 

6.4 Special precautions for storage 

 

Store below 30 C. 

 

6.5 Nature and contents of container 

 



49 

Aluminium/aluminium blisters in cartons of 28, 56 tablets per carton. 

 

Not all pack sizes may be marketed 

 

6.6 Special precautions for disposal  

 

No special requirements 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Glenmark Pharmaceuticals s.r.o. 

Hvězdova 1716/2b, 140 78 Praha 4 

Czech Republic  

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/09/592/004 

EU/1/09/592/009 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 10.12.2009 

Date of renewal of authorisation: 06.08.2014 

 

 

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 (EMA) http://www.ema.europa.eu 

http://www.emea.europa.eu/


50 

1. NAME OF THE MEDICINAL PRODUCT 

 

Olazax Disperzi 20  mg orodispersible tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each orodispersible tablet contains 20 mg olanzapine 

 

Excipient with known effect: Each orodispersible tablet contains 0.92 mg aspartame 

 

For the full list of excipients see section 6.1 

 

 

3. PHARMACEUTICAL FORM 

 

Orodispersible tablet 

 

Yellow coloured circular flat bevelled edge orodispersible tablets with ‘OL’ debossed on one side and 

‘F’ debossed on other side. 

 

 

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. 



51 

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. 

 

Olazax Disperzi orodispersible tablets should be placed in the mouth, where it will rapidly disperse in 

saliva, so it can be easily swallowed. 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. 

 

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. 

 

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 week’s 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 % 

versus 1.5 %, respectively). The higher incidence of death was not associated with olanzapine dose 

(mean daily dose 4.4 mg) or duration of treatment.  

 



52 

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 % versus 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. 

 

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 olanzapine, 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 olanzapine, 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 



53 

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, alanine transferase (ALT), aspartate 

transferase (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, 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. 

 



54 

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). 

 

Phenylalanine 

Olazax Disperzi orodispersible tablet contains aspartame, which is a source of phenylalanine. May be 

harmful for people with phenylketonuria. 

 

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 

nonsmokers 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. 



55 

 

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). 

 

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). 

 



56 

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 (< 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 

 Thrombocytope

nia11 

 

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 

 

Neuroleptic 

malignant 

syndrome (see 

section 4.4)12 

Discontinuation 

symptoms7, 12 

 



57 

Amnesia9 

Dysarthria 

Stuttering11 

Restless legs 

syndrome11
 

Cardiac disorders  

  Bradycardia 

QTc prolongation 

(see section 4.4) 

Ventricular 

tachycardia/fibri

llation, 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 

 

Skin and subcutaneous tissue disorders  

 Rash Photosensitivity 

reaction 

Alopecia 

 Drug 

Reaction 

with 

Eosinophili

a and 

Systemic 

Symptoms 

(DRESS) 

Musculoskeletal and connective tissue disorders  

 Arthralgia 9  Rhabdomyolys

is11 

 

Renal and urinary disorders  

  Urinary 

incontinence, 

urinary retention 

urinary hesitation11 

  

Pregnancy, puerperium and perinatal conditions 

    Drug 

withdrawal 

syndrome 

neonatal 



58 

(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/bre

ast 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 

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. 

 



59 

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 

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 



60 

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 gain 13, elevated triglyceride levels 14, increased appetite. 
Common: Elevated cholesterol levels 15 

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 levels 16 

 
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. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


61 

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 behavioral 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 5HT2 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 5HT2A 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). 



62 

 

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 1-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. 



63 

 

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 

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. 

 



64 

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 

 

Mannitol (E 421) 

Microcrystalline cellulose 

Aspartame (E 951) 

Crospovidone 

Magnesium stearate 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

30 months 

 

6.4 Special precautions for storage 

 

Store below 30 C. 

 

6.5 Nature and contents of container 

 

Aluminium/aluminium blisters in cartons of 28, 56 tablets per carton. 



65 

 

Not all pack sizes may be marketed 

 

6.6 Special precautions for disposal  

 

No special requirements 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Glenmark Pharmaceuticals s.r.o. 

Hvězdova 1716/2b, 140 78 Praha 4 

Czech Republic  

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/09/592/005 

EU/1/09/592/010 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 10.12.2009 

Date of renewal of authorisation: 06.08.2014 

 

 

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 (EMA) http://www.ema.europa.eu 

http://www.emea.europa.eu/


66 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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 

 

 

 



67 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

Glenmark Pharmaceuticals s.r.o 

Fibíchova 143, 566 17  

Vysoké Mýto 

Czech Republic 

 

 

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 

 



68 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



69 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 



70 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Olazax Disperzi 5 mg orodispersible tablets 

 

Olanzapine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg olanzapine. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains aspartame. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Orodispersible Tablet 

28 orodispersible tablets 

56 orodispersible tablets 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

The tablet should be dissolved in the mouth or in a drink. 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 below 30C 

 



71 

 

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 

 

Glenmark Pharmaceuticals s.r.o. 

