Consumer medicine information

What is in this leaflet

This leaflet answers some common questions about APOMINE Intermittent. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using APOMINE Intermittent against the benefits they expect it will have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet in a safe place. You may need to read it again.

For further information on APOMINE Intermittent please contact your doctor or pharmacist or your ANSSER nurse (1800 276 646).

What APOMINE Intermittent is used for

APOMINE Intermittent contains apomorphine which belongs to a group of medicines called dopaminergic compounds.

Apomorphine is used in the treatment of Parkinson's disease to reduce the number and severity of bouts of freezing and stiffness (or "off" periods).

This medicine works by acting on dopamine receptors. These receptors help control movement by the body.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is not addictive.

This medicine is available only with a doctor's prescription.

Before you use APOMINE Intermittent

When you must not use it

Do not use APOMINE Intermittent if you have an allergy to:

• apomorphine
• sodium metabisulfite or sulfites
• certain types of pain killers such as morphine or other opioid analgesics.

Some of the symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.

The amount of sodium contained in APOMINE Intermittent solution for injection is low (23 mg per 10 mL) and should not affect patients with sodium-restricted diets.

Do not use this medicine if you have or have had any of the following medical conditions:

• certain forms of dementia eg. Alzheimer's Disease
• severe kidney or liver disease
• problems with circulation of blood in the brain (cerebrovascular disease)
• breathing problems (respiratory depression).

Do not give this medicine to a child under the age of 18 years.

Do not use this medicine in combination with anti-vomiting medicines (antiemetics) known as 5HT3 antagonists, such as ondansetron, granisetron or palonosetron. People taking ondansetron together with apomorphine, the active ingredient in APOMINE Intermittent, have had very low blood pressure and lost consciousness or "blacked out".

Do not use this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start using this medicine, talk to your doctor.

Before you use it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

• a history of severe nausea and vomiting
• heart disease
• kidney disease
• liver disease
• lung disease
• problem gambling,
• any addictive behaviour (eg. sex, shopping or eating).

APOMINE can cause impulse control disorders, including addictive behaviour and cravings for more APOMINE, even when you don’t have "off" symptoms to treat.

Before you use APOMINE Intermittent, your doctor may obtain an ECG (electrocardiogram), do blood tests and ask for a list of all other medicines you take. The ECG and blood tests will be repeated in the first days of your treatment and at any point if your doctor thinks this is needed. He or she will also ask you about other diseases you may have, in particular, concerning your heart. Some of the questions and investigations may be repeated at each medical visit. If you experience symptoms which may come from the heart, eg. palpitations, fainting, or near-fainting, you should report this to your doctor immediately.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor will discuss the possible risks and benefits involved.

If you have not told your doctor about any of the above, tell them before you start using APOMINE Intermittent.

Taking other medicines

Tell your doctor or pharmacist if you are taking or using any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and APOMINE Intermittent may interfere with each other. These include:

• ondansetron, granisetron or palonosetron, anti-vomiting medicines (antiemetics)
• tetrabenazine, a medicine used to treat movement disorders
• metoclopramide, a medicine used to treat nausea
• medicines used to treat some psychiatric (mental) conditions (eg phenothiazines, haloperidol, flupenthixol)
• papaverine, a medicine which expands blood vessels
• amphetamines.

These medicines may be affected by APOMINE Intermittent or may affect how well they work. You may need different amounts of your medicine, or you may need to use different medicines.

Your doctor and pharmacist have more information on medicines to be careful of or avoid while using this medicine.

How to use APOMINE Intermittent

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

If you do not understand the instructions, ask your doctor, nurse or pharmacist for help.

Do not use APOMINE Intermittent if the solution has turned green, or if the solution is cloudy or you can see particles in it.

How much is given

Your doctor will decide what dose you will receive. This depends on your initial response to APOMINE Intermittent.

How it is given

You will usually be in hospital when you start using APOMINE Intermittent. It is recommended that you are given anti-nausea tablets (domperidone) for a few days before starting APOMINE® Intermittent and that you stop all your other anti-Parkinsonian medication before you start using APOMINE Intermittent. This medicine is given as an injection under the skin (subcutaneously), usually into your lower abdomen or outer thigh. It is injected several times a day using a device called the D-Mine® Pen and not with a conventional syringe and needle that you might be familiar with.

You and/or your carers will be trained by hospital staff to recognise when and how to give the injections.

It is advisable to change the site of injection every time you insert the needle, to avoid getting lumps under the skin.

