Olanzapine 7.5 mg film-coated tablets

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
Olanzapine
Available from:
Accord Healthcare Ireland Ltd.
ATC code:
N05AH; N05AH03
INN (International Name):
Olanzapine
Dosage:
7.5 milligram(s)
Pharmaceutical form:
Film-coated tablet
Therapeutic area:
Diazepines, oxazepines, thiazepines and oxepines; olanzapine
Authorization status:
Marketed
Authorization number:
PA2315/216/003
Authorization date:
2009-12-18

PACKAGE LEAFLET

Package leaflet: Information for the patient

Olanzapine 2.5 mg film-coated tablets

Olanzapine 5 mg film-coated tablets

Olanzapine 7.5 mg film-coated tablets

Olanzapine 10 mg film-coated tablets

Olanzapine 15 mg film-coated tablets

Olanzapine

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

information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if

their signs of illness are the same as yours.

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

not listed in this leaflet. See section 4.

What is in this leaflet

What Olanzapine tablets are and what they are used for

What you need to know before you take Olanzapine tablets

How to take Olanzapine tablets

Possible side effects

How to store Olanzapine tablets

Contents of the pack and other information

1.

What Olanzapine tablets are and what they are used for

Olanzapine tablets belongs to a group of medicines called antipsychotics and is used to treat the following

conditions:

Schizophrenia, a disease with symptoms such as hearing, seeing or sensing things which are not there,

mistaken beliefs, unusual suspiciousness, and becoming withdrawn. People with this disease may also

feel depressed, anxious or tense.

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

Olanzapine tablets have been shown to prevent recurrence of these symptoms in patients with bipolar

disorder whose manic episode has responded to olanzapine treatment.

2.

What you need to know before you take Olanzapine tablets

Do not take Olanzapine tablets

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 taking Olanzapine tablets

The use of Olanzapine tablets in elderly patients with dementia is not recommended as it may have

serious side effects.

Medicines of this type may cause unusual movements mainly of the face or tongue. If this happens

after you have been given Olanzapine tablets tell your doctor.

Very rarely, medicines of this type cause a combination of fever, faster breathing, sweating, muscle

stiffness and drowsiness or sleepiness. If this happens, contact your doctor at once.

Weight gain has been seen in patients taking Olanzapine tablets. You and your doctor should check

your weight regularly. Consider referral to a dietician or help with a diet plan if necessary.

High blood sugar and high levels of fat (triglycerides and cholesterol) have been seen in patients

taking Olanzapine tablets. Your doctor should do blood tests to check blood sugar and certain fat

levels before you start taking Olanzapine tablets and regularly during treatment.

Tell your doctor if you or someone else in your family has a history of blood clots, as medicines like

these have been associated with 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)

Parkinsons’s disease

Prostate problems

A blocked intestine (Paralytic ileus)

Liver or kidney disease

Blood disorders

Heart disease

Diabetes

Seizures

If you know that you may have salt depletion as a result of prolonged severe diarrhoea and vomiting

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

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

or “mini”stroke.

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

Children and adolescents

Olanzapine tablets are not for patients who are under 18 years.

Other medicines and Olanzapine tablets

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

might feel drowsy if Olanzapine tablets are taken in combination with antidepressants or medicines taken for

anxiety or to help you sleep (tranquillisers).

Tell your doctor if you are taking, have recently taken or might take any other medicines.

In particular, tell your doctor if you are taking:

medicines for Parkinson’s disease.

carbamazepine (an anti-epileptic and mood stabiliser), fluvoxamine (an antidepressant) or ciprofloxacin

(an antibiotic) - it may be necessary to change your Olanzapine dose.

Olanzapine tablets with alcohol

Do not drink any alcohol if you have been given Olanzapine tablets 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.

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

You should not be given this medicine when breast-feeding, as small amounts of Olanzapine tablets can pass

into breast milk.

Driving and using machines

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

operate any tools or machines. Tell your doctor.

Olanzapine tablets contain 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.

Olanzapine contains lecithin soya

If you are allergic to peanut or soya, do not take this medicine.

3.

How to take Olanzapine tablets

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or

pharmacist if you are not sure.

Your doctor will tell you how many Olanzapine tablets to take and how long you should continue to take

them. The daily dose of Olanzapine is between 5 and 20 mg. Consult your doctor if your symptoms return

but do not stop taking Olanzapine tablets unless your doctor tells you to.

