Olanzapine Cipla

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Olanzapine Cipla 2.5 mg coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each coated tablet contains 2.5 mg olanzapine.  
 
Excipient with known effect: Each coated tablet contains 80.7 mg lactose monohydrate  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Coated tablet 
 
White, round, biconvex, coated tablets with ‘2.5’ debossing on one side and ‘OLZ’ on the other. 
 
 
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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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). 
 
Elderly patients 
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). 
 

Patients with 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. 
 
Gender  

The starting dose and dose range need not be routinely altered for female patients relative to male 
patients. 
 
Smokers 

The starting dose and dose range need not be routinely altered for non-smokers relative to smokers. 
 
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) 
 
4.3 Contraindications 

 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.   
Patients with known risk for 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 approved for the treatment of dementia-related psychosis and/or behavioural 
disturbances and is not recommended for use in this particular group of patients because of an 
increase in mortality and the risk of cerebrovascular accident. In placebo-controlled clinical trials (6-
12 weeks duration) of elderly patients (mean age 78 years) with dementia-related psychosis and/or 
disturbed behaviours, there was a 2-fold increase in the incidence of death in olanzapine-treated 
patients compared to patients treated with placebo (3.5% vs. 1.5%, respectively). The higher 
incidence of death was not associated with olanzapine dose (mean daily dose 4.4 mg) or duration of 
treatment. Risk factors that may predispose this patient population to increased mortality include age 
> 65 years, dysphagia, sedation, malnutrition and dehydration, pulmonary conditions (e.g., 
pneumonia, with or without aspiration), or concomitant use of benzodiazepines. However, the 
incidence of death was higher in olanzapine-treated than in placebo-treated patients independent of 
these risk factors. 
 
In the same clinical trials, cerebrovascular adverse events (CVAE e.g., stroke, transient ischemic 
attack), including fatalities, were reported. There was a 3-fold increase in CVAE in patients treated 
with olanzapine compared to patients treated with placebo (1.3% vs. 0.4%, respectively). All 



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olanzapine- and placebo-treated patients who experienced a cerebrovascular event had pre-existing 
risk factors. Age > 75 years and vascular/mixed type dementia were identified as risk factors for 
CVAE in association with olanzapine treatment. The efficacy of olanzapine was not established in 
these trials. 
 

Parkinson's disease 

The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with 
Parkinson's disease is not recommended. In clinical trials, worsening of Parkinsonian symptomatology 
and hallucinations were reported very commonly and more frequently than with placebo (see section 
4.8), and olanzapine was not more effective than placebo in the treatment of psychotic symptoms. In 
these trials, patients were initially required to be stable on the lowest effective dose of anti-
Parkinsonian medicinal products (dopamine agonist) and to remain on the same anti-Parkinsonian 
medicinal products and dosages throughout the study. Olanzapine was started at 2.5 mg/day and 
titrated to a maximum of 15 mg/day based on investigator judgement. 
 

Neuroleptic Malignant Syndrome (NMS)  

NMS is a potentially life-threatening condition associated with antipsychotic medicinal products. 
Rare cases reported as NMS have also been received in association with olanzapine. Clinical 
manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of 
autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac 
dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria 
(rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms indicative of 
NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all 
antipsychotic medicines, including olanzapine must be discontinued. 
 
Hyperglycaemia and diabetes 

Hyperglycaemia and/or development or exacerbation of diabetes occasionally associated with 
ketoacidosis or coma has been reported uncommonly, including some fatal cases (see section 4.8). In 
some cases, a prior increase in body weight has been reported which may be a predisposing factor. 
Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines, e.g. 
measuring of blood glucose at baseline, 12 weeks after starting olanzapine treatment and annually 
thereafter. Patients treated with any antipsychotic agents, including Olanzapine Cipla, 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 agents, including Olanzapine Cipla, should 
be monitored regularly for lipids in accordance with utilised antipsychotic guidelines, e.g. at baseline, 
12 weeks after starting olanzapine treatment and every 5 years thereafter. 
 
Anticholinergic activity  
While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials 
revealed a low incidence of related events. However, as clinical experience with olanzapine in 
patients with concomitant illness is limited, caution is advised when prescribing for patients with 
prostatic hypertrophy, or paralytic ileus and related conditions. 
 
Hepatic function 

Transient, asymptomatic elevations of hepatic aminotransferases, ALT, AST have been seen 
commonly, especially in early treatment. Caution should be exercised and follow-up organised in 
patients with elevated ALT and/or AST, in patients with signs and symptoms of hepatic impairment, 
in patients with pre-existing conditions associated with limited hepatic functional reserve, and in 



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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, 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. As with 
other antipsychotics, it is recommended that blood pressure is measured periodically in patients over 
65 years. 
 



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Sudden cardiac death  

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

Olanzapine is not indicated for use in the treatment of children and adolescents. Studies in patients 
aged 13-17 years showed various adverse reactions, including weight gain, changes in metabolic 
parameters and increases in prolactin levels. Long-term outcomes associated with these events have 
not been studied and remain unknown (see sections 4.8 and 5.1). 
 
Lactose  

OLANZAPINE CIPLA tablets contain lactose. Patients with rare hereditary problems of galactose 
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this 
medicine. 
 
4.5 Interaction with other medicinal products and other forms of interaction 

 
Paediatric population 
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. 
 
Neonates 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, hypotonis, 
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. 
 

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 

 

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 



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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). 



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Very common Common Uncommon  Rare 

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 
reported 11 
 
Dystonia (including 
oculogyration) 11 
Tardive dyskinesia11 
 
Amnesia 9 
 

Dysarthria 

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

Respiratory, thoracic and mediastinal disorders 
  Epistaxis9  
Cardiac disorders 

  Bradycardia 
QTc prolongation (see 
section 4.4) 

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

Vascular disorders 

Orthostatic 
hypotension10 

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

 

Gastrointestinal disorders 

 Mild, transient 
anticholinergic effects 
including constipation 
and dry mouth 

Abdominal distension9 Pancreatitis11 

Hepato-biliary disorders 

 Transient, 
asymptomatic 
elevations of hepatic 
aminotransferases 

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



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(ALT, AST), 
especially in early 
treatment (see section 
4.4) 

Skin and subcutaneous tissue disorders 

 Rash Photosensitivity 
reaction 
Alopecia 

 

Musculoskeletal and connective tissue disorders 

 Arthralgia9  Rhabdomyolysis11 
Renal and urinary disorders 

  Urinary incontinence, 
urinary retention 
Urinary hesitation11 

 

 
    
Reproductive system and breast disorders 

 Erectile dysfunction in 
males 
Decreased libido in 
males and females 

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

Priapism12 

General disorders and administration site conditions 

 Asthenia 
Fatigue 
Oedema 
Pyrexia10 

  

Investigations 

Elevated plasma 
prolactin levels8 

Increased alkaline 
phosphatase10 
High creatine 
phosphokinase11 
High Gamma 
Glutamyltransferase10 

High Uric Acid 10 

Increased total 
bilirubin 

 

   Not known 
Pregnancy, puerperium and perinatal conditions                                        

   Drug withdrawal 
syndrome neonatal 
(see section 4.6) 

 
1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) 
categories. Following short term treatment (median duration 47 days), weight gain ≥ 7% of baseline 
body weight  was very common (22.2 %), ≥ 15 % was common (4.2 %) and ≥ 25 % was uncommon 
(0.8 %). Patients gaining ≥ 7 %, ≥ 15 % and ≥ 25 % of their baseline body weight with long-term 
exposure (at least 48 weeks) were very common (64.4 %, 31.7 % and 12.3 % respectively). 
 
2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were 
greater in patients without evidence of lipid dysregulation at baseline. 
 
3 Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high 
(≥ 6.2 mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17 - 
< 6.2 mmol/l) to high (≥ 6.2 mmol/l) were very common. 
 



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4 Observed for fasting normal levels at baseline (< 5.56 mmol/l) which increased to high (≥ 7 mmol/l). 
Changes in fasting glucose from borderline at baseline (≥ 5.56 - < 7 mmol/l) to high (≥ 7 mmol/l) 
were very common.  
 
5 Observed for fasting normal levels at baseline (< 1.69 mmol/l) which increased to high 
(≥ 2.26 mmol/l). Changes in fasting triglycerides from borderline at baseline (≥ 1.69 mmol/l - 
< 2.26 mmol/l) to high (≥ 2.26 mmol/l) were very common. 
 
6 In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was 
numerically higher, but not statistically significantly different from placebo. Olanzapine-treated 
patients had a lower incidence of Parkinsonism, akathisia and dystonia compared with titrated doses of 
haloperidol. In the absence of detailed information on the pre-existing history of individual acute and 
tardive extrapyramidal movement disorders, it cannot be concluded at present that olanzapine produces 
less tardive dyskinesia and/or other tardive extrapyramidal syndromes. 
 
7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been 
reported when olanzapine is stopped abruptly. 
 
8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of 
normal range in approximately 30% of olanzapine treated patients with normal baseline prolactin 
value. In the majority of these patients the elevations were generally mild, and remained below two 
times the upper limit of normal range.  
 
9 Adverse event identified from clinical trials in the Olanzapine Integrated Database. 
 
10 As assessed by measured values from clinical trials in the Olanzapine Integrated Database. 
 
11 Adverse event identified from spontaneous post-marketing reporting with frequency determined 
utilising the Olanzapine Integrated Database. 
 
12 Adverse event identified from spontaneous post-marketing reporting with frequency estimated at 
the upper limit of the 95% confidence interval utilising the Olanzapine Integrated Database. 
 
Long-term exposure (at least 48 weeks) 

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

Additional information on special populations 

In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher 
incidence of death and cerebrovascular adverse reactions compared to placebo (see also 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 



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bipolar disorder was associated with an increase of 7% from baseline body weight in 39.9% of 
patients. 
 
Paediatric population 

Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years. 
Although no clinical studies designed to compare adolescents to adults have been conducted, data 
from the adolescent trials were compared to those of the adult trials.  
 
The following table summarises the adverse reactions reported with a greater frequency in adolescent 
patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-
term clinical trials in adolescent patients. Clinically significant weight gain (≥ 7%) appears to occur 
more frequently in the adolescent population compared to adults with comparable exposures. The 
magnitude of weight gain and the proportion of adolescent patients who had clinically significant 
weight gain were greater with long-term exposure (at least 24 weeks) than with short-term exposure.  
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
The frequency terms listed are defined as follows: Very common (≥ 1/10), common (≥ 1/100 to 
< 1/10). 
 
Metabolism and nutrition disorders 

Very common: Weight gain13, elevated triglyceride levels14, increased appetite. 
Common: Elevated cholesterol levels15 
Nervous system disorders 

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

Common: Dry mouth 
Hepato-biliary disorders 

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

Very common: Decreased total bilirubin, increased GGT, elevated plasma prolactin levels16. 
 
13 Following short term treatment (median duration 22 days), weight gain ≥ 7 % of baseline body 
weight (kg) was very common (40.6 %), ≥ 15 % of baseline body weight was common (7.1 %) and ≥ 
25 % was common (2.5 %). With long-term exposure (at least 24 weeks), 89.4 % gained ≥ 7 %, 55.3 
% gained ≥ 15 % and 29.1 % gained ≥ 25% of their baseline body weight. 
 
14  Observed for fasting normal levels at baseline (< 1.016 mmol/l) which increased to high 
(≥ 1.467 mmol/l) and changes in fasting triglycerides from borderline at baseline (≥ 1.016 mmol/l - 
< 1.467 mmol/l) to high (≥ 1.467 mmol/l). 
 
15 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high 
(≥ 5.17 mmol/l) were observed commonly. Changes in total fasting cholesterol levels from borderline 
at baseline (≥ 4.39 - < 5.17 mmol/l) to high (≥ 5.17 mmol/l) were very common. 
 
16 Elevated plasma prolactin levels were reported in 47.4% of adolescent patients. 
 

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, 



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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: diazepines, oxazepines and thiazepines., 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; 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 5 HT2A than dopamine D2 receptor occupancy. In addition, a Single 
Photon Emission Computed Tomography (SPECT) imaging study in schizophrenic patients revealed 
that olanzapine-responsive patients had lower striatal D2 occupancy than some other antipsychotic- 
and risperidone-responsive patients, while being comparable to clozapine-responsive patients. 
 