This medicine is for individual patient use only.

If you use too much (Overdose)

Immediately notify your doctor or nurse, or if you are not in hospital, telephone the Poisons Information Centre 13 11 26 (Australia) or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else may have used too much APOMINE Intermittent. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose may include severe nausea and vomiting, slow or troubled breathing, restlessness, hallucinations or unconsciousness.

While you are using APOMINE Intermittent

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are using APOMINE Intermittent.

Tell any other doctors, dentists, and pharmacists who are treating you that you are using this medicine.

If you plan to have surgery, tell the surgeon or anaesthetist that you are using this medicine. It may affect other medicines used during surgery.

If you become pregnant while using this medicine, tell your doctor immediately.

Keep all of your doctor's appointments so that your progress can be checked.

Things you must not do

Do not use APOMINE Intermittent to treat any other complaints unless your doctor tells you to.

Do not give this medicine to anyone else, even if they have the same condition as you.

Things to be careful of

Be careful driving or operating machinery until you know how APOMINE Intermittent affects you. This medicine may cause drowsiness, dizziness or light-headedness in some people. It could also make you fall asleep without warning. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Side effects

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well while you are using APOMINE Intermittent.

APOMINE Intermittent helps most people with Parkinson's Disease but may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

If you are over 65 years of age you may have an increased chance of experiencing side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor, nurse or pharmacist to answer any questions you may have.

Tell your doctor, nurse or pharmacist if you notice any of the following and they worry you:

• nausea or vomiting, particularly when starting this medicine
• lumps under the skin, rashes or ulcers at the site of injection, which are sore, troublesome and may be red and itchy
• drowsiness, yawning or suddenly falling asleep, weight loss
• confusion
• dizziness or light-headedness when standing up, fainting
• headache
• unpleasant metallic taste, sore mouth
• runny nose, watery eyes
• reduced facial hair growth
• spontaneous penile erection
• decreased sex drive
• infertility, or inability to get pregnant
• absent, irregular or infrequence periods
• breast milk leakage in people who are not pregnant
• loss of interest in sex, painful or uncomfortable intercourse, or vaginal dryness
• acne or excess body and facial hair growth
• hot flashes.

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your doctor as soon as possible if you notice any of the following:

• increased involuntary movements or increased shakiness during ‘on’ periods
• aggression and agitation
• swelling of your arms and hands, or legs and ankles (peripheral oedema)
• pale or yellow skin, yellow eyes or mouth, dark coloured urine
• fever, weakness, dizziness, confusion, breathlessness, inability to handle physical activity, increased heart rate
• pain in the upper abdomen and bloating, or feeling full in the stomach early after eating, loss of appetite, unexplained weight loss
• bleeding or bruising
• lack of impulse control - an inability to resist the impulse, drive or temptation to perform an action that could be harmful to you or others, which can include an increased need to gamble, compulsive eating, shopping or medication use, or a highly increased sex drive.

The above list includes serious side effects that may require medical attention. Serious side effects are rare or uncommon.

If any of the following happen tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

• shortness of breath
• wheezing or difficulty breathing
• swelling of the face, lips, tongue or other parts of the body
• hallucinations (seeing, hearing or feeling things that are not there)
• severe nausea and vomiting

The above list includes serious side effects which may require medical attention. These side effects are rare.

Tell your doctor, nurse or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

Some of these side effects can only be found when your doctor does tests from time to time to check your progress.

After using APOMINE Intermittent

Storage

Store the APOMINE Intermittent below 25°C until it is time to use it. Do not refrigerate or freeze. Keep the container in the outer carton and protect from light.

APOMINE Intermittent is for single use only. After the first injection, the contents of the cartridge should be used within 72 hours. Any solution remaining after this time should be discarded.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Do not throw out the D-Mine Pen. You can keep it to use with the other cartridges.

Disposal

If your doctor tells you to stop using this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

APOMINE Intermittent is supplied as a clear, colourless to slightly yellow, sterile solution that comes in 3 mL glass cartridges, in packs of 5.

Do not use APOMINE Intermittent if it looks cloudy or develops a green colour.

Ingredients

APOMINE Intermittent contains:

• apomorphine hydrochloride hemihydrate
• sodium metabisulfite (E223)
• hydrochloric acid
• sodium chloride
• water for injections

APOMINE Intermittent does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Strength

3 mL cartridge containing apomorphine hydrochloride hemihydrate 10 mg/mL

Sponsor

InterPharma Pty Ltd
Suite 103,39 East Esplanade
Manly NSW 2095, Australia

Glass cartridges - AUST R 296520

This leaflet was prepared in September 2023.

