Olanzapine Glenmark

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ANNEX I 

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Olanzapine Glenmark 2.5 mg tablets 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 2.5 mg olanzapine. 

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

For the full list of excipients, see section 6.1. 

3. PHARMACEUTICAL FORM

Tablet 
Yellow coloured circular flat bevelled edge tablets with ‘A’ 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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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 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 % 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. 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.



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Parkinson's disease 
The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with 
Parkinson's disease is not recommended.  

In clinical trials, worsening of Parkinsonian symptomatology and hallucinations were reported very 
commonly and more frequently than with placebo (see section 4.8), and olanzapine was not more 
effective than placebo in the treatment of psychotic symptoms.  

In these trials, patients were initially required to be stable on the lowest effective dose of anti-
Parkinsonian medicinal products (dopamine agonist) and to remain on the same anti-Parkinsonian 
medicinal products and dosages throughout the study. Olanzapine was started at 2.5 mg/day and 
titrated to a maximum of 15 mg/day based on investigator judgement. 

Neuroleptic Malignant Syndrome (NMS) 
NMS is a potentially life-threatening condition associated with antipsychotic medicinal products. Rare 
cases reported as NMS have also been received in association with olanzapine.  

Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence 
of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac 
dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria 
(rhabdomyolysis), and acute renal failure.  

If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever 
without additional clinical manifestations of NMS, all antipsychotic medicines, including olanzapine 
must be discontinued. 

Hyperglycaemia and diabetes 
Hyperglycaemia and/or development or exacerbation of diabetes occasionally associated with 
ketoacidosis or coma has been reported uncommonly, including some fatal cases (see section 4.8). In 
some cases, a prior increase in body weight has been reported which may be a predisposing factor. 
Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines, e.g. 
measuring of blood glucose at baseline, 12 weeks after starting olanzapine treatment and annually 
thereafter.  Patients treated with any antipsychotic medicines, including 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. 

Hepatic function 
Transient, asymptomatic elevations of hepatic aminotransferases, alanine transferase (ALT), aspartate 
transferase (AST) have been seen commonly, especially in early treatment.  



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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 (see sections 4.8 and 5.1). 

Phenylalanine 
Olanzapine Glenmark 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 non-
smokers and 77 % in male smokers. The mean increase in olanzapine AUC was 52 % and 108 % 
respectively. A lower starting dose of olanzapine should be considered in patients who are using 
fluvoxamine or any other CYP1A2 inhibitors, such as ciprofloxacin. A decrease in the dose of 
olanzapine should be considered if treatment with an inhibitor of CYP1A2 is initiated. 

Decreased bioavailability 
Activated charcoal reduces the bioavailability of oral olanzapine by 50 to 60 % and should be taken at 
least 2 hours before or after olanzapine.

Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have 
not been found to significantly affect the pharmacokinetics of olanzapine. 

Potential for olanzapine to affect other medicinal products 
Olanzapine may antagonise the effects of direct and indirect dopamine agonists. 

Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e.g. 1A2, 2D6, 2C9, 2C19, 3A4). 
Thus no particular interaction is expected as verified through in vivo studies where no inhibition of 
metabolism of the following active substances was found: tricyclic antidepressant (representing mostly 
CYP2D6 pathway), warfarin (CYP2C9), theophylline (CYP1A2) or diazepam (CYP3A4 and 2C19). 



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Olanzapine showed no interaction when co-administered with lithium or biperiden. 

Therapeutic monitoring of valproate plasma levels did not indicate that valproate dosage adjustment is 
required after the introduction of concomitant olanzapine. 

General CNS activity 
Caution should be exercised in patients who consume alcohol or receive medicinal products that can 
cause central nervous system depression. 

The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with 
Parkinson's disease and dementia is not recommended (see section 4.4). 

QTc interval 
Caution should be used if olanzapine is being administered concomitantly with medicinal products 
known to increase QTc interval (see section 4.4). 

4.6 Fertility, pregnancy and lactation

Pregnancy 
There are no adequate and well-controlled studies in pregnant women. Patients should be advised to 
notify their physician if they become pregnant or intend to become pregnant during treatment with 
olanzapine. Nevertheless, because human experience is limited, olanzapine should be used in 
pregnancy only if the potential benefit justifies the potential risk to the foetus. 

New born infants exposed to antipsychotics (including olanzapine) during the third trimester of 
pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that 
may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, 
hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns 
should be monitored carefully. 

Breast feeding 
In a study in breast- feeding, healthy women, olanzapine was excreted in breast milk. Mean infant 
exposure (mg/kg) at steady state was estimated to be 1.8 % of the maternal olanzapine dose (mg/kg). 
Patients should be advised not to breast- feed an infant if they are taking olanzapine.

Fertility 
Effects on fertility are unknown (see section 5.3 for preclinical information). 

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. Because 
olanzapine may cause somnolence and dizziness, patients should be cautioned about operating 
machinery, including motor vehicles. 

4.8 Undesirable effects

Summary of the safety profile 

Adults 
The most frequently (seen in ≥ 1 % of patients) reported adverse reactions associated with the use of 
olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, 
cholesterol, glucose and triglyceride levels (see section 4.4), glucosuria, increased appetite, dizziness, 
akathisia, parkinsonism, leukopenia, neutropenia (see section 4.4), dyskinesia, orthostatic hypotension, 
anticholinergic effects, transient asymptomatic elevations of hepatic aminotransferases (see section 
4.4), rash, asthenia, fatigue, pyrexia, arthralgia, increased alkaline phosphatase, high gamma 
glutamyltransferase, high uric acid, high creatine phosphokinase and oedema. 



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Tabulated list of adverse reactions 
The following table lists the adverse reactions and laboratory investigations observed from 
spontaneous reporting and in clinical trials. Within each frequency grouping, adverse reactions are 
presented in order of decreasing seriousness. The frequency terms listed are defined as follows: Very 
common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 < 1/100), rare (≥ 1/10,000 to< 
1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the data available). 

Very 
common 

Common Uncommon  Rare Not known 

Blood and the lymphatic system disorders  
 Eosinophilia 

Leukopenia10
Neutropenia10

 Thrombocytopenia11

Immune system disorders  
  Hypersensitivity11
Metabolism and nutrition disorders  
Weight gain1 Elevated 

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

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

Hypothermia12

Nervous system disorders  
Somnolence Dizziness 

Akathisia6
Parkinsonism6 
Dyskinesia6

Seizures where in 
most cases a history 
of seizures or risk 
factors for seizures 
were reported11 

Dystonia (including 
oculogyration) 11
Tardive dyskinesia11

Amnesia 9 

Dysarthria 
Stuttering11
Restless Legs 
Syndrome11

Neuroleptic malignant 
syndrome (see section 
4.4)12

Discontinuation 
symptoms7, 12

Cardiac disorders  
  Bradycardia 

QTc prolongation (see 
section 4.4) 

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

Vascular disorders  
Orthostatic 
hypotension1
0

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



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

anticholinergic 
effects including 
constipation and 
dry mouth 

Abdominal 
distension9 
Salivary 
hypersecretion11

Pancreatitis11

Hepatobiliary disorders  
 Transient, 

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

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

Skin and subcutaneous tissue disorders  
 Rash Photosensitivity 

reaction 
Alopecia 

Drug 
Reaction 
with 
Eosinophili
a and 
Systemic 
Symptoms 
(DRESS)

Musculoskeletal and connective tissue disorders  
Arthralgia9 Rhabdomyolysis11

Renal and urinary disorders  
  Urinary incontinence, 

urinary retention 
Urinary hesitation11

Pregnancy, puerperium and perinatal conditions
    Drug 

withdrawal 
syndrome 
neonatal (see 
section 4.6) 

Reproductive system and breast disorders  
 Erectile dysfunction 

in males 
Decreased libido in 
males and females 

Amenorrhea 
Breast enlargement 
Galactorrhea in 
females 
Gynaecomastia/breast 
enlargement in males 

Priapism12

General disorders and administration site conditions  
 Asthenia 

Fatigue 
Oedema 
Pyrexia10

Investigations  
Elevated 
plasma 
prolactin 

Increased alkaline 
phosphatase10
High creatine 

Increased total 
bilirubin 



10 

levels8 phosphokinase11
High Gamma 
Glutamyltransferase
10 

High uric acid 10

1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) 
categories. Following short term treatment (median duration 47 days), weight gain ≥ 7 % of baseline 
body weight was very common (22.2%), ≥ 15% was common (4.2%) and ≥25% was uncommon 
(0.8%). Patients gaining ≥7%, ≥15% and ≥25% of their baseline body weight with long-term exposure 
(at least 48 weeks) were very common (64.4 %, 31.7 % and 12.3 % respectively). 

2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were 
greater in patients without evidence of lipid dysregulation at baseline. 

3 Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high (≥ 6.2 
mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17- < 6.2 mmol/l) 
to high (≥ 6.2 mmol/l) were very common. 

4 Observed for fasting normal levels at baseline (< 5.56 mmol/l) which increased to high (≥ 7 mmol/l). 
Changes in fasting glucose from borderline at baseline (≥ 5.56 - < 7 mmol/l) to high (≥ 7 mmol/l) were 
very common. 

5 Observed for fasting normal levels at baseline (< 1.69 mmol/l) which increased to high (≥ 2.26 
mmol/l). Changes in fasting triglycerides from borderline at baseline (≥ 1.69 mmol/l - < 2.26 mmol/l) 
to high (≥ 2.26 mmol/l) were very common. 

6 In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was 
numerically higher, but not statistically significantly different from placebo. Olanzapine-treated 
patients had a lower incidence of Parkinsonism, akathisia and dystonia compared with titrated doses of 
haloperidol. In the absence of detailed information on the pre-existing history of individual acute and 
tardive extrapyramidal movement disorders, it cannot be concluded at present that olanzapine 
produces less tardive dyskinesia and/or other tardive extrapyramidal syndromes. 

7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been 
reported when olanzapine is stopped abruptly. 

8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of 
normal range in approximately 30% of olanzapine treated patients with normal baseline prolactin 
value. In the majority of these patients the elevations were generally mild, and remained below two 
times the upper limit of normal range.  

9 Adverse event identified from clinical trials in the Olanzapine Integrated Database. 

10 As assessed by measured values from clinical trials in the Olanzapine Integrated Database. 

11 Adverse event identified from spontaneous post-marketing reporting with frequency determined 
utilising the Olanzapine Integrated Database. 

12 Adverse event identified from spontaneous post-marketing reporting with frequency estimated at the 
upper limit of the 95% confidence interval utilising the Olanzapine Integrated Database. 



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Long-term exposure (at least 48 weeks) 
The proportion of patients who had adverse, clinically significant changes in weight gain, glucose, 
total/LDL/HDL cholesterol or triglycerides increased over time. In adult patients who completed 9-12 
months of therapy, the rate of increase in mean blood glucose slowed after approximately 6 months. 

Additional information on special populations 
In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher 
incidence of death and cerebrovascular adverse reactions compared to placebo (see section 4.4). Very 
common adverse reactions associated with the use of olanzapine in this patient group were abnormal 
gait and falls. Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and 
urinary incontinence were observed commonly. 

In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with 
Parkinson’s disease, worsening of Parkinsonian symptomatology and hallucinations were reported 
very commonly and more frequently than with placebo. 

In one clinical trial in patients with bipolar mania, valproate combination therapy with olanzapine 
resulted in an incidence of neutropenia of 4.1 %; a potential contributing factor could be high plasma 
valproate levels. Olanzapine administered with lithium or valproate resulted in increased levels (≥ 10 
%) of tremor, dry mouth, increased appetite, and weight gain. Speech disorder was also reported 
commonly. During treatment with olanzapine in combination with lithium or divalproex, an increase 
of ≥ 7 % from baseline body weight occurred in 17.4 % of patients during acute treatment (up to 6 
weeks). Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with 
bipolar disorder was associated with an increase of ≥ 7 % from baseline body weight in 39.9 % of 
patients. 

Paediatric population 
Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years. 
Although no clinical studies designed to compare adolescents to adults have been conducted, data 
from the adolescent trials were compared to those of the adult trials. 

The following table summarises the adverse reactions reported with a greater frequency in adolescent 
patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-term 
clinical trials in adolescent patients. Clinically significant weight gain (≥ 7 %) appears to occur more 
frequently in the adolescent population compared to adults with comparable exposures. The magnitude 
of weight gain and the proportion of adolescent patients who had clinically significant weight gain 
were greater with long-term exposure (at least 24 weeks) than with short-term exposure. 

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
The frequency terms listed are defined as follows: Very common (≥ 1/10), common (≥ 1/100 to < 
1/10).

Metabolism and nutrition disorders
Very common: Weight 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 ≥ 



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25 % was common (2.5 %). With long-term exposure (at least 24 weeks), 89.4 % gained ≥ 7 %, 55.3 
% gained ≥ 15 % and 29.1 % gained ≥ 25% of their baseline body weight. 

14 Observed for fasting normal levels at baseline (< 1.016 mmol/l) which increased to high (≥ 1.467 
mmol/l) and changes in fasting triglycerides from borderline at baseline (≥ 1.016 mmol/l - < 1.467 
mmol/l) to high (≥ 1.467 mmol/l). 

15 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high (≥ 5.17 
mmol/l) were observed commonly. Changes in total fasting cholesterol levels from borderline at 
baseline (≥ 4.39 - < 5.17 mmol/l) to high (≥ 5.17 mmol/l) were very common. 

16 Elevated plasma prolactin levels were reported in 47.4 % of adolescent patients. 

Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

Signs and symptoms 
Very common symptoms in overdose (> 10 % incidence) include tachycardia, agitation/ 
aggressiveness, dysarthria, various extrapyramidal symptoms, and reduced level of consciousness 
ranging from sedation to coma. 

Other medically significant sequelae of overdose include delirium, convulsion, coma, possible 
neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, 
cardiac arrhythmias (< 2 % of overdose cases) and cardiopulmonary arrest. Fatal outcomes have been 
reported for acute overdoses as low as 450 mg but survival has also been reported following acute 
overdose of approximately 2 g of oral olanzapine. 

Management 
There is no specific antidote for olanzapine. Induction of emesis is not recommended. Standard 
procedures for management of overdose may be indicated (i.e. gastric lavage, administration of 
activated charcoal). The concomitant administration of activated charcoal was shown to reduce the 
oral bioavailability of olanzapine by 50 to 60 %. 

Symptomatic treatment and monitoring of vital organ function should be instituted according to 
clinical presentation, including treatment of hypotension and circulatory collapse and support of 
respiratory function.  

Do not use epinephrine, dopamine, or other sympathomimetic agents with beta-agonist activity since 
beta stimulation may worsen hypotension.  

Cardiovascular monitoring is necessary to detect possible arrhythmias. Close medical supervision and 
monitoring should continue until the patient recovers.

5. PHARMACOLOGICAL PROPERTIES

5.1  Pharmacodynamic properties

Pharmacotherapeutic group: psycholeptics, diazepines, oxazepines, thiazepines and oxepines, ATC 
code N05A H03. 



