Consumer medicine information

What is in this leaflet

This leaflet is designed to provide you with answers to some common questions about this medicine. It does not contain all the available information and does not take the place of talking with your doctor.
The information in this leaflet was last updated on the date shown on the final page. More recent information on this medicine may be available. Make sure you speak to your pharmacist, nurse or doctor to obtain the most up to date information on this medicine. You can also download the most up to date leaflet from www.lilly.com.au. The updated leaflet may contain important information about ZYPREXA RELPREVV and its use that you should be aware of.
All medicines have risks and benefits.
Your doctor has more information about this medicine than is contained in this leaflet. Also, your doctor has had the benefit of taking a full and detailed history from you and is in the best position to make an expert judgement to meet your individual needs.
If you have any concerns about taking this medicine, talk to your doctor or pharmacist.
Keep this leaflet with this medicine.
You may need to read it again.

What ZYPREXA RELPREVV is used for

ZYPREXA RELPREVV belongs to a group of medicines called antipsychotics. It helps to correct chemical imbalances in the brain, which may cause mental illness.
ZYPREXA RELPREVV is used to treat symptoms of schizophrenia.
Schizophrenia is a mental illness with disturbances in thinking, feelings and behaviour.
ZYPREXA RELPREVV is given as an injection into a large muscle in the buttocks where it is slowly released over 2 to 4 weeks. This injection should only be given by a doctor or nurse.
Your doctor may have prescribed ZYPREXA RELPREVV for another reason.
Ask your doctor or nurse if you have any questions about why ZYPREXA RELPREVV has been prescribed for you.
This medicine is available only with a doctor's prescription.
ZYPREXA RELPREVV is not recommended for use in children under the age of 18 years as there is not enough information on its effects in this age group.

Before you are given ZYPREXA RELPREVV

Tell your doctor or nurse if you have any of the following conditions or if you have ever experienced any of these conditions.

When you must not be given it

• if you have had an allergic reaction to ZYPREXA®, ZYPREXA RELPREVV or to any of the ingredients listed at the end of this leaflet (see 'Product Description').
  Signs of an allergic reaction may include a skin rash, itching, shortness of breath or swelling of the face, lips or tongue.

• if the packaging is torn or shows signs of tampering or the injection vials do not look quite right.

• if the expiry date on the pack has passed.
  If you have this medicine after the expiry date has passed it may not work as well.

Before you are given it

• tumour of the pituitary gland (a small gland at the base of the brain)

• disease of the blood or bone marrow with a reduced number of white or red blood cells

• disease of the blood vessels of the brain, including stroke

• prostate problems

• kidney or liver disease

• high blood sugar, diabetes or a family history of diabetes

• breast cancer or a family history of breast cancer

• paralytic ileus, a condition where the small bowel does not work properly

• epilepsy (seizures or fits)

• glaucoma, a condition in which there is usually a build up of fluid in the eye

• heart disease, including irregular heart rhythm

• neuroleptic malignant syndrome, a reaction to some medicines with a sudden increase in body temperature, extremely high blood pressure and severe convulsions

• tardive dyskinesia, a reaction to some medicines with uncontrollable twitching or jerking movements of the arms and legs.

• sleep apnoea, a sleep disorder where a person has pauses in breathing or periods of shallow breathing during sleep.

Taking other medicines

• medicines used to treat a fast or irregular heart beat (arrhythmia)

• medicines taken for anxiety or to help you sleep

• medicines taken for depression

• carbamazepine, a medicine used for mood stabilisation and to treat epilepsy

• other centrally acting medicines (eg. Tranquillisers or strong painkillers)

• ciprofloxacin, a medicine used to treat bacterial infections

• medicines that lower blood pressure

• medicines used for Parkinson's disease

• medicines that change the heart's electrical activity or make it more likely to change.

How ZYPREXA RELPREVV is given

Follow all directions given to you by your doctor or pharmacist carefully.
These may differ from the information contained in this leaflet.

How much is given

How it is given

What happens after an injection

• excessive sleepiness

• confusion

• irritability

• dizziness, disorientation

• anxiety

• aggression

• difficulty talking or walking

• weakness

• muscle stiffness or shaking

• increases in blood pressure

• convulsions

How often is it given

How many injections will you need

Overdose

While you are having ZYPREXA RELPREVV

Things you must do

• Your doctor should monitor your weight while you are having ZYPREXA RELPREVV.

• Patients with diabetes or who have a higher chance of developing diabetes should have their blood sugar checked often.

• Your doctor may request you have a blood test from time to time to monitor your cholesterol levels.

• If you are over 65, your doctor may measure your blood pressure from time to time.