You should take your Olanzapine tablets once a day following the advice of your doctor. Try to take your

tablets at the same time each day. It does not matter whether you take them with or without food.

Olanzapine film-coated tablets are for oral use. You should swallow the Olanzapine tablets whole with

water.

If you take more Olanzapine tablets than you should

Patients who have taken more Olanzapine tablets than they should, have experienced the following

symptoms: rapid beating of the heart, agitation/aggressiveness, problems with speech, unusual movements

(especially of the face or tongue) and reduced level of consciousness. Other symptoms may be: acute

confusion, seizures (epilepsy), coma, a combination of fever, faster breathing, sweating, muscle stiffness and

drowsiness or sleepiness, slowing of the breathing rate, aspiration, high blood pressure or low blood

pressure, abnormal rhythms of the heart. Contact your doctor or hospital straight away if you experience any

of the above symptoms. Show the doctor your pack of tablets.

If you forget to take Olanzapine tablets

Take your tablets as soon as you remember. Do not take a double dose to make up for a forgotten tablet.

If you stop taking Olanzapine tablets

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

Olanzapine tablets for as long as your doctor tells you.

If you suddenly stop taking Olanzapine tablets, symptoms such as sweating, inability 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; 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; prolonged and/or painful erection.

Very rare side effects

(may affect up to 1 in 10,000 people) include serious allergic reactions such as Drug

Reaction with Eosinophilia and Systemic Symptoms (DRESS). DRESS appears initially as flu-like

symptoms with a rash on the face and then with an extended rash, high temperature, enlarged lymph nodes,

increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell

(eosinophilia).

While taking olanzapine, elderly patients with dementia may suffer from stroke, pneumonia, urinary

incontinence, falls, extreme tiredness, visual hallucinations, a rise in body temperature, redness of the skin

and have trouble walking. Some fatal cases have been reported in this particular group of patients.

In patients with Parkinson’s disease Olanzapine tablets may worsen the symptoms.

Reporting of side effects

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

not listed in this leaflet.

You can also report side effects directly via HPRA Pharmacovigilance, Earlsfort

Terrace, IRL-Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail:

medsafety@hpra.ie. By reporting side effects you can help provide more information on the safety of this

medicine.

5.

How to store Olanzapine tablets

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

Do not use this medicine after the expiry date, which is stated on the carton

.

Blister packs and containers:

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

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw

away medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What Olanzapine tablets contain

The active substance is olanzapine. Each Olanzapine tablet contains either 2.5 mg, 5 mg, 7.5mg, 10

mg, 15 mg or 20 mg of the active substance.

The other ingredients are (tablet core) lactose anhydrous, microcrystalline cellulose, crospovidone,

magnesium stearate and (tablet film-coating) polyvinyl alcohol, titanium dioxide (E171), talc, lecithin

soya (E322) and xanthan gum (E415). In addition the 15 mg tablets contain indigo carmine (E132) and

the 20 mg tablets contain iron oxide red (E172).

What Olanzapine tablets looks like and contents of the pack

Film-coated tablet 2.5 mg: Round, biconvex, white film-coated tablet 6 mm in diameter, marked with “O” on

one side.

Film-coated tablet 5 mg: Round, biconvex, white film-coated tablet 8 mm in diameter, marked with “O1” on

one side.

Film-coated tablet 7.5 mg: Round, biconvex, white film-coated tablet 9 mm in diameter, marked with “O2”

on one side.

Film-coated tablet 10 mg: Round, biconvex, white film-coated tablet 10 mm in diameter, marked with “O3”

on one side.

Film-coated tablet 15 mg: Oval, biconvex, light blue film-coated tablet 7.35 x 13.35 mm in diameter, marked

with “O” on one side.

Pack sizes

In blisters: 7, 14, 28, 30, 35, 56 and 70 film-coated tablets.

In containers: 100 and 250 film-coated tablets [

250 tablets:

Not available for 15 mg

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Accord Healthcare Ireland Ltd, Euro House, Euro Business Park, Little

Island, Cork T45 K857, Ireland

Manufacturer:

Actavis hf, Reykjavikurvegur 78, 220 Hafnarfjordur, Iceland and Actavis Ltd., B16 Bulebel

Industial Estate, Zejtun ZTN3000, Malta

This leaflet was last revised in

March 2020

Health Products Regulatory Authority

07 April 2020

CRN009PGR

Page 1 of 14

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Olanzapine 7.5 mg film-coated tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 7.5 mg olanzapine.