Published by MIMS March 2024

1 Name of Medicine

Apomorphine hydrochloride hemihydrate.

2 Qualitative and Quantitative Composition

Apomine Intermittent is a sterile solution for injection containing 10 mg/mL of apomorphine hydrochloride hemihydrate in Water for Injections BP. Each 3 mL cartridge contains 30 mg apomorphine hydrochloride hemihydrate. Sodium metabisulfite 1 mg/mL is included in the formulation as an antioxidant.

Excipient(s) with known effect.

3 Pharmaceutical Form

Apomine Intermittent is a clear, colourless to slightly yellow sterile solution for subcutaneous injection, free from visible particles.

4 Clinical Particulars

4.1 Therapeutic Indications

Apomine Intermittent is indicated to reduce the number and severity of 'off' phases in patients with Parkinson's disease severely disabled by motor fluctuations refractory to conventional therapy. Initiation of therapy with Apomine Intermittent should be undertaken in a specialist unit in a hospital setting. Conventional therapy should be continued during 'on' phases.

4.2 Dose and Method of Administration

Dosage.

Patient selection.

Pretreatment.

Provoking and assessing an 'off' phase.

Determination of the threshold dose.

Initiation of treatment.

Method of administration.

Monitoring treatment.

4.3 Contraindications

Apomine Intermittent is contraindicated in patients with a known hypersensitivity or allergy to apomorphine, morphine or to any of the excipients (including sodium metabisulfite) or chemically related products.
Apomine Intermittent should not be administered to patients with pre-existing neuropsychiatric problems or dementias due to either pathological processes, e.g. Alzheimer's disease, or to patients whose 'on' response to L-dopa is marred by severe dyskinesia, hypotonia or psychotoxicity.
Apomorphine is also contraindicated in patients with inadequate renal or liver function, unstable coronary vascular disease, cerebrovascular disease, respiratory depression or CNS depression.
Concomitant use with 5HT₃ antagonists including antiemetics (for example ondansetron, granisetron, palonosetron) (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Apomine Intermittent is contraindicated for children and adolescents under 18 years of age.
Apomine Intermittent is also contraindicated in patients with a known hypersensitivity to sodium metabisulfite.

4.4 Special Warnings and Precautions for Use

For Subcutaneous Use Only (see Section 4.8 Adverse Effects (Undesirable Effects)).
Patients sensitive to morphine or its derivatives may be sensitive to apomorphine. Apomorphine should therefore not be administered to patients with a known hypersensitivity or allergy to apomorphine, morphine or chemically related compounds (see Section 4.3 Contraindications).
Apomine Intermittent contains sodium metabisulfite which may cause allergic type reactions, including anaphylactic symptoms and life threatening or less severe asthmatic episodes in susceptible people.
In patients with cardiac decompensation or cerebrovascular disease, vomiting may cause an increase in blood pressure that may lead to haemorrhage and vascular accidents. Apomorphine is therefore contraindicated in these patients (see Section 4.3 Contraindications).
Caution should be used in administering apomorphine to patients with a predisposition to nausea and vomiting. Apomorphine may cause an increased risk of persistent vomiting. A risk-benefit assessment should be considered in these patients.
Since apomorphine may produce hypotension, even when given with domperidone pre-treatment, care should be exercised in patients with pre-existing cardiac disease or in patients taking vasoactive medicinal products such as anti-hypertensives, and especially in patients with pre-existing postural hypotension.
Since apomorphine, especially at high doses, may have the potential for QT prolongation, caution should be exercised when treating patients at risk for Torsades de pointes arrhythmia.
When used in combination with domperidone, risk factors in the individual patient should be carefully assessed. This should be done before treatment initiation, and during treatment. Important risk factors include serious underlying heart conditions such as congestive cardiac failure, severe hepatic impairment or significant electrolyte disturbance. Also, medication possibly affecting electrolyte balance, CYP3A4 metabolism or QT interval should be assessed.
Monitoring for an effect on the QTc interval is advisable. An ECG should be performed:
prior to treatment with domperidone;
during the treatment initiation phase;
as clinically indicated thereafter.
The patient should be instructed to report possible cardiac symptoms including palpitations, syncope, or near-syncope. They should also report clinical changes that could lead to hypokalaemia, such as gastroenteritis or the initiation of diuretic therapy. At each medical visit, risk factors should be revisited.
Apomorphine is associated with local subcutaneous effects. These can sometimes be reduced by the rotation of injection sites or possibly by the use of ultrasound (if available) in order to avoid areas of nodularity and induration (see Section 4.8 Adverse Effects (Undesirable Effects)).
Caution is advised when combining apomorphine with other medicinal products, especially those with a narrow therapeutic range (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Neuropsychiatric problems co-exist in many patients with advanced Parkinson's disease. There is evidence that for some patients, neuropsychiatric disturbances may be exacerbated by apomorphine. Special care should be exercised when apomorphine is used in these patients.
The use of apomorphine in conjunction with levodopa treatment may cause Coombs' positive haemolytic anaemia. An initial screen prior to commencement of treatment and at 6 monthly intervals is recommended. In the event of the development of a haemolytic anaemia, a haematological specialist should be consulted. The dose of apomorphine and/or levodopa should be reduced, with careful monitoring of the patient's motor state. It may be necessary to discontinue treatment with levodopa and/or apomorphine in the event that it is not possible to control the anaemia satisfactorily.
Apomorphine has been associated with somnolence, and other dopamine agonists can be associated with sudden sleep onset episodes, particularly in patients with Parkinson's disease. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with apomorphine. Patients who have experienced somnolence, and/or an episode of sudden sleep onset, must refrain from driving or operating machines. Furthermore, a reduction of dosage or termination of therapy may be considered.
Apomorphine should be used with caution in patients with endocrine, renal, pulmonary or cardiovascular disease.
Periodic evaluation of hepatic, haemopoietic, renal and cardiovascular function is advised.
Patients with severe renal insufficiency may require the dosing interval for domperidone to be less frequent (see Section 4.2 Dose and Method of Administration, Pretreatment).