Clinical efficacy 

In two of two placebo and two of three comparator controlled trials with over 2,900 schizophrenic 
patients presenting with both positive and negative symptoms, olanzapine was associated with 
statistically significantly greater improvements in negative as well as positive symptoms. 
 

In a multinational, double-blind, comparative study of schizophrenia, schizoaffective, and related 
disorders which included 1,481 patients with varying degrees of associated depressive symptoms 
(baseline mean of 16.6 on the Montgomery-Asberg Depression Rating Scale), a prospective secondary 
analysis of baseline to endpoint mood score change demonstrated a statistically significant 
improvement (p= 0.001) favouring olanzapine (-6.0) versus haloperidol (-3.1). 



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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 

The experience in adolescents (ages 13 to 17 years) is limited to short term efficacy data 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 data on 
maintenance of effect and limited data on long term safety (see sections 4.4 and 4.8).  
 
5.2 Pharmacokinetic properties 

 
Absorption 

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

The plasma protein binding of olanzapine was about 93 % over the concentration range of about 7 to 
about 1000 ng/ml. Olanzapine is bound predominantly to albumin and 1-acid-glycoprotein. 
Biotransformation 

Olanzapine is metabolized in the liver by conjugative and oxidative pathways. The major circulating 
metabolite is the 10-N-glucuronide, which does not pass the blood brain barrier. Cytochromes P450-
CYP1A2 and P450-CYP2D6 contribute to the formation of the N-desmethyl and 2-hydroxymethyl 
metabolites, both exhibited significantly less in vivo pharmacological activity than olanzapine in 
animal studies. The predominant pharmacologic activity is from the parent olanzapine.  
 
Elimination 

After oral administration, the mean terminal elimination half-life of olanzapine in healthy subjects 
varied on the basis of age and gender. 
 



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In healthy elderly (65 and over) versus non-elderly subjects, the mean elimination half-life was 
prolonged (51.8 versus 33.8 hr) and the clearance was reduced (17.5 versus 18.2 l/hr). The 
pharmacokinetic variability observed in the elderly is within the range for the non-elderly. In 44 
patients with schizophrenia  65 years of age, dosing from 5 to 20 mg/day was not associated with 
any distinguishing profile of adverse events. 
 
In female versus male subjects the mean elimination half life was somewhat prolonged (36.7 versus 
32.3 hr) and the clearance was reduced (18.9 versus 27.3 l/hr). However, olanzapine (5-20 mg) 
demonstrated a comparable safety profile in female (n=467) as in male patients (n=869). 
 
Renal impairment 

In renally impaired patients (creatinine clearance < 10 ml/min) versus healthy subjects, there was no 
significant difference in mean elimination half-life (37.7 versus 32.4 hr) or clearance (21.2 versus 
25.0 l/hr). A mass balance study showed that approximately 57 % of radiolabelled olanzapine 
appeared in urine, principally as metabolites. 
 
Smokers 

In smoking subjects with mild hepatic dysfunction, mean elimination half-life (39.3 hr) was prolonged 
and clearance (18.0 l/hr) was reduced analogous to non-smoking healthy subjects (48.8 hr and 
14.1 l/hr, respectively). 
 
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. 
 



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Haematologic toxicity 

Effects on haematology parameters were found in each species, including dose-related reductions in 
circulating leukocytes in mice and non-specific reductions of circulating leukocytes in rats; however, 
no evidence of bone marrow cytotoxicity was found. Reversible neutropenia, thrombocytopenia, or 
anaemia developed in a few dogs treated with 8 or 10 mg/kg/day (total olanzapine exposure [AUC] is 
12- to 15-fold greater than that of a man given a 12-mg dose). In cytopenic dogs, there were no 
adverse effects on progenitor and proliferating cells in the bone marrow.  
 
Reproductive toxicity 

Olanzapine had no teratogenic effects. Sedation affected mating performance of male rats. Estrous 
cycles were affected at doses of 1.1 mg/kg (3 times the maximum human dose) and reproduction 
parameters were influenced in rats given 3 mg/kg (9 times the maximum human dose). In the 
offspring of rats given olanzapine, delays in foetal development and transient decreases in offspring 
activity levels were seen. 
 

Mutagenicity 

Olanzapine was not mutagenic or clastogenic in a full range of standard tests, which included 
bacterial mutation tests and in vitro and in vivo mammalian tests. 
 
Carcinogenicity 

Based on the results of studies in mice and rats, it was concluded that olanzapine is not carcinogenic. 
 

 

6. PHARMACEUTICAL PARTICULARS 

 
6.1 List of excipients 
 
Tablet core  

Lactose monohydrate,  
Maize starch 
Hydroxypropyl cellulose  
Magnesium stearate  
 
Tablet coat  

Opadry II White containing: 
Hypromellose (E464) 
Titanium dioxide (E171) 
Lactose monohydrate 
Polyethylene glycol 3000 
Glycerol triacetate 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Store in the original package. 
 
Store below 30°C. 
 
6.5 Nature and contents of container 



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Cold-formed aluminium blisters in cartons of 28 or 56 tablets per carton.  
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
No special requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Cipla (EU) Limited 
Hillbrow House 
Hillbrow Road 
Esher 
Surrey 
KT10 9NW 
UK 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  

 
EU/1/07/426/001 – Olanzapine Cipla – 2.5 mg – coated tablets – 28 tablets per box 
 
EU/1/07/426/002 –  Olanzapine Cipla – 2.5 mg – coated tablets – 56 tablets per box 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 14 November 2007 
 
Date of latest renewal: 01 October 2012 
 
 
10. DATE OF REVISION OF THE TEXT 

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



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1. NAME OF THE MEDICINAL PRODUCT 
 
Olanzapine Cipla 5 mg coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each coated tablet contains 5 mg olanzapine.  
 
Excipient with known effect: Each coated tablet contains 161.3 mg lactose monohydrate 
 
For the full list of excipients, see section 6.1. 
 

 

3. PHARMACEUTICAL FORM 
 
Coated tablet 
 
White, round, biconvex, coated tablets with ‘OLZ 5’ debossing on one side and ‘NEO’ on the other. 
 
 
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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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). 
 
Elderly patients 
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). 
 

Patients with 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. 
 
Gender  

The starting dose and dose range need not be routinely altered for female patients relative to male 
patients. 
 
Smokers 

The starting dose and dose range need not be routinely altered for non-smokers relative to smokers. 
 
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) 
 
4.3 Contraindications 

 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.   
Patients with known risk for 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 approved for the treatment of dementia-related psychosis and/or behavioural 
disturbances and is not recommended for use in this particular group of patients because of an 
increase in mortality and the risk of cerebrovascular accident. In placebo-controlled clinical trials (6-
12 weeks duration) of elderly patients (mean age 78 years) with dementia-related psychosis and/or 
disturbed behaviours, there was a 2-fold increase in the incidence of death in olanzapine-treated 
patients compared to patients treated with placebo (3.5% vs. 1.5%, respectively). The higher 
incidence of death was not associated with olanzapine dose (mean daily dose 4.4 mg) or duration of 
treatment. Risk factors that may predispose this patient population to increased mortality include age 
> 65 years, dysphagia, sedation, malnutrition and dehydration, pulmonary conditions (e.g., 
pneumonia, with or without aspiration), or concomitant use of benzodiazepines. However, the 
incidence of death was higher in olanzapine-treated than in placebo-treated patients independent of 
these risk factors. 
 
In the same clinical trials, cerebrovascular adverse events (CVAE e.g., stroke, transient ischemic 
attack), including fatalities, were reported. There was a 3-fold increase in CVAE in patients treated 
with olanzapine compared to patients treated with placebo (1.3% vs. 0.4%, respectively). All 



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olanzapine- and placebo-treated patients who experienced a cerebrovascular event had pre-existing 
risk factors. Age > 75 years and vascular/mixed type dementia were identified as risk factors for 
CVAE in association with olanzapine treatment. The efficacy of olanzapine was not established in 
these trials. 
 

Parkinson's disease 

The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with 
Parkinson's disease is not recommended. In clinical trials, worsening of Parkinsonian symptomatology 
and hallucinations were reported very commonly and more frequently than with placebo (see section 
4.8), and olanzapine was not more effective than placebo in the treatment of psychotic symptoms. In 
these trials, patients were initially required to be stable on the lowest effective dose of anti-
Parkinsonian medicinal products (dopamine agonist) and to remain on the same anti-Parkinsonian 
medicinal products and dosages throughout the study. Olanzapine was started at 2.5 mg/day and 
titrated to a maximum of 15 mg/day based on investigator judgement. 
 

Neuroleptic Malignant Syndrome (NMS)  

NMS is a potentially life-threatening condition associated with antipsychotic medicinal products. 
Rare cases reported as NMS have also been received in association with olanzapine. Clinical 
manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of 
autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac 
dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria 
(rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms indicative of 
NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all 
antipsychotic medicines, including olanzapine must be discontinued. 
 
Hyperglycaemia and diabetes 

Hyperglycaemia and/or development or exacerbation of diabetes occasionally associated with 
ketoacidosis or coma has been reported uncommonly, including some fatal cases (see section 4.8). In 
some cases, a prior increase in body weight has been reported which may be a predisposing factor. 
Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines, e.g. 
measuring of blood glucose at baseline, 12 weeks after starting olanzapine treatment and annually 
thereafter. Patients treated with any antipsychotic agents, including Olanzapine Cipla, 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 agents, including Olanzapine Cipla, should 
be monitored regularly for lipids in accordance with utilised antipsychotic guidelines, e.g. at baseline, 
12 weeks after starting olanzapine treatment and every 5 years thereafter. 
 
Anticholinergic activity  
While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials 
revealed a low incidence of related events. However, as clinical experience with olanzapine in 
patients with concomitant illness is limited, caution is advised when prescribing for patients with 
prostatic hypertrophy, or paralytic ileus and related conditions. 
 
Hepatic function 

Transient, asymptomatic elevations of hepatic aminotransferases, ALT, AST have been seen 
commonly, especially in early treatment. Caution should be exercised and follow-up organised in 
patients with elevated ALT and/or AST, in patients with signs and symptoms of hepatic impairment, 
in patients with pre-existing conditions associated with limited hepatic functional reserve, and in 



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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, 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. As with 
other antipsychotics, it is recommended that blood pressure is measured periodically in patients over 
65 years. 
 



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Sudden cardiac death  

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

Olanzapine is not indicated for use in the treatment of children and adolescents. Studies in patients 
aged 13-17 years showed various adverse reactions, including weight gain, changes in metabolic 
parameters and increases in prolactin levels. Long-term outcomes associated with these events have 
not been studied and remain unknown (see sections 4.8 and 5.1). 
 
Lactose  

OLANZAPINE CIPLA tablets contain lactose. Patients with rare hereditary problems of galactose 
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this 
medicine. 
 
4.5 Interaction with other medicinal products and other forms of interaction 

 
Paediatric population 
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. 
 
Neonates 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, hypotonis, 
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. 
 

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 

 

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 



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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). 



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Very common Common Uncommon  Rare 

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 

Development or 
exacerbation of 
diabetes occasionally 
associated with 
ketoacidosis or coma, 
including some fatal 
cases (see section 4.4) 
Hypothermia12 

Nervous system disorders 

Somnolence Dizziness 
Akathisia6 
Parkinsonism6 
Dyskinesia6 

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

Dysarthria 

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

Respiratory, thoracic and mediastinal disorders 
  Epistaxis9  
Cardiac disorders 

  Bradycardia 
QTc prolongation (see 
section 4.4) 

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

Vascular disorders 

Orthostatic 
hypotension10 

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

 

Gastrointestinal disorders 

 Mild, transient 
anticholinergic effects 
including constipation 
and dry mouth 

Abdominal distension9 Pancreatitis11 

Hepato-biliary disorders 

 Transient, 
asymptomatic 
elevations of hepatic 
aminotransferases 

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



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(ALT, AST), 
especially in early 
treatment (see section 
4.4) 

Skin and subcutaneous tissue disorders 

 Rash Photosensitivity 
reaction 
Alopecia 

 

Musculoskeletal and connective tissue disorders 

 Arthralgia9  Rhabdomyolysis 
Renal and urinary disorders 

  Urinary incontinence, 
urinary retention 
Urinary hesitation11 

 

 
    
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 
High Uric Acid 10 

Increased total 
bilirubin 

 

   Not known 
Pregnancy, puerperium and perinatal conditions  

   Drug withdrawal 
syndrome neonatal 
(see section 4.6) 

 
1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) 
categories. Following short term treatment (median duration 47 days), weight gain ≥ 7% of baseline 
body weight  was very common (22.2 %), ≥ 15 % was common (4.2 %) and ≥ 25 % was uncommon 
(0.8 %). Patients gaining ≥ 7 %, ≥ 15 % and ≥ 25 % of their baseline body weight with long-term 
exposure (at least 48 weeks) were very common (64.4 %, 31.7 % and 12.3 % respectively). 
 
