Zalasta

1

ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



2

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 2.5 mg tablets
Zalasta 5 mg tablets
Zalasta 7.5 mg tablets
Zalasta 10 mg tablets
Zalasta 15 mg tablets
Zalasta 20 mg tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Zalasta 2.5 mg tablets
Each tablet contains 2.5 mg olanzapine.

Zalasta 5 mg tablets
Each tablet contains 5 mg olanzapine.

Zalasta 7.5 mg tablets
Each tablet contains 7.5 mg olanzapine.

Zalasta 10 mg tablets
Each tablet contains 10 mg olanzapine.

Zalasta 15 mg tablets
Each tablet contains 15 mg olanzapine.

Zalasta 20 mg tablets
Each tablet contains 20 mg olanzapine.

Excipient with known effect

Zalasta 2.5 mg tablets
Each tablet contains 40.4 mg lactose.

Zalasta 5 mg tablets
Each tablet contains 80.9 mg lactose.

Zalasta 7.5 mg tablets
Each tablet contains 121.3 mg lactose.

Zalasta 10 mg tablets
Each tablet contains 161.8 mg lactose.

Zalasta 15 mg tablets
Each tablet contains 242.7 mg lactose.

Zalasta 20 mg tablets
Each tablet contains 323.5 mg lactose.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet.



3

Zalasta 2.5 mg tablets
Tablets are round, slightly biconvex, slightly yellow tablets with possible individual yellow spots.

Zalasta 5 mg tablets
Tablets are round, slightly biconvex, slightly yellow tablets with possible individual yellow spots 
and an inscription “5”.

Zalasta 7.5 mg tablets
Tablets are round, slightly biconvex, slightly yellow tablets with possible individual yellow spots
and an inscription “7.5”.

Zalasta 10 mg tablets
Tablets are round, slightly biconvex, slightly yellow tablets with possible individual yellow spots 
and an inscription “10”.

Zalasta 15 mg tablets
Tablets are round, slightly biconvex, slightly yellow tablets with possible individual yellow spots 
and an inscription “15”.

Zalasta 20 mg tablets
Tablets are round, slightly biconvex, slightly yellow tablets with possible individual yellow spots 
and an inscription “20”.

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 



4

only after appropriate clinical reassessment and should generally occur at intervals of not less than 
24 hours. 
Olanzapine can be given without regards for meals as absorption is not affected by food. Gradual 
tapering of the dose should be considered when discontinuing olanzapine.

Special populations

Elderly
A lower starting dose (5 mg/day) is not routinely indicated but should be considered for those 65 
and over when clinical factors warrant (see also section 4.4).

Renal and/or hepatic impairment
A lower starting dose (5 mg) should be considered for such patients. In cases of moderate hepatic 
insufficiency (cirrhosis, Child-Pugh Class A or B), the starting dose should be 5 mg and only 
increased with caution.

Smokers
The starting dose and dose range need not be routinely altered for non-smokers relative to smokers.
The metabolism of olanzapine may be induced by smoking. Clinical monitoring is recommended 
and an increase of olanzapine dose may be considered if necessary (see section 4.5).

When more than one factor is present which might result in slower metabolism (female gender, 
geriatric age, non-smoking status), consideration should be given to decreasing the starting dose. 
Dose escalation, when indicated, should be conservative in such patients.

(See sections 4.5 and 5.2.)

Paediatric population
Olanzapine is not recommended for use in children and adolescents below 18 years of age due to a 
lack of data on safety and efficacy. A greater magnitude of weight gain, lipid and prolactin 
alterations has been reported in short term studies of adolescent patients than in studies of adult 
patients (see sections 4.4, 4.8, 5.1 and 5.2).

4.3 Contraindications

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



5

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 medicines, including 
Zalasta, should be observed for signs and symptoms of hyperglycaemia (such as polydipsia, 
polyuria, polyphagia, and weakness) and patients with diabetes mellitus or with risk factors for 
diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be 
monitored regularly, e.g. at baseline, 4, 8 and 12 weeks after starting olanzapine treatment and 
quarterly thereafter.

Lipid alterations
Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebo-
controlled clinical trials (see section 4.8). Lipid alterations should be managed as clinically 
appropriate, particularly in dyslipidemic patients and in patients with risk factors for the 
development of lipids disorders. Patients treated with any antipsychotic medicines, including 
Zalasta, 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.



6

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, 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 was 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.



7

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

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

Paediatric population
Olanzapine is not indicated for use in the treatment of children and adolescents. Studies in patients 
aged 13-17 years showed various adverse reactions, including weight gain, changes in metabolic 
parameters and increases in prolactin levels (see sections 4.8 and 5.1).

Lactose
Zalasta tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total
lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Interaction studies have only been performed in adults.

Potential interactions affecting olanzapine
Since olanzapine is metabolised by CYP1A2, substances that can specifically induce or inhibit this 
isoenzyme may affect the pharmacokinetics of olanzapine.

Induction of CYP1A2
The metabolism of olanzapine may be induced by smoking and carbamazepine, which may lead to 
reduced olanzapine concentrations. Only slight to moderate increase in olanzapine clearance has 
been observed. The clinical consequences are likely to be limited, but clinical monitoring is 
recommended and an increase of olanzapine dose may be considered if necessary (see section 4.2).

Inhibition of CYP1A2
Fluvoxamine, a specific CYP 1A2 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 CYP 1A2 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).



8

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

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

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

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

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

4.6 Fertility, pregnancy and lactation

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

New born infants exposed to antipsychotics (including olanzapine) during the third trimester of 
pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms 
that may vary in severity and duration following delivery. There have been reports of agitation, 
hypertonia, 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.

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

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

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



9

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

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

Eosinophilia
Leukopenia10

Neutropenia10

Thrombocytopenia1
1

Immune system disorders
Hypersensitivity11

Metabolism and nutrition disorders
Weight gain1 Elevated cholesterol 

levels2,3

Elevated glucose 
levels4

Elevated triglyceride 
levels2,5

Glucosuria
Increased appetite

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

Hypothermia12

Nervous system disorders
Somnolence Dizziness

Akathisia6

Parkinsonism6

Dyskinesia6

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

Dystonia (including 
oculogyration)11

Tardive dyskinesia11

Amnesia9

Dysarthria
Stuttering11

Restless legs 
syndrome11

Neuroleptic 
malignant 
syndrome (see 
section 4.4)12

Discontinuation 
symptoms7, 12

Cardiac disorders
Bradycardia
QTc prolongation (see 
section 4.4)

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

Vascular disorders
Orthostatic 
hypotension10

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

Respiratory, thoracic and mediastinal disorders
Epistaxis9

Gastrointestinal disorders
Mild, transient 
anticholinergic effects 
including constipation 
and dry mouth

Abdominal distension9

Salivary 
hypersecretion11

Pancreatitis11



10

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

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

Skin and subcutaneous tissue disorders
Rash Photosensitivity 

reaction
Alopecia

Drug Reaction 
with 
Eosinophilia and 
Systemic 
Symptoms 
(DRESS)

Musculoskeletal and connective tissue disorders
Arthralgia9 Rhabdomyolysis11

Renal and urinary disorders
Urinary incontinence, 
urinary retention
Urinary hesitation11

Pregnancy, puerperium and perinatal conditions
Drug 
withdrawal 
syndrome 
neonatal (see 
section 4.6)

Reproductive system and breast disorders
Erectile dysfunction in 
males
Decreased libido in 
males and females

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

Priapism12

General disorders and administration site conditions
Asthenia
Fatigue
Oedema
Pyrexia10

Investigations
Elevated plasma 
prolactin levels8

Increased alkaline 
phosphatase10

High creatine 
phosphokinase11

High Gamma 
Glutamyltransferase10

High uric acid10

Increased total 
bilirubin

1
Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) 

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



11

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

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

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

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

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

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

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

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

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

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

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

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

Additional information on special populations
In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a 
higher incidence of death and cerebrovascular adverse reactions compared to placebo (see section 
4.4). Very 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.



