Consumer medicine information

Movapo Pen

Apomorphine hydrochloride hemihydrate

BRAND INFORMATION

Brand name

Movapo Pen

Active ingredient

Apomorphine hydrochloride hemihydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Movapo Pen.

SUMMARY CMI

MOVAPO® PEN

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using MOVAPO PEN?

MOVAPO PEN contains the active ingredient apomorphine hydrochloride hemihydrate. MOVAPO PEN is used in the treatment of Parkinson's disease to reduce the number and severity of bouts of freezing and stiffness (or “off” periods).

For more information, see Section 1. Why am I using MOVAPO PEN? in the full CMI.

2. What should I know before I use MOVAPO PEN?

Do not use if you have ever had an allergic reaction to apomorphine hydrochloride hemihydrate, sodium metabisulfite or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use MOVAPO PEN? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with MOVAPO PEN and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use MOVAPO PEN?

  • Your doctor will tell you how much to use.
  • MOVAPO PEN are designed for injection under the skin (subcutaneous).
  • You will be trained to recognise when and how to inject. Follow the instructions given by your doctor or pharmacist.

More instructions can be found in Section 4. How do I use MOVAPO PEN? in the full CMI.

5. What should I know while using MOVAPO PEN?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using MOVAPO PEN.
  • If you become pregnant while you are using this medicine, tell your doctor immediately.
Things you should not do
  • Do not use MOVAPO PEN 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.
  • Do not stop MOVAPO PEN abruptly or change the dose, without speaking to your doctor to discuss a taper treatment plan.
Driving or using machines
  • MOVAPO PEN may cause drowsiness, sudden onset of sleepiness, dizziness or light-headedness in some people.
  • If you have any of these symptoms do not drive, operate machinery or do anything else that could be dangerous.
Looking after your medicine
  • Store below 25°C. Store in the medicine in its original carton to protect from light. Do not freeze.
  • Store at the same conditions after opening and between withdrawals.
  • Discard after 48 hours of first use.

For more information, see Section 5. What should I know while using MOVAPO PEN? in the full CMI.

6. Are there any side effects?

Like all medicines, this medicine can cause side effects, although not everybody gets them. Some side effects can be serious and you need to know what symptoms to look out for. MOVAPO PEN can cause allergic reactions which may be very serious. If you develop symptoms of allergic reaction, you may need urgent medical attention or hospitalisation.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

MOVAPO® PEN

Active ingredient(s): apomorphine (a-poe-MOR-feen) hydrochloride hemihydrate


Consumer Medicine Information (CMI)

This leaflet provides important information about using MOVAPO PEN.

You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using MOVAPO PEN.

Where to find information in this leaflet:

1. Why am I using MOVAPO PEN?
2. What should I know before I use MOVAPO PEN?
3. What if I am taking other medicines?
4. How do I use MOVAPO PEN?
5. What should I know while using MOVAPO PEN?
6. Are there any side effects?
7. Product details

1. Why am I using MOVAPO PEN?

MOVAPO PEN contains the active ingredient apomorphine hydrochloride hemihydrate. Apomorphine 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.

2. What should I know before I use MOVAPO PEN?

Warnings

Do not use MOVAPO PEN if you have an allergy to:

  • any medicine containing apomorphine or sodium metabisulfite
  • any of the ingredients listed at the end of this leaflet
  • certain types of pain killers such as morphine or other opioid analgesics

Some symptoms of 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.

Always check the ingredients to make sure you can use this medicine.

Do not use MOVAPO PEN if you have or have had any of the following medical conditions:

  • Certain forms of dementia, e.g. Alzheimer's Disease
  • Severe kidney or liver disease
  • Problems with circulation of blood in the brain (cerebrovascular disease)
  • Breathing problems (respiratory depression)

Do not use MOVAPO PEN if:

  • the packaging is torn or shows signs of tampering
  • the expiry date printed on the pack has passed
  • the solution has turned greed or if the solution is cloudy or you can see particles in it.