2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were 
greater in patients without evidence of lipid dysregulation at baseline. 
 
3 Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high 
(≥ 6.2 mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17 - 
< 6.2 mmol/l) to high (≥ 6.2 mmol/l) were very common. 
 



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4 Observed for fasting normal levels at baseline (< 5.56 mmol/l) which increased to high (≥ 7 mmol/l). 
Changes in fasting glucose from borderline at baseline (≥ 5.56 - < 7 mmol/l) to high (≥ 7 mmol/l) 
were very common.  
 
5 Observed for fasting normal levels at baseline (< 1.69 mmol/l) which increased to high 
(≥ 2.26 mmol/l). Changes in fasting triglycerides from borderline at baseline (≥ 1.69 mmol/l - 
< 2.26 mmol/l) to high (≥ 2.26 mmol/l) were very common. 
 
6 In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was 
numerically higher, but not statistically significantly different from placebo. Olanzapine-treated 
patients had a lower incidence of Parkinsonism, akathisia and dystonia compared with titrated doses of 
haloperidol. In the absence of detailed information on the pre-existing history of individual acute and 
tardive extrapyramidal movement disorders, it cannot be concluded at present that olanzapine produces 
less tardive dyskinesia and/or other tardive extrapyramidal syndromes. 
 
7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been 
reported when olanzapine is stopped abruptly. 
 
8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of 
normal range in approximately 30% of olanzapine treated patients with normal baseline prolactin 
value. In the majority of these patients the elevations were generally mild, and remained below two 
times the upper limit of normal range.  
 
9 Adverse event identified from clinical trials in the Olanzapine Integrated Database. 
 
10 As assessed by measured values from clinical trials in the Olanzapine Integrated Database. 
 
11 Adverse event identified from spontaneous post-marketing reporting with frequency determined 
utilising the Olanzapine Integrated Database. 
 
12 Adverse event identified from spontaneous post-marketing reporting with frequency estimated at 
the upper limit of the 95% confidence interval utilising the Olanzapine Integrated Database. 
 
Long-term exposure (at least 48 weeks) 

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

Additional information on special populations 

In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher 
incidence of death and cerebrovascular adverse reactions compared to placebo (see also 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 



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bipolar disorder was associated with an increase of 7% from baseline body weight in 39.9% of 
patients. 
 
Paediatric population 

Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years. 
Although no clinical studies designed to compare adolescents to adults have been conducted, data 
from the adolescent trials were compared to those of the adult trials.  
 
The following table summarises the adverse reactions reported with a greater frequency in adolescent 
patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-
term clinical trials in adolescent patients. Clinically significant weight gain (≥ 7%) appears to occur 
more frequently in the adolescent population compared to adults with comparable exposures. The 
magnitude of weight gain and the proportion of adolescent patients who had clinically significant 
weight gain were greater with long-term exposure (at least 24 weeks) than with short-term exposure.  
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
The frequency terms listed are defined as follows: Very common (≥ 1/10), common (≥ 1/100 to 
< 1/10). 
 
Metabolism and nutrition disorders 

Very common: Weight gain13, elevated triglyceride levels14, increased appetite. 
Common: Elevated cholesterol levels15 
Nervous system disorders 

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

Common: Dry mouth 
Hepato-biliary disorders 

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

Very common: Decreased total bilirubin, increased GGT, elevated plasma prolactin levels16. 
 
13 Following short term treatment (median duration 22 days), weight gain ≥ 7 % of baseline body 
weight (kg) was very common (40.6 %), ≥ 15 % of baseline body weight was common (7.1 %) and ≥ 
25 % was common (2.5 %). With long-term exposure (at least 24 weeks), 89.4 % gained ≥ 7 %, 55.3 
% gained ≥ 15 % and 29.1 % gained ≥ 25% of their baseline body weight. 
 
14  Observed for fasting normal levels at baseline (< 1.016 mmol/l) which increased to high 
(≥ 1.467 mmol/l) and changes in fasting triglycerides from borderline at baseline (≥ 1.016 mmol/l - 
< 1.467 mmol/l) to high (≥ 1.467 mmol/l). 
 
15 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high 
(≥ 5.17 mmol/l) were observed commonly. Changes in total fasting cholesterol levels from borderline 
at baseline (≥ 4.39 - < 5.17 mmol/l) to high (≥ 5.17 mmol/l) were very common. 
 
16 Elevated plasma prolactin levels were reported in 47.4% of adolescent patients. 

 

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, 



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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: diazepines, oxazepines and thiazepines., 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; 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 5 HT2A than dopamine D2 receptor occupancy. In addition, a Single 
Photon Emission Computed Tomography (SPECT) imaging study in schizophrenic patients revealed 
that olanzapine-responsive patients had lower striatal D2 occupancy than some other antipsychotic- 
and risperidone-responsive patients, while being comparable to clozapine-responsive patients. 
 
Clinical efficacy 

In two of two placebo and two of three comparator controlled trials with over 2,900 schizophrenic 
patients presenting with both positive and negative symptoms, olanzapine was associated with 
statistically significantly greater improvements in negative as well as positive symptoms. 
 

In a multinational, double-blind, comparative study of schizophrenia, schizoaffective, and related 
disorders which included 1,481 patients with varying degrees of associated depressive symptoms 
(baseline mean of 16.6 on the Montgomery-Asberg Depression Rating Scale), a prospective secondary 
analysis of baseline to endpoint mood score change demonstrated a statistically significant 
improvement (p= 0.001) favouring olanzapine (-6.0) versus haloperidol (-3.1). 



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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 

The experience in adolescents (ages 13 to 17 years) is limited to short term efficacy data 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 data on 
maintenance of effect and limited data on long term safety (see sections 4.4 and 4.8).  
 
5.2 Pharmacokinetic properties 

 
Absorption 

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

The plasma protein binding of olanzapine was about 93 % over the concentration range of about 7 to 
about 1000 ng/ml. Olanzapine is bound predominantly to albumin and 1-acid-glycoprotein. 
Biotransformation 

Olanzapine is metabolized in the liver by conjugative and oxidative pathways. The major circulating 
metabolite is the 10-N-glucuronide, which does not pass the blood brain barrier. Cytochromes P450-
CYP1A2 and P450-CYP2D6 contribute to the formation of the N-desmethyl and 2-hydroxymethyl 
metabolites, both exhibited significantly less in vivo pharmacological activity than olanzapine in 
animal studies. The predominant pharmacologic activity is from the parent olanzapine.  
 
Elimination 

After oral administration, the mean terminal elimination half-life of olanzapine in healthy subjects 
varied on the basis of age and gender. 
 



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In healthy elderly (65 and over) versus non-elderly subjects, the mean elimination half-life was 
prolonged (51.8 versus 33.8 hr) and the clearance was reduced (17.5 versus 18.2 l/hr). The 
pharmacokinetic variability observed in the elderly is within the range for the non-elderly. In 44 
patients with schizophrenia  65 years of age, dosing from 5 to 20 mg/day was not associated with 
any distinguishing profile of adverse events. 
 
In female versus male subjects the mean elimination half life was somewhat prolonged (36.7 versus 
32.3 hr) and the clearance was reduced (18.9 versus 27.3 l/hr). However, olanzapine (5-20 mg) 
demonstrated a comparable safety profile in female (n=467) as in male patients (n=869). 
 
Renal impairment 

In renally impaired patients (creatinine clearance < 10 ml/min) versus healthy subjects, there was no 
significant difference in mean elimination half-life (37.7 versus 32.4 hr) or clearance (21.2 versus 
25.0 l/hr). A mass balance study showed that approximately 57 % of radiolabelled olanzapine 
appeared in urine, principally as metabolites. 
 
Smokers 

In smoking subjects with mild hepatic dysfunction, mean elimination half-life (39.3 hr) was prolonged 
and clearance (18.0 l/hr) was reduced analogous to non-smoking healthy subjects (48.8 hr and 
14.1 l/hr, respectively). 
 
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. 
 



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Haematologic toxicity 

Effects on haematology parameters were found in each species, including dose-related reductions in 
circulating leukocytes in mice and non-specific reductions of circulating leukocytes in rats; however, 
no evidence of bone marrow cytotoxicity was found. Reversible neutropenia, thrombocytopenia, or 
anaemia developed in a few dogs treated with 8 or 10 mg/kg/day (total olanzapine exposure [AUC] is 
12- to 15-fold greater than that of a man given a 12-mg dose). In cytopenic dogs, there were no 
adverse effects on progenitor and proliferating cells in the bone marrow.  
 
Reproductive toxicity 

Olanzapine had no teratogenic effects. Sedation affected mating performance of male rats. Estrous 
cycles were affected at doses of 1.1 mg/kg (3 times the maximum human dose) and reproduction 
parameters were influenced in rats given 3 mg/kg (9 times the maximum human dose). In the 
offspring of rats given olanzapine, delays in foetal development and transient decreases in offspring 
activity levels were seen. 
 

Mutagenicity 

Olanzapine was not mutagenic or clastogenic in a full range of standard tests, which included 
bacterial mutation tests and in vitro and in vivo mammalian tests. 
 
Carcinogenicity 

Based on the results of studies in mice and rats, it was concluded that olanzapine is not carcinogenic. 
 

 

6. PHARMACEUTICAL PARTICULARS 

 
6.1 List of excipients 
 
Tablet core  

Lactose monohydrate,  
Maize starch 
Hydroxypropyl cellulose  
Magnesium stearate  
 
Tablet coat  

Opadry II White containing: 
Hypromellose (E464) 
Titanium dioxide (E171) 
Lactose monohydrate 
Polyethylene glycol 3000 
Glycerol triacetate 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Store in the original package. 
 
Store below 30°C. 
 
6.5 Nature and contents of container 



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Cold-formed aluminium blisters in cartons of 28 or 56 tablets per carton. 
 
Not all pack sizes may be marketed. 
 
 

6.6 Special precautions for disposal and other handling 
 
No special requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Cipla (EU)  Limited 
Hillbrow House 
Hillbrow Road 
Esher 
Surrey 
KT10 9NW 
UK 
 
 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/07/426/003 – Olanzapine Cipla – 5 mg – coated tablets – 28 tablets per box 
 
EU/1/07/426/004 –  Olanzapine Cipla – 5 mg – coated tablets – 56 tablets per box 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 14 November 2007 
 
Date of latest renewal: 01 October 2012 
 
 
10. DATE OF REVISION OF THE TEXT 

 
{MM/YYYY} 
 

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



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1. NAME OF THE MEDICINAL PRODUCT 
 
Olanzapine Cipla 7.5 mg coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each coated tablet contains 7.5 mg olanzapine.  
 
Excipient with known effect: Each coated tablet contains 242 mg lactose monohydrate 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Coated tablet 
 
White, round, biconvex, coated tablets with ‘OLZ 7.5’ debossing on one side and ‘NEO’ on the other.  
 
 
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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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). 
 
Elderly patients 
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). 
 

Patients with 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. 
 
Gender  

The starting dose and dose range need not be routinely altered for female patients relative to male 
patients. 
 
Smokers 

The starting dose and dose range need not be routinely altered for non-smokers relative to smokers. 
 
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) 
 
4.3 Contraindications 

 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.   
Patients with known risk for 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 approved for the treatment of dementia-related psychosis and/or behavioural 
disturbances and is not recommended for use in this particular group of patients because of an 
increase in mortality and the risk of cerebrovascular accident. In placebo-controlled clinical trials (6-
12 weeks duration) of elderly patients (mean age 78 years) with dementia-related psychosis and/or 
disturbed behaviours, there was a 2-fold increase in the incidence of death in olanzapine-treated 
patients compared to patients treated with placebo (3.5% vs. 1.5%, respectively). The higher 
incidence of death was not associated with olanzapine dose (mean daily dose 4.4 mg) or duration of 
treatment. Risk factors that may predispose this patient population to increased mortality include age 
> 65 years, dysphagia, sedation, malnutrition and dehydration, pulmonary conditions (e.g., 
pneumonia, with or without aspiration), or concomitant use of benzodiazepines. However, the 
incidence of death was higher in olanzapine-treated than in placebo-treated patients independent of 
these risk factors. 
 