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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 behavioural studies with olanzapine indicated 5HT, 
dopamine, and cholinergic antagonism, consistent with the receptor-binding profile. Olanzapine 
demonstrated a greater in vitro affinity for serotonin 5HT2 than dopamine D2 receptors and greater 5 
HT2 than D2 activity in vivo, models. Electrophysiological studies demonstrated that olanzapine 
selectively reduced the firing of mesolimbic (A10) dopaminergic neurons, while having little effect on 
the striatal (A9) pathways involved in motor function. Olanzapine reduced a conditioned avoidance 
response, a test indicative of antipsychotic activity, at doses below those producing catalepsy, an effect 
indicative of motor side-effects. Unlike some other antipsychotic agents, olanzapine increases 
responding in an “anxiolytic” test. 

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



14 

Paediatric population 
Controlled efficacy data in adolescents (ages 13 to 17 years) are limited to short term studies in 
schizophrenia (6 weeks) and mania associated with bipolar I disorder (3 weeks), involving less than 
200 adolescents. Olanzapine was used as a flexible dose starting with 2.5 and ranging up to 
20 mg/day. During treatment with olanzapine, adolescents gained significantly more weight compared 
with adults. The magnitude of changes in fasting total cholesterol, LDL cholesterol, triglycerides, and 
prolactin (see sections 4.4 and 4.8) were greater in adolescents than in adults. There are no controlled 
data on maintenance of effect or long term safety (see sections 4.4 and 4.8). Information on long term 
safety is primarily limited to open-label, uncontrolled data. 

5.2 Pharmacokinetic properties 

Absorption 
Olanzapine is well absorbed after oral administration, reaching peak plasma concentrations within 5 to 
8 hours. The absorption is not affected by food. Absolute oral bioavailability relative to intravenous 
administration has not been determined. 

Distribution 
The plasma protein binding of Olanzapine was about 93 % over the concentration range of about 7 to 
about 1000 ng/ml. Olanzapine is bound predominantly to albumin and α1-acid-glycoprotein. 

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 %). 



15 

Smoking 
In non-smoking versus smoking subjects (males and females) the mean elimination half-life was 
prolonged (38.6 versus 30.4 hr) and the clearance was reduced (18.6 versus 27.7 l/hr). 

The plasma clearance of olanzapine is lower in elderly versus young subjects, in females versus males, 
and in non-smokers versus smokers. However, the magnitude of the impact of age, gender, or smoking 
on olanzapine clearance and half-life is small in comparison to the overall variability between 
individuals. 

In a study of Caucasians, Japanese, and Chinese subjects, there were no differences in the 
pharmacokinetic parameters among the three populations. 

Paediatric population 
Adolescents (ages 13 to 17 years):  
The pharmacokinetics of olanzapine are similar between adolescents and adults. In clinical studies, the 
average olanzapine exposure was approximately 27 % higher in adolescents. Demographic differences 
between the adolescents and adults include a lower average body weight and fewer adolescents were 
smokers. Such factors possibly contribute to the higher average exposure observed in adolescents. 

5.3 Preclinical safety data

Acute (single-dose) toxicity 
Signs of oral toxicity in rodents were characteristic of potent neuroleptic compounds: hypoactivity, 
coma, tremors, clonic convulsions, salivation, and depressed weight gain. The median lethal doses 
were approximately 210 mg/kg (mice) and 175 mg/kg (rats).  

Dogs tolerated single oral doses up to 100 mg/kg without mortality. Clinical signs included sedation, 
ataxia, tremors, increased heart rate, labored respiration, miosis, and anorexia. In monkeys, single oral 
doses up to 100 mg/kg resulted in prostration and, at higher doses, semi-consciousness. 

Repeated-dose toxicity 
In studies up to 3 months duration in mice and up to 1 year in rats and dogs, the predominant effects 
were CNS depression, anticholinergic effects, and peripheral haematological disorders. Tolerance 
developed to the CNS depression. Growth parameters were decreased at high doses. Reversible effects 
consistent with elevated prolactin in rats included decreased weights of ovaries and uterus and 
morphologic changes in vaginal epithelium and in mammary gland. 

Haematologic toxicity: 
Effects on haematology parameters were found in each species, including dose-related reductions in 
circulating leukocytes in mice and non-specific reductions of circulating leukocytes in rats; however, 
no evidence of bone marrow cytotoxicity was found.  

Reversible neutropenia, thrombocytopenia, or anaemia developed in a few dogs treated with 8 or 
10 mg/kg/day (total olanzapine exposure [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. 



16 

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, 70, 98 tablets per carton. 

Not all pack sizes may be marketed 

6.6 Special precautions for disposal 

No special requirements 

7. MARKETING AUTHORISATION HOLDER

Glenmark Arzneimittel GmbH 
Industriestr. 31, 82194 
Gröbenzell, Germany 

8. MARKETING AUTHORISATION NUMBER(S)  

EU/1/09/587/001 
EU/1/09/587/002 
EU/1/09/587/003 
EU/1/09/587/020 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 03 December 2009 
Date of latest renewal: 19 August 2014 



17 

10. DATE OF REVISION OF THE TEXT 

{MM/YYYY} 

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



18 

1. NAME OF THE MEDICINAL PRODUCT

Olanzapine Glenmark 5 mg tablets 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 5 mg olanzapine. 

Excipient with known effect: Each tablet contains 0.23 mg of aspartame 
For the full list of excipients, see section 6.1. 

3. PHARMACEUTICAL FORM

Tablet 

Yellow coloured circular flat bevelled edge 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. 

Special populations 



19 

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 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 % 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. 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.  



20 

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. 

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.  



21 

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. 

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. 



22 

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 
Olanzapine Glenmark 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 non 
smokers and 77 % in male smokers. The mean increase in olanzapine AUC was 52 % and 108 % 
respectively.  

A lower starting dose of olanzapine should be considered in patients who are using fluvoxamine or 
any other CYP1A2 inhibitors, such as ciprofloxacin.  

A decrease in the dose of olanzapine should be considered if treatment with an inhibitor of CYP1A2 is 
initiated. 

Decreased bioavailability 
Activated charcoal reduces the bioavailability of oral olanzapine by 50 to 60 % and should be taken at 
least 2 hours before or after olanzapine.

Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have 
not been found to significantly affect the pharmacokinetics of olanzapine. 

Potential for olanzapine to affect other medicinal products 
Olanzapine may antagonise the effects of direct and indirect dopamine agonists. 

Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e.g. 1A2, 2D6, 2C9, 2C19, 3A4). 
Thus no particular interaction is expected as verified through in vivo studies where no inhibition of 
metabolism of the following active substances was found: tricyclic antidepressant (representing mostly 
CYP2D6 pathway), warfarin (CYP2C9), theophylline (CYP1A2) or diazepam (CYP3A4 and 2C19). 



23 

Olanzapine showed no interaction when co-administered with lithium or biperiden. 

Therapeutic monitoring of valproate plasma levels did not indicate that valproate dosage adjustment is 
required after the introduction of concomitant olanzapine. 

General CNS activity 
Caution should be exercised in patients who consume alcohol or receive medicinal products that can 
cause central nervous system depression. 

The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with 
Parkinson's disease and dementia is not recommended (see section 4.4). 

QTc interval 
Caution should be used if olanzapine is being administered concomitantly with medicinal products 
known to increase QTc interval (see section 4.4). 

4.6 Fertility, pregnancy and lactation

Pregnancy 
There are no adequate and well-controlled studies in pregnant women. Patients should be advised to 
notify their physician if they become pregnant or intend to become pregnant during treatment with 
olanzapine. Nevertheless, because human experience is limited, olanzapine should be used in 
pregnancy only if the potential benefit justifies the potential risk to the foetus. 

New born infants exposed to antipsychotics (including olanzapine) during the third trimester of 
pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that 
may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, 
hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns 
should be monitored carefully. 

Breast feeding  
In a study in breast- feeding, healthy women, olanzapine was excreted in breast milk. Mean infant 
exposure (mg/kg) at steady state was estimated to be 1.8 % of the maternal olanzapine dose (mg/kg). 
Patients should be advised not to breast- feed an infant if they are taking olanzapine. 

Fertility 
Effects on fertility are unknown (see section 5.3 for preclinical information). 

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. Because 
olanzapine may cause somnolence and dizziness, patients should be cautioned about operating 
machinery, including motor vehicles. 

4.8 Undesirable effects 

Summary of the safety profile

Adults 
The most frequently (seen in ≥ 1 % of patients) reported adverse reactions associated with the use of 
olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, 
cholesterol, glucose and triglyceride levels (see section 4.4), glucosuria, increased appetite, dizziness, 
akathisia, parkinsonism, leukopenia, neutropenia (see section 4.4), dyskinesia, orthostatic hypotension, 
anticholinergic effects, transient asymptomatic elevations of hepatic aminotransferases (see section 
4.4), rash, asthenia, fatigue, pyrexia, arthralgia, increased alkaline phosphatase, high gamma 
glutamyltransferase, high uric acid, high creatine phosphokinase and oedema. 



24 

Tabulated list of adverse reactions 
The following table lists the adverse reactions and laboratory investigations observed from 
spontaneous reporting and in clinical trials. Within each frequency grouping, adverse reactions are 
presented in order of decreasing seriousness. The frequency terms listed are defined as follows: Very 
common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to 
< 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the data available). 

Very common Common Uncommon  Rare Not known 
Blood and the lymphatic system disorders  
 Eosinophilia 

Leukopenia10
Neutropenia10

 Thrombocytopeni
a11

Immune system disorders  
  Hypersensitivity11
Metabolism and nutrition disorders 
Weight gain1 Elevated 

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

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

Hypothermia12

Nervous system disorders  
Somnolence Dizziness 

Akathisia6
Parkinsonism6 
Dyskinesia6

Seizures where in 
most cases a 
history of seizures 
or risk factors for 
seizures were 
reported11 

Dystonia 
(including 
oculogyration)11
Tardive 
dyskinesia11

Amnesia 9 

Dysarthria 
Stuttering11
Restless legs 
syndrome11

Neuroleptic 
malignant 
syndrome (see 
section 
4.4)12Discontinuat
ion symptoms7, 12

Cardiac disorders  
  Bradycardia 

QTc prolongation 
(see section 4.4) 

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

Vascular disorders  
Orthostatic 
hypotension10

 Thromboembolis
m (including 
pulmonary 



25 

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 

dysfunction in 
males 
Decreased libido 
in males and 
females 

Amenorrhea 
Breast 
enlargement 
Galactorrhea in 
females 
Gynaecomastia/br
east enlargement 
in males 

Priapism12

General disorders and administration site conditions  
 Asthenia 

Fatigue 
Oedema 
Pyrexia10

Investigations  



26 

Elevated plasma 
prolactin levels8

Increased alkaline 
phosphatase10
High creatine 
phosphokinase11
High Gamma 
Glutamyltransferase 
10 

High uric acid 10

Increased total 
bilirubin 

1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) 
categories. Following short term treatment (median duration 47 days), weight gain ≥ 7 % of baseline 
body weight was very common (22.2%), ≥ 15% was common (4.2%) and ≥25% was uncommon 
(0.8%). Patients gaining ≥7%, ≥15% and ≥25% of their baseline body weight with long-term exposure 
(at least 48 weeks) were very common (64.4 %, 31.7 % and 12.3 % respectively). 

2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were 
greater in patients without evidence of lipid dysregulation at baseline. 

3 Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high (≥ 6.2 
mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17- < 6.2 mmol/l) 
to high (≥ 6.2 mmol/l) were very common. 

4 Observed for fasting normal levels at baseline (< 5.56 mmol/l) which increased to high (≥ 7 mmol/l). 
Changes in fasting glucose from borderline at baseline (≥ 5.56 - < 7 mmol/l) to high (≥ 7 mmol/l) were 
very common. 

5 Observed for fasting normal levels at baseline (< 1.69 mmol/l) which increased to high (≥ 2.26 
mmol/l). Changes in fasting triglycerides from borderline at baseline (≥ 1.69 mmol/l - < 2.26 mmol/l) 
to high (≥ 2.26 mmol/l) were very common. 

6 In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was 
numerically higher, but not statistically significantly different from placebo. Olanzapine-treated 
patients had a lower incidence of Parkinsonism, akathisia and dystonia compared with titrated doses of 
haloperidol. In the absence of detailed information on the pre-existing history of individual acute and 
tardive extrapyramidal movement disorders, it cannot be concluded at present that olanzapine 
produces less tardive dyskinesia and/or other tardive extrapyramidal syndromes. 

7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been 
reported when olanzapine is stopped abruptly. 

8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of 
normal range in approximately 30% of olanzapine treated patients with normal baseline prolactin 
value. In the majority of these patients the elevations were generally mild, and remained below two 
times the upper limit of normal range.  

9 Adverse event identified from clinical trials in the Olanzapine Integrated Database. 

10 As assessed by measured values from clinical trials in the Olanzapine Integrated Database. 

11 Adverse event identified from spontaneous post-marketing reporting with frequency determined 
utilising the Olanzapine Integrated Database. 

12 Adverse event identified from spontaneous post-marketing reporting with frequency estimated at the 
upper limit of the 95% confidence interval utilising the Olanzapine Integrated Database. 



27 

Long-term exposure (at least 48 weeks) 
The proportion of patients who had adverse, clinically significant changes in weight gain, glucose, 
total/LDL/HDL cholesterol or triglycerides increased over time. In adult patients who completed 9-12 
months of therapy, the rate of increase in mean blood glucose slowed after approximately 6 months. 

Additional information on special populations 
In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher 
incidence of death and cerebrovascular adverse reactions compared to placebo (see section 4.4). Very 
common adverse reactions associated with the use of olanzapine in this patient group were abnormal 
gait and falls. Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and 
urinary incontinence were observed commonly. 

In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with 
Parkinson’s disease, worsening of Parkinsonian symptomatology and hallucinations were reported 
very commonly and more frequently than with placebo. 

In one clinical trial in patients with bipolar mania, valproate combination therapy with olanzapine 
resulted in an incidence of neutropenia of 4.1 %; a potential contributing factor could be high plasma 
valproate levels. Olanzapine administered with lithium or valproate resulted in increased levels (≥ 10 
%) of tremor, dry mouth, increased appetite, and weight gain. Speech disorder was also reported 
commonly. During treatment with olanzapine in combination with lithium or divalproex, an increase 
of ≥ 7 % from baseline body weight occurred in 17.4 % of patients during acute treatment (up to 6 
weeks). Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with 
bipolar disorder was associated with an increase of ≥ 7 % from baseline body weight in 39.9 % of 
patients. 

Paediatric population 
Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years. 
Although no clinical studies designed to compare adolescents to adults have been conducted, data 
from the adolescent trials were compared to those of the adult trials. 

The following table summarises the adverse reactions reported with a greater frequency in adolescent 
patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-term 
clinical trials in adolescent patients. Clinically significant weight gain (≥ 7 %) appears to occur more 
frequently in the adolescent population compared to adults with comparable exposures. The magnitude 
of weight gain and the proportion of adolescent patients who had clinically significant weight gain 
were greater with long-term exposure (at least 24 weeks) than with short-term exposure. 

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
The frequency terms listed are defined as follows: Very common (≥ 1/10), common (≥ 1/100 to < 
1/10). 

Metabolism and nutrition disorders
Very common: Weight 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 ≥ 



28 

25 % was common (2.5 %). With long-term exposure (at least 24 weeks), 89.4 % gained ≥ 7 %, 55.3 
% gained ≥ 15 % and 29.1 % gained ≥ 25% of their baseline body weight. 

14 Observed for fasting normal levels at baseline (< 1.016 mmol/l) which increased to high (≥ 1.467 
mmol/l) and changes in fasting triglycerides from borderline at baseline (≥ 1.016 mmol/l - 
< 1.467 mmol/l) to high (≥ 1.467 mmol/l). 