12

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

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

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

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

Metabolism and nutrition disorders
Very common: Weight gain13, elevated triglyceride levels14, increased appetite.
Common: Elevated cholesterol levels15

Nervous system disorders
Very common: Sedation (including: hypersomnia, lethargy, somnolence).
Gastrointestinal disorders
Common: Dry mouth
Hepatobiliary disorders
Very common: Elevations of hepatic aminotransferases (ALT/AST; see section 4.4).
Investigations 
Very common: Decreased total bilirubin, increased GGT, elevated plasma prolactin levels16.

13 Following short term treatment (median duration 22 days), weight gain ≥ 7 % of baseline body 
weight (kg) was very common (40.6 %), ≥ 15 % of baseline body weight was common (7.1 %) and 
≥ 25 % was common (2.5 %). With long-term exposure (at least 24 weeks), 89.4 % gained ≥ 7 %, 
55.3 % gained ≥ 15 % and 29.1 % gained ≥ 25% of their baseline body weight.

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

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

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

Reporting of suspected adverse reactions



13

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

4.9 Overdose

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

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

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

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

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: psycholeptics, diazepines, oxazepines, thiazepines and oxepines, ATC 
code: N05AH03.

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

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



14

Photon Emission Computed Tomography (SPECT) imaging study in schizophrenic patients 
revealed that olanzapine-responsive patients had lower striatal D2 occupancy than some other 
antipsychotic- and risperidone-responsive patients, while being comparable to clozapine-responsive 
patients.

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

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

In patients with a manic or mixed episode of bipolar disorder, olanzapine demonstrated superior 
efficacy to placebo and valproate semisodium (divalproex) in reduction of manic symptoms over 3 
weeks. Olanzapine also demonstrated comparable efficacy results to haloperidol in terms of the 
proportion of patients in symptomatic remission from mania and depression at 6 and 12 weeks. In a 
co-therapy study of patients treated with lithium or valproate for a minimum of 2 weeks, the 
addition of olanzapine 10 mg (co-therapy with lithium or valproate) resulted in a greater reduction 
in symptoms of mania than lithium or valproate monotherapy after 6 weeks.

In a 12-month recurrence prevention study in manic episode patients who achieved remission on 
olanzapine and were then randomised to olanzapine or placebo, olanzapine demonstrated 
statistically significant superiority over placebo on the primary endpoint of bipolar recurrence. 
Olanzapine also showed a statistically significant advantage over placebo in terms of preventing 
either recurrence into mania or recurrence into depression.

In a second 12-month recurrence prevention study in manic episode patients who achieved 
remission with a combination of olanzapine and lithium and were then randomised to olanzapine or 
lithium alone, olanzapine was statistically non-inferior to lithium on the primary endpoint of 
bipolar recurrence (olanzapine 30.0%, lithium 38.3%; p=0.055).

In an 18-month co-therapy study in manic or mixed episode patients stabilised with olanzapine plus 
a mood stabiliser (lithium or valproate), long-term olanzapine co-therapy with lithium or valproate 
was not statistically significantly superior to lithium or valproate alone in delaying bipolar 
recurrence, defined according to syndromic (diagnostic) criteria.

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

5.2 Pharmacokinetic properties

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.



15

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

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

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

In healthy elderly (65 and over) versus non-elderly subjects, the mean elimination half-life was 
prolonged (51.8 versus 33.8 hr) and the clearance was reduced (17.5 versus 18.2 l/hr). The 
pharmacokinetic variability observed in the elderly is within the range for the non-elderly. In 44 
patients with schizophrenia 65 years of age, dosing from 5 to 20 mg/day was not associated with 
any distinguishing profile of adverse events.

In female versus male subjects the mean elimination half life was somewhat prolonged (36.7 versus 
32.3 hr) and the clearance was reduced (18.9 versus 27.3 l/hr). However, olanzapine (5-20 mg) 
demonstrated a comparable safety profile in female (n=467) as in male patients (n=869).

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

Hepatic impairment 
A small study of the effect of impaired liver function in 6 subjects with clinically significant 
(Childs Pugh Classification A (n = 5) and B (n = 1)) cirrhosis revealed little effect on the 
pharmacokinetics of orally administered olanzapine (2.5 – 7.5 mg single dose): Subjects with mild 
to moderate hepatic dysfunction had slightly increased systemic clearance and faster elimination 
half-time compared to subjects with no hepatic dysfunction (n = 3). There were more smokers 
among subjects with cirrhosis (4/6; 67 %) than among subjects with no hepatic dysfunction (0/3; 
0 %).

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

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

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

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



16

average body weight and fewer adolescents were smokers. Such factors possibly contribute to the 
higher average exposure observed in adolescents.

5.3 Preclinical safety data

Acute (single-dose) toxicity
Signs of oral toxicity in rodents were characteristic of potent neuroleptic compounds: 
hypoactivity, coma, tremors, clonic convulsions, salivation, and depressed weight gain. The 
median lethal doses were approximately 210 mg/kg (mice) and 175 mg/kg (rats). Dogs tolerated 
single oral doses up to 100 mg/kg without mortality. Clinical signs included sedation, ataxia, 
tremors, increased heart rate, labored respiration, miosis, and anorexia. In monkeys, single oral 
doses up to 100 mg/kg resulted in prostration and, at higher doses, semi-consciousness.

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

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

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

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

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

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose monohydrate
Powdered cellulose
Pregelatinised maize starch
Maize starch
Colloidal anhydrous silica
Magnesium stearate

6.2 Incompatibilities



17

Not applicable.

6.3 Shelf life

5 years

6.4 Special precautions for storage

Store in the original package in order to protect from light and moisture. This medicinal product 
does not require any special temperature storage conditions.

6.5 Nature and contents of container

Zalasta 2.5 mg tablets
Blister (OPA/Alu/PVC, Alu-foil): 14, 28, 35, 56 or 70 tablets in a box.

Zalasta 5 mg tablets
Blister (OPA/Alu/PVC, Alu-foil): 14, 28, 35, 56 or 70 tablets in a box.

Zalasta 7.5 mg tablets
Blister (OPA/Alu/PVC, Alu-foil): 14, 28, 35, 56 or 70 tablets in a box.

Zalasta 10 mg tablets
Blister (OPA/Alu/PVC, Alu-foil): 7, 14, 28, 35, 56 or 70 tablets in a box.

Zalasta 15 mg tablets
Blister (OPA/Alu/PVC, Alu-foil): 14, 28, 35, 56 or 70 tablets in a box.

Zalasta 20 mg tablets
Blister (OPA/Alu/PVC, Alu-foil): 14, 28, 35, 56 or 70 tablets in a box.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused product or waste material should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

8. MARKETING AUTHORISATION NUMBER(S)

Zalasta 2.5 mg tablets
EU/1/07/415/001-005

Zalasta 5 mg tablets
EU/1/07/415/006-010

Zalasta 7.5 mg tablets
EU/1/07/415/011-015

Zalasta 10 mg tablets



18

EU/1/07/415/016-021

Zalasta 15 mg tablets
EU/1/07/415/022-026

Zalasta 20 mg tablets
EU/1/07/415/027-031

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 27 September 2007
Date of latest renewal: 26 July 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 http://www.ema.europa.eu



19

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 5 mg orodispersible tablets
Zalasta 7.5 mg orodispersible tablets
Zalasta 10 mg orodispersible tablets
Zalasta 15 mg orodispersible tablets
Zalasta 20 mg orodispersible tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Zalasta 5 mg orodispersible tablets
Each orodispersible tablet contains 5 mg olanzapine.

Zalasta 7.5 mg orodispersible tablets
Each orodispersible tablet contains 7.5 mg olanzapine.

Zalasta 10 mg orodispersible tablets
Each orodispersible tablet contains 10 mg olanzapine.

Zalasta 15 mg orodispersible tablets
Each orodispersible tablet contains 15 mg olanzapine.

Zalasta 20 mg orodispersible tablets
Each orodispersible tablet contains 20 mg olanzapine.