In the same clinical trials, cerebrovascular adverse events (CVAE e.g., stroke, transient ischemic 
attack), including fatalities, were reported. There was a 3-fold increase in CVAE in patients treated 
with olanzapine compared to patients treated with placebo (1.3% vs. 0.4%, respectively). All 



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olanzapine- and placebo-treated patients who experienced a cerebrovascular event had pre-existing 
risk factors. Age > 75 years and vascular/mixed type dementia were identified as risk factors for 
CVAE in association with olanzapine treatment. The efficacy of olanzapine was not established in 
these trials. 
 

Parkinson's disease 

The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with 
Parkinson's disease is not recommended. In clinical trials, worsening of Parkinsonian symptomatology 
and hallucinations were reported very commonly and more frequently than with placebo (see section 
4.8), and olanzapine was not more effective than placebo in the treatment of psychotic symptoms. In 
these trials, patients were initially required to be stable on the lowest effective dose of anti-
Parkinsonian medicinal products (dopamine agonist) and to remain on the same anti-Parkinsonian 
medicinal products and dosages throughout the study. Olanzapine was started at 2.5 mg/day and 
titrated to a maximum of 15 mg/day based on investigator judgement. 
 

Neuroleptic Malignant Syndrome (NMS)  

NMS is a potentially life-threatening condition associated with antipsychotic medicinal products. 
Rare cases reported as NMS have also been received in association with olanzapine. Clinical 
manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of 
autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac 
dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria 
(rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms indicative of 
NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all 
antipsychotic medicines, including olanzapine must be discontinued. 
 
Hyperglycaemia and diabetes 

Hyperglycaemia and/or development or exacerbation of diabetes occasionally associated with 
ketoacidosis or coma has been reported uncommonly, including some fatal cases (see section 4.8). In 
some cases, a prior increase in body weight has been reported which may be a predisposing factor. 
Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines, e.g. 
measuring of blood glucose at baseline, 12 weeks after starting olanzapine treatment and annually 
thereafter. Patients treated with any antipsychotic agents, including Olanzapine Cipla, 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 agents, including Olanzapine Cipla, should 
be monitored regularly for lipids in accordance with utilised antipsychotic guidelines, e.g. at baseline, 
12 weeks after starting olanzapine treatment and every 5 years thereafter. 
 
Anticholinergic activity  
While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials 
revealed a low incidence of related events. However, as clinical experience with olanzapine in 
patients with concomitant illness is limited, caution is advised when prescribing for patients with 
prostatic hypertrophy, or paralytic ileus and related conditions. 
 
Hepatic function 

Transient, asymptomatic elevations of hepatic aminotransferases, ALT, AST have been seen 
commonly, especially in early treatment. Caution should be exercised and follow-up organised in 
patients with elevated ALT and/or AST, in patients with signs and symptoms of hepatic impairment, 
in patients with pre-existing conditions associated with limited hepatic functional reserve, and in 



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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, 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. As with 
other antipsychotics, it is recommended that blood pressure is measured periodically in patients over 
65 years. 
 



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Sudden cardiac death  

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

Olanzapine is not indicated for use in the treatment of children and adolescents. Studies in patients 
aged 13-17 years showed various adverse reactions, including weight gain, changes in metabolic 
parameters and increases in prolactin levels. Long-term outcomes associated with these events have 
not been studied and remain unknown (see sections 4.8 and 5.1). 
 
Lactose  

OLANZAPINE CIPLA tablets contain lactose. Patients with rare hereditary problems of galactose 
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this 
medicine. 
 
4.5 Interaction with other medicinal products and other forms of interaction 

 
Paediatric population 
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. 
 
Neonates 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, hypotonis, 
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. 
 

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 

 

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 



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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). 



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Very common Common Uncommon  Rare 

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 
reported 11 
 

Dystonia (including 
oculogyration)11 
Tardive dyskinesia11 
 
Amnesia 9 
 

Dysarthria 

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

Respiratory, thoracic and mediastinal disorders 
  Epistaxis9  
Cardiac disorders 

  Bradycardia 
QTc prolongation (see 
section 4.4) 

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

Vascular disorders 

Orthostatic 
hypotension10 

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

 

Gastrointestinal disorders 

 Mild, transient 
anticholinergic effects 
including constipation 
and dry mouth 

Abdominal distension9 Pancreatitis11 

Hepato-biliary disorders 

 Transient, 
asymptomatic 
elevations of hepatic 
aminotransferases 

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



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(ALT, AST), 
especially in early 
treatment (see section 
4.4) 

Skin and subcutaneous tissue disorders 

 Rash Photosensitivity 
reaction 
Alopecia 

 

Musculoskeletal and connective tissue disorders 

 Arthralgia9  Rhabdomyolysis11 
Renal and urinary disorders 

  Urinary incontinence, 
urinary retention 
Urinary hesitation11 

Urinary hesitation 

 
    
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 

High Uric Acid 10 
 

Increased total 
bilirubin 

 

   Not known 
Pregnancy, puerperium and perinatal conditions 

   Drug withdrawal 
syndrome neonatal 
(see section 4.6) 

 
1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) 
categories. Following short term treatment (median duration 47 days), weight gain ≥ 7% of baseline 
body weight  was very common (22.2 %), ≥ 15 % was common (4.2 %) and ≥ 25 % was uncommon 
(0.8 %). Patients gaining ≥ 7 %, ≥ 15 % and ≥ 25 % of their baseline body weight with long-term 
exposure (at least 48 weeks) were very common (64.4 %, 31.7 % and 12.3 % respectively). 
 
2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were 
greater in patients without evidence of lipid dysregulation at baseline. 
 
3 Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high 
(≥ 6.2 mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17 - 
< 6.2 mmol/l) to high (≥ 6.2 mmol/l) were very common. 



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

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

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

 
Long-term exposure (at least 48 weeks) 

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

Additional information on special populations 

In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher 
incidence of death and cerebrovascular adverse reactions compared to placebo (see also 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 



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of  7% from baseline body weight occurred in 17.4% of patients during acute treatment (up to 6 
weeks). Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with 
bipolar disorder was associated with an increase of 7% from baseline body weight in 39.9% of 
patients. 
 
Paediatric population 

Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years. 
Although no clinical studies designed to compare adolescents to adults have been conducted, data 
from the adolescent trials were compared to those of the adult trials.  
 
The following table summarises the adverse reactions reported with a greater frequency in adolescent 
patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-
term clinical trials in adolescent patients. Clinically significant weight gain (≥ 7%) appears to occur 
more frequently in the adolescent population compared to adults with comparable exposures. The 
magnitude of weight gain and the proportion of adolescent patients who had clinically significant 
weight gain were greater with long-term exposure (at least 24 weeks) than with short-term exposure.  
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
The frequency terms listed are defined as follows: Very common (≥ 1/10), common (≥ 1/100 to 
< 1/10). 
 
Metabolism and nutrition disorders 

Very common: Weight gain13, elevated triglyceride levels14, increased appetite. 
Common: Elevated cholesterol levels15 
Nervous system disorders 

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

Common: Dry mouth 
Hepato-biliary disorders 

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

Very common: Decreased total bilirubin, increased GGT, elevated plasma prolactin levels16. 
 
13 Following short term treatment (median duration 22 days), weight gain ≥ 7 % of baseline body 
weight (kg) was very common (40.6 %), ≥ 15 % of baseline body weight was common (7.1 %) and ≥ 
25 % was common (2.5 %). With long-term exposure (at least 24 weeks), 89.4 % gained ≥ 7 %, 55.3 
% gained ≥ 15 % and 29.1 % gained ≥ 25% of their baseline body weight. 
 
14  Observed for fasting normal levels at baseline (< 1.016 mmol/l) which increased to high 
(≥ 1.467 mmol/l) and changes in fasting triglycerides from borderline at baseline (≥ 1.016 mmol/l - 
< 1.467 mmol/l) to high (≥ 1.467 mmol/l). 
 
15 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high 
(≥ 5.17 mmol/l) were observed commonly. Changes in total fasting cholesterol levels from borderline 
at baseline (≥ 4.39 - < 5.17 mmol/l) to high (≥ 5.17 mmol/l) were very common. 
 
16 Elevated plasma prolactin levels were reported in 47.4% of adolescent patients. 
 

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.  
 



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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: diazepines, oxazepines and thiazepines., 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; 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 5 HT2A than dopamine D2 receptor occupancy. In addition, a Single 
Photon Emission Computed Tomography (SPECT) imaging study in schizophrenic patients revealed 
that olanzapine-responsive patients had lower striatal D2 occupancy than some other antipsychotic- 
and risperidone-responsive patients, while being comparable to clozapine-responsive patients. 
 
Clinical efficacy 

In two of two placebo and two of three comparator controlled trials with over 2,900 schizophrenic 
patients presenting with both positive and negative symptoms, olanzapine was associated with 
statistically significantly greater improvements in negative as well as positive symptoms. 
 

In a multinational, double-blind, comparative study of schizophrenia, schizoaffective, and related 
disorders which included 1,481 patients with varying degrees of associated depressive symptoms 
(baseline mean of 16.6 on the Montgomery-Asberg Depression Rating Scale), a prospective secondary 



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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 

The experience in adolescents (ages 13 to 17 years) is limited to short term efficacy data 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 data on 
maintenance of effect and limited data on long term safety (see sections 4.4 and 4.8).  
 
5.2 Pharmacokinetic properties 

 
Absorption 

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

The plasma protein binding of olanzapine was about 93 % over the concentration range of about 7 to 
about 1000 ng/ml. Olanzapine is bound predominantly to albumin and 1-acid-glycoprotein. 
Biotransformation 

Olanzapine is metabolized in the liver by conjugative and oxidative pathways. The major circulating 
metabolite is the 10-N-glucuronide, which does not pass the blood brain barrier. Cytochromes P450-
CYP1A2 and P450-CYP2D6 contribute to the formation of the N-desmethyl and 2-hydroxymethyl 
metabolites, both exhibited significantly less in vivo pharmacological activity than olanzapine in 
animal studies. The predominant pharmacologic activity is from the parent olanzapine.  
 
Elimination 

After oral administration, the mean terminal elimination half-life of olanzapine in healthy subjects 
varied on the basis of age and gender. 



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In healthy elderly (65 and over) versus non-elderly subjects, the mean elimination half-life was 
prolonged (51.8 versus 33.8 hr) and the clearance was reduced (17.5 versus 18.2 l/hr). The 
pharmacokinetic variability observed in the elderly is within the range for the non-elderly. In 44 
patients with schizophrenia  65 years of age, dosing from 5 to 20 mg/day was not associated with 
any distinguishing profile of adverse events. 
 
In female versus male subjects the mean elimination half life was somewhat prolonged (36.7 versus 
32.3 hr) and the clearance was reduced (18.9 versus 27.3 l/hr). However, olanzapine (5-20 mg) 
demonstrated a comparable safety profile in female (n=467) as in male patients (n=869). 
 
Renal impairment 

In renally impaired patients (creatinine clearance < 10 ml/min) versus healthy subjects, there was no 
significant difference in mean elimination half-life (37.7 versus 32.4 hr) or clearance (21.2 versus 
25.0 l/hr). A mass balance study showed that approximately 57 % of radiolabelled olanzapine 
appeared in urine, principally as metabolites. 
 
Smokers 

In smoking subjects with mild hepatic dysfunction, mean elimination half-life (39.3 hr) was prolonged 
and clearance (18.0 l/hr) was reduced analogous to non-smoking healthy subjects (48.8 hr and 
14.1 l/hr, respectively). 
 
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. 



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Haematologic toxicity 

Effects on haematology parameters were found in each species, including dose-related reductions in 
circulating leukocytes in mice and non-specific reductions of circulating leukocytes in rats; however, 
no evidence of bone marrow cytotoxicity was found. Reversible neutropenia, thrombocytopenia, or 
anaemia developed in a few dogs treated with 8 or 10 mg/kg/day (total olanzapine exposure [AUC] is 
12- to 15-fold greater than that of a man given a 12-mg dose). In cytopenic dogs, there were no 
adverse effects on progenitor and proliferating cells in the bone marrow.  
 