Check with your doctor if you:

  • have allergies to any other medicines, foods, preservatives or dyes
  • you have or have had any of the following medical conditions:
    - a history of nausea and vomiting
    - heart disease
    - kidney disease
    - liver disease
    - lung disease
    - problem gambling
    - any addictive behaviour (e.g. sex, shopping or eating)

Before you use MOVAPO PEN, your doctor will obtain an ECG (electrocardiogram) and will ask for a list of all medicines you take. This ECG will be repeated in the first days of your treatment and at any point if your doctor thinks this is needed. Your doctor will also ask you about other diseases you have, in particular concerning your heart. Some questions and investigations may be repeated at each medical visit. If you experience symptoms which may come from the heart, e.g. palpitations, fainting or near-fainting, you should report this to your doctor immediately. Also, if you experience diarrhoea or start a new medication, this should be reported to your doctor too.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Children and adolescents

MOVAPO PEN should not be used in children and adolescents under the age of 18 years.

3. What if I am taking other medicines?

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

Some medicines may interfere with MOVAPO PEN and affect how it works.

These include:

  • tetrabenazine, a medicine used to treat movement disorders
  • metoclopramide, a medicine used to treat nausea
  • medicines used to treat some psychiatric (mental) conditions (e.g. phenothiazines, haloperidol, flupenthixol)
  • papaverine, a medicine which expands blood vessels
  • amphetamines
  • ondansetron, a medicine used to treat nausea and vomiting. This may result in a severe drop in blood pressure or loss of consciousness.

MOVAPO PEN may affect these medicines and how well they work. You may need different amounts of your medicines, or different medicines.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect MOVAPO PEN.

4. How do I use MOVAPO PEN?

How much to use

  • Your doctor will tell you what dose to use. This depends on your initial response to MOVAPO.
  • Follow the instructions provided and use MOVAPO PEN until your doctor tells you to stop.

When to use MOVAPO PEN

  • You and/or your carer will be trained by hospital staff to recognise when to use MOVAPO PEN.

How to use MOVAPO PEN

  • You will usually be in hospital when you start using this medicine. It is recommended you are given an anti-nausea drug (domperidone) for a few days, and that you will temporarily stop all other anti-Parkinsonian medication so that the correct dose of MOVAPO can be determined.
  • You and/or your carer will be trained by hospital staff on how to give the injections. Instructions are also included in this CMI. If you do not understand the instructions, ask your doctor, nurse or pharmacist to help.
  • MOVAPO PEN is to be given as an injection under the skin (subcutaneously), usually in your lower abdomen or outer thigh. It is injected several times a day.
  • It is advisable to change the site of injection every time you insert the needle to avoid getting lumps under the skin.
  • MOVAPO PEN is a cartridge contained in a Pen injector. The product is for individual patient use only.
  • Before using MOVAPO PEN, study the diagram below to familiarise yourself with the medicine.
  • IMPORTANT: Do not pull the red capped dosage dial (see 1) before you have set the dosage (see “Selecting the correct dosage”).

Attaching the needle

  • Before using MOVAPO PEN you will need some surgical wipes and one needle in its protective cone (see 2).
  • Take the pen out of its box and remove the outer sleeve (see 3).

  • Wipe the membrane of the Pen (see 4) with a surgical wipe.

  • Peel off the paper from the needle cone (see 2).

  • It is important to bring the needle to the Pen in a straight line, as shown below. If the needle is presented at an angle, it may cause the Pen to leak.

  • Screw the cone (see 2) clockwise onto the membrane until it is tight. This securely attaches the needle.
  • Remove the protective cone (see 5), but do not throw it away. Do not remove the needle protector (see 6) at this stage.

  • Replace the Pen's outer sleeve (see 3).

Selecting the correct dose

  • Press the red capped dosage dial (see 1) and whilst holding it down, turn the dial clockwise until the arrow point to the dose your doctor chose for you (see 7 & 8). Release the downward pressure on the red capped dial. The dose if now set and you do not need to redial for subsequent injections.

  • IMPORTANT: If you pass your prescribed dose while turning the dial, just continue pressing and turning in the same direction until the arrow points to the dose your doctor chose for you.
  • Never pull and turn the red capped dosage dial at the same time.
  • If your dose is 1 mg, start by emptying a 1 mg dose onto a paper tissue and discarding it. This is called ‘priming’ and is important because it ensures you get the full dose the first time you use your Pen. Then, set the dose you require for injection and inject it the usual way (see “Injecting”).
  • If the first dose required is more than 1 mg, you do not need to prime the Pen.