Excipient with known effect

Zalasta 5 mg orodispersible tablets
Each orodispersible tablet contains 0.50 mg aspartame.

Zalasta 7.5 mg orodispersible tablets
Each orodispersible tablet contains 0.75 mg aspartame.

Zalasta 10 mg orodispersible tablets
Each orodispersible tablet contains 1.00 mg aspartame.

Zalasta 15 mg orodispersible tablets
Each orodispersible tablet contains 1.50 mg aspartame.

Zalasta 20 mg orodispersible tablets
Each orodispersible tablet contains 2.00 mg aspartame.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Orodispersible tablet.

Zalasta 5 mg orodispersible tablets
Tablets are round, slightly biconvex, yellow marbled tablets with possible individual spots.

Zalasta 7.5 mg orodispersible tablets
Tablets are round, slightly biconvex, yellow marbled tablets with possible individual spots.



20

Zalasta 10 mg orodispersible tablets
Tablets are round, slightly biconvex, yellow marbled tablets with possible individual spots.

Zalasta 15 mg orodispersible tablets
Tablets are round, slightly biconvex, yellow marbled tablets with possible individual spots.

Zalasta 20 mg orodispersible tablets
Tablets are round, slightly biconvex, yellow marbled tablets with possible individual spots.

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.
Zalasta orodispersible tablet should be placed in the mouth, where it will rapidly disperse in saliva, 
so it can be easily swallowed. Removal of the intact orodispersible tablet from the mouth is 
difficult. Since the orodispersible tablet is fragile, it should be taken immediately on opening the 
blister. Alternatively, it may be dispersed in a full glass of water immediately before 
administration.

Olanzapine orodispersible tablet is bioequivalent to olanzapine tablets, with a similar rate and 
extent of absorption. It has the same dosage and frequency of administration as olanzapine tablets. 
Olanzapine orodispersible tablets may be used as an alternative to olanzapine tablets.

Special populations



21

Elderly
A lower starting dose (5 mg/day) is not routinely indicated but should be considered for those 65 
and over when clinical factors warrant (see also section 4.4).

Renal and/or hepatic impairment
A lower starting dose (5 mg) should be considered for such patients. In cases of moderate hepatic 
insufficiency (cirrhosis, Child-Pugh Class A or B), the starting dose should be 5 mg and only 
increased with caution.

Smokers
The starting dose and dose range need not be routinely altered for non-smokers relative to smokers. 
The metabolism of olanzapine may be induced by smoking. Clinical monitoring is recommended 
and an increase of olanzapine dose may be considered if necessary (see section 4.5).

When more than one factor is present which might result in slower metabolism (female gender, 
geriatric age, non-smoking status), consideration should be given to decreasing the starting dose. 
Dose escalation, when indicated, should be conservative in such patients.

(See sections 4.5 and 5.2.)

Paediatric population
Olanzapine is not recommended for use in children and adolescents below 18 years of age due to a 
lack of data on safety and efficacy. A greater magnitude of weight gain, lipid and prolactin 
alterations has been reported in short term studies of adolescent patients than in studies of adult 
patients (see sections 4.4, 4.8, 5.1 and 5.2).

4.3 Contraindications

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

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



22

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

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

Hyperglycaemia and diabetes
Hyperglycaemia and/or development or exacerbation of diabetes occasionally associated with 
ketoacidosis or coma has been reported uncommonly, including some fatal cases (see section 4.8). 
In some cases, a prior increase in body weight has been reported which may be a predisposing 
factor. Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic 
guidelines, e.g. measuring of blood glucose at baseline, 12 weeks after starting olanzapine 
treatment and annually thereafter. Patients treated with any antipsychotic medicines, including 
Zalasta, should be observed for signs and symptoms of hyperglycaemia (such as polydipsia, 
polyuria, polyphagia, and weakness) and patients with diabetes mellitus or with risk factors for 
diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be 
monitored regularly, e.g. at baseline, 4, 8 and 12 weeks after starting olanzapine treatment and 
quarterly thereafter.

Lipid alterations
Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebo-
controlled clinical trials (see section 4.8). Lipid alterations should be managed as clinically 
appropriate, particularly in dyslipidemic patients and in patients with risk factors for the 
development of lipids disorders. Patients treated with any antipsychotic medicines, including 
Zalasta, should be monitored regularly for lipids in accordance with utilised antipsychotic 
guidelines, e.g. at baseline, 12 weeks after starting olanzapine treatment and every 5 years 
thereafter.

Anticholinergic activity
While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical 
trials revealed a low incidence of related events. However, as clinical experience with olanzapine in 
patients with concomitant illness is limited, caution is advised when prescribing for patients with 
prostatic hypertrophy, or paralytic ileus and related conditions.

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



23

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

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

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

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

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

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

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

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

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



24

using antipsychotics. In the study, the risk of olanzapine was comparable to the risk of atypical 
antipsychotics included in a pooled analysis.

Paediatric population
Olanzapine is not indicated for use in the treatment of children and adolescents. Studies in patients 
aged 13-17 years showed various adverse reactions, including weight gain, changes in metabolic 
parameters and increases in prolactin levels (see sections 4.8 and 5.1).

Aspartame
Aspartame is a source of phenylalanine. It may be harmful for patient with phenylketonuria (PKU).
This medicine should be used with caution in patients with phenylketonuria.

4.5 Interaction with other medicinal products and other forms of interaction

Interaction studies have only been performed in adults.

Potential interactions affecting olanzapine
Since olanzapine is metabolised by CYP1A2, substances that can specifically induce or inhibit this 
isoenzyme may affect the pharmacokinetics of olanzapine.

Induction of CYP1A2
The metabolism of olanzapine may be induced by smoking and carbamazepine, which may lead to 
reduced olanzapine concentrations. Only slight to moderate increase in olanzapine clearance has 
been observed. The clinical consequences are likely to be limited, but clinical monitoring is 
recommended and an increase of olanzapine dose may be considered if necessary (see section 4.2).

Inhibition of CYP1A2
Fluvoxamine, a specific CYP 1A2 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 CYP 1A2 is initiated.

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

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

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

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

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

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



25

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

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

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

4.6 Fertility, pregnancy and lactation

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

New born infants exposed to antipsychotics (including olanzapine) during the third trimester of 
pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms 
that may vary in severity and duration following delivery. There have been reports of agitation, 
hypertonia, 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.

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

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

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

Tabulated list of adverse reactions
The following table lists the adverse reactions  and laboratory investigations observed from 
spontaneous reporting and in clinical trials. Within each frequency grouping, adverse reactions are 
presented in order of decreasing seriousness. The frequency terms listed are defined as follows: Very 



26

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

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

Eosinophilia
Leukopenia10

Neutropenia10

Thrombocytopenia1
1

Immune system disorders
Hypersensitivity11

Metabolism and nutrition disorders
Weight gain1 Elevated cholesterol 

levels2,3

Elevated glucose 
levels4

Elevated triglyceride 
levels2,5

Glucosuria
Increased appetite

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

Hypothermia12

Nervous system disorders
Somnolence Dizziness

Akathisia6

Parkinsonism6

Dyskinesia6

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

Dystonia (including 
oculogyration)11

Tardive dyskinesia11

Amnesia9

Dysarthria
Stuttering11

Restless legs 
syndrome11

Neuroleptic 
malignant 
syndrome (see 
section 4.4)12

Discontinuation 
symptoms7, 12

Cardiac disorders
Bradycardia
QTc prolongation (see 
section 4.4)

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

Vascular disorders
Orthostatic 
hypotension10

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

Respiratory, thoracic and mediastinal disorders
Epistaxis9

Gastrointestinal disorders
Mild, transient 
anticholinergic effects 
including constipation 
and dry mouth

Abdominal distension9

Salivary 
hypersecretion11

Pancreatitis11

Hepatobiliary disorders
Transient, 
asymptomatic 
elevations of hepatic 
aminotransferases 

Hepatitis (including 
hepatocellular,
cholestatic or 
mixed liver 



27

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

injury)11

Skin and subcutaneous tissue disorders
Rash Photosensitivity 

reaction
Alopecia

Drug Reaction 
with Eosinophilia 
and Systemic 
Symptoms 
(DRESS)