15 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high (≥ 5.17 
mmol/l) were observed commonly. Changes in total fasting cholesterol levels from borderline at 
baseline (≥ 4.39 - < 5.17 mmol/l) to high (≥ 5.17 mmol/l) were very common. 

16 Elevated plasma prolactin levels were reported in 47.4 % of adolescent patients. 

Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

Signs and symptoms 
Very common symptoms in overdose (> 10 % incidence) include tachycardia, agitation/ 
aggressiveness, dysarthria, various extrapyramidal symptoms, and reduced level of consciousness 
ranging from sedation to coma. 

Other medically significant sequelae of overdose include delirium, convulsion, coma, possible 
neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, 
cardiac arrhythmias (< 2 % of overdose cases) and cardiopulmonary arrest. Fatal outcomes have been 
reported for acute overdoses as low as 450 mg but survival has also been reported following acute 
overdose of approximately 2 g of oral olanzapine. 

Management 
There is no specific antidote for olanzapine. Induction of emesis is not recommended. Standard 
procedures for management of overdose may be indicated (i.e. gastric lavage, administration of 
activated charcoal). The concomitant administration of activated charcoal was shown to reduce the 
oral bioavailability of olanzapine by 50 to 60 %. 

Symptomatic treatment and monitoring of vital organ function should be instituted according to 
clinical presentation, including treatment of hypotension and circulatory collapse and support of 
respiratory function.  

Do not use epinephrine, dopamine, or other sympathomimetic agents with beta-agonist activity since 
beta stimulation may worsen hypotension. Cardiovascular monitoring is necessary to detect possible 
arrhythmias. Close medical supervision and monitoring should continue until the patient recovers.

5. PHARMACOLOGICAL PROPERTIES

5.1  Pharmacodynamic properties

Pharmacotherapeutic group: psycholeptics, diazepines, oxazepines, thiazepines and oxepines, ATC 
code N05A H03.3 

Pharmacodynamic effects 
Olanzapine is an antipsychotic, antimanic and mood stabilising agent that demonstrates a broad 
pharmacologic profile across a number of receptor systems. 



29 

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 behavioural studies with olanzapine indicated 5HT, 
dopamine, and cholinergic antagonism, consistent with the receptor-binding profile. Olanzapine 
demonstrated a greater in vitro affinity for serotonin 5HT2 than dopamine D2 receptors and greater 5 
HT2 than D2 activity in vivo, models. Electrophysiological studies demonstrated that olanzapine 
selectively reduced the firing of mesolimbic (A10) dopaminergic neurons, while having little effect on 
the striatal (A9) pathways involved in motor function. Olanzapine reduced a conditioned avoidance 
response, a test indicative of antipsychotic activity, at doses below those producing catalepsy, an effect 
indicative of motor side-effects. Unlike some other antipsychotic agents, olanzapine increases 
responding in an “anxiolytic” test. 

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



30 

20 mg/day. During treatment with olanzapine, adolescents gained significantly more weight compared 
with adults. The magnitude of changes in fasting total cholesterol, LDL cholesterol, triglycerides, and 
prolactin (see sections 4.4 and 4.8) were greater in adolescents than in adults. There are no controlled 
data on maintenance of effect or long term safety (see sections 4.4 and 4.8). Information on long term 
safety is primarily limited to open-label, uncontrolled data. 

5.2 Pharmacokinetic properties

Absorption 
Olanzapine is well absorbed after oral administration, reaching peak plasma concentrations within 5 to 
8 hours. The absorption is not affected by food. Absolute oral bioavailability relative to intravenous 
administration has not been determined. 

Distribution 
The plasma protein binding of olanzapine was about 93 % over the concentration range of about 7 to 
about 1000 ng/ml. Olanzapine is bound predominantly to albumin and α1-acid-glycoprotein. 

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). 



31 

The plasma clearance of olanzapine is lower in elderly versus young subjects, in females versus males, 
and in non-smokers versus smokers. However, the magnitude of the impact of age, gender, or smoking 
on olanzapine clearance and half-life is small in comparison to the overall variability between 
individuals. 

In a study of Caucasians, Japanese, and Chinese subjects, there were no differences in the 
pharmacokinetic parameters among the three populations. 

Paediatric population 
Adolescents (ages 13 to 17 years):  
The pharmacokinetics of olanzapine are similar between adolescents and adults. In clinical studies, the 
average olanzapine exposure was approximately 27 % higher in adolescents. Demographic differences 
between the adolescents and adults include a lower average body weight and fewer adolescents were 
smokers. Such factors possibly contribute to the higher average exposure observed in adolescents. 

5.3 Preclinical safety data

Acute (single-dose) toxicity 
Signs of oral toxicity in rodents were characteristic of potent neuroleptic compounds: hypoactivity, 
coma, tremors, clonic convulsions, salivation, and depressed weight gain. The median lethal doses 
were approximately 210 mg/kg (mice) and 175 mg/kg (rats).  

Dogs tolerated single oral doses up to 100 mg/kg without mortality. Clinical signs included sedation, 
ataxia, tremors, increased heart rate, labored respiration, miosis, and anorexia. In monkeys, single oral 
doses up to 100 mg/kg resulted in prostration and, at higher doses, semi-consciousness. 

Repeated-dose toxicity 
In studies up to 3 months duration in mice and up to 1 year in rats and dogs, the predominant effects 
were CNS depression, anticholinergic effects, and peripheral haematological disorders. Tolerance 
developed to the CNS depression. Growth parameters were decreased at high doses. Reversible effects 
consistent with elevated prolactin in rats included decreased weights of ovaries and uterus and 
morphologic changes in vaginal epithelium and in mammary gland. 

Haematologic toxicity 
Effects on haematology parameters were found in each species, including dose-related reductions in 
circulating leukocytes in mice and non-specific reductions of circulating leukocytes in rats; however, 
no evidence of bone marrow cytotoxicity was found.  

Reversible neutropenia, thrombocytopenia, or anaemia developed in a few dogs treated with 8 or 
10 mg/kg/day (total olanzapine exposure [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.



32 

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, 70, 98 tablets per carton. 

Not all pack sizes may be marketed 

6.6 Special precautions for disposal 

No special requirements 

7. MARKETING AUTHORISATION HOLDER

Glenmark Arzneimittel GmbH 
Industriestr. 31, D – 82194 
Gröbenzell, Germany 

8. MARKETING AUTHORISATION NUMBER(S)  

EU/1/09/587/004 
EU/1/09/587/005 
EU/1/09/587/006 
EU/1/09/587/021 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 03 December 2009 
Date of latest renewal: 19 August 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 http://www.ema.europa.eu



33 

1. NAME OF THE MEDICINAL PRODUCT

Olanzapine Glenmark 7.5 mg tablets 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 7.5 mg olanzapine. 

Excipient with known effect: Each tablet contains 0.35 mg of aspartame 
For the full list of excipients, see section 6.1. 

3. PHARMACEUTICAL FORM

Tablet 
Yellow coloured circular flat bevelled edge tablets with ‘C’ 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. 



34 

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 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 % 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. 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.



35 

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. 

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. 



36 

Neutropenia 
Caution should be exercised in patients with low leukocyte and/or neutrophil counts for any reason, in 
patients receiving medicines known to cause neutropenia, in patients with a history of drug-induced 
bone marrow depression/toxicity, in patients with bone marrow depression caused by concomitant 
illness, radiation therapy or chemotherapy and in patients with hypereosinophilic conditions or with 
myeloproliferative disease. Neutropenia has been reported commonly when olanzapine and valproate 
are used concomitantly (see section 4.8). 

Discontinuation of treatment 
Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting have been reported 
rarely ≥0.01% and < 0.1%) when olanzapine is stopped abruptly. 

QT interval 
In clinical trials, clinically meaningful QTc prolongations (Fridericia QT correction [QTcF] ≥ 500 
milliseconds [msec] at any time post baseline in patients with baseline QTcF < 500 msec) were 
uncommon (0.1 % to 1 %) in patients treated with olanzapine, with no significant differences in 
associated cardiac events compared to placebo. However, caution should be exercised when 
olanzapine is prescribed with medicines known to increase QTc interval, especially in the elderly, in 
patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalaemia 
or hypomagnesaemia. 

Thromboembolism 
Temporal association of olanzapine treatment and venous thromboembolism has been reported 
uncommonly (≥ 0.1% and < 1%). A causal relationship between the occurrence of venous 
thromboembolism and treatment with olanzapine has not been established. However, since patients 
with schizophrenia often present with acquired risk factors for venous thromboembolism all possible 
risk factors of VTE e.g. immobilisation of patients, should be identified and preventive measures 
undertaken. 

General CNS activity 
Given the primary CNS effects of olanzapine, caution should be used when it is taken in combination 
with other centrally acting medicines and alcohol. As it exhibits in vitro dopamine antagonism, 
olanzapine may antagonize the effects of direct and indirect dopamine agonists. 

Seizures 
Olanzapine should be used cautiously in patients who have a history of seizures or are subject to 
factors, which may lower the seizure threshold.  

Seizures have been reported to occur uncommonly in patients when treated with olanzapine. In most 
of these cases, a history of seizures or risk factors for seizures were reported. 

Tardive Dyskinesia 
In comparator studies of one year or less duration, olanzapine was associated with a statistically 
significant lower incidence of treatment emergent dyskinesia. However the risk of tardive dyskinesia 
increases with long-term exposure, and therefore if signs or symptoms of tardive dyskinesia appear in 
a patient on olanzapine, a dose reduction or discontinuation should be considered. These symptoms 
can temporally deteriorate or even arise after discontinuation of treatment. 

Postural hypotension 
Postural hypotension was infrequently observed in the elderly in olanzapine clinical trials. It is 
recommended that blood pressure is measured periodically in patients over 65 years. 

Sudden cardiac death  
In postmarketing reports with olanzapine, the event of sudden cardiac death has been reported in 
patients with olanzapine. In a retrospective observational cohort study, the risk of presumed sudden 
cardiac death in patients treated with olanzapine was approximately twice the risk in patients not using 



37 

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 
Olanzapine Glenmark 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.

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. 



38 

The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with 
Parkinson's disease and dementia is not recommended (see section 4.4). 

QTc interval 
Caution should be used if olanzapine is being administered concomitantly with medicinal products 
known to increase QTc interval (see section 4.4). 

4.6 Fertility, pregnancy and lactation

Pregnancy 
There are no adequate and well-controlled studies in pregnant women. Patients should be advised to 
notify their physician if they become pregnant or intend to become pregnant during treatment with 
olanzapine. Nevertheless, because human experience is limited, olanzapine should be used in 
pregnancy only if the potential benefit justifies the potential risk to the foetus. 

New born infants exposed to antipsychotics (including olanzapine) during the third trimester of 
pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that 
may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, 
hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns 
should be monitored carefully. 

Breast feeding  
In a study in breast- feeding, healthy women, olanzapine was excreted in breast milk. Mean infant 
exposure (mg/kg) at steady state was estimated to be 1.8 % of the maternal olanzapine dose (mg/kg). 

Patients should be advised not to breast- feed an infant if they are taking olanzapine.

Fertility 
Effects on fertility are unknown (see section 5.3 for preclinical information). 

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. Because 
olanzapine may cause somnolence and dizziness, patients should be cautioned about operating 
machinery, including motor vehicles. 

4.8  Undesirable effects 

Summary of the safety profile 

Adults 
The most frequently (seen in ≥ 1 % of patients) reported adverse reactions associated with the use of 
olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, 
cholesterol, glucose and triglyceride levels (see section 4.4), glucosuria, increased appetite, dizziness, 
akathisia, parkinsonism, leukopenia, neutropenia (see section 4.4), dyskinesia, orthostatic hypotension, 
anticholinergic effects, transient asymptomatic elevations of hepatic  aminotransferases (see section 
4.4), rash, asthenia, fatigue, pyrexia, arthralgia, increased alkaline phosphatase, high gamma 
glutamyltransferase, high uric acid, high creatine phosphokinase and oedema. 

Tabulated list of adverse reactions 
The following table lists the adverse reactions and laboratory investigations observed from 
spontaneous reporting and in clinical trials. Within each frequency grouping, adverse reactions are 
presented in order of decreasing seriousness. The frequency terms listed are defined as follows: Very 
common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to 
< 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the data available). 



39 

Very common Common Uncommon  Rare Not known 
Blood and the lymphatic system disorders  
 Eosinophilia 

Leukopenia10
Neutropenia10

 Thrombocytopeni
a11

Immune system disorders  
  Hypersensitivity11
Metabolism and nutrition disorders 
Weight gain1 Elevated 

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

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

Hypothermia12

Nervous system disorders  
Somnolence Dizziness 

Akathisia6
Parkinsonism6 
Dyskinesia6

Seizures where in 
most cases a 
history of seizures 
or risk factors for 
seizures were 
reported11 

Dystonia 
(including 
oculogyration)11
Tardive 
dyskinesia11

Amnesia 9 

Dysarthria 
Stuttering11
Restless legs 
syndrome11

Neuroleptic 
malignant 
syndrome (see 
section 
4.4)12Discontinuat
ion symptoms7, 12

Cardiac disorders  
  Bradycardia 

QTc prolongation 
(see section 4.4) 

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

Vascular disorders  
Orthostatic 
hypotension10

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

Respiratory, thoracic and mediastinal disorders
  Epistaxis9



40 

Gastrointestinal disorders  
 Mild, transient 

anticholinergic 
effects including 
constipation and 
dry mouth 

Abdominal 
distension9 
Salivary 
hypersecretion11 

Pancreatitis11

Hepatobiliary disorders  
 Transient, 

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

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

Skin and subcutaneous tissue disorders  
 Rash Photosensitivity 

reaction 
Alopecia 

 Drug Reaction 
with Eosinophilia 
and Systemic 
Symptoms 
(DRESS)

Musculoskeletal and connective tissue disorders  
Arthralgia9 Rhabdomyolysis11

Renal and urinary disorders  
  Urinary 

incontinence, 
urinary retention 
Urinary 
hesitation11

Pregnancy, puerperium and perinatal conditions
    Drug withdrawal 

syndrome 
neonatal (see 
section 4.6) 

Reproductive system and breast disorders  
 Erectile 

dysfunction in 
males 
Decreased libido 
in males and 
females 

Amenorrhea 
Breast 
enlargement 
Galactorrhea in 
females 
Gynaecomastia/br
east 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 

Increased total 
bilirubin 



41 

10 

High uric acid 10

1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) 
categories. Following short term treatment (median duration 47 days), weight gain ≥ 7 % of baseline 
body weight was very common (22.2%), ≥ 15% was common (4.2%) and ≥25% was uncommon 
(0.8%). Patients gaining ≥7%, ≥15% and ≥25% of their baseline body weight with long-term exposure 
(at least 48 weeks) were very common (64.4 %, 31.7 % and 12.3 % respectively). 

2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were 
greater in patients without evidence of lipid dysregulation at baseline. 

3 Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high (≥ 6.2 
mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17- < 6.2 mmol/l) 
to high (≥ 6.2 mmol/l) were very common. 

4 Observed for fasting normal levels at baseline (< 5.56 mmol/l) which increased to high (≥ 7 mmol/l). 
Changes in fasting glucose from borderline at baseline (≥ 5.56 - < 7 mmol/l) to high (≥ 7 mmol/l) were 
very common. 