Reproductive toxicity 

Olanzapine had no teratogenic effects. Sedation affected mating performance of male rats. Estrous 
cycles were affected at doses of 1.1 mg/kg (3 times the maximum human dose) and reproduction 
parameters were influenced in rats given 3 mg/kg (9 times the maximum human dose). In the 
offspring of rats given olanzapine, delays in foetal development and transient decreases in offspring 
activity levels were seen. 
 

Mutagenicity 

Olanzapine was not mutagenic or clastogenic in a full range of standard tests, which included 
bacterial mutation tests and in vitro and in vivo mammalian tests. 
 
Carcinogenicity 

Based on the results of studies in mice and rats, it was concluded that olanzapine is not carcinogenic. 
 
 

6. PHARMACEUTICAL PARTICULARS 

 
6.1 List of excipients 
 
Tablet core  

Lactose monohydrate,  
Maize starch 
Hydroxypropyl cellulose  
Magnesium stearate  
 
Tablet coat  

Opadry II White containing: 
Hypromellose (E464) 
Titanium dioxide (E171) 
Lactose monohydrate 
Polyethylene glycol 3000 
Glycerol triacetate 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Store in the original package. 
 
Store below 30°C. 
 



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6.5 Nature and contents of container 

 

Cold-formed aluminium blisters in cartons of 28 or 56 tablets per carton. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
No special requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Cipla (EU)  Limited 
Hillbrow House 
Hillbrow Road 
Esher 
Surrey 
KT10 9NW 
UK 
 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  

 
EU/1/07/426/005 – Olanzapine Cipla – 7.5 mg – coated tablets – 28 tablets per box 
 
EU/1/07/426/006 –  Olanzapine Cipla – 7.5 mg – coated tablets – 56 tablets per box 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 14 November 2007 
 
Date of latest renewal: 01 October 2012 
 
 
10. DATE OF REVISION OF THE TEXT 

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



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1. NAME OF THE MEDICINAL PRODUCT 
 
Olanzapine Cipla 10 mg coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each coated tablet contains 10 mg olanzapine.  
 
Excipient with known effect: Each coated tablet contains 322.6 mg lactose monohydrate 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Coated tablet 
 
White, round, biconvex, coated tablets with ‘OLZ 10’ debossing on one side and ‘NEO’ on the other.  
 
 
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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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). 
 
Elderly patients 
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). 
 

Patients with 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. 
 
Gender  

The starting dose and dose range need not be routinely altered for female patients relative to male 
patients. 
 
Smokers 

The starting dose and dose range need not be routinely altered for non-smokers relative to smokers. 
 
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) 
 
4.3 Contraindications 

 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.   
Patients with known risk for 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 approved for the treatment of dementia-related psychosis and/or behavioural 
disturbances and is not recommended for use in this particular group of patients because of an 
increase in mortality and the risk of cerebrovascular accident. In placebo-controlled clinical trials (6-
12 weeks duration) of elderly patients (mean age 78 years) with dementia-related psychosis and/or 
disturbed behaviours, there was a 2-fold increase in the incidence of death in olanzapine-treated 
patients compared to patients treated with placebo (3.5% vs. 1.5%, respectively). The higher 
incidence of death was not associated with olanzapine dose (mean daily dose 4.4 mg) or duration of 
treatment. Risk factors that may predispose this patient population to increased mortality include age 
> 65 years, dysphagia, sedation, malnutrition and dehydration, pulmonary conditions (e.g., 
pneumonia, with or without aspiration), or concomitant use of benzodiazepines. However, the 
incidence of death was higher in olanzapine-treated than in placebo-treated patients independent of 
these risk factors. 
 
In the same clinical trials, cerebrovascular adverse events (CVAE e.g., stroke, transient ischemic 
attack), including fatalities, were reported. There was a 3-fold increase in CVAE in patients treated 
with olanzapine compared to patients treated with placebo (1.3% vs. 0.4%, respectively). All 



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olanzapine- and placebo-treated patients who experienced a cerebrovascular event had pre-existing 
risk factors. Age > 75 years and vascular/mixed type dementia were identified as risk factors for 
CVAE in association with olanzapine treatment. The efficacy of olanzapine was not established in 
these trials. 
 

Parkinson's disease 

The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with 
Parkinson's disease is not recommended. In clinical trials, worsening of Parkinsonian symptomatology 
and hallucinations were reported very commonly and more frequently than with placebo (see section 
4.8), and olanzapine was not more effective than placebo in the treatment of psychotic symptoms. In 
these trials, patients were initially required to be stable on the lowest effective dose of anti-
Parkinsonian medicinal products (dopamine agonist) and to remain on the same anti-Parkinsonian 
medicinal products and dosages throughout the study. Olanzapine was started at 2.5 mg/day and 
titrated to a maximum of 15 mg/day based on investigator judgement. 
 

Neuroleptic Malignant Syndrome (NMS)  

NMS is a potentially life-threatening condition associated with antipsychotic medicinal products. 
Rare cases reported as NMS have also been received in association with olanzapine. Clinical 
manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of 
autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac 
dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria 
(rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms indicative of 
NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all 
antipsychotic medicines, including olanzapine must be discontinued. 
 
Hyperglycaemia and diabetes 

Hyperglycaemia and/or development or exacerbation of diabetes occasionally associated with 
ketoacidosis or coma has been reported uncommonly, including some fatal cases (see section 4.8). In 
some cases, a prior increase in body weight has been reported which may be a predisposing factor. 
Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines, e.g. 
measuring of blood glucose at baseline, 12 weeks after starting olanzapine treatment and annually 
thereafter. Patients treated with any antipsychotic agents, including Olanzapine Cipla, 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 agents, including Olanzapine Cipla, should 
be monitored regularly for lipids in accordance with utilised antipsychotic guidelines, e.g. at baseline, 
12 weeks after starting olanzapine treatment and every 5 years thereafter. 
 
Anticholinergic activity  
While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials 
revealed a low incidence of related events. However, as clinical experience with olanzapine in 
patients with concomitant illness is limited, caution is advised when prescribing for patients with 
prostatic hypertrophy, or paralytic ileus and related conditions. 
 
Hepatic function 

Transient, asymptomatic elevations of hepatic aminotransferases, ALT, AST have been seen 
commonly, especially in early treatment. Caution should be exercised and follow-up organised in 
patients with elevated ALT and/or AST, in patients with signs and symptoms of hepatic impairment, 
in patients with pre-existing conditions associated with limited hepatic functional reserve, and in 



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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, 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. As with 
other antipsychotics, it is recommended that blood pressure is measured periodically in patients over 
65 years. 
 



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Sudden cardiac death  

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

Olanzapine is not indicated for use in the treatment of children and adolescents. Studies in patients 
aged 13-17 years showed various adverse reactions, including weight gain, changes in metabolic 
parameters and increases in prolactin levels. Long-term outcomes associated with these events have 
not been studied and remain unknown (see sections 4.8 and 5.1). 
 
Lactose  

OLANZAPINE CIPLA tablets contain lactose. Patients with rare hereditary problems of galactose 
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this 
medicine. 
 
4.5 Interaction with other medicinal products and other forms of interaction 

 
Paediatric population 
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. 
 
Neonates 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, hypotonis, 
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. 
 

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 

 

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 



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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). 



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Very common Common Uncommon  Rare 

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 

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

Respiratory, thoracic and mediastinal disorders 
  Epistaxis9  
Cardiac disorders 

  Bradycardia 
QTc prolongation (see 
section 4.4) 

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

Vascular disorders 

Orthostatic 
hypotension10 

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

 

Gastrointestinal disorders 

 Mild, transient 
anticholinergic effects 
including constipation 
and dry mouth 

Abdominal distension9 Pancreatitis11 

Hepato-biliary disorders 

 Transient, 
asymptomatic 
elevations of hepatic 
aminotransferases 

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



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Very common Common Uncommon  Rare 

(ALT, AST), 
especially in early 
treatment (see section 
4.4) 

Skin and subcutaneous tissue disorders 

 Rash Photosensitivity 
reaction 
Alopecia 

 

Musculoskeletal and connective tissue disorders 

 Arthralgia9  Rhabdomyolysis11 
Renal and urinary disorders 

  Urinary incontinence, 
urinary retention 
Urinary hesitation11 

 

 
    
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 

High Uric Acid 10 
 

Increased total 
bilirubin 

 

   Not known 
Pregnancy, puerperium and perinatal conditions 

   Drug withdrawal 
syndrome neonatal 
(see section 4.6) 

 
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. 
 



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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 also 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 



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valproate levels. Olanzapine administered with lithium or valproate resulted in increased levels 
(10%) of tremor, dry mouth, increased appetite, and weight gain. Speech disorder was also reported 
commonly. During treatment with olanzapine in combination with lithium or divalproex, an increase 
of  7% from baseline body weight occurred in 17.4% of patients during acute treatment (up to 6 
weeks). Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with 
bipolar disorder was associated with an increase of 7% from baseline body weight in 39.9% of 
patients. 
 
Paediatric population 

Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years. 
Although no clinical studies designed to compare adolescents to adults have been conducted, data 
from the adolescent trials were compared to those of the adult trials.  
 
The following table summarises the adverse reactions reported with a greater frequency in adolescent 
patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-
term clinical trials in adolescent patients. Clinically significant weight gain (≥ 7%) appears to occur 
more frequently in the adolescent population compared to adults with comparable exposures. The 
magnitude of weight gain and the proportion of adolescent patients who had clinically significant 
weight gain were greater with long-term exposure (at least 24 weeks) than with short-term exposure.  
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
The frequency terms listed are defined as follows: Very common (≥ 1/10), common (≥ 1/100 to 
< 1/10). 
 
Metabolism and nutrition disorders 

Very common: Weight gain13, elevated triglyceride levels14, increased appetite. 
Common: Elevated cholesterol levels15 
Nervous system disorders 

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

Common: Dry mouth 
Hepato-biliary disorders 

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

Very common: Decreased total bilirubin, increased GGT, elevated plasma prolactin levels16. 
 
13 Following short term treatment (median duration 22 days), weight gain ≥ 7 % of baseline body 
weight (kg) was very common (40.6 %), ≥ 15 % of baseline body weight was common (7.1 %) and ≥ 
25 % was common (2.5 %). With long-term exposure (at least 24 weeks), 89.4 % gained ≥ 7 %, 55.3 
% gained ≥ 15 % and 29.1 % gained ≥ 25% of their baseline body weight. 
 
14  Observed for fasting normal levels at baseline (< 1.016 mmol/l) which increased to high 
(≥ 1.467 mmol/l) and changes in fasting triglycerides from borderline at baseline (≥ 1.016 mmol/l - 
< 1.467 mmol/l) to high (≥ 1.467 mmol/l). 
 
15 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high 
(≥ 5.17 mmol/l) were observed commonly. Changes in total fasting cholesterol levels from borderline 
at baseline (≥ 4.39 - < 5.17 mmol/l) to high (≥ 5.17 mmol/l) were very common. 
 
16 Elevated plasma prolactin levels were reported in 47.4% of adolescent patients. 
 



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4.9 Overdose 

 
Signs and symptoms 

Very common symptoms in overdose (> 10% incidence) include tachycardia, 
agitation/aggressiveness, dysarthria, various extrapyramidal symptoms, and reduced level of 
consciousness ranging from sedation to coma.  
 
Other medically significant sequelae of overdose include delirium, convulsion, coma, possible 
neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, 
cardiac arrhythmias (< 2% of overdose cases) and cardiopulmonary arrest. Fatal outcomes have been 
reported for acute overdoses as low as 450 mg but survival has also been reported following acute 
overdose of approximately 2 g of oral olanzapine. 
 
Management  

There is no specific antidote for olanzapine. Induction of emesis is not recommended. Standard 
procedures for management of overdose may be indicated (i.e. gastric lavage, administration of 
activated charcoal). The concomitant administration of activated charcoal was shown to reduce the 
oral bioavailability of olanzapine by 50 to 60%. 
 
Symptomatic treatment and monitoring of vital organ function should be instituted according to 
clinical presentation, including treatment of hypotension and circulatory collapse and support of 
respiratory function. Do not use epinephrine, dopamine, or other sympathomimetic agents with beta-
agonist activity since beta stimulation may worsen hypotension. Cardiovascular monitoring is 
necessary to detect possible arrhythmias. Close medical supervision and monitoring should continue 
until the patient recovers. 
 