Excipient(s) with known effect:

7.5 mg film-coated tablet contains 174.9 mg lactose anhydrous and 0.192 mg lecithin soya (E322).

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Film-coated tablet.

Round, biconvex, white film-coated tablet 9 mm in diameter, marked with “O2” on one side.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Adults

Olanzapine is indicated for the treatment of schizophrenia.

Olanzapine is effective in maintaining the clinical improvement during continuation therapy in patients who have shown an

initial treatment response.

Olanzapine is indicated for the treatment of moderate to severe manic episode.

In patients whose manic episode has responded to olanzapine treatment, olanzapine is indicated for the prevention of

recurrence in patients with bipolar disorder (see section 5.1).

4.2 Posology and method of administration

Posology

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, therapy for preventing recurrence should be continued 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.

Special populations

Health Products Regulatory Authority

07 April 2020

CRN009PGR

Page 2 of 14

Paediatric population

Olanzapine is not recommended for use in children and adolescents below 18 years of age due to a lack of data on safety and

efficacy. A greater magnitude of weight gain, lipid and prolactin alterations has been reported in short term studies of

adolescent patients than in studies of adult patients (see sections 4.4, 4.8, 5.1 and 5.2).

Elderly patients

A lower starting dose (5 mg/day) is not routinely indicated but should be considered for those 65 and over when clinical

factors warrant (see also section 4.4).

Patients with renal and/or hepatic impairment

A lower starting dose (5 mg) should be considered for such patients. In cases of moderate hepatic insufficiency (cirrhosis,

Child-Pugh Class A or B), the starting dose should be 5 mg and only increased with caution.

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.)

Method of administration

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.

4.3 Contraindications

Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

Patients with known risk of narrow-angle glaucoma.

4.4 Special warnings and precautions for use

During antipsychotic treatment, improvement in the patient's clinical condition may take several days to some weeks. Patients

should be closely monitored during this period.

Dementia-related psychosis and/or behavioural disturbances

Olanzapine is not recommended for use in patients with dementia-related psychosis and/or behavioural disturbances because

of an increase in mortality and the risk of cerebrovascular accident. In placebo-controlled clinical trials (6‑12 weeks duration)

of elderly patients (mean age 78 years) with dementia-related psychosis and/or disturbed behaviours, there was a 2‑fold

increase in the incidence of death in olanzapine-treated patients compared to patients treated with placebo (3.5% vs. 1.5%,

respectively). The higher incidence of death was not associated with olanzapine dose (mean daily dose 4.4 mg) or duration of

treatment. Risk factors that may predispose this patient population to increased mortality include age > 65 years, dysphagia,

sedation, malnutrition and dehydration, pulmonary conditions (e.g., pneumonia, with or without aspiration), or concomitant

use of benzodiazepines. However, the incidence of death was higher in olanzapine-treated than in placebo-treated patients

independent of these risk factors.

In the same clinical trials, cerebrovascular adverse events (CVAE e.g., stroke, transient ischemic attack), including fatalities, were

reported. There was a 3-fold increase in CVAE in patients treated with olanzapine compared to patients treated with placebo

(1.3% vs. 0.4%, respectively). All olanzapine- and placebo-treated patients who experienced a cerebrovascular event had

pre-existing risk factors. Age > 75 years and vascular/mixed type dementia were identified as risk factors for CVAE in

association with olanzapine treatment. The efficacy of olanzapine was not established in these trials.

Parkinson's disease

Health Products Regulatory Authority

07 April 2020

CRN009PGR

Page 3 of 14

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

recommended. In clinical trials, worsening of Parkinsonian symptomatology and hallucinations were reported very commonly

and more frequently than with placebo (see section 4.8), and olanzapine was not more effective than placebo in the treatment

of psychotic symptoms. In these trials, patients were initially required to be stable on the lowest effective dose of

anti-Parkinsonian medicinal products (dopamine agonist) and to remain on the same anti-Parkinsonian medicinal products and

dosages throughout the study. Olanzapine was started at 2.5 mg/day and titrated to a maximum of 15 mg/day based on

investigator judgement.

Neuroleptic Malignant Syndrome (NMS)

NMS is a potentially life-threatening condition associated with antipsychotic medicinal products. Rare cases reported as NMS

have also been received in association with olanzapine. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered

mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac

dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal

failure. If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional

clinical manifestations of NMS, all antipsychotic medicines, including olanzapine must be discontinued.