Things you must not do

Things to be careful of

Side effects

All medicines may have some unwanted side effects. Sometimes they are serious, but most of the time they are not. Your doctor has weighed the risks of using this medicine against the benefits they expect it will have for you.
Like other medicines, ZYPREXA RELPREVV may cause some unwanted side effects. These are likely to vary from patient to patient. Some side effects may be related to the dose of ZYPREXA RELPREVV. Accordingly, it is important that you tell your doctor as soon as possible about any unwanted effects. Your doctor may then decide to adjust the dose of ZYPREXA RELPREVV you are taking.
A serious side effect can occur if ZYPREXA RELPREVV enters the blood stream too quickly. There is more information about this in the section named "What happens after an injection".
A common side effect seen with ZYPREXA RELPREVV was sleepiness/drowsiness.
A rare side effect seen with ZYPREXA RELPREVV is an abscess (infection) at the place the injection was given.
The information below concerns side effects seen with other forms of ZYPREXA. They may also occur in people who use ZYPREXA RELPREVV.
Tell your doctor or nurse if you notice any of the following side effects and they worry you:

• drowsiness

• unusual tiredness or weakness

• fever

• restlessness or difficulty sitting still

• increased appetite, weight gain

• dizziness, confusion, forgetfulness

• constipation, bloating

• dry mouth

• swelling of your hands, feet and ankles

• aching joints

• nose bleeds

• low blood pressure

• slow heart beat

• fast heart beat.

• speech disorder

• sleepwalking

• sleep eating

• symptoms of sunburn (such as redness, itching, swelling or blistering of the skin) which occur more quickly than normal

• rash or allergic reaction

• slow heart beat

• changes in sexual functioning or sex drive in men or women

• prolonged and/or painful erection

• unusual secretion of breast milk

• breast enlargement in men or women

• symptoms of high sugar levels in the blood (including passing large amounts of urine, excessive thirst, having a dry mouth and skin and weakness). These may indicate the onset or worsening of diabetes

• reaction following abrupt discontinuation (profuse sweating, nausea or vomiting)

• absence of menstrual periods and changes in the regularity of menstrual periods

• involuntary passing of urine or difficulty in initiating urination

• unusual hair loss or thinning.

• excessive saliva in the mouth.

• sudden signs of an allergic reaction such as a skin rash, itching, shortness of breath or swelling of the face, lips or tongue

• drowsiness, confusion or excessive sleepiness

• frequent infections such as fever, severe chills, sore throat or mouth ulcers

• bleeding or bruising more easily than normal

• painful swollen leg, chest pain, or shortness of breath as these can be signs of blood clots in the lungs or legs

• seizures, fits or convulsions

• yellowing of the skin and/or eyes

• nausea, vomiting, loss of appetite, generally feeling unwell, fever, itching, yellowing of the skin and/or eyes

• severe upper stomach pain often with nausea and vomiting (inflammation of the pancreas)

• worm-like movements of the tongue, or other uncontrolled movements of the tongue, mouth, cheeks, or jaw which may progress to the arms and legs

• sudden increase in body temperature, sweating, fast heart beat, muscle stiffness, high blood pressure and convulsions

• sharp chest pain, coughing of blood, or sudden shortness of breath

• pain/tenderness in the calf muscle area

• muscle pain, muscle weakness and brown urine

• heart attack

• heart palpitations and dizziness, which may lead to collapse.

• fast breathing, shortness of breath, fever with chills, feeling tired or weak, chest pain while coughing, fast heartbeat. You may have pneumonia.

• fever or swollen glands, especially if they occur together with or shortly after a skin rash

Elderly patients with dementia-related psychosis

• unusual manner of walking

• falls

• pneumonia

• involuntary passing of urine.

• stroke

• transient ischemic attack – symptoms maybe, but not limited to, paralysis in face, arm or leg.

Parkinson's disease psychosis

Zyprexa in combination with lithium or valproate

• tremors

• speech disorder.

After using ZYPREXA RELPREVV

Storage

Disposal

Product Description

What it looks like

Ingredients

Supplier

Australian Registration Numbers

Boxed Warnings

Warning. The potential for signs and symptoms of sedation and/or delirium consistent with olanzapine overdose exists after every injection of Zyprexa Relprevv. Zyprexa Relprevv should be administered by appropriately qualified health professionals in a healthcare facility with access to emergency services for management of olanzapine overdose. Healthcare professionals who prescribe or administer Zyprexa Relprevv should be aware of this potential risk and the consequent need to monitor patients for at least two hours after each injection. The two hour period should be extended as clinically appropriate for patients who exhibit any potential signs or symptoms of a post-injection syndrome event. See Section 4.4 Special Warnings and Precautions for Use, Post-injection syndrome.

1 Name of Medicine

Zyprexa Relprevv (olanzapine pamoate monohydrate - alternatively named olanzapine embonate monohydrate).

2 Qualitative and Quantitative Composition

Olanzapine pamoate monohydrate, equivalent to olanzapine 210 mg.
Olanzapine pamoate monohydrate, equivalent to olanzapine 300 mg.
Olanzapine pamoate monohydrate, equivalent to olanzapine 405 mg.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Zyprexa Relprevv 210 mg, 300 mg and 405 mg is available in a Type I cerium oxide vial. One carton provides a kit containing 1 vial of olanzapine pamoate monohydrate, one vial of sterile diluent, one 3 mL syringe with pre-attached 19-gauge 38 mm Hypodermic Needle-Pro safety needle, one 19-gauge 38 mm Hypodermic Needle-Pro safety needle and two 19-gauge 50 mm Hypodermic Needle-Pro safety needles.