5 Observed for fasting normal levels at baseline (< 1.69 mmol/l) which increased to high (≥ 2.26 
mmol/l). Changes in fasting triglycerides from borderline at baseline (≥ 1.69 mmol/l - < 2.26 mmol/l) 
to high (≥ 2.26 mmol/l) were very common. 

6 In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was 
numerically higher, but not statistically significantly different from placebo. Olanzapine-treated 
patients had a lower incidence of Parkinsonism, akathisia and dystonia compared with titrated doses of 
haloperidol. In the absence of detailed information on the pre-existing history of individual acute and 
tardive extrapyramidal movement disorders, it cannot be concluded at present that olanzapine 
produces less tardive dyskinesia and/or other tardive extrapyramidal syndromes. 

7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been 
reported when olanzapine is stopped abruptly. 

8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of 
normal range in approximately 30% of olanzapine treated patients with normal baseline prolactin 
value. In the majority of these patients the elevations were generally mild, and remained below two 
times the upper limit of normal range.  

9 Adverse event identified from clinical trials in the Olanzapine Integrated Database. 

10 As assessed by measured values from clinical trials in the Olanzapine Integrated Database. 

11 Adverse event identified from spontaneous post-marketing reporting with frequency determined 
utilising the Olanzapine Integrated Database. 

12 Adverse event identified from spontaneous post-marketing reporting with frequency estimated at the 
upper limit of the 95% confidence interval utilising the Olanzapine Integrated Database. 

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 



42 

common adverse reactions associated with the use of olanzapine in this patient group were abnormal 
gait and falls. Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and 
urinary incontinence were observed commonly. 

In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with 
Parkinson’s disease, worsening of Parkinsonian symptomatology and hallucinations were reported 
very commonly and more frequently than with placebo. 

In one clinical trial in patients with bipolar mania, valproate combination therapy with olanzapine 
resulted in an incidence of neutropenia of 4.1 %; a potential contributing factor could be high plasma 
valproate levels. Olanzapine administered with lithium or valproate resulted in increased levels (≥ 10 
%) of tremor, dry mouth, increased appetite, and weight gain. Speech disorder was also reported 
commonly. During treatment with olanzapine in combination with lithium or divalproex, an increase 
of ≥ 7 % from baseline body weight occurred in 17.4 % of patients during acute treatment (up to 6 
weeks). Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with 
bipolar disorder was associated with an increase of ≥ 7 % from baseline body weight in 39.9 % of 
patients. 

Paediatric population 
Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years. 
Although no clinical studies designed to compare adolescents to adults have been conducted, data 
from the adolescent trials were compared to those of the adult trials. 

The following table summarises the adverse reactions reported with a greater frequency in adolescent 
patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-term 
clinical trials in adolescent patients. Clinically significant weight gain (≥ 7 %) appears to occur more 
frequently in the adolescent population compared to adults with comparable exposures. The magnitude 
of weight gain and the proportion of adolescent patients who had clinically significant weight gain 
were greater with long-term exposure (at least 24 weeks) than with short-term exposure. 

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
The frequency terms listed are defined as follows: Very common (≥ 1/10), common (≥ 1/100 to < 
1/10). 

Metabolism and nutrition disorders
Very common: Weight 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). 



43 

15 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high (≥ 5.17 
mmol/l) were observed commonly. Changes in total fasting cholesterol levels from borderline at 
baseline (≥ 4.39 - < 5.17 mmol/l) to high (≥ 5.17 mmol/l) were very common. 

16 Elevated plasma prolactin levels were reported in 47.4 % of adolescent patients. 

Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

Signs and symptoms 
Very common symptoms in overdose (> 10 % incidence) include tachycardia, agitation/ 
aggressiveness, dysarthria, various extrapyramidal symptoms, and reduced level of consciousness 
ranging from sedation to coma. 

Other medically significant sequelae of overdose include delirium, convulsion, coma, possible 
neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, 
cardiac arrhythmias (< 2 % of overdose cases) and cardiopulmonary arrest. Fatal outcomes have been 
reported for acute overdoses as low as 450 mg but survival has also been reported following acute 
overdose of approximately 2 g of oral olanzapine. 

Management 
There is no specific antidote for olanzapine. Induction of emesis is not recommended. Standard 
procedures for management of overdose may be indicated (i.e. gastric lavage, administration of 
activated charcoal). The concomitant administration of activated charcoal was shown to reduce the 
oral bioavailability of olanzapine by 50 to 60 %. 

Symptomatic treatment and monitoring of vital organ function should be instituted according to 
clinical presentation, including treatment of hypotension and circulatory collapse and support of 
respiratory function. Do not use epinephrine, dopamine, or other sympathomimetic agents with beta-
agonist activity since beta stimulation may worsen hypotension. Cardiovascular monitoring is 
necessary to detect possible arrhythmias. Close medical supervision and monitoring should continue 
until the patient recovers. 

5. PHARMACOLOGICAL PROPERTIES

5.1  Pharmacodynamic properties

Pharmacotherapeutic group: psycholeptics, diazepines, oxazepines, thiazepines and oxepines, ATC 
code N05A H03. 

Pharmacodynamic effects 
Olanzapine is an antipsychotic, antimanic and mood stabilising agent that demonstrates a broad 
pharmacologic profile across a number of receptor systems. 

In preclinical studies, olanzapine exhibited a range of receptor affinities (Ki< 100 nM) for serotonin 5 
HT2A/2C, 5 HT3, 5 HT6; dopamine D1, D2, D3, D4, D5; cholinergic muscarinic receptors M1-M5 α1
adrenergic; and histamine H1 receptors. Animal behavioural studies with olanzapine indicated 5HT, 
dopamine, and cholinergic antagonism, consistent with the receptor-binding profile. Olanzapine 
demonstrated a greater in vitro affinity for serotonin 5HT2 than dopamine D2 receptors and greater 5 
HT2 than D2 activity in vivo, models. Electrophysiological studies demonstrated that olanzapine 
selectively reduced the firing of mesolimbic (A10) dopaminergic neurons, while having little effect on 
the striatal (A9) pathways involved in motor function. Olanzapine reduced a conditioned avoidance 



44 

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).  

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. 



45 

5.2 Pharmacokinetic properties

Absorption 
Olanzapine is well absorbed after oral administration, reaching peak plasma concentrations within 5 to 
8 hours. The absorption is not affected by food. Absolute oral bioavailability relative to intravenous 
administration has not been determined. 

Distribution 
The plasma protein binding of Olanzapine was about 93 % over the concentration range of about 7 to 
about 1000 ng/ml. Olanzapine is bound predominantly to albumin and α1-acid-glycoprotein. 

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. 



46 

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 
Magnesium stearate 



47 

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, 70, 98 tablets per carton 

Not all pack sizes may be marketed 

6.6 Special precautions for disposal 

No special requirements 

7. MARKETING AUTHORISATION HOLDER

Glenmark Arzneimittel GmbH 
Industriestr. 31, D – 82194 
Gröbenzell, Germany 

8. MARKETING AUTHORISATION NUMBER(S)  

EU/1/09/587/007 
EU/1/09/587/008 
EU/1/09/587/009 
EU/1/09/587/022 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 03 December 2009 
Date of latest renewal: 19 August 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 http://www.ema.europa.eu



48 

1. NAME OF THE MEDICINAL PRODUCT

Olanzapine Glenmark 10 mg tablets 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 10 mg olanzapine. 

Excipient with known effect: Each tablet contains 0.46 mg of aspartame 
For the full list of excipients, see section 6.1. 

3. PHARMACEUTICAL FORM 

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. 



49 

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 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 % 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. 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.



50 

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. 

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. 



51 

Neutropenia 
Caution should be exercised in patients with low leukocyte and/or neutrophil counts for any reason, in 
patients receiving medicines known to cause neutropenia, in patients with a history of drug-induced 
bone marrow depression/toxicity, in patients with bone marrow depression caused by concomitant 
illness, radiation therapy or chemotherapy and in patients with hypereosinophilic conditions or with 
myeloproliferative disease.  

Neutropenia has been reported commonly when olanzapine and valproate are used concomitantly (see 
section 4.8). 

Discontinuation of treatment 
Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting have been reported 
rarely (≥ 0.01% and < 0.1%) when olanzapine is stopped abruptly. 

QT interval 
In clinical trials, clinically meaningful QTc prolongations (Fridericia QT correction [QTcF] ≥ 500 
milliseconds [msec] at any time post baseline in patients with baseline QTcF < 500 msec) were 
uncommon (0.1 % to 1 %) in patients treated with olanzapine, with no significant differences in 
associated cardiac events compared to placebo. However, caution should be exercised when 
olanzapine is prescribed with medicines known to increase QTc interval, especially in the elderly, in 
patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalaemia 
or hypomagnesaemia. 

Thromboembolism 
Temporal association of olanzapine treatment and venous thromboembolism has been reported 
uncommonly (≥ 0.1% and < 1%). A causal relationship between the occurrence of venous 
thromboembolism and treatment with olanzapine has not been established. However, since patients 
with schizophrenia often present with acquired risk factors for venous thromboembolism all possible 
risk factors of VTE e.g. immobilisation of patients, should be identified and preventive measures 
undertaken. 

General CNS activity 
Given the primary CNS effects of olanzapine, caution should be used when it is taken in combination 
with other centrally acting medicines and alcohol. As it exhibits in vitro dopamine antagonism, 
olanzapine may antagonize the effects of direct and indirect dopamine agonists. 

Seizures 
Olanzapine should be used cautiously in patients who have a history of seizures or are subject to 
factors, which may lower the seizure threshold.  

Seizures have been reported to occur uncommonly in patients when treated with olanzapine. In most 
of these cases, a history of seizures or risk factors for seizures were reported. 

Tardive Dyskinesia 
In comparator studies of one year or less duration, olanzapine was associated with a statistically 
significant lower incidence of treatment emergent dyskinesia. However the risk of tardive dyskinesia 
increases with long-term exposure, and therefore if signs or symptoms of tardive dyskinesia appear in 
a patient on olanzapine, a dose reduction or discontinuation should be considered. These symptoms 
can temporally deteriorate or even arise after discontinuation of treatment. 

Postural hypotension 
Postural hypotension was infrequently observed in the elderly in olanzapine clinical trials. It is 
recommended that blood pressure is measured periodically in patients over 65 years. 



52 

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 
Olanzapine Glenmark 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.

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 
CYP2C19). 

Olanzapine showed no interaction when co-administered with lithium or biperiden. 



53 

Therapeutic monitoring of valproate plasma levels did not indicate that valproate dosage adjustment is 
required after the introduction of concomitant olanzapine. 

General CNS activity 
Caution should be exercised in patients who consume alcohol or receive medicinal products that can 
cause central nervous system depression. 

The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with 
Parkinson's disease and dementia is not recommended (see section 4.4). 

QTc interval 
Caution should be used if olanzapine is being administered concomitantly with medicinal products 
known to increase QTc interval (see section 4.4). 

4.6 Fertility, pregnancy and lactation

Pregnancy 
There are no adequate and well-controlled studies in pregnant women. Patients should be advised to 
notify their physician if they become pregnant or intend to become pregnant during treatment with 
olanzapine. Nevertheless, because human experience is limited, olanzapine should be used in 
pregnancy only if the potential benefit justifies the potential risk to the foetus. 

New born infants exposed to antipsychotics (including olanzapine) during the third trimester of 
pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that 
may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, 
hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns 
should be monitored carefully. 

Breast feeding  
In a study in breast- feeding, healthy women, olanzapine was excreted in breast milk. Mean infant 
exposure (mg/kg) at steady state was estimated to be 1.8 % of the maternal olanzapine dose (mg/kg). 
Patients should be advised not to breast- feed an infant if they are taking olanzapine.

Fertility 
Effects on fertility are unknown (see section 5.3 for preclinical information). 

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. Because 
olanzapine may cause somnolence and dizziness, patients should be cautioned about operating 
machinery, including motor vehicles. 

4.8     Undesirable effects

Summary of the safety profile

Adults 
The most frequently (seen in ≥ 1 % of patients) reported adverse reactions associated with the use of 
olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, 
cholesterol, glucose and triglyceride levels (see section 4.4), glucosuria, increased appetite, dizziness, 
akathisia, parkinsonism, leukopenia, neutropenia (see section 4.4), dyskinesia, orthostatic hypotension, 
anticholinergic effects, transient asymptomatic elevations of hepatic aminotransferases (see section 
4.4), rash, asthenia, fatigue, pyrexia, arthralgia, increased alkaline phosphatase, high gamma 
glutamyltransferase, high uric acid, high creatine phosphokinase and oedema. 



54 

Tabulated list of adverse reactions 
The following table lists the adverse reactions and laboratory investigations observed from 
spontaneous reporting and in clinical trials. Within each frequency grouping, adverse reactions are 
presented in order of decreasing seriousness. The frequency terms listed are defined as follows: Very 
common (≥ 1/10), common (≥ 1/100 to  < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to 
< 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the data available). 

Very 
common 

Common Uncommon  Rare Not known 

Blood and the lymphatic system disorders  
 Eosinophilia 

Leukopenia10
Neutropenia10

 Thrombocytopenia11

Immune system disorders  
  Hypersensitivity11
Metabolism and nutrition disorders  
Weight gain1 Elevated 

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

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

Hypothermia12

Nervous system disorders  
Somnolence Dizziness 

Akathisia6
Parkinsonism6 
Dyskinesia6

Seizures where in 
most cases a history 
of seizures or risk 
factors for seizures 
were reported11 

Dystonia (including 
oculogyration) 11
Tardive dyskinesia11

Amnesia 9 

Dysarthria 
Stuttering11
Restless Legs 
Syndrome11

Neuroleptic malignant 
syndrome (see section 
4.4)12

Discontinuation 
symptoms7, 12

Cardiac disorders  
  Bradycardia 

QTc prolongation (see 
section 4.4) 

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

Vascular disorders  
Orthostatic 
hypotension1
0

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

Respiratory, thoracic and mediastinal disorders  
  Epistaxis9
Gastrointestinal disorders  
 Mild, transient Abdominal Pancreatitis11



55 

anticholinergic 
effects including 
constipation and 
dry mouth 

distension9
Salivary 
hypersecretion11

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 Rhabdomyolysis11

Renal and urinary disorders  
  Urinary incontinence, 

urinary retention 
Urinary hesitation11

Pregnancy, puerperium and perinatal conditions
    Drug 

withdrawal 
syndrome 
neonatal (see 
section 4.6) 

Reproductive system and breast disorders  
 Erectile dysfunction 

in males 
Decreased libido in 
males and females 

Amenorrhea 
Breast enlargement 
Galactorrhea in 
females 
Gynaecomastia/breast 
enlargement in males 

Priapism12

General disorders and administration site conditions  
 Asthenia 

Fatigue 
Oedema 
Pyrexia10

Investigations  
Elevated 
plasma 
prolactin 
levels8

Increased alkaline 
phosphatase10
High creatine 
phosphokinase11
High Gamma 
Glutamyltransferase
10 

Increased total 
bilirubin 



56 

High uric acid 10

1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) 
categories. Following short term treatment (median duration 47 days), weight gain ≥ 7 % of baseline 
body weight was very common (22.2%), ≥ 15% was common (4.2%) and ≥25% was uncommon 
(0.8%). Patients gaining ≥7%, ≥15% and ≥25% of their baseline body weight with long-term exposure 
(at least 48 weeks) were very common (64.4 %, 31.7 % and 12.3 % respectively). 