 
5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: diazepines, oxazepines and thiazepines., 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; 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 5 HT2A than dopamine D2 receptor occupancy. In addition, a Single 
Photon Emission Computed Tomography (SPECT) imaging study in schizophrenic patients revealed 
that olanzapine-responsive patients had lower striatal D2 occupancy than some other antipsychotic- 
and risperidone-responsive patients, while being comparable to clozapine-responsive patients. 
 
Clinical efficacy 



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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 

The experience in adolescents (ages 13 to 17 years) is limited to short term efficacy data 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 data on 
maintenance of effect and limited data on long term safety (see sections 4.4 and 4.8).  
 
5.2 Pharmacokinetic properties 

 
Absorption 

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

The plasma protein binding of olanzapine was about 93 % over the concentration range of about 7 to 
about 1000 ng/ml. Olanzapine is bound predominantly to albumin and 1-acid-glycoprotein. 
Biotransformation 

Olanzapine is metabolized in the liver by conjugative and oxidative pathways. The major circulating 
metabolite is the 10-N-glucuronide, which does not pass the blood brain barrier. Cytochromes P450-



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CYP1A2 and P450-CYP2D6 contribute to the formation of the N-desmethyl and 2-hydroxymethyl 
metabolites, both exhibited significantly less in vivo pharmacological activity than olanzapine in 
animal studies. The predominant pharmacologic activity is from the parent olanzapine.  
 
Elimination 

After oral administration, the mean terminal elimination half-life of olanzapine in healthy subjects 
varied on the basis of age and gender. 
 
In healthy elderly (65 and over) versus non-elderly subjects, the mean elimination half-life was 
prolonged (51.8 versus 33.8 hr) and the clearance was reduced (17.5 versus 18.2 l/hr). The 
pharmacokinetic variability observed in the elderly is within the range for the non-elderly. In 44 
patients with schizophrenia  65 years of age, dosing from 5 to 20 mg/day was not associated with 
any distinguishing profile of adverse events. 
 
In female versus male subjects the mean elimination half life was somewhat prolonged (36.7 versus 
32.3 hr) and the clearance was reduced (18.9 versus 27.3 l/hr). However, olanzapine (5-20 mg) 
demonstrated a comparable safety profile in female (n=467) as in male patients (n=869). 
 
Renal impairment 

In renally impaired patients (creatinine clearance < 10 ml/min) versus healthy subjects, there was no 
significant difference in mean elimination half-life (37.7 versus 32.4 hr) or clearance (21.2 versus 
25.0 l/hr). A mass balance study showed that approximately 57 % of radiolabelled olanzapine 
appeared in urine, principally as metabolites. 
 
Smokers 

In smoking subjects with mild hepatic dysfunction, mean elimination half-life (39.3 hr) was prolonged 
and clearance (18.0 l/hr) was reduced analogous to non-smoking healthy subjects (48.8 hr and 
14.1 l/hr, respectively). 
 
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. 



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Repeated-dose toxicity  

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

Effects on haematology parameters were found in each species, including dose-related reductions in 
circulating leukocytes in mice and non-specific reductions of circulating leukocytes in rats; however, 
no evidence of bone marrow cytotoxicity was found. Reversible neutropenia, thrombocytopenia, or 
anaemia developed in a few dogs treated with 8 or 10 mg/kg/day (total olanzapine exposure [AUC] is 
12- to 15-fold greater than that of a man given a 12-mg dose). In cytopenic dogs, there were no 
adverse effects on progenitor and proliferating cells in the bone marrow.  
 
Reproductive toxicity 

Olanzapine had no teratogenic effects. Sedation affected mating performance of male rats. Estrous 
cycles were affected at doses of 1.1 mg/kg (3 times the maximum human dose) and reproduction 
parameters were influenced in rats given 3 mg/kg (9 times the maximum human dose). In the 
offspring of rats given olanzapine, delays in foetal development and transient decreases in offspring 
activity levels were seen. 
 

Mutagenicity 

Olanzapine was not mutagenic or clastogenic in a full range of standard tests, which included 
bacterial mutation tests and in vitro and in vivo mammalian tests. 
 
Carcinogenicity 

Based on the results of studies in mice and rats, it was concluded that olanzapine is not carcinogenic. 
 

 

6. PHARMACEUTICAL PARTICULARS 

 
6.1 List of excipients 
 
Tablet core  

Lactose monohydrate,  
Maize starch 
Hydroxypropyl cellulose  
Magnesium stearate  
 
Tablet coat  

Opadry II White containing: 
Hypromellose (E464) 
Titanium dioxide (E171) 
Lactose monohydrate 
Polyethylene glycol 3000 
Glycerol triacetate 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 



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6.4 Special precautions for storage 
 
Store in the original package. 
 
Store below 30°C. 
 
6.5 Nature and contents of container 

 

Cold-formed aluminium blisters in cartons of 7, 28 or 56 tablets per carton. 
 
Not all pack sizes may be marketed. 
 
 

6.6 Special precautions for disposal and other handling 
 
No special requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Cipla (EU)  Limited 
Hillbrow House 
Hillbrow Road 
Esher 
Surrey 
KT10 9NW 
UK 
 
 
 

8. MARKETING AUTHORISATION NUMBER(S)  

 
EU/1/07/426/007 – Olanzapine Cipla – 10 mg – coated tablets – 7 tablets per box 
 
EU/1/07/426/008 –  Olanzapine Cipla – 10 mg – coated tablets – 28 tablets per box 
 
EU/1/07/426/009 –  Olanzapine Cipla – 10 mg – coated tablets – 56 tablets per box 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 14 November 2007 
 
Date of latest renewal: 01 October 2012 
 
10. DATE OF REVISION OF THE TEXT 

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



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1. NAME OF THE MEDICINAL PRODUCT 
 
Olanzapine Cipla 15 mg coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each coated tablet contains 15 mg olanzapine.  
 
Excipient with known effect: Each coated tablet contains 315 mg lactose monohydrate 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Coated tablet 
 
Blue, elliptical, convex, coated tablets with ‘NEO’ debossed on one side and plain on the 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. 



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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. 
 
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). 
 
Elderly patients 
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). 
 

Patients with 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. 
 
Gender  

The starting dose and dose range need not be routinely altered for female patients relative to male 
patients. 
 
Smokers 

The starting dose and dose range need not be routinely altered for non-smokers relative to smokers. 
 
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) 
 
4.3 Contraindications 

 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.   
Patients with known risk for 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 approved for the treatment of dementia-related psychosis and/or behavioural 
disturbances and is not recommended for use in this particular group of patients 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. 
 



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In the same clinical trials, cerebrovascular adverse events (CVAE e.g., stroke, transient ischemic 
attack), including fatalities, were reported. There was a 3-fold increase in CVAE in patients treated 
with olanzapine compared to patients treated with placebo (1.3% vs. 0.4%, respectively). All 
olanzapine- and placebo-treated patients who experienced a cerebrovascular event had pre-existing 
risk factors. Age > 75 years and vascular/mixed type dementia were identified as risk factors for 
CVAE in association with olanzapine treatment. The efficacy of olanzapine was not established in 
these trials. 
 

Parkinson's disease 

The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with 
Parkinson's disease is not recommended. In clinical trials, worsening of Parkinsonian symptomatology 
and hallucinations were reported very commonly and more frequently than with placebo (see section 
4.8), and olanzapine was not more effective than placebo in the treatment of psychotic symptoms. In 
these trials, patients were initially required to be stable on the lowest effective dose of anti-
Parkinsonian medicinal products (dopamine agonist) and to remain on the same anti-Parkinsonian 
medicinal products and dosages throughout the study. Olanzapine was started at 2.5 mg/day and 
titrated to a maximum of 15 mg/day based on investigator judgement. 
 

Neuroleptic Malignant Syndrome (NMS)  

NMS is a potentially life-threatening condition associated with antipsychotic medicinal products. 
Rare cases reported as NMS have also been received in association with olanzapine. Clinical 
manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of 
autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac 
dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria 
(rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms indicative of 
NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all 
antipsychotic medicines, including olanzapine must be discontinued. 
 
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 agents, including Olanzapine Cipla, 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 agents, including Olanzapine Cipla, should 
be monitored regularly for lipids in accordance with utilised antipsychotic guidelines, e.g. at baseline, 
12 weeks after starting olanzapine treatment and every 5 years thereafter. 
 
Anticholinergic activity  
While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials 
revealed a low incidence of related events. However, as clinical experience with olanzapine in 
patients with concomitant illness is limited, caution is advised when prescribing for patients with 
prostatic hypertrophy, or paralytic ileus and related conditions. 
 



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Hepatic function 

Transient, asymptomatic elevations of hepatic aminotransferases, ALT, AST have been seen 
commonly, especially in early treatment. Caution should be exercised and follow-up organised in 
patients with elevated ALT and/or AST, in patients with signs and symptoms of hepatic impairment, 
in patients with pre-existing conditions associated with limited hepatic functional reserve, and in 
patients who are being treated with potentially hepatotoxic medicines. In cases where hepatitis 
(including hepatocellular, cholestatic or mixed liver injury) has been diagnosed, olanzapine treatment 
should be discontinued. 
 
Neutropenia 

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

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

In clinical trials, 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.  
 



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Postural hypotension 

Postural hypotension was infrequently observed in the elderly in olanzapine clinical trials. As with 
other antipsychotics, it is recommended that blood pressure is measured periodically in patients over 
65 years. 
 
Sudden cardiac death  

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

Olanzapine is not indicated for use in the treatment of children and adolescents. Studies in patients 
aged 13-17 years showed various adverse reactions, including weight gain, changes in metabolic 
parameters and increases in prolactin levels. Long-term outcomes associated with these events have 
not been studied and remain unknown (see sections 4.8 and 5.1). 
 
Lactose  

OLANZAPINE CIPLA tablets contain lactose. Patients with rare hereditary problems of galactose 
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this 
medicine. 
 
4.5 Interaction with other medicinal products and other forms of interaction 

 
Paediatric population 
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. 
 



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Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e.g. 1A2, 2D6, 2C9, 2C19, 3A4). 
Thus no particular interaction is expected as verified through in vivo studies where no inhibition of 
metabolism of the following active substances was found: tricyclic antidepressant (representing 
mostly CYP2D6 pathway), warfarin (CYP2C9), theophylline (CYP1A2) or diazepam (CYP3A4 and 
2C19).  
 
Olanzapine showed no interaction when co-administered with lithium or biperiden. 
 
Therapeutic monitoring of valproate plasma levels did not indicate that valproate dosage adjustment is 
required after the introduction of concomitant olanzapine. 
 
General CNS activity 

Caution should be exercised in patients who consume alcohol or receive medicinal products that can 
cause central nervous system depression. 
 
The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with 
Parkinson's disease and dementia is not recommended (see section 4.4).  
 
QTc interval 

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

 

Pregnancy 

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

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 

 

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 



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(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). 



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Very common Common Uncommon  Rare 

Blood and the lymphatic system disorders 

 Eosinophilia 
Leukopenia10 
Neutropenia10 

 Thrombocytopenia11 

Immune system disorders 

  Hypersensitivity11 Allergic reaction 
Metabolism and nutrition disorders 

Weight gain1 Elevated cholesterol 
levels2,3 
Elevated glucose 
levels4 
Elevated triglyceride 
levels2,5 
Glucosuria  
Increased appetite 
 

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

Hypothermia12 

Nervous system disorders 

Somnolence Dizziness 
Akathisia6 
Parkinsonism6 
Dyskinesia6 

Seizures where in most 
cases a history of 
seizures or risk factors 
for seizures were 
reported11 
 
Dystonia (including 
oculogyration)11 
Tardive dyskinesia11 
 
Amnesia9 
 

Dysarthria 

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

Respiratory, thoracic and mediastinal disorders 
  Epistaxis9  
Cardiac disorders 

  Bradycardia 
QTc prolongation (see 
section 4.4) 

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

Vascular disorders 

Orthostatic 
hypotension10 

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

 

Gastrointestinal disorders 

 Mild, transient 
anticholinergic effects 
including constipation 
and dry mouth 

Abdominal distension9 Pancreatitis11 

Hepato-biliary disorders 

 Transient, 
asymptomatic 
elevations of hepatic 
aminotransferases 

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



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(ALT, AST), 
especially in early 
treatment (see section 
4.4) 

Skin and subcutaneous tissue disorders 

 Rash Photosensitivity 
reaction 
Alopecia 

 

Musculoskeletal and connective tissue disorders 

 Arthralgia9  Rhabdomyolysis11 
Renal and urinary disorders 

  Urinary incontinence, 
urinary retention 
Urinary hesitation11 

 

 
    
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 

High Uric Acid 10 
 

Increased total 
bilirubin 

 

   Not known 
Pregnancy, puerperium and perinatal conditions 

   Drug withdrawal 
syndrome neonatal 
(see section 4.6) 

 
1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) 
categories. Following short term treatment (median duration 47 days), weight gain ≥ 7% of baseline 
body weight  was very common (22.2 %), ≥ 15 % was common (4.2 %) and ≥ 25 % was uncommon 
(0.8 %). Patients gaining ≥ 7 %, ≥ 15 % and ≥ 25 % of their baseline body weight with long-term 
exposure (at least 48 weeks) were very common (64.4 %, 31.7 % and 12.3 % respectively). 
 