4 Clinical Particulars

4.9 Overdose

If signs and symptoms of overdose consistent with inadvertent intravascular administration are observed appropriate supportive measures should be instituted (see Section 4.4 Special Warnings and Precautions for Use, Post-injection syndrome). Although overdose is less likely with this parenteral preparation that is administered by a healthcare professional, reference information for oral olanzapine overdose is presented below.
Signs of oral toxicity in rodents were characteristic of potent neuroleptic compounds: hypoactivity, coma, tremors, clonic convulsions and salivation. In dogs, olanzapine caused sedation, ataxia, tremors, tachycardia, laboured respiration, miosis and anorexia. In monkeys, prostration and semi-consciousness were observed.
Signs and symptoms. Very common symptoms (≥ 10% incidence) reported in Zyprexa overdose include tachycardia, agitation/aggressiveness, dysarthria, various extrapyramidal symptoms and reduced level of consciousness ranging from sedation to coma.
Other medically significant sequelae of Zyprexa overdose include delirium, convulsion, 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 2 g.
Management of overdose. There is no specific antidote to Zyprexa. Induction of emesis is not recommended. Standard procedures for management of overdose may be indicated. The possibility of multiple drug involvement should be considered.
In case of acute overdosage, establish and maintain an airway and ensure adequate oxygenation and ventilation. The use of activated charcoal for overdose should be considered because the concomitant administration of activated charcoal was shown to reduce the oral bioavailability of olanzapine by 50% to 60%. In patients who are not fully conscious or who have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected. Olanzapine is not substantially removed by haemodialysis.
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. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids and/or sympathomimetic agents such as noradrenaline. Adrenaline, dopamine or other sympathomimetic agents should not be used since beta stimulation may worsen hypotension in the setting of alpha blockade induced by Zyprexa. Cardiovascular monitoring should be considered to detect possible arrhythmias. Close medical supervision and monitoring should continue until the patient recovers.
Contact the Poisons Information Centre in Australia (telephone 13 11 26) or the National Poisons Centre in New Zealand (telephone 0800 POISON or 0800 764 766) for advice on management of overdose with Zyprexa or Zyprexa Relprevv.

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Olanzapine was not genotoxic in a full range of standard tests, which included bacterial mutation tests and in vitro and in vivo tests. Pamoic acid was positive in an in vitro chromosome aberration assay but negative in a range of other in vitro and in vivo tests, with the weight of evidence indicating that it does not represent a genotoxic liability at the proposed clinical dose.
Carcinogenicity. Carcinogenicity studies with olanzapine showed the development of mammary adenocarcinomas at oral doses of 2 mg/kg/day or greater in mice and 2.5 mg/kg/day or greater in rats (similar to or less than the maximum recommended clinical oral dose, based on mg/m². The respective no-effect doses were 0.5 and 1 mg/kg/day (less than the maximum recommended clinical oral dose). Monthly intramuscular administration of olanzapine pamoate monohydrate to rats at doses up to 20 mg/kg (males) or 50 mg/kg (females) for 2 years was not associated with tumour formation, although rat exposures (plasma AUC) to pamoic acid and olanzapine were similar to and less than the respective exposures to pamoic acid and olanzapine at the maximum recommended clinical dose of Zyprexa Relprevv.
The increased incidence of mammary tumours may be due to an endocrine mechanism, possibly involving elevation of circulating prolactin levels in response to the dopamine D₂-receptor antagonistic activity of olanzapine. Mammary tumours are known to occur in rats and mice treated with other drugs that antagonise dopamine D₂-receptors. Neither clinical studies nor epidemiological studies, conducted to date, have shown an association between these drugs and carcinogenesis, but the available evidence is considered too limited to be conclusive at this time. The use of Zyprexa Relprevv in patients with familial history or previously detected breast cancer should be avoided. Caution should also be exercised when considering Zyprexa Relprevv treatment in patients with pituitary tumours.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Chemical structure. Chemically, olanzapine pamoate monohydrate is 10H-thieno[2,3-b][1,5]benzodiazepine, 2-methyl-4-(4-methyl-1-piperazinyl)- 4,4'-methylenebis [3-hydroxy-2-naphthalene-carboxylate] (1:1) monohydrate. The formula is C₁₇H₂₂N₄SC₂₃H₁₄O₆H₂O. Olanzapine pamoate monohydrate is a yellow solid that is practically insoluble in water with a molecular weight of 718.8.
Olanzapine pamoate monohydrate has the following structural formula:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSOLAPAM.gif CAS number. The CAS number for olanzapine pamoate monohydrate is 221373-18-8.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription only Medicine.

Summary Table of Changes

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