2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were 
greater in patients without evidence of lipid dysregulation at baseline. 

3 Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high (≥ 6.2 
mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17- < 6.2 mmol/l) 
to high (≥ 6.2 mmol/l) were very common. 

4 Observed for fasting normal levels at baseline (< 5.56 mmol/l) which increased to high (≥ 7 mmol/l). 
Changes in fasting glucose from borderline at baseline (≥ 5.56 - < 7 mmol/l) to high (≥ 7 mmol/l) were 
very common. 

5 Observed for fasting normal levels at baseline (< 1.69 mmol/l) which increased to high (≥ 2.26 
mmol/l). Changes in fasting triglycerides from borderline at baseline  (≥ 1.69 mmol/l - < 2.26 mmol/l) 
to high (≥ 2.26 mmol/l) were very common. 

6 In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was 
numerically higher, but not statistically significantly different from placebo. Olanzapine-treated 
patients had a lower incidence of Parkinsonism, akathisia and dystonia compared with titrated doses of 
haloperidol. In the absence of detailed information on the pre-existing history of individual acute and 
tardive extrapyramidal movement disorders, it cannot be concluded at present that olanzapine 
produces less tardive dyskinesia and/or other tardive extrapyramidal syndromes. 

7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been 
reported when olanzapine is stopped abruptly. 

8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of 
normal range in approximately 30% of olanzapine treated patients with normal baseline prolactin 
value. In the majority of these patients the elevations were generally mild, and remained below two 
times the upper limit of normal range.  

9 Adverse event identified from clinical trials in the Olanzapine Integrated Database. 

10 As assessed by measured values from clinical trials in the Olanzapine Integrated Database. 

11 Adverse event identified from spontaneous post-marketing reporting with frequency determined 
utilising the Olanzapine Integrated Database. 

12 Adverse event identified from spontaneous post-marketing reporting with frequency estimated at the 
upper limit of the 95% confidence interval utilising the Olanzapine Integrated Database. 

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 



57 

common adverse reactions associated with the use of olanzapine in this patient group were abnormal 
gait and falls. Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and 
urinary incontinence were observed commonly. 

In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with 
Parkinson’s disease, worsening of Parkinsonian symptomatology and hallucinations were reported 
very commonly and more frequently than with placebo. 

In one clinical trial in patients with bipolar mania, valproate combination therapy with olanzapine 
resulted in an incidence of neutropenia of 4.1 %; a potential contributing factor could be high plasma 
valproate levels. Olanzapine administered with lithium or valproate resulted in increased levels (≥ 10 
%) of tremor, dry mouth, increased appetite, and weight gain. Speech disorder was also reported 
commonly. During treatment with olanzapine in combination with lithium or divalproex, an increase 
of ≥ 7 % from baseline body weight occurred in 17.4 % of patients during acute treatment (up to 6 
weeks). Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with 
bipolar disorder was associated with an increase of ≥ 7 % from baseline body weight in 39.9 % of 
patients. 

Paediatric population 
Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years. 
Although no clinical studies designed to compare adolescents to adults have been conducted, data 
from the adolescent trials were compared to those of the adult trials. 

The following table summarises the adverse reactions reported with a greater frequency in adolescent 
patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-term 
clinical trials in adolescent patients. Clinically significant weight gain (≥ 7 %) appears to occur more 
frequently in the adolescent population compared to adults with comparable exposures. The magnitude 
of weight gain and the proportion of adolescent patients who had clinically significant weight gain 
were greater with long-term exposure (at least 24 weeks) than with short-term exposure. 

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
The frequency terms listed are defined as follows: Very common (≥ 1/10), common (≥ 1/100 to < 
1/10).

Metabolism and nutrition disorders
Very common: Weight 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). 



58 

15 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high (≥ 5.17 
mmol/l) were observed commonly. Changes in total fasting cholesterol levels from borderline at 
baseline (≥ 4.39 - < 5.17 mmol/l) to high (≥ 5.17 mmol/l) were very common. 

16 Elevated plasma prolactin levels were reported in 47.4 % of adolescent patients. 

Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

Signs and symptoms 
Very common symptoms in overdose (> 10 % incidence) include tachycardia, agitation/ 
aggressiveness, dysarthria, various extrapyramidal symptoms, and reduced level of consciousness 
ranging from sedation to coma. 

Other medically significant sequelae of overdose include delirium, convulsion, coma, possible 
neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, 
cardiac arrhythmias (< 2 % of overdose cases) and cardiopulmonary arrest. Fatal outcomes have been 
reported for acute overdoses as low as 450 mg but survival has also been reported following acute 
overdose of  approximately 2 g of oral olanzapine. 

Management 
There is no specific antidote for olanzapine. Induction of emesis is not recommended. Standard 
procedures for management of overdose may be indicated (i.e. gastric lavage, administration of 
activated charcoal). The concomitant administration of activated charcoal was shown to reduce the 
oral bioavailability of olanzapine by 50 to 60 %. 

Symptomatic treatment and monitoring of vital organ function should be instituted according to 
clinical presentation, including treatment of hypotension and circulatory collapse and support of 
respiratory function. Do not use epinephrine, dopamine, or other sympathomimetic agents with beta-
agonist activity since beta stimulation may worsen hypotension. Cardiovascular monitoring is 
necessary to detect possible arrhythmias. Close medical supervision and monitoring should continue 
until the patient recovers. 

5. PHARMACOLOGICAL PROPERTIES

5.1  Pharmacodynamic properties

Pharmacotherapeutic group: psycholeptics, diazepines, oxazepines, thiazepines and oxepines, ATC 
code N05A H03. 

Pharmacodynamic effects 
Olanzapine is an antipsychotic, antimanic and mood stabilising agent that demonstrates a broad 
pharmacologic profile across a number of receptor systems. 

In preclinical studies, olanzapine exhibited a range of receptor affinities (Ki < 100 nM) for serotonin 5 
HT2A/2C, 5 HT3, 5 HT6; dopamine D1, D2, D3, D4, D5; cholinergic muscarinic receptors M1-M5; α1
adrenergic; and histamine H1 receptors. Animal behavioural studies with olanzapine indicated 5HT, 
dopamine, and cholinergic antagonism, consistent with the receptor-binding profile.  

Olanzapine demonstrated a greater in vitro affinity for serotonin 5HT2 than dopamine D2 receptors and 
greater 5 HT2 than D2 activity in vivo, models. Electrophysiological studies demonstrated that 
olanzapine selectively reduced the firing of mesolimbic (A10) dopaminergic neurons, while having 



59 

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).  

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. 



60 

5.2 Pharmacokinetic properties

Absorption 
Olanzapine is well absorbed after oral administration, reaching peak plasma concentrations within 5 to 
8 hours. The absorption is not affected by food. Absolute oral bioavailability relative to intravenous 
administration has not been determined. 

Distribution 
The plasma protein binding of Olanzapine was about 93 % over the concentration range of about 7 to 
about 1000 ng/ml. Olanzapine is bound predominantly to albumin and α1-acid-glycoprotein. 

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 %). 

SmokingIn 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. 



61 

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 



62 

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, 70, 98 tablets per carton. 

Not all pack sizes may be marketed 

6.6 Special precautions for disposal 

No special requirements 

7. MARKETING AUTHORISATION HOLDER

Glenmark Arzneimittel GmbH 
Industriestr. 31, 82194 
Gröbenzell, Germany 

8. MARKETING AUTHORISATION NUMBER(S)  

EU/1/09/587/010 
EU/1/09/587/011 
EU/1/09/587/012 
EU/1/09/587/023 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 03 December 2009 
Date of latest renewal: 19 August 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 http://www.ema.europa.eu



63 

1. NAME OF THE MEDICINAL PRODUCT

Olanzapine Glenmark 15 mg tablets 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 15 mg olanzapine. 

Excipient with known effect: Each tablet contains 0.69 mg of aspartame 
For the full list of excipients, see section 6.1. 

3. PHARMACEUTICAL FORM 

Tablet 
Yellow coloured circular flat bevelled edge 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. 
Olanzapine can be given without regards for meals as absorption is not affected by food. Gradual 
tapering of the dose should be considered when discontinuing olanzapine. 

Special populations



64 

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 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 % 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. 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.



65 

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. 

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 



66 

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. 

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. 



67 

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 
Olanzapine Glenmark 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.

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. 



68 

General CNS activity 
Caution should be exercised in patients who consume alcohol or receive medicinal products that can 
cause central nervous system depression. 

The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with 
Parkinson's disease and dementia is not recommended (see section 4.4). 

QTc interval 
Caution should be used if olanzapine is being administered concomitantly with medicinal products 
known to increase QTc interval (see section 4.4). 

4.6 Fertility, pregnancy and lactation

Pregnancy 
There are no adequate and well-controlled studies in pregnant women. Patients should be advised to 
notify their physician if they become pregnant or intend to become pregnant during treatment with 
olanzapine. Nevertheless, because human experience is limited, olanzapine should be used in 
pregnancy only if the potential benefit justifies the potential risk to the foetus. 

New born infants exposed to antipsychotics (including olanzapine) during the third trimester of 
pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that 
may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, 
hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns 
should be monitored carefully. 

Breast feeding  
In a study in breast- feeding, healthy women, olanzapine was excreted in breast milk. Mean infant 
exposure (mg/kg) at steady state was estimated to be 1.8 % of the maternal olanzapine dose (mg/kg). 
Patients should be advised not to breast- feed an infant if they are taking olanzapine. 

Fertility 
Effects on fertility are unknown (see section 5.3 for preclinical information). 

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. Because 
olanzapine may cause somnolence and dizziness, patients should be cautioned about operating 
machinery, including motor vehicles. 

4.8 Undesirable effects 

Summary of the safety profile 

Adults 
The most frequently (seen in ≥ 1 % of patients) reported adverse reactions associated with the use of 
olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, 
cholesterol, glucose and triglyceride levels (see section 4.4), glucosuria, increased appetite, dizziness, 
akathisia, parkinsonism, leukopenia, neutropenia (see section 4.4), dyskinesia, orthostatic hypotension, 
anticholinergic effects, transient asymptomatic elevations of hepatic aminotransferases (see section 
4.4), rash, asthenia, fatigue, pyrexia, arthralgia, increased alkaline phosphatase, high gamma 
glutamyltransferase, high uric acid, high creatine phosphokinase and oedema. 

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 



69 

common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to 
< 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the data available). 

Very common Common Uncommon  Rare Not known 
Blood and the lymphatic system disorders  
 Eosinophilia 

Leukopenia10
Neutropenia10

 Thrombocytopeni
a11

Immune system disorders  
  Hypersensitivity11
Metabolism and nutrition disorders 
Weight gain1 Elevated 

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

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

Hypothermia12

Nervous system disorders  
Somnolence Dizziness 

Akathisia6
Parkinsonism6 
Dyskinesia6

Seizures where in 
most cases a 
history of seizures 
or risk factors for 
seizures were 
reported11 

Dystonia 
(including 
oculogyration)11
Tardive 
dyskinesia11

Amnesia 9 

Dysarthria 
Stuttering11
Restless legs 
syndrome11

Neuroleptic 
malignant 
syndrome (see 
section 
4.4)12Discontinuat
ion symptoms7, 12

Cardiac disorders  
  Bradycardia 

QTc prolongation 
(see section 4.4) 

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

Vascular disorders  
Orthostatic 
hypotension10

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

Respiratory, thoracic and mediastinal disorders



70 

  Epistaxis9
Gastrointestinal disorders  
 Mild, transient 

anticholinergic 
effects including 
constipation and 
dry mouth 

Abdominal 
distension9 
Salivary 
hypersecretion11

Pancreatitis11

Hepatobiliary disorders  
 Transient, 

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

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

Skin and subcutaneous tissue disorders  
 Rash Photosensitivity 

reaction 
Alopecia 

 Drug Reaction 
with Eosinophilia 
and Systemic 
Symptoms 
(DRESS)

Musculoskeletal and connective tissue disorders  
Arthralgia9 Rhabdomyolysis11

Renal and urinary disorders  
  Urinary 

incontinence, 
urinary retention 
Urinary 
hesitation11

Pregnancy, puerperium and perinatal conditions
    Drug withdrawal 

syndrome 
neonatal (see 
section 4.6) 

Reproductive system and breast disorders  
 Erectile 

dysfunction in 
males 
Decreased libido 
in males and 
females 

Amenorrhea 
Breast 
enlargement 
Galactorrhea in 
females 
Gynaecomastia/br
east 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 

Increased total 
bilirubin 



71 

Glutamyltransferase 
10 

High uric acid 10

1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) 
categories. Following short term treatment (median duration 47 days), weight gain ≥ 7 % of baseline 
body weight was very common (22.2%), ≥ 15% was common (4.2%) and ≥25% was uncommon 
(0.8%). Patients gaining ≥7%, ≥15% and ≥25% of their baseline body weight with long-term exposure 
(at least 48 weeks) were very common (64.4 %, 31.7 % and 12.3 % respectively). 

2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were 
greater in patients without evidence of lipid dysregulation at baseline. 

3 Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high (≥ 6.2 
mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17- < 6.2 mmol/l) 
to high (≥ 6.2 mmol/l) were very common. 

4 Observed for fasting normal levels at baseline (< 5.56 mmol/l) which increased to high (≥ 7 mmol/l). 
Changes in fasting glucose from borderline at baseline (≥ 5.56 - < 7 mmol/l) to high (≥ 7 mmol/l) were 
very common. 

5 Observed for fasting normal levels at baseline (< 1.69 mmol/l) which increased to high (≥ 2.26 
mmol/l). Changes in fasting triglycerides from borderline at baseline (≥ 1.69 mmol/l - < 2.26 mmol/l) 
to high (≥ 2.26 mmol/l) were very common. 

6 In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was 
numerically higher, but not statistically significantly different from placebo. Olanzapine-treated 
patients had a lower incidence of Parkinsonism, akathisia and dystonia compared with titrated doses of 
haloperidol. In the absence of detailed information on the pre-existing history of individual acute and 
tardive extrapyramidal movement disorders, it cannot be concluded at present that olanzapine 
produces less tardive dyskinesia and/or other tardive extrapyramidal syndromes. 

7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been 
reported when olanzapine is stopped abruptly. 

8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of 
normal range in approximately 30% of olanzapine treated patients with normal baseline prolactin 
value. In the majority of these patients the elevations were generally mild, and remained below two 
times the upper limit of normal range.  

9 Adverse event identified from clinical trials in the Olanzapine Integrated Database. 

10 As assessed by measured values from clinical trials in the Olanzapine Integrated Database. 

11 Adverse event identified from spontaneous post-marketing reporting with frequency determined 
utilising the Olanzapine Integrated Database. 

12 Adverse event identified from spontaneous post-marketing reporting with frequency estimated at the 
upper limit of the 95% confidence interval utilising the Olanzapine Integrated Database. 

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. 



72 

Additional information on special populations 
In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher 
incidence of death and cerebrovascular adverse reactions compared to placebo (see section 4.4). Very 
common adverse reactions associated with the use of olanzapine in this patient group were abnormal 
gait and falls. Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and 
urinary incontinence were observed commonly. 