Musculoskeletal and connective tissue disorders
Arthralgia9 Rhabdomyolysis11

Renal and urinary disorders
Urinary incontinence, 
urinary retention
Urinary hesitation11

Pregnancy, puerperium and perinatal conditions
Drug withdrawal 
syndrome neonatal 
(see section 4.6)

Reproductive system and breast disorders
Erectile dysfunction in 
males
Decreased libido in 
males and females

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

Priapism12

General disorders and administration site conditions
Asthenia
Fatigue
Oedema
Pyrexia10

Investigations
Elevated plasma 
prolactin levels8

Increased alkaline 
phosphatase10

High creatine 
phosphokinase11

High Gamma 
Glutamyltransferase10

High uric acid10

Increased total 
bilirubin

1
Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) 

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

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

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



28

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

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

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

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

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

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

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

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

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

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

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

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

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



29

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

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

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

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

Metabolism and nutrition disorders
Very common: Weight gain13, elevated triglyceride levels14, increased appetite.
Common: Elevated cholesterol levels15

Nervous system disorders
Very common: Sedation (including: hypersomnia, lethargy, somnolence).
Gastrointestinal disorders
Common: Dry mouth
Hepatobiliary disorders
Very common: Elevations of hepatic aminotransferases (ALT/AST; see section 4.4).
Investigations 
Very common: Decreased total bilirubin, increased GGT, elevated plasma prolactin levels16.

13 Following short term treatment (median duration 22 days), weight gain ≥ 7 % of baseline body 
weight (kg) was very common (40.6 %), ≥ 15 % of baseline body weight was common (7.1 %) and 
≥ 25 % was common (2.5 %). With long-term exposure (at least 24 weeks), 89.4 % gained ≥ 7 %, 
55.3 % gained ≥ 15 % and 29.1 % gained ≥ 25% of their baseline body weight.

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

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

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

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

4.9 Overdose

Signs and symptoms



30

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

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

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

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

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: psycholeptics, diazepines, oxazepines, thiazepines and oxepines, ATC 
code: N05AH03.

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

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



31

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

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

In patients with a manic or mixed episode of bipolar disorder, olanzapine demonstrated superior 
efficacy to placebo and valproate semisodium (divalproex) in reduction of manic symptoms over 3 
weeks. Olanzapine also demonstrated comparable efficacy results to haloperidol in terms of the 
proportion of patients in symptomatic remission from mania and depression at 6 and 12 weeks. In a 
co-therapy study of patients treated with lithium or valproate for a minimum of 2 weeks, the 
addition of olanzapine 10 mg (co-therapy with lithium or valproate) resulted in a greater reduction 
in symptoms of mania than lithium or valproate monotherapy after 6 weeks.

In a 12-month recurrence prevention study in manic episode patients who achieved remission on 
olanzapine and were then randomised to olanzapine or placebo, olanzapine demonstrated 
statistically significant superiority over placebo on the primary endpoint of bipolar recurrence. 
Olanzapine also showed a statistically significant advantage over placebo in terms of preventing 
either recurrence into mania or recurrence into depression.

In a second 12-month recurrence prevention study in manic episode patients who achieved 
remission with a combination of olanzapine and lithium and were then randomised to olanzapine or 
lithium alone, olanzapine was statistically non-inferior to lithium on the primary endpoint of 
bipolar recurrence (olanzapine 30.0%, lithium 38.3%; p=0.055).

In an 18-month co-therapy study in manic or mixed episode patients stabilised with olanzapine plus 
a mood stabiliser (lithium or valproate), long-term olanzapine co-therapy with lithium or valproate 
was not statistically significantly superior to lithium or valproate alone in delaying bipolar 
recurrence, defined according to syndromic (diagnostic) criteria.

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

5.2 Pharmacokinetic properties

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

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

Distribution



32

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

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

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

In healthy elderly (65 and over) versus non-elderly subjects, the mean elimination half-life was 
prolonged (51.8 versus 33.8 hr) and the clearance was reduced (17.5 versus 18.2 l/hr). The 
pharmacokinetic variability observed in the elderly is within the range for the non-elderly. In 44 
patients with schizophrenia 65 years of age, dosing from 5 to 20 mg/day was not associated with 
any distinguishing profile of adverse events.

In female versus male subjects the mean elimination half life was somewhat prolonged (36.7 versus 
32.3 hr) and the clearance was reduced (18.9 versus 27.3 l/hr). However, olanzapine (5-20 mg) 
demonstrated a comparable safety profile in female (n=467) as in male patients (n=869).

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

Hepatic impairment 
A small study of the effect of impaired liver function in 6 subjects with clinically significant 
(Childs Pugh Classification A (n = 5) and B (n = 1)) cirrhosis revealed little effect on the 
pharmacokinetics of orally administered olanzapine (2.5 – 7.5 mg single dose): Subjects with mild 
to moderate hepatic dysfunction had slightly increased systemic clearance and faster elimination 
half-time compared to subjects with no hepatic dysfunction (n = 3). There were more smokers 
among subjects with cirrhosis (4/6; 67 %) than among subjects with no hepatic dysfunction (0/3; 
0 %).

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

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

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

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



33

average body weight and fewer adolescents were smokers. Such factors possibly contribute to the 
higher average exposure observed in adolescents.

5.3 Preclinical safety data

Acute (single-dose) toxicity
Signs of oral toxicity in rodents were characteristic of potent neuroleptic compounds: 
hypoactivity, coma, tremors, clonic convulsions, salivation, and depressed weight gain. The 
median lethal doses were approximately 210 mg/kg (mice) and 175 mg/kg (rats). Dogs tolerated 
single oral doses up to 100 mg/kg without mortality. Clinical signs included sedation, ataxia, 
tremors, increased heart rate, labored respiration, miosis, and anorexia. In monkeys, single oral 
doses up to 100 mg/kg resulted in prostration and, at higher doses, semi-consciousness.

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

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

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

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

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

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Mannitol
Microcrystalline cellulose
Crospovidone
Low-substituted hydroxypropylcellulose
Aspartame
Calcium silicate
Magnesium stearate



34

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

5 years

6.4 Special precautions for storage

Store in the original package in order to protect from light and moisture. This medicinal product 
does not require any special temperature storage conditions.

6.5 Nature and contents of container

Zalasta orodispersible tablets are available in boxes of 14, 28, 35, 56 or 70 tablets in blisters 
(Alu/OPA/Alu/PVC).

6.6 Special precautions for disposal

Any unused product or waste material should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

8. MARKETING AUTHORISATION NUMBER(S)

Zalasta 5 mg orodispersible tablets
EU/1/07/415/032-036

Zalasta 7.5 mg orodispersible tablets
EU/1/07/415/037-041

Zalasta 10 mg orodispersible tablets
EU/1/07/415/042-046

Zalasta 15 mg orodispersible tablets
EU/1/07/415/047-051

Zalasta 20 mg orodispersible tablets
EU/1/07/415/052-056

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 27 September 2007
Date of latest renewal: 26 July 2012

10. DATE OF REVISION OF THE TEXT

{MM/YYYY}



35

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



36

ANNEX II

A. MANUFACTURER(S) 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



37

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers responsible for batch release

KRKA, d.d., Novo mesto
Šmarješka cesta 6
8501 Novo mesto
Slovenia

KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
Poland

TAD Pharma GmbH
Heinz-Lohmann-Straße 5
27472 Cuxhaven
Germany

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

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in 
the list of Union reference dates (EURD list) provided for under Article 107c(7) of 
Directive 2001/83/EC and any subsequent updates published on the European 
medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk management plan (RMP)

Not applicable.



38

ANNEX III

LABELLING AND PACKAGE LEAFLET



39

A. LABELLING



40

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON FOR ZALASTA 2.5 mg TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 2.5 mg tablets
olanzapine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 2.5 mg olanzapine.