2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were 
greater in patients without evidence of lipid dysregulation at baseline. 
 
3 Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high 
(≥ 6.2 mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17 - 
< 6.2 mmol/l) to high (≥ 6.2 mmol/l) were very common. 



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

utilising the Olanzapine Integrated Database. 
 
12 Adverse event identified from spontaneous post-marketing reporting with frequency estimated at 
the upper limit of the 95% confidence interval utilising the Olanzapine Integrated Database. 
 
Long-term exposure (at least 48 weeks) 

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

Additional information on special populations 

In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher 
incidence of death and cerebrovascular adverse reactions compared to placebo (see also 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 



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weeks). Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with 
bipolar disorder was associated with an increase of 7% from baseline body weight in 39.9% of 
patients. 
 
Paediatric population 

Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years. 
Although no clinical studies designed to compare adolescents to adults have been conducted, data 
from the adolescent trials were compared to those of the adult trials.  
 
The following table summarises the adverse reactions reported with a greater frequency in adolescent 
patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-
term clinical trials in adolescent patients. Clinically significant weight gain (≥ 7%) appears to occur 
more frequently in the adolescent population compared to adults with comparable exposures. The 
magnitude of weight gain and the proportion of adolescent patients who had clinically significant 
weight gain were greater with long-term exposure (at least 24 weeks) than with short-term exposure.  
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
The frequency terms listed are defined as follows: Very common (≥ 1/10), common (≥ 1/100 to 
< 1/10). 
 
Metabolism and nutrition disorders 

Very common: Weight gain13, elevated triglyceride levels14, increased appetite. 
Common: Elevated cholesterol levels15 
Nervous system disorders 

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

Common: Dry mouth 
Hepato-biliary disorders 

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

Very common: Decreased total bilirubin, increased GGT, elevated plasma prolactin levels16. 
 
13 Following short term treatment (median duration 22 days), weight gain ≥ 7 % of baseline body 
weight (kg) was very common (40.6 %), ≥ 15 % of baseline body weight was common (7.1 %) and ≥ 
25 % was common (2.5 %). With long-term exposure (at least 24 weeks), 89.4 % gained ≥ 7 %, 55.3 
% gained ≥ 15 % and 29.1 % gained ≥ 25% of their baseline body weight. 
 
14  Observed for fasting normal levels at baseline (< 1.016 mmol/l) which increased to high 
(≥ 1.467 mmol/l) and changes in fasting triglycerides from borderline at baseline (≥ 1.016 mmol/l - 
< 1.467 mmol/l) to high (≥ 1.467 mmol/l). 
 
15 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high 
(≥ 5.17 mmol/l) were observed commonly. Changes in total fasting cholesterol levels from borderline 
at baseline (≥ 4.39 - < 5.17 mmol/l) to high (≥ 5.17 mmol/l) were very common. 
 
16 Elevated plasma prolactin levels were reported in 47.4% of adolescent patients. 
 

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.  
 



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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: diazepines, oxazepines and thiazepines., 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; 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 5 HT2A than dopamine D2 receptor occupancy. In addition, a Single 
Photon Emission Computed Tomography (SPECT) imaging study in schizophrenic patients revealed 
that olanzapine-responsive patients had lower striatal D2 occupancy than some other antipsychotic- 
and risperidone-responsive patients, while being comparable to clozapine-responsive patients. 
 
Clinical efficacy 

In two of two placebo and two of three comparator controlled trials with over 2,900 schizophrenic 
patients presenting with both positive and negative symptoms, olanzapine was associated with 
statistically significantly greater improvements in negative as well as positive symptoms. 
 

In a multinational, double-blind, comparative study of schizophrenia, schizoaffective, and related 
disorders which included 1,481 patients with varying degrees of associated depressive symptoms 
(baseline mean of 16.6 on the Montgomery-Asberg Depression Rating Scale), a prospective secondary 



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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 

The experience in adolescents (ages 13 to 17 years) is limited to short term efficacy data 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 data on 
maintenance of effect and limited data on long term safety (see sections 4.4 and 4.8).  
 
5.2 Pharmacokinetic properties 

 
Absorption 

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

The plasma protein binding of olanzapine was about 93 % over the concentration range of about 7 to 
about 1000 ng/ml. Olanzapine is bound predominantly to albumin and 1-acid-glycoprotein. 
Biotransformation 

Olanzapine is metabolized in the liver by conjugative and oxidative pathways. The major circulating 
metabolite is the 10-N-glucuronide, which does not pass the blood brain barrier. Cytochromes P450-
CYP1A2 and P450-CYP2D6 contribute to the formation of the N-desmethyl and 2-hydroxymethyl 
metabolites, both exhibited significantly less in vivo pharmacological activity than olanzapine in 
animal studies. The predominant pharmacologic activity is from the parent olanzapine.  
 
Elimination 

After oral administration, the mean terminal elimination half-life of olanzapine in healthy subjects 
varied on the basis of age and gender. 



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In healthy elderly (65 and over) versus non-elderly subjects, the mean elimination half-life was 
prolonged (51.8 versus 33.8 hr) and the clearance was reduced (17.5 versus 18.2 l/hr). The 
pharmacokinetic variability observed in the elderly is within the range for the non-elderly. In 44 
patients with schizophrenia  65 years of age, dosing from 5 to 20 mg/day was not associated with 
any distinguishing profile of adverse events. 
 
In female versus male subjects the mean elimination half life was somewhat prolonged (36.7 versus 
32.3 hr) and the clearance was reduced (18.9 versus 27.3 l/hr). However, olanzapine (5-20 mg) 
demonstrated a comparable safety profile in female (n=467) as in male patients (n=869). 
 
Renal impairment 

In renally impaired patients (creatinine clearance < 10 ml/min) versus healthy subjects, there was no 
significant difference in mean elimination half-life (37.7 versus 32.4 hr) or clearance (21.2 versus 
25.0 l/hr). A mass balance study showed that approximately 57 % of radiolabelled olanzapine 
appeared in urine, principally as metabolites. 
 
Smokers 

In smoking subjects with mild hepatic dysfunction, mean elimination half-life (39.3 hr) was prolonged 
and clearance (18.0 l/hr) was reduced analogous to non-smoking healthy subjects (48.8 hr and 
14.1 l/hr, respectively). 
 
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. 



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Haematologic toxicity 

Effects on haematology parameters were found in each species, including dose-related reductions in 
circulating leukocytes in mice and non-specific reductions of circulating leukocytes in rats; however, 
no evidence of bone marrow cytotoxicity was found. Reversible neutropenia, thrombocytopenia, or 
anaemia developed in a few dogs treated with 8 or 10 mg/kg/day (total olanzapine exposure [AUC] is 
12- to 15-fold greater than that of a man given a 12-mg dose). In cytopenic dogs, there were no 
adverse effects on progenitor and proliferating cells in the bone marrow.  
 
Reproductive toxicity 

Olanzapine had no teratogenic effects. Sedation affected mating performance of male rats. Estrous 
cycles were affected at doses of 1.1 mg/kg (3 times the maximum human dose) and reproduction 
parameters were influenced in rats given 3 mg/kg (9 times the maximum human dose). In the 
offspring of rats given olanzapine, delays in foetal development and transient decreases in offspring 
activity levels were seen. 
 

Mutagenicity 

Olanzapine was not mutagenic or clastogenic in a full range of standard tests, which included 
bacterial mutation tests and in vitro and in vivo mammalian tests. 
 
Carcinogenicity 

Based on the results of studies in mice and rats, it was concluded that olanzapine is not carcinogenic. 
 
 
6. PHARMACEUTICAL PARTICULARS 

 
6.1 List of excipients 
 
Tablet core  

Lactose monohydrate,  
Maize starch 
Hydroxypropyl cellulose  
Magnesium stearate  
 
Tablet coat  

Opadry Blue containing: 
Hypromellose (E464) 
Titanium dioxide (E171) 
Polyethylene glycol 6000 
Indigo carmine aluminium lake (E132) 
Brilliant blue FCF aluminium lake (E133) 
Iron oxide black (E172) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
2 years 
 
6.4 Special precautions for storage 
 
Store in the original package. 
 
Store below 30°C. 



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6.5 Nature and contents of container 

 

Cold-formed aluminium blisters in cartons of 28 or 56 tablets per carton. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
No special requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Cipla (EU)  Limited 
Hillbrow House 
Hillbrow Road 
Esher 
Surrey 
KT10 9NW 
UK 
 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  

 
EU/1/07/426/010 – Olanzapine Cipla – 15 mg – coated tablets – 28 tablets per box 
 
EU/1/07/426/011 –  Olanzapine Cipla – 15 mg – coated tablets – 56 tablets per box 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 14 November 2007 
 
Date of latest renewal: 01 October 2012 
 
10. DATE OF REVISION OF THE TEXT 

 
{MM/YYYY} 
 

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



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 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 

 



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A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Pharmadox Healthcare Limited 
KW20A Kordin Industrial Park 
Paola PLA 3000 
Malta 
 
 
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 
 The marketing authorisation holder shall submit periodic safety update reports for this product in 
accordance with the requirements set out 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) 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 

agreed RMP presented in Module 1.8.2. of the Marketing Authorisation and any agreed subsequent 

updates of the RMP. 
In addition, an updated RMP should be submitted: 

 At the request of the European Medicines Agency. 
 

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

 
If the submission of a PSUR and the update of a RMP coincide, they can be submitted at the same 
time. 
 
 

 
 



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ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



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A. LABELLING 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 
CARTON OF COATED TABLETS IN BLISTERS  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Olanzapine Cipla 2.5 mg coated tablets 
olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 
Each coated tablet contains 2.5 mg olanzapine 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate, see package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 coated tablets 
56 coated tablets 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 

Oral use 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package. 
Store below 30°C. 
 



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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 

 
Cipla (EU)  Limited, Hillbrow House, Hillbrow Road, Esher, Surrey, KT10 9NW, UK 
Tel: +44 (0)1372 461407 
Fax: +44 (0)1372 461401 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/426/001, 28 coated tablets 
EU/1/07/426/002, 56 coated tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Olanzapine Cipla 2.5 mg 



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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

COLD-FORMED ALUMINIUM BLISTER STRIPS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 
Olanzapine Cipla 2.5 mg coated tablets 
olanzapine 
 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Cipla (EU)  Ltd 
 

 

3. EXPIRY DATE 

 
EXP 
 
 
4. BATCH NUMBER 

 
Lot 
 
 
5. OTHER 

 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 
CARTON OF COATED TABLETS IN BLISTERS  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Olanzapine Cipla 5 mg coated tablets 
olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 
Each coated tablet contains 5 mg olanzapine 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate, see package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 coated tablets 
56 coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 

Oral use 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package. 
Store below 30°C. 



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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 

 
Cipla (EU) Limited, Hillbrow House, Hillbrow Road, Esher, Surrey, KT10 9NW, UK 
Tel: +44 (0)1372 461407 
Fax: +44 (0)1372 461401 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/426/003, 28 coated tablets 
EU/1/07/426/004, 56 coated tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Olanzapine Cipla 5 mg 



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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

COLD-FORMED ALUMINIUM BLISTER STRIPS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 
Olanzapine Cipla 5 mg coated tablets 
olanzapine 
 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Cipla (EU)  Ltd 
 

 

3. EXPIRY DATE 

 
EXP 
 
 
4. BATCH NUMBER 

 
Lot 
 
 
5. OTHER 

 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 
CARTON OF COATED TABLETS IN BLISTERS  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Olanzapine Cipla 7.5 mg coated tablets 
olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 
Each coated tablet contains 7.5 mg olanzapine 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate, see package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 coated tablets 
56 coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 

Oral use 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package. 
Store below 30°C. 