In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with 
Parkinson’s disease, worsening of Parkinsonian symptomatology and hallucinations were reported 
very commonly and more frequently than with placebo. 

In one clinical trial in patients with bipolar mania, valproate combination therapy with olanzapine 
resulted in an incidence of neutropenia of 4.1 %; a potential contributing factor could be high plasma 
valproate levels. Olanzapine administered with lithium or valproate resulted in increased levels (≥ 10 
%) of tremor, dry mouth, increased appetite, and weight gain. Speech disorder was also reported 
commonly. During treatment with olanzapine in combination with lithium or divalproex, an increase 
of ≥ 7 % from baseline body weight occurred in 17.4 % of patients during acute treatment (up to 6 
weeks). Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with 
bipolar disorder was associated with an increase of ≥ 7 % from baseline body weight in 39.9 % of 
patients. 

Paediatric population 
Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years. 
Although no clinical studies designed to compare adolescents to adults have been conducted, data 
from the adolescent trials were compared to those of the adult trials. 

The following table summarises the adverse reactions reported with a greater frequency in adolescent 
patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-term 
clinical trials in adolescent patients. Clinically significant weight gain (≥ 7 %) appears to occur more 
frequently in the adolescent population compared to adults with comparable exposures. The magnitude 
of weight gain and the proportion of adolescent patients who had clinically significant weight gain 
were greater with long-term exposure (at least 24 weeks) than with short-term exposure. 

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
The frequency terms listed are defined as follows: Very common (≥ 1/10), common (≥ 1/100 to < 
1/10). 

Metabolism and nutrition disorders
Very common: Weight gain 13, elevated triglyceride levels 14, increased appetite.
Common: Elevated cholesterol levels 11

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). 



73 

15 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high (≥ 5.17 
mmol/l) were observed commonly. Changes in total fasting cholesterol levels from borderline at 
baseline (≥ 4.39 - < 5.17 mmol/l) to high (≥ 5.17 mmol/l) were very common. 

16 Elevated plasma prolactin levels were reported in 47.4 % of adolescent patients. 

Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

Signs and symptoms 
Very common symptoms in overdose (> 10 % incidence) include tachycardia, agitation/ 
aggressiveness, dysarthria, various extrapyramidal symptoms, and reduced level of consciousness 
ranging from sedation to coma. 

Other medically significant sequelae of overdose include delirium, convulsion, coma, possible 
neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, 
cardiac arrhythmias (< 2 % of overdose cases) and cardiopulmonary arrest. Fatal outcomes have been 
reported for acute overdoses as low as 450 mg but survival has also been reported following acute 
overdose of  approximately 2 g of oral olanzapine. 

Management 
There is no specific antidote for olanzapine. Induction of emesis is not recommended. Standard 
procedures for management of overdose may be indicated (i.e. gastric lavage, administration of 
activated charcoal). The concomitant administration of activated charcoal was shown to reduce the 
oral bioavailability of olanzapine by 50 to 60 %. 

Symptomatic treatment and monitoring of vital organ function should be instituted according to 
clinical presentation, including treatment of hypotension and circulatory collapse and support of 
respiratory function. Do not use epinephrine, dopamine, or other sympathomimetic agents with beta-
agonist activity since beta stimulation may worsen hypotension. Cardiovascular monitoring is 
necessary to detect possible arrhythmias. Close medical supervision and monitoring should continue 
until the patient recovers. 

5. PHARMACOLOGICAL PROPERTIES

5.1  Pharmacodynamic properties

Pharmacotherapeutic group: psycholeptics, diazepines, oxazepines, thiazepines and oxepines, ATC 
code N05A H03. 

Pharmacodynamic effects 
Olanzapine is an antipsychotic, antimanic and mood stabilising agent that demonstrates a broad 
pharmacologic profile across a number of receptor systems. 

In preclinical studies, olanzapine exhibited a range of receptor affinities (Ki < 100 nM) for serotonin 5 
HT2A/2C, 5 HT3, 5 HT6; dopamine D1, D2, D3, D4, D5; cholinergic muscarinic receptors M1-M5; α1
adrenergic; and histamine H1 receptors. Animal behavioural studies with olanzapine indicated 5HT, 
dopamine, and cholinergic antagonism, consistent with the receptor-binding profile. Olanzapine 
demonstrated a greater in vitro affinity for serotonin 5 HT2 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 



74 

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).  

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. 



75 

5.2 Pharmacokinetic properties

Absorption 
Olanzapine is well absorbed after oral administration, reaching peak plasma concentrations within 5 to 
8 hours. The absorption is not affected by food. Absolute oral bioavailability relative to intravenous 
administration has not been determined. 

Distribution 
The plasma protein binding of Olanzapine was about 93 % over the concentration range of about 7 to 
about 1000 ng/ml. Olanzapine is bound predominantly to albumin and α1-acid-glycoprotein. 

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. 



76 

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 
Magnesium stearate 



77 

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, 70, 98 tablets per carton 
Not all pack sizes may be marketed 

6.6 Special precautions for disposal 

No special requirements 

7. MARKETING AUTHORISATION HOLDER

Glenmark Arzneimittel GmbH 
Industriestr. 31, 82194 
Gröbenzell, Germany 

8. MARKETING AUTHORISATION NUMBER(S)  

EU/1/09/587/013 
EU/1/09/587/014 
EU/1/09/587/015 
EU/1/09/587/024 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 03 December 2009 
Date of latest renewal: 19 August 2014 

10. DATE OF REVISION OF THE TEXT 

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



78 

1. NAME OF THE MEDICINAL PRODUCT

Olanzapine Glenmark 20 mg tablets 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 20 mg olanzapine 

Excipient with known effect: Each tablet contains 0.92 mg of aspartame 
For the full list of excipients, see section 6.1. 

3. PHARMACEUTICAL FORM 

Tablet 
Yellow coloured circular flat bevelled edge 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. 
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. 



79 

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 % vs 1.5 %, 
respectively). The higher incidence of death was not associated with olanzapine dose (mean daily dose 
4.4 mg) or duration of treatment. Risk factors that may predispose this patient population to increased 
mortality include age > 65 years, dysphagia, sedation, malnutrition and dehydration, pulmonary 
conditions (e.g., pneumonia, with or without aspiration), or concomitant use of benzodiazepines. 
However, the incidence of death was higher in olanzapine-treated than in placebo-treated patients 
independent of these risk factors. 

In the same clinical trials, cerebrovascular adverse events (CVAE e.g., stroke, transient ischemic 
attack), including fatalities, were reported. There was a 3-fold increase in CVAE in patients treated 
with olanzapine compared to patients treated with placebo (1.3 % 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.



80 

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. 

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. 



81 

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, as with other antipsychotics, caution should 
be exercised when olanzapine is prescribed with medicines known to increase QTc interval, especially 
in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart 
hypertrophy, hypokalaemia or hypomagnesaemia. 

Thromboembolism 
Temporal association of olanzapine treatment and venous thromboembolism has been reported 
uncommonly (≥ 0.1% and < 1%). A causal relationship between the occurrence of venous 
thromboembolism and treatment with olanzapine has not been established. However, since patients 
with schizophrenia often present with acquired risk factors for venous thromboembolism all possible 
risk factors of VTE e.g. immobilisation of patients, should be identified and preventive measures 
undertaken. 

General CNS activity 
Given the primary CNS effects of olanzapine, caution should be used when it is taken in combination 
with other centrally acting medicines and alcohol. As it exhibits in vitro dopamine antagonism, 
olanzapine may antagonize the effects of direct and indirect dopamine agonists. 

Seizures 
Olanzapine should be used cautiously in patients who have a history of seizures or are subject to 
factors, which may lower the seizure threshold. Seizures have been reported to occur uncommonly in 
patients when treated with olanzapine. In most of these cases, a history of seizures or risk factors for 
seizures were reported. 

Tardive Dyskinesia 
In comparator studies of one year or less duration, olanzapine was associated with a statistically 
significant lower incidence of treatment emergent dyskinesia. However the risk of tardive dyskinesia 
increases with long-term exposure, and therefore if signs or symptoms of tardive dyskinesia appear in 
a patient on olanzapine, a dose reduction or discontinuation should be considered. These symptoms 
can temporally deteriorate or even arise after discontinuation of treatment. 

Postural hypotension 
Postural hypotension was infrequently observed in the elderly in olanzapine clinical trials. It is 
recommended that blood pressure is measured periodically in patients over 65 years. 

Sudden cardiac death  
In postmarketing reports with olanzapine, the event of sudden cardiac death has been reported in 
patients with olanzapine. In a retrospective observational cohort study, the risk of presumed sudden 
cardiac death in patients treated with olanzapine was approximately twice the risk in patients not using 
antipsychotics. In the study, the risk of olanzapine was comparable to the risk of atypical 
antipsychotics included in a pooled analysis. 



82 

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 
Olanzapine Glenmark 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.

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. 



83 

The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with 
Parkinson's disease and dementia is not recommended (see section 4.4). 

QTc interval 
Caution should be used if olanzapine is being administered concomitantly with medicinal products 
known to increase QTc interval (see section 4.4). 

4.6 Fertility, pregnancy and lactation

Pregnancy 
There are no adequate and well-controlled studies in pregnant women. Patients should be advised to 
notify their physician if they become pregnant or intend to become pregnant during treatment with 
olanzapine. Nevertheless, because human experience is limited, olanzapine should be used in 
pregnancy only if the potential benefit justifies the potential risk to the foetus. 

New born infants exposed to antipsychotics (including olanzapine) during the third trimester of 
pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that 
may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, 
hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns 
should be monitored carefully. 

Breast feeding  
In a study in breast- feeding, healthy women, olanzapine was excreted in breast milk. Mean infant 
exposure (mg/kg) at steady state was estimated to be 1.8 % of the maternal olanzapine dose (mg/kg). 

Patients should be advised not to breast- feed an infant if they are taking olanzapine.

Fertility 
Effects on fertility are unknown (see section 5.3 for preclinical information). 

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. Because 
olanzapine may cause somnolence and dizziness, patients should be cautioned about operating 
machinery, including motor vehicles. 

4.8 Undesirable effects 

Summary of the safety profile 

Adults
The most frequently (seen in ≥ 1 % of patients) reported adverse reactions associated with the use of 
olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, 
cholesterol, glucose and triglyceride levels (see section 4.4), glucosuria, increased appetite, dizziness, 
akathisia, parkinsonism, leukopenia, neutropenia (see section 4.4), dyskinesia, orthostatic hypotension, 
anticholinergic effects, transient asymptomatic elevations of hepatic aminotransferases (see section 
4.4), rash, asthenia, fatigue, pyrexia, arthralgia, increased alkaline phosphatase, high gamma 
glutamyltransferase, high uric acid, high creatine phosphokinase and oedema. 

Tabulated list of adverse reactions 
The following table lists the adverse reactions and laboratory investigations observed from 
spontaneous reporting and in clinical trials. Within each frequency grouping, adverse reactions are 
presented in order of decreasing seriousness. The frequency terms listed are defined as follows: Very 
common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to 
< 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the data available). 



84 

Very common Common Uncommon  Rare Not known 
Blood and the lymphatic system disorders  
 Eosinophilia 

Leukopenia10
Neutropenia10

 Thrombocytopeni
a11

Immune system disorders  
  Hypersensitivity11
Metabolism and nutrition disorders 
Weight gain1 Elevated 

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

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

Hypothermia12

Nervous system disorders  
Somnolence Dizziness 

Akathisia6
Parkinsonism6 
Dyskinesia6

Seizures where in 
most cases a 
history of seizures 
or risk factors for 
seizures were 
reported11 

Dystonia 
(including 
oculogyration)11
Tardive 
dyskinesia11

Amnesia 9 

Dysarthria 
Stuttering11
Restless legs 
syndrome11

Neuroleptic 
malignant 
syndrome (see 
section 
4.4)12Discontinuat
ion symptoms7, 12

Cardiac disorders  
  Bradycardia 

QTc prolongation 
(see section 4.4) 

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

Vascular disorders  
Orthostatic 
hypotension10

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

Respiratory, thoracic and mediastinal disorders
  Epistaxis9
Gastrointestinal disorders  
 Mild, transient Abdominal Pancreatitis11



85 

anticholinergic 
effects including 
constipation and 
dry mouth 

distension9
Salivary 
hypersecretion11

Hepatobiliary disorders  
 Transient, 

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

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

Skin and subcutaneous tissue disorders  
 Rash Photosensitivity 

reaction 
Alopecia 

 Drug Reaction 
with Eosinophilia 
and Systemic 
Symptoms 
(DRESS)

Musculoskeletal and connective tissue disorders  
Arthralgia9 Rhabdomyolysis11

Renal and urinary disorders  
  Urinary 

incontinence, 
urinary retention 
Urinary 
hesitation11

Pregnancy, puerperium and perinatal conditions
    Drug withdrawal 

syndrome 
neonatal (see 
section 4.6) 

Reproductive system and breast disorders  
 Erectile 

dysfunction in 
males 
Decreased libido 
in males and 
females 

Amenorrhea 
Breast 
enlargement 
Galactorrhea in 
females 
Gynaecomastia/br
east 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 



86 

1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) 
categories. Following short term treatment (median duration 47 days), weight gain ≥ 7 % of baseline 
body weight was very common (22.2%), ≥ 15% was common (4.2%) and ≥25% was uncommon 
(0.8%). Patients gaining ≥7%, ≥15% and ≥25% of their baseline body weight with long-term exposure 
(at least 48 weeks) were very common (64.4 %, 31.7 % and 12.3 % respectively). 

2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were 
greater in patients without evidence of lipid dysregulation at baseline. 

3 Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high (≥ 6.2 
mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17- < 6.2 mmol/l) 
to high (≥ 6.2 mmol/l) were very common. 

4 Observed for fasting normal levels at baseline (< 5.56 mmol/l) which increased to high (≥ 7 mmol/l). 
Changes in fasting glucose from borderline at baseline (≥ 5.56 - < 7 mmol/l) to high (≥ 7 mmol/l) were 
very common. 

5 Observed for fasting normal levels at baseline (< 1.69 mmol/l) which increased to high (≥ 2.26 
mmol/l). Changes in fasting triglycerides from borderline at baseline (≥ 1.69 mmol/l - < 2.26 mmol/l) 
to high (≥ 2.26 mmol/l) were very common. 

6 In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was 
numerically higher, but not statistically significantly different from placebo. Olanzapine-treated 
patients had a lower incidence of Parkinsonism, akathisia and dystonia compared with titrated doses of 
haloperidol. In the absence of detailed information on the pre-existing history of individual acute and 
tardive extrapyramidal movement disorders, it cannot be concluded at present that olanzapine 
produces less tardive dyskinesia and/or other tardive extrapyramidal syndromes. 

7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been 
reported when olanzapine is stopped abruptly. 

8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of 
normal range in approximately 30% of olanzapine treated patients with normal baseline prolactin 
value. In the majority of these patients the elevations were generally mild, and remained below two 
times the upper limit of normal range.  

9 Adverse event identified from clinical trials in the Olanzapine Integrated Database. 

10 As assessed by measured values from clinical trials in the Olanzapine Integrated Database. 

11 Adverse event identified from spontaneous post-marketing reporting with frequency determined 
utilising the Olanzapine Integrated Database. 

12 Adverse event identified from spontaneous post-marketing reporting with frequency estimated at the 
upper limit of the 95% confidence interval utilising the Olanzapine Integrated Database. 

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. 