Compulsive behaviour.

Use in debilitated patients.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Patients selected for treatment with apomorphine are almost certain to be taking concomitant medications for their Parkinson's disease. In the initial stages of apomorphine therapy, the patient should be monitored for unusual side-effects or signs of potentiation of effect.
Drugs which interfere with central amine mechanisms such as tetrabenazine, metoclopramide, antipsychotic dopamine blocking agents (such as phenothiazines, thioxanthines and butyrophenones), amphetamines and papaverine should be avoided. If their administration is considered essential, extreme care should be taken and the patient monitored for signs of potentiation, antagonism or other interactions and for any unusual adverse effects.
Neuroleptic medicinal products may have an antagonistic effect if used with apomorphine. There is a potential interaction between clozapine and apomorphine.
The possible side effects of apomorphine on the plasma concentrations of other medicinal products have not yet been studied. Therefore, caution is advised when combining apomorphine with other medicinal products, especially those with a narrow therapeutic range.

Antihypertensive and cardiac active medicinal drugs.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

Apomorphine has varying degrees of impairment which influences the ability to drive and use machines.
Patients being treated with apomorphine and presenting with somnolence and/or sudden sleep episodes must be informed to refrain from driving or engaging in activities (e.g. operating machines) where impaired alertness may put themselves or others at risk of serious injury or death until such recurrent episodes and somnolence have resolved (also see Section 4.4 Special Warnings and Precautions for Use).

4.8 Adverse Effects (Undesirable Effects)

Very common (> 10%).

Common (1-10%).

Uncommon (0.1-1%).

Rare (0.01-0.1%).

Other.

Reporting suspected adverse effects.

4.9 Overdose

Symptoms.

Treatment.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

5.2 Pharmacokinetic Properties

The peripheral pharmacokinetics of apomorphine have been studied following subcutaneous injection, subcutaneous infusion and intravenous infusion.

Absorption.

Distribution.

Metabolism.

Excretion.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium metabisulfite, water for injections, hydrochloric acid, sodium hydroxide.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine. Also see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.
Chemical and physical in-use stability has been demonstrated for 15 days at 25°C. However, as the product contains no antimicrobial agent, for microbial reasons, once opened, the contents of the cartridge should be used within 72 hours.

6.4 Special Precautions for Storage

Store below 25°C. Do not refrigerate or freeze.
Protect from light. (Keep the container in the outer carton).

6.5 Nature and Contents of Container

Clear type I glass cartridges, with bromobutyl rubber stopper and an aluminium cap with bromobutyl rubber seal.
30 mg/3 mL cartridge. Pack of 5 cartridges.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

The pH of the injection is 2.5 to 4.0.

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

Schedule 4.

Summary Table of Changes