Hyperglycaemia and diabetes

Hyperglycaemia and/or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma has been

reported uncommonly, including some fatal cases (see section 4.8). In some cases, a prior increase in body weight has been

reported which may be a predisposing factor.

Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines, e.g. measuring of blood

glucose at baseline, 12 weeks after starting olanzapine treatment and annually thereafter. Patients treated with any

antipsychotic medicines, including Olanzapine film-coated tablets, should be observed for signs and symptoms of

hyperglycaemia (such as polydipsia, polyuria, polyphagia, and weakness) and patients with diabetes mellitus or with risk factors

for diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be monitored regularly,

e.g. at baseline, 4, 8 and 12 weeks after starting olanzapine treatment and quarterly thereafter.

Lipid alterations

Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebo-controlled clinical trials(see

section 4.8). Lipid alterations should be managed as clinically appropriate, particularly in dyslipidemic patients and in patients

with risk factors for the development of lipids disorders. Patients treated with any antipsychotic medicines, including

Olanzapine film-coated tablets, 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.

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

Health Products Regulatory Authority

07 April 2020

CRN009PGR

Page 4 of 14

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 preventative measures undertaken.

General CNS activity

Given the primary CNS effects of olanzapine, caution should be used when it is taken in combination with other centrally acting

medicines and alcohol. As it exhibits in vitro dopamine antagonism, olanzapine may antagonize the effects of direct and

indirect dopamine agonists.

Seizures

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

seizure threshold. Seizures have been reported to occur uncommonly in patients when treated with olanzapine. In most of

these cases, a history of seizures or risk factors for seizures were reported.

Tardive Dyskinesia

In comparator studies of one year or less duration, olanzapine was associated with a statistically significant lower incidence of

treatment emergent dyskinesia. However the risk of tardive dyskinesia increases with long term exposure, and therefore if signs

or symptoms of tardive dyskinesia appear in a patient on olanzapine, a dose reduction or discontinuation should be

considered. These symptoms can temporally deteriorate or even arise after discontinuation of treatment.

Postural hypotension

Postural hypotension was infrequently observed in the elderly in olanzapine clinical trials. It is recommended that blood

pressure is measured periodically in patients over 65 years.

Sudden cardiac death

In postmarketing reports with olanzapine, the event of sudden cardiac death has been reported in patients with olanzapine. In

a retrospective observational cohort study, the risk of presumed sudden cardiac death in patients treated with olanzapine was

approximately twice the risk in patients not using antipsychotics. In the study, the risk of olanzapine was comparable to the risk

of atypical antipsychotics included in a pooled analysis.

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

Olanzapine film-coated tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp

lactase deficiency or glucose-galactose malabsorption should not take this medicine

Lecithin soya

If a patient is hypersensitive to peanut or soya, this medicine should not be used.

4.5 Interaction with other medicinal products and other forms of interactions

Paediatric population

Interaction studies have only been performed in adults.

Potential interactions affecting olanzapine

Since olanzapine is metabolised by CYP1A2, substances that can specifically induce or inhibit this isoenzyme may affect the

pharmacokinetics of olanzapine.

Health Products Regulatory Authority

07 April 2020

CRN009PGR

Page 5 of 14

Induction of CYP1A2

The metabolism of olanzapine may be induced by smoking and carbamazepine, which may lead to reduced olanzapine

concentrations. Only slight to moderate increase in olanzapine clearance has been observed. The clinical consequences are

likely to be limited, but clinical monitoring is recommended and an increase of olanzapine dose may be considered if necessary

(see section 4.2).

Inhibition of CYP1A2

Fluvoxamine, a specific CYP1A2 inhibitor, has been shown to significantly inhibit the metabolism of olanzapine. The mean

increase in olanzapine C

following fluvoxamine was 54% in female non-smokers and 77% in male smokers. The mean

increase in olanzapine AUC was 52% and 108% respectively. A lower starting dose of olanzapine should be considered in

patients who are using fluvoxamine or any other CYP1A2 inhibitors, such as ciprofloxacin. A decrease in the dose of olanzapine

should be considered if treatment with an inhibitor of CYP1A2 is initiated.

Decreased bioavailability

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

after olanzapine.

Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have not been found to

significantly affect the pharmacokinetics of olanzapine.