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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 

 
Cipla (EU) Limited, Hillbrow House, Hillbrow Road, Esher, Surrey, KT10 9NW, UK 
Tel: +44 (0)1372 461407 
Fax: +44 (0)1372 461401 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/426/005, 28 coated tablets 
EU/1/07/426/006, 56 coated tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Olanzapine Cipla 7.5 mg 



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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

COLD-FORMED ALUMINIUM BLISTER STRIPS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 
Olanzapine Cipla 7.5 mg coated tablets 
olanzapine 
 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Cipla (EU) Ltd 
 

 

3. EXPIRY DATE 

 
EXP 
 
 
4. BATCH NUMBER 

 
Lot 
 
 
5. OTHER 

 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 
CARTON OF COATED TABLETS IN BLISTERS  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Olanzapine Cipla 10 mg coated tablets 
olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 
Each coated tablet contains 10 mg olanzapine 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate, see package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
7 coated tablets 
28 coated tablets 
56 coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 

Oral use 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package. 
Store below 30°C. 



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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 

 
Cipla (EU) Limited, Hillbrow House, Hillbrow Road, Esher, Surrey, KT10 9NW, UK 
Tel: +44 (0)1372 461407 
Fax: +44 (0)1372 461401 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/426/007, 7 coated tablets 
EU/1/07/426/008, 28 coated tablets 
EU/1/07/426/009, 56 coated tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Olanzapine Cipla 10 mg 



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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

COLD-FORMED ALUMINIUM BLISTER STRIPS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 
Olanzapine Cipla 10 mg coated tablets 
olanzapine 
 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Cipla (EU)  Ltd 
 

 

3. EXPIRY DATE 

 
EXP 
 
 
4. BATCH NUMBER 

 
Lot 
 
 
5. OTHER 

 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 
CARTON OF COATED TABLETS IN BLISTERS  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Olanzapine Cipla 15 mg coated tablets 
olanzapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 
Each coated tablet contains 15 mg olanzapine 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate, see package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 coated tablets 
56 coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 

Oral use 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package. 
Store below 30°C. 



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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 

 
Cipla (EU) Limited, Hillbrow House, Hillbrow Road, Esher, Surrey, KT10 9NW, UK 
Tel: +44 (0)1372 461407 
Fax: +44 (0)1372 461401 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/426/010, 28 coated tablets 
EU/1/07/426/011, 56 coated tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Olanzapine Cipla 15 mg 



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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

COLD-FORMED ALUMINIUM BLISTER STRIPS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 
Olanzapine Cipla 15 mg coated tablets 
olanzapine 
 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Cipla (EU)  Ltd 
 

 

3. EXPIRY DATE 

 
EXP 
 
 
4. BATCH NUMBER 

 
Lot 
 
 
5. OTHER 

 
 



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B. PACKAGE LEAFLET 
 



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Package leaflet: Information for the user 

 

OLANZAPINE CIPLA 2.5 mg coated tablets 

OLANZAPINE CIPLA 5 mg coated tablets 

OLANZAPINE CIPLA 7.5 mg coated tablets 

OLANZAPINE CIPLA 10 mg coated tablets 

OLANZAPINE CIPLA 15 mg coated tablets 

olanzapine 
 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

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

effects not listed in this leaflet. 
 
What is in this leaflet 
 
1. What OLANZAPINE CIPLA is and what it is used for 
2. What you need to know before you take OLANZAPINE CIPLA 
3. How to take OLANZAPINE CIPLA 
4. Possible side effects 
5. How to store OLANZAPINE CIPLA 
6. Contents of the pack and other information 
 

 
1. What OLANZAPINE CIPLA is and what it is used for 

 

OLANZAPINE CIPLA belongs to a group of medicines called antipsychotics and is used to treat the 
following conditions: 

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

 Moderate to severe manic episodes, a condition with symptoms of excitement or euphoria. 
 
OLANZAPINE CIPLA 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 CIPLA 

 

Do not take OLANZAPINE CIPLA 

 iIf 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 CIPLA. 
 The use of OLANZAPINE CIPLA in elderly patients with dementia is not recommended as it may 

have serious side effects. 



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 Medicines of this type may cause unusual movements mainly of the face or tongue. If this 
happens after you have been given OLANZAPINE CIPLA 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 CIPLA. You and your doctor should 
check your weight regularly.  

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

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

 
If you suffer from any of the following illnesses tell your doctor as soon as possible: 
 
 Stroke or “mini” stroke (temporary symptoms of stroke) 
 Parkinson’s disease 
 Prostate problems 
 A blocked intestine (Paralytic ileus) 
 Liver or kidney disease 
 Blood disorders 
 Heart disease 
 Diabetes 
 Seizures 
 
If you 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 CIPLA is not for patients who are under 18 years. 
 
Other medicines and OLANZAPINE CIPLA 

Only take other medicines while you are on OLANZAPINE CIPLA if your doctor tells you that you 
can. You might feel drowsy if OLANZAPINE CIPLA is taken in combination with antidepressants or 
medicines taken for anxiety or to help you sleep (tranquillisers).  
 
Tell your doctor if you are taking, have recently taken or might take any other medicines.  
 
In particular, tell your doctor if you are taking: 
 medicines for Parkinson’s disease. 
 carbamazepine (an anti-epileptic and mood stabiliser), fluvoxamine (an antidepressant) or 

ciprofloxacin (an antibiotic) - it may be necessary to change your OLANZAPINE CIPLA dose. 
 
OLANZAPINE CIPLA with alcohol 

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

Pregnancy and breast-feeding 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. You should not be given this medicine when 
breast-feeding, as small amounts of OLANZAPINE CIPLA can pass into breast milk. 
 



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The following symptoms may occur in newborn babies, of mothers that have used OLANZAPINE 
CIPLA 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 CIPLA. If this happens do not 
drive or operate any tools or machines. Tell your doctor. 
 

OLANZAPINE CIPLA contains lactose.  
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicinal product. 
 

 
3. How to take OLANZAPINE CIPLA 

 

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 CIPLA tablets to take and how long you should 
continue to take them. The daily dose of OLANZAPINE CIPLA is between 5 and 20 mg. Consult 
your doctor if your symptoms return but do not stop taking OLANZAPINE CIPLA unless your doctor 
tells you to.  
 
You should take your OLANZAPINE CIPLA 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 CIPLA coated tablets are for oral use. You should swallow the 
OLANZAPINE CIPLA tablets whole with water. 
 
If you take more OLANZAPINE CIPLA than you should 

Patients who have taken more OLANZAPINE CIPLA 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 CIPLA 

Take your tablets as soon as you remember. Do not take two doses in one day. 
 
If you stop taking OLANZAPINE CIPLA 

Do not stop taking your tablets just because you feel better. It is important that you carry on taking 
OLANZAPINE CIPLA for as long as your doctor tells you. 
 
If you suddenly stop taking OLANZAPINE CIPLA, symptoms such as sweating, unable to sleep, 
tremor, anxiety or nausea and vomiting might occur. Your doctor may suggest you to reduce the dose 
gradually before stopping treatment. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 

 

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



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Tell your doctor immediately if you have:  

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

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

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

 
Very common side effects (may affect more than 1 in 10 people) include weight gain; sleepiness; and 
increases in levels of prolactin in the blood. In the early stages of treatment, some people may feel 
dizzy or faint (with a slow heart rate), especially when getting up from a lying or sitting position. This 
will usually pass on its own but if it does not, tell your doctor. 
 
Common side effects (may affect up to 1 in 10 people) include changes in the levels of some blood cells 
circulating fats and early in treatment, temporary increases in liver enzymes; increases in the level of 
sugars in the blood and urine; increases in levels of uric acid and creatine phosphokinase in the blood; 
feeling more hungry; dizziness; restlessness; tremor;; unusual movements(dyskinesias); constipation; 
dry mouth; rash; loss of strength; extreme tiredness; water retention leading to swelling of the hands, 
ankles or feet; fever; joint pain; and sexual dysfunctions such as decreased libido in males and females 
or erectile dysfunction in males..  
 
Uncommon side effects (may affect up to 1 in 100 people) include hypersensitivity (e.g. swelling in the 
mouth and throat, itching, rash); diabetes or the worsening of diabetes, occasionally associated with 
ketoacidosis (ketones in the blood and urine) or coma; seizures, usually associated with a history of 
seizures (epilepsy); muscle stiffness or spasms (including eye movements); problems with speech; slow 
heart rate; sensitivity to sunlight; bleeding from the nose; abdominal distension; memory loss or 
forgetfulness;urinary incontinence; lack of ability to urinate; hair loss; absence or decrease in menstrual 
periods; and changes in breasts in males and females such as an abnormal production of breast milk or 
abnormal growth. 
 
Rare side effects (may affect up to 1 in 1000 people) include lowering of normal body temperature; 
abnormal rhythms of the heart; sudden unexplained death; inflammation of the pancreas causing severe 
stomach pain, fever and sickness; liver disease appearing as yellowing of the skin and white parts of the 
eyes; muscle disease presenting as unexplained aches and pains; and prolonged and/or painful erection. 
 
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 CIPLA may worsen the symptoms. 
 
If you get any side effects, talk to your doctor or pharmacist.  This includes any possible side effects 
not listed in this leaflet. 
 

 
5. How to store OLANZAPINE CIPLA COATED TABLETS 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton after Exp. 
Store in the original package.  Store below 30ºC. 
 



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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 Cipla contains 
 
- The active substance is olanzapine.  Each Olanzapine Cipla coated tablet contains either 

2.5 mg, 5 mg, 7.5 mg, 10 mg or 15 mg of the active substance. 
- The other ingredients are: 
- Tablet core: lactose monohydrate (See also end of section 2 – important information about 

some of the ingredients of Olanzapine Cipla), maize starch, hydroxypropyl cellulose, 
magnesium stearate. 

- Tablet coat:  
- 2.5 mg, 5 mg, 7.5 mg and 10 mg tablets: Opadry white containing hypromellose (E464), 

titanium dioxide (E171), lactose monohydrate, polyethylene glycol 3000 and glycerol triacetate 
- 15 mg tablets: Opadry Blue containing hypromellose (E464), titanium dioxide (E171), 

polyethylene glycol 6000, indigo carmine aluminium lake (E132), brilliant blue FCF aluminium 
lake (E133) and iron oxide black (E172) 

 
What OLANZAPINE CIPLA looks like and contents of the pack 

Olanzapine Cipla 2.5 mg coated tablets are white, round, biconvex, coated tablets with ‘2.5’ debossed 
on one side and ‘OLZ’ on the other. 
 
Olanzapine Cipla 5 mg coated tablets are white, round, biconvex, coated tablets with ‘OLZ 5’ 
debossed on one side and ‘NEO’ on the other. 
 
Olanzapine Cipla 7.5 mg coated tablets are white, round, biconvex, coated tablets with ‘OLZ 7.5’ 
debossed on one side and ‘NEO’ on the other.  
 
Olanzapine Cipla 10 mg coated tablets are white, round, biconvex, coated tablets with ‘OLZ 10’ 
debossed on one side and ‘NEO’ on the other.  
 
Olanzapine Cipla 15 mg coated tablets are blue, elliptical, convex, coated tablets with ‘NEO’ 
debossed on one side and plain on the other side. 
 
Olanzapine Cipla 2.5 mg, 5 mg, 7.5 mg and 15 mg coated tablets are available in 28 and 56 blister 
packs. 
 
Olanzapine Cipla 10 mg coated tablets are available in 7, 28 and 56 blister packs. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 

Marketing Authorisation Holder: Cipla (EU) Limited, Hillbrow House, Hillbrow Road, Esher, 
Surrey, KT10 9NW, UK 
Tel: +44 (0)1372 461407 
Fax: +44 (0)1372 461401 
 
Manufacturer:  
Pharmadox Healthcare Limited, KW20A Kordin Industrial Park, Paola, PLA 3000, Malta 
Tel: +356 21 808662 
Fax: +356 21 808663 
 



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This leaflet was last revised in {month YYYY} 

 
Detailed information on this medicine is available on the European Medicines Agency (EMA) web 
site: http://www.ema.europa.eu/. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	LABELLING
	PACKAGE LEAFLET