3. LIST OF EXCIPIENTS

Contains lactose monohydrate. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

tablet

14 tablets
28 tablets
35 tablets
56 tablets
70 tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

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

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



41

Store in the original package in order to protect from light and moisture.

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

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/415/001 (14 tablets)
EU/1/07/415/002 (28 tablets)
EU/1/07/415/003 (35 tablets)
EU/1/07/415/004 (56 tablets)
EU/1/07/415/005 (70 tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Zalasta 2.5 mg tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC
SN
NN



42

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR ZALASTA 2.5 mg TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 2.5 mg tablets
olanzapine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



43

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON FOR ZALASTA 5 mgTABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 5 mg tablets
olanzapine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 5 mg olanzapine.

3. LIST OF EXCIPIENTS

Contains lactose monohydrate. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

tablet

14 tablets
28 tablets
35 tablets
56 tablets
70 tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

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

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



44

Store in the original package in order to protect from light and moisture.

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

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/415/006 (14 tablets)
EU/1/07/415/007 (28 tablets)
EU/1/07/415/008 (35 tablets)
EU/1/07/415/009 (56 tablets)
EU/1/07/415/010 (70 tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Zalasta 5 mg tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC
SN
NN



45

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR ZALASTA 5 mg TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 5 mg tablets
olanzapine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



46

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON FOR ZALASTA 7.5 mg TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 7.5 mg tablets
olanzapine 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 7.5 mg olanzapine.

3. LIST OF EXCIPIENTS

Contains lactose monohydrate. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

tablet

14 tablets
28 tablets
35 tablets
56 tablets
70 tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

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

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



47

Store in the original package in order to protect from light and moisture.

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

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/415/011 (14 tablets)
EU/1/07/415/012 (28 tablets)
EU/1/07/415/013 (35 tablets)
EU/1/07/415/014 (56 tablets)
EU/1/07/415/015 (70 tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Zalasta 7.5 mg tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC
SN
NN



48

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR ZALASTA 7.5 mg TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 7.5 mg tablets
olanzapine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



49

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON FOR ZALASTA 10 mg TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 10 mg tablets
olanzapine 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 10 mg olanzapine.

3. LIST OF EXCIPIENTS

Contains lactose monohydrate. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

tablet

7 tablets 
14 tablets
28 tablets
35 tablets
56 tablets
70 tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

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

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



50

Store in the original package in order to protect from light and moisture.

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

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/415/016 (7 tablets)
EU/1/07/415/017 (14 tablets)
EU/1/07/415/018 (28 tablets)
EU/1/07/415/019 (35 tablets)
EU/1/07/415/020 (56 tablets)
EU/1/07/415/021 (70 tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Zalasta 10 mg tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC
SN
NN



51

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR ZALASTA 10 mg TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 10 mg tablets
olanzapine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



52

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON FOR ZALASTA 15 mg TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 15 mg tablets
olanzapine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 15 mg olanzapine.

3. LIST OF EXCIPIENTS

Contains lactose monohydrate. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

tablet

14 tablets
28 tablets
35 tablets
56 tablets
70 tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

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

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



53

Store in the original package in order to protect from light and moisture.

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

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/415/022 (14 tablets)
EU/1/07/415/023 (28 tablets)
EU/1/07/415/024 (35 tablets)
EU/1/07/415/025 (56 tablets)
EU/1/07/415/026 (70 tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Zalasta 15 mg tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC
SN
NN



54

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR ZALASTA 15 mg TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 15 mg tablets
olanzapine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



55

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON FOR ZALASTA 20 mg TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 20 mg tablets
olanzapine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 20 mg olanzapine.

3. LIST OF EXCIPIENTS

Contains lactose monohydrate. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

tablet

14 tablets
28 tablets
35 tablets
56 tablets
70 tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

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

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



56

Store in the original package in order to protect from light and moisture.

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

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/415/027 (14 tablets)
EU/1/07/415/028 (28 tablets)
EU/1/07/415/029 (35 tablets)
EU/1/07/415/030 (56 tablets)
EU/1/07/415/031 (70 tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Zalasta 20 mg tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC
SN
NN



57

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR ZALASTA 20 mg TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 20 mg tablets
olanzapine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



58

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON FOR ZALASTA 5 mg ORODISPERSIBLE TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 5 mg orodispersible tablets
olanzapine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each orodispersible tablet contains 5 mg olanzapine.

3. LIST OF EXCIPIENTS

Contains aspartame. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

orodispersible tablet

14 orodispersible tablets
28 orodispersible tablets
35 orodispersible tablets
56 orodispersible tablets
70 orodispersible tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

Do not handle the tablets with wet hands as the tablets may break up.

1. Hold the blister at the edges and separate one blister cell from the rest of the blister by gently 
tearing along the perforations around it.

2. Pull up the edge of the foil and peel foil off completely.
3. Tip the tablet out onto your hand.
4. Put the tablet on the tongue as soon as it is removed from the packaging.

Swallow the tablet with or without water.
You can also place the tablet in a full glass or cup of water and drink it straight away.

I I

I I

I I

I I

3.us



59

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

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from light and moisture.

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/415/032 (14 orodispersible tablets)
EU/1/07/415/033 (28 orodispersible tablets)
EU/1/07/415/034 (35 orodispersible tablets)
EU/1/07/415/035 (56 orodispersible tablets)
EU/1/07/415/036 (70 orodispersible tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Zalasta 5 mg orodispersible tablets



60

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC
SN
NN



61

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR ZALASTA 5 mg ORODISPERSIBLE TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 5 mg orodispersible tablets
olanzapine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

1. Tear.
2. Peel.



62

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON FOR ZALASTA 7.5 mg ORODISPERSIBLE TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 7.5 mg orodispersible tablets
olanzapine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each orodispersible tablet contains 7.5 mg olanzapine.

3. LIST OF EXCIPIENTS

Contains aspartame. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

orodispersible tablet

14 orodispersible tablets
28 orodispersible tablets
35 orodispersible tablets
56 orodispersible tablets
70 orodispersible tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

Do not handle the tablets with wet hands as the tablets may break up.

1. Hold the blister at the edges and separate one blister cell from the rest of the blister by gently 
tearing along the perforations around it.

2. Pull up the edge of the foil and peel foil off completely.
3. Tip the tablet out onto your hand.
4. Put the tablet on the tongue as soon as it is removed from the packaging.

Swallow the tablet with or without water.
You can also place the tablet in a full glass or cup of water and drink it straight away.

I I

I I

I I

I I



63

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

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from light and moisture.

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/415/037 (14 orodispersible tablets)
EU/1/07/415/038 (28 orodispersible tablets)
EU/1/07/415/039 (35 orodispersible tablets)
EU/1/07/415/040 (56 orodispersible tablets)
EU/1/07/415/041 (70 orodispersible tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Zalasta 7.5 mg orodispersible tablets



64

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC
SN
NN



65

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR ZALASTA 7.5 mg ORODISPERSIBLE TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 7.5 mg orodispersible tablets
olanzapine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

1. Tear.
2. Peel.



66

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON FOR ZALASTA 10 mg ORODISPERSIBLE TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 10 mg orodispersible tablets
olanzapine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each orodispersible tablet contains 10 mg olanzapine.

3. LIST OF EXCIPIENTS

Contains aspartame. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

orodispersible tablet

14 orodispersible tablets
28 orodispersible tablets
35 orodispersible tablets
56 orodispersible tablets
70 orodispersible tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

Do not handle the tablets with wet hands as the tablets may break up.

1. Hold the blister at the edges and separate one blister cell from the rest of the blister by gently 
tearing along the perforations around it.

2. Pull up the edge of the foil and peel foil off completely.
3. Tip the tablet out onto your hand.
4. Put the tablet on the tongue as soon as it is removed from the packaging.

Swallow the tablet with or without water.
You can also place the tablet in a full glass or cup of water and drink it straight away.

I I

I I

I I

I I



67

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

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from light and moisture.