Hvězdova 1716/2b, 140 78 Praha 4 

Czech Republic  

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/09/592/001 

EU/1/09/592/006 

 

13. BATCH NUMBER 

 

BN 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Olazax Disperzi 5 mg orodispersible tablets 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC  

SN  

NN 

 

 



72 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

ALUMINIUM BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Olazax Disperzi 5 mg orodispersible tablets 

 

Olanzapine 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Glenmark Pharmaceuticals s.r.o. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

BN 

 

 

5. OTHER 

 



73 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

ALUMINIUM BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Olazax Disperzi 7.5 mg orodispersible tablets 

 

Olanzapine 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Glenmark Pharmaceuticals s.r.o. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

BN 

 

 

5. OTHER 

 



74 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Olazax Disperzi 10 mg orodispersible tablets 

 

Olanzapine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg olanzapine. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains aspartame. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Orodispersible Tablet 

28 orodispersible tablets 

56 orodispersible tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

The tablet should be dissolved in the mouth or in a drink. 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 below 30C 



75 

 

 

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 

 

Glenmark Pharmaceuticals s.r.o. 

Hvězdova 1716/2b, 140 78 Praha 4 

Czech Republic  

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/09/592/003 

EU/1/09/592/008 

 

13. BATCH NUMBER 

 

BN 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Olazax Disperzi 10 mg orodispersible tablets 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC  

SN  

NN 

 

 



76 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

ALUMINIUM BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Olazax Disperzi 10 mg orodispersible tablets 

 

Olanzapine 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Glenmark Pharmaceuticals s.r.o. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

BN 

 

 

5. OTHER 

 



77 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Olazax Disperzi 15 mg orodispersible tablets 

 

Olanzapine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 15 mg olanzapine. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains aspartame. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Orodispersible Tablet 

28 orodispersible tablets 

56 orodispersible tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

The tablet should be dissolved in the mouth or in a drink. 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 

 



78 

Store below 30C 

 

 

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 

 

Glenmark Pharmaceuticals s.r.o. 

Hvězdova 1716/2b, 140 78 Praha 4 

Czech Republic  

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/09/592/004 

EU/1/09/592/009 

 

13. BATCH NUMBER 

 

BN 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Olazax Disperzi 15 mg orodispersible tablets 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC  

SN  

NN 

 

 



79 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

ALUMINIUM BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Olazax Disperzi 15 mg orodispersible tablets 

 

Olanzapine 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Glenmark Pharmaceuticals s.r.o. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

BN 

 

 

5. OTHER 

 



80 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Olazax Disperzi 20 mg orodispersible tablets 

 

Olanzapine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 20 mg olanzapine 

 

 

3. LIST OF EXCIPIENTS 

 

Contains aspartame. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Orodispersible Tablet 

28 orodispersible tablets 

56 orodispersible tablets 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

The tablet should be dissolved in the mouth or in a drink. 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 below 30C 

 



81 

 

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 

 

Glenmark Pharmaceuticals s.r.o. 

Hvězdova 1716/2b, 140 78 Praha 4 

Czech Republic  

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/09/592/005 

EU/1/09/592/010 

 

13. BATCH NUMBER 

 

BN 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Olazax Disperzi 20 mg orodispersible tablets 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC  

SN  

NN 

 

 



82 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

ALUMINIUM BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Olazax Disperzi 20 mg orodispersible tablets 

 

Olanzapine 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Glenmark Pharmaceuticals s.r.o. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

BN 

 

 

5. OTHER 

 

 

 



83 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 

 



84 

Package leaflet: Information for the user 

 

Olazax Disperzi 5 mg orodispersible tablets 

Olazax Disperzi 10 mg orodispersible tablets 

Olazax Disperzi 15 mg orodispersible tablets 

Olazax Disperzi 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 Olazax Disperzi is and what it is used for 

2. What you need to know before you take Olazax Disperzi 

3. How to take Olazax Disperzi 

4. Possible side effects 

5. How to store Olazax Disperzi 

6. Contents of the pack and other information 

 

 

1. What Olazax Disperzi is and what it is used for 
 

Olazax Disperzi contains the active substance olanzapine. Olazax Disperzi 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. 

 
Olazax Disperzi 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 Olazax Disperzi 

 

Do not take Olazax Disperzi 

- 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 Olazax Disperzi. 

 The use of Olazax Disperzi 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 Olazax Disperzi 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. 