Potential for olanzapine to affect other medicinal products

Olanzapine may antagonise the effects of direct and indirect dopamine agonists.

Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e.g. 1A2, 2D6, 2C9, 2C19, 3A4).

Thus no particular interaction is expected as verified through in vivo studies where no inhibition of metabolism of the following

active substances was found: tricyclic antidepressant (representing mostly CYP2D6 pathway), warfarin (CYP2C9), theophylline

(CYP1A2) or diazepam (CYP3A4 and 2C19).

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

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

introduction of concomitant olanzapine.

General CNS activity

Caution should be exercised in patients who consume alcohol or receive medicinal products that can cause central nervous

system depression.

The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with Parkinson's disease and

dementia is not recommended (see section 4.4).

QTc interval

Caution should be used if olanzapine is being administered concomitantly with medicinal products known to increase QTc

interval (see section 4.4).

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Patients should be advised to notify their physician if

they become pregnant or intend to become pregnant during treatment with olanzapine. Nevertheless, because human

experience is limited, olanzapine should be used in pregnancy only if the potential benefit justifies the potential risk to the

foetus.

New born infants exposed to antipsychotics (including olanzapine) during the third trimester of pregnancy are at risk of

adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following

delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding

disorder. Consequently, newborns should be monitored carefully.

Health Products Regulatory Authority

07 April 2020

CRN009PGR

Page 6 of 14

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 phospatase, high gamma glutamyltransferase, high uric acid,

high creatine phosphokinase and oedema.

Tabulated list of adverse reactions

The following table lists the adverse reactions and laboratory investigations observed from spontaneous reporting and in

clinical trials. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The

frequency terms listed are defined as follows:

Very common (≥ 1/10)

Common (≥ 1/100 to <1/10)

Uncommon (≥ 1/1,000 to <1/100)

Rare (≥ 1/10,000 to <1/1,000)

Very rare (< 1/10,000)

Not known (cannot be estimated from the available data).

Very common

Common

Uncommon

Rare

Not known

Blood and the

lymphatic

system disorders

Eosinophilia

Leukopenia

Neutropenia

Thrombocytopenia

Immune system

disorders

Hypersensitivity

Metabolism and

nutrition

disorders

Weight gain

Elevated

cholesterol

levels

Elevated glucose

levels

Elevated

triglyceride

levels

Development or exacerbation of diabetes

occasionally associated with ketoacidosis

or coma, including some fatal cases (see

section 4.4)

Hypothermia

Health Products Regulatory Authority

07 April 2020

CRN009PGR

Page 7 of 14

Glucosuria

Increased appetite

Nervous system

disorders

Somnolence

Dizziness

Akathisia

Parkinsonism

Dyskinesia

Seizures where in most cases a history of

seizures or risk factors for seizures were

reported

Dystonia (including oculogyration)

Tardive dyskinesia

Amnesia

Dysarthria

Restless leg syndrome

Neuroleptic malignant

syndrome (see section

4.4)

Discontinuation

symptoms

7,12

Cardiac

disorders

Bradycardia

QTc prolongation (see section 4.4)

Ventricular

tachycardia/fibrillation,

sudden death (see

section 4.4)

Vascular

disorders

Orthostatic

hypotension

Thromboembolism (including pulmonary

embolism and deep vein thrombosis) (see

section 4.4)

Respiratory,

thoracic and

mediastinal

disorders

Epistaxis

Gastrointestinal

disorders

Mild, transient

anticholinergic

effects including

constipation and dry

mouth

Abdominal distension

Salivary hypersecretion

Pancreatitis

Hepato-biliary

disorders

Transient,

asymptomatic

elevations of hepatic

aminotransferases

(ALT, AST), especially

early

treatment

(see section 4.4)

Hepatitis (including

hepatocellular,

cholestatic or mixed

liver injury)

Skin and

subcutaneous

tissue disorders

Rash

Photosensitivity reaction

Alopecia

Drug

Reaction

with

Eosinophilia

Systemic

Health Products Regulatory Authority

07 April 2020

CRN009PGR

Page 8 of 14

Symptoms

(DRESS)

Musculoskeletal

and connective

tissue disorders

Arthralgia

Rhabdomyolysis

Renal and

urinary

disorders

Urinary incontinence, urinary retention

Urinary hesitation

Pregnancy,

puerperium and

perinatal

conditions

Drug

withdrawal

syndrome

neonatal

(see section

4.6)

Reproductive

system and

breast disorders

Erectile dysfunction

in males

Decreased

libido

males and females

Amenorrhea

Breast enlargement

Galactorrhea in females

Gynaecomastia/breast enlargement in

males

Priapism

General

disorders and

administration

site conditions

Asthenia

Fatigue

Oedema

Pyrexia

Investigations

Elevated plasma

prolactin levels

Increased alkaline

phosphatase

High creatine

phosphokinase

High Gamma

glutamyltransferase

High uric acid

Increased total bilirubin

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).

Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without

evidence of lipid dysregulation at baseline.

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.

Health Products Regulatory Authority

07 April 2020

CRN009PGR

Page 9 of 14

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.

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.

In clinical trials, the incidence of parkinsonism and dystonia in olanzapine-treated patients was numerically higher, but not

statistically significantly different from placebo. Olanzapine-treated patients had a lower incidence of parkinsonism, akathisia

and dystonia compared with titrated doses of haloperidol. In the absence of detailed information on the pre-existing history of

individual acute and tardive extrapyramidal movement disorders, it can not be concluded at present that olanzapine produces

less tardive dyskinesia and/or other tardive extrapyramidal syndromes.

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

stopped abruptly.

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.

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

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

Adverse event identified from spontaneous post-marketing reporting with frequency determined utilising the Olanzapine

Integrated Database.

Adverse event identified from spontaneous post-marketing reporting with frequency estimated at the upper limit of the 95%

confidence interval utilising the Olanzapine Integrated Database.

Long-term exposure (at least 48 weeks)

The proportion of patients who had adverse, clinically significant changes in weight gain, glucose, total/LDL/HDL cholesterol or

triglycerides increased over time. In adult patients who completed 9-12 months of therapy, the rate of increase in mean blood

glucose slowed after approximately 6 months.

Additional information on special populations

In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher incidence of death and

cerebrovascular adverse reactions compared to placebo (see section 4.4). Very common adverse reactions associated with the

use of olanzapine in this patient group were abnormal gait and falls. Pneumonia, increased body temperature, lethargy,

erythema, visual hallucinations and urinary incontinence were observed commonly.

In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with Parkinson's disease, worsening of

Parkinsonian symptomatology and hallucinations were reported very commonly and more frequently than with placebo.

In one clinical trial in patients with bipolar mania, valproate combination therapy with olanzapine resulted in an incidence of

neutropenia of 4.1%; a potential contributing factor could be high plasma valproate levels. Olanzapine administered with

lithium or valproate resulted in increased levels (≥ 10%) of tremor, dry mouth, increased appetite, and weight gain. Speech

disorder was also reported commonly. During treatment with olanzapine in combination with lithium or divalproex, an increase

of ≥7% from baseline body weight occurred in 17.4% of patients during acute treatment (up to 6 weeks). Long-term

olanzapine treatment (up to 12 months) for recurrence prevention in patients with bipolar disorder was associated with an

increase of ≥7% from baseline body weight in 39.9% of patients.

Paediatric population

Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years. Although no clinical studies

designed to compare adolescents to adults have been conducted, data from the adolescent trials were compared to those of

the adult trials.

Health Products Regulatory Authority

07 April 2020

CRN009PGR

Page 10 of 14

The following table summarises the adverse reactions reported with a greater frequency in adolescent patients (aged

13‑17 years) than in adult patients or adverse reactions only identified during short-term clinical trials in adolescent patients.

Clinically significant weight gain (≥ 7%) appears to occur more frequently in the adolescent population compared to adults

with comparable exposures. The magnitude of weight gain and the proportion of adolescent patients who had clinically

significant weight gain were greater with long-term exposure (at least 24 weeks) than with short-term exposure.

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

The frequency terms listed are defined as follows:

Very common (≥ 1/10)

Common (≥ 1/100 to < 1/10).

Metabolism and nutrition disorders

Very common: Weight gain

, elevated triglyceride levels

levels

, increased appetite.

Common: Elevated cholesterol levels

levels

Nervous system disorders

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

Gastrointestinal disorders

Common: Dry mouth

Hepato-biliary disorders

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

Investigations

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

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.

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).

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.

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517.

Website: www.hpra.ie; E-mail: medsafety@hpra.ie

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

Similar products

Search alerts related to this product

View documents history

Share this information