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/415/042 (14 orodispersible tablets)
EU/1/07/415/043 (28 orodispersible tablets)
EU/1/07/415/044 (35 orodispersible tablets)
EU/1/07/415/045 (56 orodispersible tablets)
EU/1/07/415/046 (70 orodispersible tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Zalasta 10 mg orodispersible tablets



68

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC
SN
NN



69

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR ZALASTA 10 mg  ORODISPERSIBLE TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 10 mg orodispersible tablets
olanzapine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

1. Tear.
2. Peel.



70

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON FOR ZALASTA 15 mg ORODISPERSIBLE TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 15 mg orodispersible tablets
olanzapine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each orodispersible tablet contains 15 mg olanzapine.

3. LIST OF EXCIPIENTS

Contains aspartame. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

orodispersible tablet

14 orodispersible tablets
28 orodispersible tablets
35 orodispersible tablets
56 orodispersible tablets
70 orodispersible tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

Do not handle the tablets with wet hands as the tablets may break up.

1. Hold the blister at the edges and separate one blister cell from the rest of the blister by gently 
tearing along the perforations around it.

2. Pull up the edge of the foil and peel foil off completely.
3. Tip the tablet out onto your hand.
4. Put the tablet on the tongue as soon as it is removed from the packaging.

Swallow the tablet with or without water.
You can also place the tablet in a full glass or cup of water and drink it straight away.

I I

I I

I I

I I



71

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

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from light and moisture.

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/415/047 (14 orodispersible tablets)
EU/1/07/415/048 (28 orodispersible tablets)
EU/1/07/415/049 (35 orodispersible tablets)
EU/1/07/415/050 (56 orodispersible tablets)
EU/1/07/415/051 (70 orodispersible tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Zalasta 15 mg orodispersible tablets



72

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC
SN
NN



73

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR ZALASTA 15 mg ORODISPERSIBLE TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 15 mg orodispersible tablets
olanzapine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

1. Tear.
2. Peel.



74

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON FOR ZALASTA 20 mg ORODISPERSIBLE TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 20 mg orodispersible tablets
olanzapine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each orodispersible tablet contains 20 mg olanzapine.

3. LIST OF EXCIPIENTS

Contains aspartame. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

orodispersible tablet

14 orodispersible tablets
28 orodispersible tablets
35 orodispersible tablets
56 orodispersible tablets
70 orodispersible tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

Do not handle the tablets with wet hands as the tablets may break up.

1. Hold the blister at the edges and separate one blister cell from the rest of the blister by gently 
tearing along the perforations around it.

2. Pull up the edge of the foil and peel foil off completely.
3. Tip the tablet out onto your hand.
4. Put the tablet on the tongue as soon as it is removed from the packaging.

Swallow the tablet with or without water.
You can also place the tablet in a full glass or cup of water and drink it straight away.

I I

I I

I I

I I



75

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

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from light and moisture.

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/415/052 (14 orodispersible tablets)
EU/1/07/415/053 (28 orodispersible tablets)
EU/1/07/415/054 (35 orodispersible tablets)
EU/1/07/415/055 (56 orodispersible tablets)
EU/1/07/415/056 (70 orodispersible tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Zalasta 20 mg orodispersible tablets



76

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC
SN
NN



77

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR ZALASTA 20 mg ORODISPERSIBLE TABLETS

1. NAME OF THE MEDICINAL PRODUCT

Zalasta 20 mg orodispersible tablets
olanzapine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

1. Tear.
2. Peel.



78

B. PACKAGE LEAFLET



79

Package leaflet: Information for the user

Zalasta 2.5 mg tablets
Zalasta 5 mg tablets

Zalasta 7.5 mg tablets
Zalasta 10 mg tablets
Zalasta 15 mg tablets
Zalasta 20 mg tablets

olanzapine

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

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

effects not listed in this leaflet. See section 4.

In this leaflet:
1. What Zalasta is and what it is used for
2. What you need to know before you take Zalasta
3. How to take Zalasta
4. Possible side effects
5. How to store Zalasta
6. Contents of the pack and other information

1. What Zalasta is and what it is used for

Zalasta contains the active substance olanzapine. Zalasta 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.

Zalasta 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 Zalasta

Do not take Zalasta
- If you are allergic (hypersensitive) to olanzapine or any of the other ingredients of this 

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

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

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

side effects
─ Medicines of this type may cause unusual movements mainly of the face or tongue. If this 

happens after you have been given Zalasta tell your doctor.



80

─ 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 Zalasta. You and your doctor should check your 
weight regularly. Consider referral to a dietician or help with a diet plan if necessary.

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

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

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

vomiting (being sick) or usage of diuretics (water tablets)

If you suffer from dementia, you or your carer/relative should tell your doctor if you have ever had 
a stroke or “mini” stroke.

As a routine precaution, if you are over 65 years your blood pressure may be monitored by your 
doctor.

Children and adolescents
Zalasta is not for patients who are under 18 years.

Other medicines and Zalasta
Only take other medicines while you are on Zalasta if your doctor tells you that you can. You 
might feel drowsy if Zalasta 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 Zalasta dose.

Zalasta with alcohol
Do not drink any alcohol if you have been given Zalasta 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 take this medicine when 
pregnant unless you have discussed this with your doctor.

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



81

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

Zalasta 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 Zalasta

Always take this medicine exactly as your doctor has told you. Check with your doctor or 
pharmacists if you are not sure.

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

You should take your Zalasta 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.
You should swallow the tablets whole with water.

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

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

If you suddenly stop taking Zalasta, symptoms such as sweating, unable to sleep, tremor, anxiety 
or nausea and vomiting might occur. Your doctor may suggest you to reduce the dose gradually 
before stopping treatment.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

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

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

especially in the legs (symptoms include swelling, pain, and redness in the leg), which may 



82

travel through blood vessels to the lungs causing chest pain and difficulty in breathing. If you 
notice any of these symptoms seek medical advice immediately;

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

Very common side effects (may affect more than 1 in 10 people) include weight gain; sleepiness 
and increases in levels of prolactin in the blood. In the early stages of treatment, some people may 
feel dizzy or faint (with a slow heart rate), especially when getting up from a lying or sitting 
position. This will usually pass on its own but if it does not, tell your doctor.

Common side effects (may affect up to 1 in 10 people) include changes in the levels of some blood 
cells, circulating fats and early in treatment, temporary increases in liver enzymes; increases in the 
level of sugars in the blood and urine; increases in levels of uric acid and creatine phosphokinase in 
the blood; feeling more hungry; dizziness; restlessness; tremor; unusual movements (dyskinesias); 
constipation; dry mouth; rash; loss of strength; extreme tiredness; water retention leading to 
swelling of the hands, ankles or feet; fever; joint pain; and sexual dysfunctions such as decreased 
libido in males and females or erectile dysfunction in males.

Uncommon side effects (may affect up to 1 in 100 people) include hypersensitivity (e.g. swelling in 
the mouth and throat, itching, rash); diabetes or the worsening of diabetes, occasionally associated 
with ketoacidosis (ketones in the blood and urine) or coma; seizures, usually associated with a 
history of seizures (epilepsy); muscle stiffness or spasms (including eye movements); restless legs 
syndrome; problems with speech; stuttering; slow heart rate; sensitivity to sunlight; bleeding from 
the nose; abdominal distension; drooling; memory loss or forgetfulness;  urinary incontinence; lack 
of ability to urinate; hair loss; absence or decrease in menstrual periods; and changes in breasts in 
males and females such as an abnormal production of breast milk or abnormal growth.

Rare side effects (may affect up to 1 in 1000 people) include lowering of normal body temperature; 
abnormal rhythms of the heart; sudden unexplained death; inflammation of the pancreas causing 
severe stomach pain, fever and sickness; liver disease appearing as yellowing of the skin and white 
parts of the eyes; muscle disease presenting as unexplained aches and pains; and prolonged and/or 
painful erection.

Very rare side effects include serious allergic reactions such as Drug Reaction with Eosinophilia 
and Systemic Symptoms (DRESS). DRESS appears initially as flu-like symptoms with a rash on 
the face and then with an extended rash, high temperature, enlarged lymph nodes, increased levels 
of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia).