85 

 Weight gain has been seen in patients taking Olazax Disperzi. 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 Olazax Disperzi. Your doctor should do blood tests to check blood sugar and certain fat 

levels before you start taking Olazax Disperzi 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 

Olazax Disperzi is not for patients who are under 18 years.  

 

Other medicines and Olazax Disperzi 

Only take other medicines while you are on Olazax Disperzi if your doctor tells you that you can. You 

might feel drowsy if Olazax Disperzi 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 Olazax Disperzi dose. 

 

Olazax Disperzi with alcohol 

Do not drink any alcohol if you have been given Olazax Disperzi as together with alcohol it may make 

you feel drowsy. 

 

Pregnancy and breast-feeding 

If you are pregnant or breast-feeding, think you might 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  Olazax Disperzi can 

pass into breast milk.  

 

The following symptoms may occur in newborn babies, of mothers that have used Olazax Disperzi 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. 



86 

 

Driving and using machines 

There is a risk of feeling drowsy when you are given Olazax Disperzi. If this happens do not drive or 

operate any tools or machines. Tell your doctor. 

 

Olazax Disperzi contains aspartame  

Patients who cannot take phenylalanine should note that Olazax Disperzi contains aspartmae, which is 

a source of phenylalanine. This may be harmful for people with phenylketonuria. 

 

 

3. How to take Olazax Disperzi 
 

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 Olazax Disperzi tablets to take and how long you should 

continue to take them. The daily dose of Olazax Disperzi is between 5 mg and 20 mg. Consult your 

doctor if your symptoms return but do not stop taking Olazax Disperzi unless your doctor tells you 

to. 

 

You should take your Olazax Disperzi 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. Olazax Disperzi tablets are for oral use. 

 

Put the tablet in your mouth. It will dissolve directly in your mouth, so 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. Drink it straight away.  

 

If you take more Olazax Disperzi than you should 

Patients who have taken more Olazax Disperzi 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 Olazax Disperzi 

Take your tablets as soon as you remember. Do not take two doses in one day. 

 

If you stop taking Olazax Disperzi 

Do not stop taking your tablets just because you feel better. It is important that you carry on taking  

Olazax Disperzi for as long as your doctor tells you. 

 

If you suddenly stop taking Olazax Disperzi, 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. 

 



87 

 

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 (may affect up to 1 in 10,000) 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 in 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 Olazax Disperzi may worsen the symptoms 

 

Reporting of side effects 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. You can also report side effects directly via the national reporting system 



88 

listed in Appendix V. By reporting side effects you can help provide more information on the safety 

of this medicine. 

 

 

5. How to store Olazax Disperzi 

 

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 and blister after EXP. The 

expiry date refers to the last day of that month.   

 

Store below 30 C. 

 

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 Olazax Disperzi contains 

- The active substance is olanzapine 

- Each tablet contains 5 mg,  10 mg, 15 mg, or 20 mg olanzapine 

 

- The other ingredients are mannitol (E 421), microcrystalline cellulose, aspartame (E 951), 

crospovidone, magnesium stearate 

 

What Olazax Disperzi looks like and contents of the pack 

 

Olazax Disperzi 5 mg is supplied as a yellow coloured circular flat beveled edge orodispersible tablet 

with ‘B’ debossed on one side. 

 

 

Olazax Disperzi 10 mg is supplied as a yellow coloured circular flat bevelled edge orodispersible 

tablets with ‘OL’ debossed on one side and ‘D’ debossed on other side. 

 

Olazax Disperzi 15 mg is supplied as a yellow coloured circular flat bevelled edge orodispersible 

tablets with ‘OL’ debossed on one side and ‘E’ debossed on other side. 

 

Olazax Disperzi 20 mg is supplied as a yellow coloured circular flat bevelled edge orodispersible 

tablets with ‘OL’ debossed on one side and ‘F’ debossed on other side. 

 

Olazax Disperzi 5mg, 10 mg, 15 mg, 20 mg are available in aluminium foil blisters of 28, 56 

orodispersible tablets  

 

Marketing Authorisation Holder and Manufacturer 

Glenmark Pharmaceuticals s.r.o. 

Hvězdova 1716/2b, 140 78 Praha 4 

Czech Republic  

 

Manufacturer 

Glenmark Pharmaceuticals s.r.o. 

Hvězdova 1716/2b, 140 78 Praha 4 

Czech Republic  

 

This leaflet was last revised in {MM/YYYY}. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


89 

 

Detailed information on this medicine is available on the European Medicines Agency (EMA) 

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

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


90 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Annex IV 

 

Scientific conclusions and grounds for the variation to the terms of the marketing 

authorisation(s) 

 



91 

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 MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
	Scientific conclusions and grounds for the variation to the terms of the marketingauthorisation(s)