87 

Additional information on special populations 
In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher 
incidence of death and cerebrovascular adverse reactions compared to placebo (see section 4.4). Very 
common adverse reactions associated with the use of olanzapine in this patient group were abnormal 
gait and falls. Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and 
urinary incontinence were observed commonly. 

In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with 
Parkinson’s disease, worsening of Parkinsonian symptomatology and hallucinations were reported 
very commonly and more frequently than with placebo. 

In one clinical trial in patients with bipolar mania, valproate combination therapy with olanzapine 
resulted in an incidence of neutropenia of 4.1 %; a potential contributing factor could be high plasma 
valproate levels. Olanzapine administered with lithium or valproate resulted in increased levels (≥ 10 
%) of tremor, dry mouth, increased appetite, and weight gain. Speech disorder was also reported 
commonly. During treatment with olanzapine in combination with lithium or divalproex, an increase 
of ≥ 7 % from baseline body weight occurred in 17.4 % of patients during acute treatment (up to 6 
weeks). Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with 
bipolar disorder was associated with an increase of ≥ 7 % from baseline body weight in 39.9 % of 
patients. 

Paediatric population 
Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years. 
Although no clinical studies designed to compare adolescents to adults have been conducted, data 
from the adolescent trials were compared to those of the adult trials. 

The following table summarises the adverse reactions reported with a greater frequency in adolescent 
patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-term 
clinical trials in adolescent patients. Clinically significant weight gain (≥ 7 %) appears to occur more 
frequently in the adolescent population compared to adults with comparable exposures. The magnitude 
of weight gain and the proportion of adolescent patients who had clinically significant weight gain 
were greater with long-term exposure (at least 24 weeks) than with short-term exposure. 

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
The frequency terms listed are defined as follows: Very common (≥ 1/10), common (≥ 1/100 to < 
1/10).

Metabolism and nutrition disorders
Very common: Weight 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). 



88 

15 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high (≥ 5.17 
mmol/l) were observed commonly. Changes in total fasting cholesterol levels from borderline at 
baseline (≥ 4.39 - < 5.17 mmol/l) to high (≥ 5.17 mmol/l) were very common. 

16 Elevated plasma prolactin levels were reported in 47.4 % of adolescent patients. 

Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

Signs and symptoms 
Very common symptoms in overdose (> 10 % incidence) include tachycardia, agitation/ 
aggressiveness, dysarthria, various extrapyramidal symptoms, and reduced level of consciousness 
ranging from sedation to coma. 

Other medically significant sequelae of overdose include delirium, convulsion, coma, possible 
neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, 
cardiac arrhythmias (< 2 % of overdose cases) and cardiopulmonary arrest. Fatal outcomes have been 
reported for acute overdoses as low as 450 mg but survival has also been reported following acute 
overdose of approximately 2 g of oral olanzapine. 

Management 
There is no specific antidote for olanzapine. Induction of emesis is not recommended. Standard 
procedures for management of overdose may be indicated (i.e. gastric lavage, administration of 
activated charcoal). The concomitant administration of activated charcoal was shown to reduce the 
oral bioavailability of olanzapine by 50 to 60 %. 

Symptomatic treatment and monitoring of vital organ function should be instituted according to 
clinical presentation, including treatment of hypotension and circulatory collapse and support of 
respiratory function. Do not use epinephrine, dopamine, or other sympathomimetic agents with beta-
agonist activity since beta stimulation may worsen hypotension. Cardiovascular monitoring is 
necessary to detect possible arrhythmias. Close medical supervision and monitoring should continue 
until the patient recovers. 

5. PHARMACOLOGICAL PROPERTIES

5.1  Pharmacodynamic properties

Pharmacotherapeutic group: psycholeptics, diazepines, oxazepines, thiazepines and oxepines, ATC 
code N05A H03. 

Pharmacodynamic effects 
Olanzapine is an antipsychotic, antimanic and mood stabilising agent that demonstrates a broad 
pharmacologic profile across a number of receptor systems. 

In preclinical studies, olanzapine exhibited a range of receptor affinities (Ki < 100 nM) for serotonin 5 
HT2A/2C, 5 HT3, 5 HT6; dopamine D1, D2, D3, D4, D5; cholinergic muscarinic receptors M1-M5; α1
adrenergic; and histamine H1 receptors. Animal behavioural studies with olanzapine indicated 5 HT, 
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 



89 

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).  

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. 



90 

5.2 Pharmacokinetic properties

Absorption 
Olanzapine is well absorbed after oral administration, reaching peak plasma concentrations within 5 to 
8 hours. The absorption is not affected by food. Absolute oral bioavailability relative to intravenous 
administration has not been determined. 

Distribution 
The plasma protein binding of Olanzapine was about 93 % over the concentration range of about 7 to 
about 1000 ng/ml. Olanzapine is bound predominantly to albumin and α1-acid-glycoprotein. 

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 %). 

SmokingIn 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. 



91 

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 



92 

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, 35, 56, 70 and 98 tablets per carton. 

Not all pack sizes may be marketed 

6.6 Special precautions for disposal 

No special requirements 

7. MARKETING AUTHORISATION HOLDER

Glenmark Arzneimittel GmbH 
Industriestr. 31, D – 82194 
Gröbenzell, Germany 

8. MARKETING AUTHORISATION NUMBER(S)  

EU/1/09/587/016 
EU/1/09/587/017 
EU/1/09/587/018 
EU/1/09/587/019 
EU/1/09/587/025 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 03 December 2009 
Date of latest renewal: 19 August 2014 

10. DATE OF REVISION OF THE TEXT 

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



93 

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



94 

A. MANUFACTURER(S) 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 

Glenmark Pharmaceuticals Europe Limited 
Building 2, Croxley Green Business Park, 
Croxley Green 
Hertfordshire, WD18 8YA, 
United Kingdom 

The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 

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 

At the time of granting the marketing authorisation, the submission of periodic safety update reports is 
not required for this medicinal product. However, the marketing authorisation holder shall submit 
periodic safety update reports for this medicinal product if the product is included in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and 
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) 

Not applicable. 



95 

ANNEX III 

LABELLING AND PACKAGE LEAFLET



96 

A. LABELLING



97 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON

1. NAME OF THE MEDICINAL PRODUCT

Olanzapine Glenmark 2.5 mg tablets 

Olanzapine 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each tablet contains 2.5 mg olanzapine. 

3. LIST OF EXCIPIENTS

Contains aspartame. 

See package leaflet for further information 

4. PHARMACEUTICAL FORM AND CONTENTS

Tablet 

28 tablets 
56 tablets 
70 tablets 
98 tablets 

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use. 

Oral use 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children 

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 



98 

9. SPECIAL STORAGE CONDITIONS

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 Arzneimittel GmbH 
Industriestr. 31, D – 82194 
Gröbenzell, Germany 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/09/587/001 
EU/1/09/587/002 
EU/1/09/587/003 
EU/1/09/587/020 

13. BATCH NUMBER

BN 

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Olanzapine Glenmark 2.5 mg tablets 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number}  
SN: {number}  
NN: {number} 



99 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

Aluminium blisters 

1. NAME OF THE MEDICINAL PRODUCT 

Olanzapine Glenmark 2.5 mg tablets 

Olanzapine 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

Glenmark Arzneimittel GmbH 

3. EXPIRY DATE 

EXP 

4. BATCH NUMBER 

BN 

5. OTHER 



100 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON

1. NAME OF THE MEDICINAL PRODUCT

Olanzapine Glenmark 5 mg tablets 

Olanzapine 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each tablet contains 5 mg olanzapine. 

3. LIST OF EXCIPIENTS

Contains aspartame. 
See package leaflet for further information 

4. PHARMACEUTICAL FORM AND CONTENTS

Tablet 

28 tablets 
56 tablets 
70 tablets 
98 tablets 

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use. 

Oral use 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children 

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 



101 

9. SPECIAL STORAGE CONDITIONS

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 Arzneimittel GmbH 
Industriestr. 31, D – 82194 
Gröbenzell, Germany 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/09/587/004 
EU/1/09/587/005 
EU/1/09/587/006 
EU/1/09/587/021 

13. BATCH NUMBER

BN 

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Olanzapine Glenmark 5 mg tablets 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number}  
SN: {number}  
NN: {number} 



102 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

Aluminium blisters 

1. NAME OF THE MEDICINAL PRODUCT 

Olanzapine Glenmark 5 mg tablets 

Olanzapine 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

Glenmark Arzneimittel GmbH 

3. EXPIRY DATE 

EXP 

4. BATCH NUMBER 

BN 

5. OTHER 



103 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON

1. NAME OF THE MEDICINAL PRODUCT

Olanzapine Glenmark 7.5 mg tablets 

Olanzapine 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each tablet contains 7.5 mg olanzapine. 

3. LIST OF EXCIPIENTS

Contains aspartame. 
See package leaflet for further information 

4. PHARMACEUTICAL FORM AND CONTENTS

Tablet 

28 tablets 
56 tablets 
70 tablets 
98 tablets 

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use. 

Oral use 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children 

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 



104 

9. SPECIAL STORAGE CONDITIONS

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 Arzneimittel GmbH 
Industriestr. 31, D – 82194 
Gröbenzell, Germany 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/09/587/007 
EU/1/09/587/008 
EU/1/09/587/009 
EU/1/09/587/022 

13. BATCH NUMBER

BN 

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Olanzapine Glenmark 7.5 mg tablets 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number}  
SN: {number}  
NN: {number} 



105 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

Aluminium blisters 

1. NAME OF THE MEDICINAL PRODUCT 

Olanzapine Glenmark 7.5 mg tablets 

Olanzapine 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

Glenmark Arzneimittel GmbH 

3. EXPIRY DATE 

EXP 

4. BATCH NUMBER 

BN 

5. OTHER 



106 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON

1. NAME OF THE MEDICINAL PRODUCT

Olanzapine Glenmark 10 mg tablets 

Olanzapine 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each tablet contains 10 mg olanzapine. 

3. LIST OF EXCIPIENTS

Contains aspartame. 
See package leaflet for further information 

4. PHARMACEUTICAL FORM AND CONTENTS

Tablet 

28 tablets 
56 tablets 
70 tablets 
98 tablets 

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use. 

Oral use 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children 

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 



107 

9. SPECIAL STORAGE CONDITIONS

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 Arzneimittel GmbH 
Industriestr. 31, D – 82194 
Gröbenzell, Germany 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/09/587/010 
EU/1/09/587/011 
EU/1/09/587/012 
EU/1/09/587/023 

13. BATCH NUMBER

BN 

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Olanzapine Glenmark 10 mg tablets 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number}  
SN: {number}  
NN: {number} 



108 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

Aluminium blisters 

1. NAME OF THE MEDICINAL PRODUCT 

Olanzapine Glenmark 10 mg tablets 

Olanzapine 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

Glenmark Arzneimittel GmbH 

3. EXPIRY DATE 

EXP 

4. BATCH NUMBER 

BN 

5. OTHER 



109 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON

1. NAME OF THE MEDICINAL PRODUCT

Olanzapine Glenmark 15 mg tablets 

Olanzapine 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each tablet contains 15 mg olanzapine. 

3. LIST OF EXCIPIENTS

Contains aspartame. 
See package leaflet for further information 

4. PHARMACEUTICAL FORM AND CONTENTS

Tablet 

28 tablets 
56 tablets 
70 tablets 
98 tablets 

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use. 

Oral use 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children 

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 



110 

9. SPECIAL STORAGE CONDITIONS

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 Arzneimittel GmbH 
Industriestr. 31, D – 82194 
Gröbenzell, Germany 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/09/587/013 
EU/1/09/587/014 
EU/1/09/587/015 
EU/1/09/587/024 

13. BATCH NUMBER

BN 

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Olanzapine Glenmark 15 mg tablets 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number}  
SN: {number}  
NN: {number} 



111 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

Aluminium blisters 

1. NAME OF THE MEDICINAL PRODUCT 

Olanzapine Glenmark 15 mg tablets 
Olanzapine 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

Glenmark Arzneimittel GmbH 

3. EXPIRY DATE 

EXP 

4. BATCH NUMBER 

BN 

5. OTHER 



112 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON

1. NAME OF THE MEDICINAL PRODUCT

Olanzapine Glenmark 20 mg tablets 

Olanzapine 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each tablet contains 20 mg olanzapine 

3. LIST OF EXCIPIENTS

Contains aspartame. 
See package leaflet for further information 

4. PHARMACEUTICAL FORM AND CONTENTS

Tablet 

28 tablets 
35 tablets 
56 tablets 
70 tablets 
98 tablets 

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use. 

Oral use 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children 

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 



113 

9. SPECIAL STORAGE CONDITIONS

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 Arzneimittel GmbH 
Industriestr. 31, D – 82194 
Gröbenzell, Germany 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/09/587/016 
EU/1/09/587/017 
EU/1/09/587/018 
EU/1/09/587/019 
EU/1/09/587/025 

13. BATCH NUMBER

BN 

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Olanzapine Glenmark 20 mg tablets 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number}  
SN: {number}  
NN: {number} 



114 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

Aluminium blisters 

1. NAME OF THE MEDICINAL PRODUCT 

Olanzapine Glenmark 20 mg tablets 

Olanzapine 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

Glenmark Arzneimittel GmbH 

3. EXPIRY DATE 

EXP 

4. BATCH NUMBER 

BN 

5. OTHER 



115 

B. PACKAGE LEAFLET



116 

Package leaflet: Information for the user 

Olanzapine Glenmark 2.5 mg tablets 
Olanzapine Glenmark 5 mg tablets 

Olanzapine Glenmark 7.5 mg tablets 
Olanzapine Glenmark 10 mg tablets 
Olanzapine Glenmark 15 mg tablets 
Olanzapine Glenmark 20 mg 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 Olanzapine Glenmark is and what it is used for 
2. What you need to know before you take Olanzapine Glenmark 
3. How to take Olanzapine Glenmark 
4. Possible side effects 
5. How to store Olanzapine Glenmark  
6. Contents of the pack and other information 

1. What Olanzapine Glenmark is and what it is used for 

Olanzapine Glenmark contains the active substance olanzapine. Olanzapine Glenmark belongs to a 
group of medicines called antipsychotics. 

Olanzapine Glenmark 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. 

Olanzapine Glenmark 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 Olanzapine Glenmark

Do not take Olanzapine Glenmark 
- 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 Olanzapine Glenmark 



117 

- The use of Olanzapine Glenmark 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 Olanzapine Glenmark  tell your doctor. 

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

- Weight gain has been seen in patients taking Olanzapine Glenmark. 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 Olanzapine Glenmark. Your doctor should do blood tests to check blood sugar and 
certain fat levels before you start taking Olanzapine Glenmark and regularly during treatment. 

- Tell your 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 
Olanzapine Glenmark is not for patients who are under 18 years.  

Other medicines and Olanzapine Glenmark 
Only take other medicines while you are on Olanzapine Glenmark if your doctor tells you that you 
can. You might feel drowsy if Olanzapine Glenmark 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 antidepresant) or 

ciprofloxacin (an antibiotic) – it may be necessary to change your Olanzapine Glenmark dose. 

Olanzapine Glenmark with alcohol 
Do not drink any alcohol if you have been given Olanzapine Glenmark as together with alcohol it may 
make you feel drowsy. 



118 

Pregnancy and breast-feeding 

If you are pregnant or breast-feeding, think you might 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  Olanzapine Glenmark can pass into breast milk.  