While taking olanzapine, elderly patients with dementia may suffer from stroke, pneumonia, 
urinary incontinence, falls, extreme tiredness, visual hallucinations, a rise in body temperature, 
redness of the skin and have trouble walking. Some fatal cases have been reported in this particular 
group of patients.

In patients with Parkinson's disease Zalasta may worsen the symptoms.

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Zalasta

Keep this medicine out of the sight and reach of children.



83

Do not use this medicine after the expiry date which is stated on the packaging. The expiry date 
refers to the last day of that month.

Store in the original package in order to protect from light and moisture. This medicine does not 
require any special temperature storage conditions.

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 Zalasta contains
- The active substance is olanzapine. Each tablet contains 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg 

or 20 mg olanzapine.
- The other ingredients are lactose monohydrate, powdered cellulose, pregelatinised maize 

starch, maize starch, colloidal anhydrous silica, magnesium stearate.
See section 2 "Zalasta contains lactose".

What Zalasta looks like and contents of the pack
Zalasta 2.5 mg tablets are: round, slightly biconvex, slightly yellow tablets with possible 
individual yellow spots.
Zalasta 5 mg tablets are: round, slightly biconvex, slightly yellow tablets with possible individual 
yellow spots and an inscription 5.
Zalasta 7.5 mg tablets are: round, slightly biconvex, slightly yellow tablets with possible 
individual yellow spots and an inscription 7.5.
Zalasta 10 mg tablets are: round, slightly biconvex, slightly yellow tablets with possible individual 
yellow spots and an inscription 10.
Zalasta 15 mg tablets are: round, slightly biconvex, slightly yellow tablets with possible individual 
yellow spots and an inscription 15.
Zalasta 20 mg tablets are: round, slightly biconvex, slightly yellow tablets with possible individual 
yellow spots and an inscription 20.

Zalasta 2.5 mg tablets: available in boxes of 14, 28, 35, 56 and 70 tablets in blister.
Zalasta 5 mg tablets: available in boxes of 14, 28, 35, 56 and 70 tablets in blisters.
Zalasta 7.5 mg tablets: available in boxes of 14, 28, 35, 56 and 70 tablets in blisters.
Zalasta 10 mg tablets: available in boxes of 7, 14, 28, 35, 56 and 70 tablets in blisters.
Zalasta 15 mg tablets: available in boxes of 14, 28, 35, 56 and 70 tablets in blisters.
Zalasta 20 mg tablets: available in boxes of 14, 28, 35, 56 and 70 tablets in blisters.

Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
KRKA-POLSKA Sp. z o.o., ul. Równoległa 5, 02-235 Warszawa, Poland
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

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

België/Belgique/Belgien
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62

Lietuva
UAB KRKA Lietuva
Tel: + 370 5 236 27 40



84

България
КРКА България ЕООД
Teл.: + 359 (02) 962 34 50

Luxembourg/Luxemburg
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62 (BE)

Česká republika
KRKA ČR, s.r.o.
Tel: + 420 (0) 221 115 150

Magyarország
KRKA Magyarország Kereskedelmi Kft.
Tel.: + 36 (1) 355 8490

Danmark
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Malta
E. J. Busuttil Ltd.
Tel: + 356 21 445 885

Deutschland
TAD Pharma GmbH
Tel: + 49 (0) 4721 606-0

Nederland
KRKA Belgium, SA.
Tel: + 32 (0) 487 50 73 62 (BE)

Eesti
KRKA, d.d., Novo mesto Eesti filiaal
Tel: + 372 (0) 6 671 658

Norge
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Ελλάδα
QUALIA PHARMA S.A.
Τηλ: + 30 210 6256177

Österreich
KRKA Pharma GmbH, Wien
Tel: + 43 (0)1 66 24 300

España
KRKA Farmacéutica, S.L.
Tel: + 34 911 61 03 81

Polska
KRKA-POLSKA Sp. z o.o.
Tel.: + 48 (0)22 573 7500

France
KRKA France Eurl
Tél: + 33 (0)1 57 40 82 25

Portugal
KRKA Farmacêutica, Sociedade Unipessoal Lda.
Tel: + 351 (0)21 46 43 650

Hrvatska
KRKA - FARMA d.o.o.
Tel: + 385 1 6312 100

România
KRKA Romania S.R.L., Bucharest
Tel: + 4 021 310 66 05

Ireland
KRKA Pharma Dublin, Ltd.
Tel: + 353 1 293 91 80

Slovenija
KRKA, d.d., Novo mesto
Tel: + 386 (0) 1 47 51 100

Ísland
LYFIS ehf.
Sími: + 354 534 3500

Slovenská republika
KRKA Slovensko, s.r.o.
Tel: + 421 (0) 2 571 04 501

Italia
KRKA Farmaceutici Milano S.r.l.
Tel: + 39 02 3300 8841

Suomi/Finland
KRKA Finland Oy
Puh/Tel: + 358 20 754 5330

Κύπρος
Kipa Pharmacal Ltd.
Τηλ: + 357 24 651 882

Sverige
KRKA Sverige AB
Tel: + 46 (0)8 643 67 66 (SE)

Latvija
KRKA Latvija SIA
Tel: + 371 6 733 86 10

United Kingdom
Consilient Health (UK) Ltd.
Tel: + 44(0)203 751 1888



85

This leaflet was last revised in {MM/YYYY}

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



86

Package leaflet: Information for the user

Zalasta 5 mg orodispersible tablets
Zalasta 7.5 mg orodispersible tablets
Zalasta 10 mg orodispersible tablets
Zalasta 15 mg orodispersible tablets
Zalasta 20 mg orodispersible tablets

olanzapine

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

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

effects not listed in this leaflet. See section 4.

In this leaflet:
1. What Zalasta is and what it is used for
2. What you need to know before you take Zalasta
3. How to take Zalasta
4. Possible side effects
5. How to store Zalasta
6. Contents of the pack and other information

1. What Zalasta is and what it is used for

Zalasta contains the active substance olanzapine. Zalasta 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.

Zalasta 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 Zalasta

Do not take Zalasta
- If you are allergic (hypersensitive) to olanzapine or any of the other ingredients of this 

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

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

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

side effects
─ Medicines of this type may cause unusual movements mainly of the face or tongue. If this 

happens after you have been given Zalasta tell your doctor.



87

─ 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 Zalasta. You and your doctor should check your 
weight regularly. Consider referral to a dietician or help with a diet plan if necessary.

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

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

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

vomiting (being sick) or usage of diuretics (water tablets)

If you suffer from dementia, you or your carer/relative should tell your doctor if you have ever had 
a stroke or “mini” stroke.

As a routine precaution, if you are over 65 years your blood pressure may be monitored by your 
doctor.

Children and adolescents
Zalasta is not for patients who are under 18 years.

Other medicines and Zalasta
Only take other medicines while you are on Zalasta if your doctor tells you that you can. You 
might feel drowsy if Zalasta 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 Zalasta dose.

Zalasta with alcohol
Do not drink any alcohol if you have been given Zalasta 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 take this medicine when 
pregnant unless you have discussed this with your doctor.

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



88

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

Zalasta contains aspartame
This medicine contains 0.50 mg aspartame in each 5 mg orodispersible tablet.
This medicine contains 0.75 mg aspartame in each 7.5 mg orodispersible tablet.
This medicine contains 1.00 mg aspartame in each 10 mg orodispersible tablet.
This medicine contains 1.50 mg aspartame in each 15 mg orodispersible tablet.
This medicine contains 2.00 mg aspartame in each 20 mg orodispersible tablet.

Aspartame is a source of phenylalanine. It may be harmful if you have phenylketonuria (PKU), a 
rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.

3. How to take Zalasta

Always take this medicine exactly as your doctor has told you. You should check with your doctor 
or pharmacists if you are not sure.

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

You should take your Zalasta 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.

How to take Zalasta
Zalasta tablets break easily, so you should handle the tablets carefully. Do not handle the tablets 
with wet hands as the tablets may break up. To take a tablet out of the packaging:

1. Hold the blister at the edges and separate one blister cell from the rest of the blister by gently 
tearing along the perforations around it.

2. Pull up the edge of the foil and peel foil off completely.
3. Tip the tablet out onto your hand.
4. Put the tablet on the tongue as soon as it is removed from the packaging.

The tablet begins breaking up in the mouth within seconds and can then be swallowed with or 
without water. Your mouth should be empty before placing the tablet on the tongue.

You can also place the tablet in a full glass or cup of water. Drink it straight away.

If you take more Zalasta than you should
Patients who have taken more Zalasta 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, 



89

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

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

If you suddenly stop taking Zalasta, symptoms such as sweating, unable to sleep, tremor, anxiety 
or nausea and vomiting might occur. Your doctor may suggest you to reduce the dose gradually 
before stopping treatment.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

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

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

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

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

Very common side effects (may affect more than 1 in 10 people) include weight gain; sleepiness 
and increases in levels of prolactin in the blood. In the early stages of treatment, some people may 
feel dizzy or faint (with a slow heart rate), especially when getting up from a lying or sitting 
position. This will usually pass on its own but if it does not, tell your doctor.

Common side effects (may affect up to 1 in 10 people) include changes in the levels of some blood 
cells, circulating fats and early in treatment, temporary increases in liver enzymes; increases in the 
level of sugars in the blood and urine; increases in levels of uric acid and creatine phosphokinase in 
the blood; feeling more hungry; dizziness; restlessness; tremor; unusual movements (dyskinesias); 
constipation; dry mouth; rash; loss of strength; extreme tiredness; water retention leading to 
swelling of the hands, ankles or feet; fever; joint pain; and sexual dysfunctions such as decreased 
libido in males and females or erectile dysfunction in males.

Uncommon side effects (may affect up to 1 in 100 people) include hypersensitivity (e.g. swelling in 
the mouth and throat, itching, rash); diabetes or the worsening of diabetes, occasionally associated 
with ketoacidosis (ketones in the blood and urine) or coma; seizures, usually associated with a 
history of seizures (epilepsy); muscle stiffness or spasms (including eye movements); restless legs 
syndrome; problems with speech; stuttering; slow heart rate; sensitivity to sunlight; bleeding from 
the nose; abdominal distension; drooling; memory loss or forgetfulness;  urinary incontinence; lack 
of ability to urinate; hair loss; absence or decrease in menstrual periods; and changes in breasts in 
males and females such as an abnormal production of breast milk or abnormal growth.

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 



90

parts of the eyes; muscle disease presenting as unexplained aches and pains; and prolonged and/or 
painful erection.

Very rare side effects include serious allergic reactions such as Drug Reaction with Eosinophilia 
and Systemic Symptoms (DRESS). DRESS appears initially as flu-like symptoms with a rash on 
the face and then with an extended rash, high temperature, enlarged lymph nodes, increased levels 
of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia).

While taking olanzapine, elderly patients with dementia may suffer from stroke, pneumonia, 
urinary incontinence, falls, extreme tiredness, visual hallucinations, a rise in body temperature, 
redness of the skin and have trouble walking. Some fatal cases have been reported in this particular 
group of patients.

In patients with Parkinson's disease Zalasta may worsen the symptoms.

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Zalasta

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 packaging. The expiry date 
refers to the last day of that month.

Store in the original package in order to protect from light and moisture. This medicine does not 
require any special temperature storage conditions.

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 Zalasta contains
- The active substance is olanzapine. Each orodispersible tablet contains 5 mg, 7.5 mg, 10 mg, 

15 mg or 20 mg olanzapine.
- The other ingredients are mannitol, microcrystalline cellulose, crospovidone, low-substituted 

hydroxypropylcellulose, aspartame, calcium silicate, magnesium stearate.
See section 2 "Zalasta contains aspartame".

What Zalasta looks like and contents of the pack
Zalasta 5 mg, 7.5 mg, 10 mg, 15 mg and 20 mg orodispersible tablets are: round, slightly biconvex, 
yellow marbled tablets with possible individual spots.

Zalasta 5 mg, 7.5 mg, 10 mg, 15 mg and 20 mg orodispersible tablets: available in boxes of 14, 28, 
35, 56 and 70 tablets in blisters.

Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia



91

KRKA-POLSKA Sp. z o.o., ul. Równoległa 5, 02-235 Warszawa, Poland
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

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

België/Belgique/Belgien
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62

Lietuva
UAB KRKA Lietuva
Tel: + 370 5 236 27 40

България
КРКА България ЕООД
Teл.: + 359 (02) 962 34 50

Luxembourg/Luxemburg
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62 (BE)

Česká republika
KRKA ČR, s.r.o.
Tel: + 420 (0) 221 115 150

Magyarország
KRKA Magyarország Kereskedelmi Kft.
Tel.: + 36 (1) 355 8490

Danmark
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Malta
E. J. Busuttil Ltd.
Tel: + 356 21 445 885

Deutschland
TAD Pharma GmbH
Tel: + 49 (0) 4721 606-0

Nederland
KRKA Belgium, SA.
Tel: + 32 (0) 487 50 73 62 (BE)

Eesti
KRKA, d.d., Novo mesto Eesti filiaal
Tel: + 372 (0) 6 671 658

Norge
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Ελλάδα
QUALIA PHARMA S.A.
Τηλ: + 30 210 6256177

Österreich
KRKA Pharma GmbH, Wien
Tel: + 43 (0)1 66 24 300

España
KRKA Farmacéutica, S.L.
Tel: + 34 911 61 03 81

Polska
KRKA-POLSKA Sp. z o.o.
Tel.: + 48 (0)22 573 7500

France
KRKA France Eurl
Tél: + 33 (0)1 57 40 82 25

Portugal
KRKA Farmacêutica, Sociedade Unipessoal Lda.
Tel: + 351 (0)21 46 43 650

Hrvatska
KRKA - FARMA d.o.o.
Tel: + 385 1 6312 100

România
KRKA Romania S.R.L., Bucharest
Tel: + 4 021 310 66 05

Ireland
KRKA Pharma Dublin, Ltd.
Tel: + 353 1 293 91 80

Slovenija
KRKA, d.d., Novo mesto
Tel: + 386 (0) 1 47 51 100

Ísland
LYFIS ehf.
Sími: + 354 534 3500

Slovenská republika
KRKA Slovensko, s.r.o.
Tel: + 421 (0) 2 571 04 501



92

Italia
KRKA Farmaceutici Milano S.r.l.
Tel: + 39 02 3300 8841

Suomi/Finland
KRKA Finland Oy
Puh/Tel: + 358 20 754 5330

Κύπρος
Kipa Pharmacal Ltd.
Τηλ: + 357 24 651 882

Sverige
KRKA Sverige AB
Tel: + 46 (0)8 643 67 66 (SE)

Latvija
KRKA Latvija SIA
Tel: + 371 6 733 86 10

United Kingdom
Consilient Health (UK) Ltd.
Tel: + 44(0)203 751 1888

This leaflet was last revised in {MM/YYYY}

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



93

Annex IV

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



94

Scientific conclusions

Taking into account the PRAC Assessment Report on the PSUR(s) for olanzapine, the scientific 

conclusions of CHMP are as follows: 

Following the review of case reports in the UK Sentinel database, the EudraVigilance database, 

and the literature, a signal for salivary hypersecretion with olanzapine was identified on 14 

February 2019 by the Medicines and Healthcare products Regulatory Agency (MHRA) and 

validated by the PRAC.

Based on signal analysis presented by the MAH including mechanistic plausibility, number of 

dechallenge/rechallenge cases and strong temporal relationship, the PRAC agrees that salivary 

hypersecretion may be associated with olanzapine and the adverse reaction salivary 

hypersecretion should be added to the product information.

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

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

On the basis of the scientific conclusions for olanzapine the CHMP is of the opinion that the 

benefit-risk balance of the medicinal product(s) containing olanzapine is unchanged subject to 

the proposed changes to the product information

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


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