The following symptoms may occur in newborn babies, of mothers that have used Olanzapine 
Glenmark in the last trimester (last three months of their pregnancy): shaking, muscle stiffness and/or 
weakness, sleepiness, agitation, breathing problems, and difficulty in feeding. If your baby develops 
any of these symptoms you may need to contact your doctor. 

Driving and using machines 
There is a risk of feeling drowsy when you are given Olanzapine Glenmark. If this happens do not 
drive or operate any tools or machines. Tell your doctor. 

Olanzapine Glenmark contains aspartame  
Olanzapine Glenmark contains a source of phenylalanine. This may be harmful for people with 
phenylketonuria. 

3. How to take Olanzapine Glenmark 

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 Olanzapine Glenmark tablets to take and how long you should 
continue to take them. The daily dose of Olanzapine Glenmark is between 5 mg and 20 mg. Consult 
your doctor if your symptoms return but do not stop taking Olanzapine Glenmark unless your 
doctor tells you to. 

You should take your Olanzapine Glenmark 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. Olanzapine Glenmark tablets are for oral use. You should swallow the Olanzapine 
Glenmark tablets whole, with water. 

If you take more Olanzapine Glenmark than you should 
Patients who have taken more Olanzapine Glenmark 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 Olanzapine Glenmark 
Take your tablets as soon as you remember. Do not take two doses in one day. 

If you stop taking Olanzapine Glenmark 
Do not stop taking your tablets just because you feel better. It is important that you carry on taking  
Olanzapine Glenmark for as long as your doctor tells you. 

If you suddenly stop taking Olanzapine Glenmark, 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.  



119 

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

Tell your doctor immediately if you have: 
unusual movement (a common side effect that may affect up to 1 in 10 people) mainly of the 
face or tongue; 
blood clots in the veins (an uncommon side effect that may affect up to 1 in 100 people) 
especially in the legs (symptoms include swelling, pain, and redness in the leg), which may travel 
through blood vessels to the lungs causing chest pain and difficulty in breathing. If you notice any 
of these symptoms seek medical advice immediately; 
a combination of fever, faster breathing, sweating, muscle stiffness and drowsiness or sleepiness 

(the frequency of this side effect cannot be estimated from the available data). 

Very common side effects (may affect more than 1 in 10 people) include: 
Weight gain
Sleepiness  
Increases in the 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 
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. 



120 

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. 
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.  
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 cell (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 Olanzapine Glenmark may worsen the symptoms. 

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

5. How to store Olanzapine Glenmark 

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 Olanzapine Glenmark contains 
- The active substance is olanzapine
- Each Olanzapine Glenmark tablet contains 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg or 20 mg 

olanzapine



121 

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

What Olanzapine Glenmark looks like and contents of the pack 
Olanzapine Glenmark 2.5mg:  
yellow coloured circular flat bevelled edge tablets with ‘A’ debossed on one side. 
Olanzapine Glenmark 5 mg:  
yellow coloured circular flat bevelled edge tablets with ‘B’ debossed on one side. 
Olanzapine Glenmark 7.5 mg: 
yellow coloured circular flat bevelled edge tablets with ‘C’ debossed on one side. 
Olanzapine Glenmark 10 mg:  
yellow coloured circular flat bevelled edge tablets with ‘OL’ debossed on one side and ‘D’ debossed 
on other side. 
Olanzapine Glenmark 15 mg:  
yellow coloured circular flat bevelled edge tablets with ‘OL’ debossed on one side and ‘E’ debossed 
on other side. 
Olanzapine Glenmark 20 mg:  
yellow coloured circular flat bevelled edge tablets with ‘OL’ debossed on one side and ‘F’ debossed 
on other side. 

Olanzapine Glenmark 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg are available in aluminium foil blisters of 
28, 56, 70 and 98tablets  

Olanzapine Glenmark 20 mg tablets are available in aluminium foil blisters of 28, 35, 56, 70 and 98 
tablets 

Not all pack sizes may be marketed. 

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder 
Glenmark Arzneimittel GmbH 
Industriestr. 31, 82194 
Gröbenzell, Germany 

Manufacturer 
Glenmark Pharmaceuticals s.r.o. 
City Tower, Hvězdova 1716/2b, 140 78 Praha 4 
Czech Republic 

Glenmark Pharmaceuticals Europe Limited 
Building 2, Croxley Green Business Park, 
Croxley Green 
Hertfordshire, WD18 8YA, 
United Kingdom 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 

België/Belgique/Belgien
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

Luxembourg/Luxemburg
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

България 
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

Magyarország 
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 



122 

Česká republika
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

Malta 
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

Danmark
Glenmark Pharmaceuticals Nordic AB 
Tél/Tel: + 46 (0) 40 35 48 10 

Nederland
Glenmark Pharmaceuticals B.V. 
Tél/Tel: + 31 629 62 4818 / +31 40 245 3611 

Deutschland
Glenmark Arzneimittel GmbH 
Tel: + 49 (8142) 44392 0 

Norge
Glenmark Pharmaceuticals Nordic AB  
Tél/Tel: + 46 (0) 40 35 48 10 

Eesti 
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

Österreich
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

Ελλάδα
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

Polska
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

España 
Viso Farmacéutica S.L.U 
Tél/Tel: + 34 911 593 944 

Portugal
Glenmark Arzneimittel GmbH 
Tel: + 49 (8142) 44392 199 

France 
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

Hrvatska
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

România 
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

Ireland
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

Slovenija
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

Ísland 
Glenmark Pharmaceuticals Nordic AB  
Tél/Tel: + 46 (0) 40 35 48 10 

Slovenská republika 
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

Italia
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

Suomi/Finland
Glenmark Pharmaceuticals Nordic AB  
Tél/Tel: + 46 (0)40 35 48 10 

Κύπρος 
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

Sverige 
Glenmark Pharmaceuticals Nordic AB  
Tél/Tel: + 46 (0)40 35 48 10 

Latvija 
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 

United Kingdom 
Glenmark Pharmaceuticals Europe Limited 
Tél/Tel: + 44 (0) 800 4580 383/0 1923 693939 

Lietuva
Glenmark Arzneimittel GmbH, Germany 
Tel: + 49 (8142) 44392 199 



123 

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

Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu


	SUMMARY OF PRODUCT CHARACTERISTICS
	Olanzapine Glenmark 2.5 mg tablets
	1. NAME OF THE MEDICINAL PRODUCT
	2. QUALITATIVE AND QUANTITATIVE COMPOSITION
	3. PHARMACEUTICAL FORM
	4. CLINICAL PARTICULARS
	4.1 Therapeutic indications
	4.2 Posology and method of administration
	4.3 Contraindications
	4.4 Special warnings and precautions for use
	4.5 Interaction with other medicinal products and other forms of interaction
	4.6 Fertility, pregnancy and lactation
	4.7 Effects on ability to drive and use machines
	4.8 Undesirable effects
	4.9 Overdose

	5. PHARMACOLOGICAL PROPERTIES
	5.1 Pharmacodynamic properties
	5.2 Pharmacokinetic properties
	5.3 Preclinical safety data

	6. PHARMACEUTICAL PARTICULARS
	6.1 List of excipients
	6.2 Incompatibilities
	6.3 Shelf life
	6.4 Special precautions for storage
	6.5 Nature and contents of container
	6.6 Special precautions for disposal

	7. MARKETING AUTHORISATION HOLDER
	8. MARKETING AUTHORISATION NUMBER(S)
	9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
	10. DATE OF REVISION OF THE TEXT

	Olanzapine Glenmark 5 mg tablets
	1. NAME OF THE MEDICINAL PRODUCT
	2. QUALITATIVE AND QUANTITATIVE COMPOSITION
	3. PHARMACEUTICAL FORM
	4. CLINICAL PARTICULARS
	4.1 Therapeutic indications
	4.2 Posology and method of administration
	4.3 Contraindications
	4.4 Special warnings and precautions for use
	4.5 Interaction with other medicinal products and other forms of interaction
	4.6 Fertility, pregnancy and lactation
	4.7 Effects on ability to drive and use machines
	4.8 Undesirable effects
	4.9 Overdose

	5. PHARMACOLOGICAL PROPERTIES
	5.1 Pharmacodynamic properties
	5.2 Pharmacokinetic properties
	5.3 Preclinical safety data

	6. PHARMACEUTICAL PARTICULARS
	6.1 List of excipients
	6.2 Incompatibilities
	6.3 Shelf life
	6.4 Special precautions for storage
	6.5 Nature and contents of container
	6.6 Special precautions for disposal

	7. MARKETING AUTHORISATION HOLDER
	8. MARKETING AUTHORISATION NUMBER(S)
	9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
	10. DATE OF REVISION OF THE TEXT

	Olanzapine Glenmark 7.5 mg tablets
	1. NAME OF THE MEDICINAL PRODUCT
	2. QUALITATIVE AND QUANTITATIVE COMPOSITION
	3. PHARMACEUTICAL FORM
	4. CLINICAL PARTICULARS
	4.1 Therapeutic indications
	4.2 Posology and method of administration
	4.3 Contraindications
	4.4 Special warnings and precautions for use
	4.5 Interaction with other medicinal products and other forms of interaction
	4.6 Fertility, pregnancy and lactation
	4.7 Effects on ability to drive and use machines
	4.8 Undesirable effects
	4.9 Overdose

	5. PHARMACOLOGICAL PROPERTIES
	5.1 Pharmacodynamic properties
	5.2 Pharmacokinetic properties
	5.3 Preclinical safety data

	6. PHARMACEUTICAL PARTICULARS
	6.1 List of excipients
	6.2 Incompatibilities
	6.3 Shelf life
	6.4 Special precautions for storage
	6.5 Nature and contents of container
	6.6 Special precautions for disposal

	7. MARKETING AUTHORISATION HOLDER
	8. MARKETING AUTHORISATION NUMBER(S)
	9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
	10. DATE OF REVISION OF THE TEXT

	Olanzapine Glenmark 10 mg tablets
	1. NAME OF THE MEDICINAL PRODUCT
	2. QUALITATIVE AND QUANTITATIVE COMPOSITION
	3. PHARMACEUTICAL FORM
	4. CLINICAL PARTICULARS
	4.1 Therapeutic indications
	4.2 Posology and method of administration
	4.3 Contraindications
	4.4 Special warnings and precautions for use
	4.5 Interaction with other medicinal products and other forms of interaction
	4.6 Fertility, pregnancy and lactation
	4.7 Effects on ability to drive and use machines
	4.8 Undesirable effects
	4.9 Overdose

	5. PHARMACOLOGICAL PROPERTIES
	5.1 Pharmacodynamic properties
	5.2 Pharmacokinetic properties
	5.3 Preclinical safety data

	6. PHARMACEUTICAL PARTICULARS
	6.1 List of excipients
	6.2 Incompatibilities
	6.3 Shelf life
	6.4 Special precautions for storage
	6.5 Nature and contents of container
	6.6 Special precautions for disposal

	7. MARKETING AUTHORISATION HOLDER
	8. MARKETING AUTHORISATION NUMBER(S)
	9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
	10. DATE OF REVISION OF THE TEXT

	Olanzapine Glenmark 15 mg tablets
	1. NAME OF THE MEDICINAL PRODUCT
	2. QUALITATIVE AND QUANTITATIVE COMPOSITION
	3. PHARMACEUTICAL FORM
	4. CLINICAL PARTICULARS
	4.1 Therapeutic indications
	4.2 Posology and method of administration
	4.3 Contraindications
	4.4 Special warnings and precautions for use
	4.5 Interaction with other medicinal products and other forms of interaction
	4.6 Fertility, pregnancy and lactation
	4.7 Effects on ability to drive and use machines
	4.8 Undesirable effects
	4.9 Overdose

	5. PHARMACOLOGICAL PROPERTIES
	5.1 Pharmacodynamic properties
	5.2 Pharmacokinetic properties
	5.3 Preclinical safety data

	6. PHARMACEUTICAL PARTICULARS
	6.1 List of excipients
	6.2 Incompatibilities
	6.3 Shelf life
	6.4 Special precautions for storage
	6.5 Nature and contents of container
	6.6 Special precautions for disposal

	7. MARKETING AUTHORISATION HOLDER
	8. MARKETING AUTHORISATION NUMBER(S)
	9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
	10. DATE OF REVISION OF THE TEXT

	Olanzapine Glenmark 20 mg tablets
	1. NAME OF THE MEDICINAL PRODUCT
	2. QUALITATIVE AND QUANTITATIVE COMPOSITION
	3. PHARMACEUTICAL FORM
	4. CLINICAL PARTICULARS
	4.1 Therapeutic indications
	4.2 Posology and method of administration
	4.3 Contraindications
	4.4 Special warnings and precautions for use
	4.5 Interaction with other medicinal products and other forms of interaction
	4.6 Fertility, pregnancy and lactation
	4.7 Effects on ability to drive and use machines
	4.8 Undesirable effects
	4.9 Overdose

	5. PHARMACOLOGICAL PROPERTIES
	5.1 Pharmacodynamic properties
	5.2 Pharmacokinetic properties
	5.3 Preclinical safety data

	6. PHARMACEUTICAL PARTICULARS
	6.1 List of excipients
	6.2 Incompatibilities
	6.3 Shelf life
	6.4 Special precautions for storage
	6.5 Nature and contents of container
	6.6 Special precautions for disposal

	7. MARKETING AUTHORISATION HOLDER
	8. MARKETING AUTHORISATION NUMBER(S)
	9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
	10. DATE OF REVISION OF THE TEXT


	A. MANUFACTURER(S) 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 AND EFFECTIVEUSE OF THE MEDICINAL PRODUCT
	LABELLING AND PACKAGE LEAFLET
	A. LABELLING
	Olanzapine Glenmark 2.5 mg tablets
	PARTICULARS TO APPEAR ON THE OUTER PACKAGING
	MINIMUM PARTICULARS TO APPEAR ON BLISTERS

	Olanzapine Glenmark 5 mg tablets
	PARTICULARS TO APPEAR ON THE OUTER PACKAGING
	MINIMUM PARTICULARS TO APPEAR ON BLISTERS

	Olanzapine Glenmark 7.5 mg tablets
	PARTICULARS TO APPEAR ON THE OUTER PACKAGING
	MINIMUM PARTICULARS TO APPEAR ON BLISTERS

	Olanzapine Glenmark 10 mg tablets
	PARTICULARS TO APPEAR ON THE OUTER PACKAGING
	MINIMUM PARTICULARS TO APPEAR ON BLISTERS

	Olanzapine Glenmark 15 mg tablets
	PARTICULARS TO APPEAR ON THE OUTER PACKAGING
	MINIMUM PARTICULARS TO APPEAR ON BLISTERS

	Olanzapine Glenmark 20 mg tablets
	PARTICULARS TO APPEAR ON THE OUTER PACKAGING
	MINIMUM PARTICULARS TO APPEAR ON BLISTERS


	B. PACKAGE LEAFLET
	1. What Olanzapine Glenmark is and what it is used for
	2. What you need to know before you take Olanzapine Glenmark
	3. How to take Olanzapine Glenmark
	4. Possible side effects
	5. How to store Olanzapine Glenmark
	6. Contents of the pack and other information
	What Olanzapine Glenmark looks like and contents of the pack
	Marketing Authorisation Holder and Manufacturer
	This leaflet was last revised in