Injecting

  • Once you have set the dose, gently pull out the red capped dosage dial as far as it will go. Check the red scale on the plunger (see 9) and inject only if the line that is just visible matches the intended dose.

  • Using a surgical wipe, clean the area of skin where you plan to inject the medicine and around it.
  • Remove the Pen's outer sleeve (see 3).
  • Remove the needle protector (see 6).
  • Inset the needle (see 10) into the skin as shown by your doctor.
  • To inject, press the red capped dosage dial (see 1) down as far as it will go, using your thumb if possible. Once the red capped dosage dial is fully depressed, count to three before withdrawing the needle.

  • Replace the protective cone (see 5) and push gently into place. Once secure, turn the needle anticlockwise to unscrew it. Keep the needle in its protective cone and discard it in a “Sharps” container.

Preparing for the next injection

  • Remove the outer sleeve of the Pen and check there is enough apomorphine left in the cartridge for your next injection. If there is, put a new needle in place in the same way as before.
  • If there is not enough apomorphine left for another injection, prepare another Pen.
  • Finally, replace the outer sleeve of your Pen.

If you use too much MOVAPO PEN

If you think that you have used too much MOVAPO PEN, you may need urgent medical attention. Symptoms of overdose may include severe nausea and vomiting, slow or troubled breathing, restlessness, hallucinations or unconsciousness.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using MOVAPO PEN?

Things you should do

  • If you plan to have surgery, tell the surgeon or anaesthetist you are taking this medicine. It may affect any medicines used during surgery.
  • Keep all your doctor's appointments so that your progress can be checked.

Call your doctor straight away if you:

  • are about to start on any new medication
  • become pregnant
  • have any symptoms which may come from your heart, e.g. palpitations, fainting, or near-fainting
  • experience diarrhoea

Remind any doctor, dentist or pharmacist you visit that you are using MOVAPO PEN.

Things you should not do

  • Do not use MOVAPO PEN 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.
  • Do not stop MOVAPO PEN abruptly or change the dose, without speaking to your doctor to discuss a taper treatment plan.
  • It is important not to suddenly stop taking your MOVAPO PEN, unless advised to do so by your doctor. If you stop taking it suddenly, your condition may worsen or you may have unwanted side effects. The dose will normally be reduced gradually over several days.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how MOVAPO PEN affects you.

MOVAPO PEN may cause drowsiness, sudden onset of sleepiness, dizziness or light-headedness in some people. If you have any of these symptoms do not drive, operate machinery or do anything else that could be dangerous.

Looking after your medicine

Store MOVAPO PEN below 25°C.

  • Do not freeze.
  • Keep in the original carton to protect from light.
  • Store at the same conditions after opening and between withdrawals.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

When to discard your medicine

When you start using a new MOVAPO PEN, it can be used for up to 48 hours. Do not re-use MOVAPO PEN after this time. Use a new Pen.

Getting rid of any unwanted medicine

To dispose of your pens safely, always remove the needle from the pend before discarding it in a “Sharps” container.

Ask your doctor, nurse or pharmacist where you can dispose of the container when it is full.

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal. If the pen is completely empty, you may dispose of it in your household waste.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Gut related:
  • Nausea or vomiting particularly when starting this medicine
Skin and Hair related:
  • Lumps under the skin, rashes or ulcers at the site of injection which are sore, troublesome and may be red and itchy
  • Reduced facial hair
Nervous system related:
  • Drowsiness or suddenly falling asleep
  • Confusion
  • Dizziness or light-headedness when standing up, fainting
  • Headache
Eyes, nose and mouth related:
  • Unpleasant metallic taste, sore mouth
  • Runny nose
  • Watery eyes
Other:
  • Weight loss
  • Spontaneous penile erection
  • Yawning
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Nervous system or behaviour related:
  • Increased involuntary movements or increased shakiness during “on” periods
  • Aggression, agitation
  • Inability to resist impulse, drive or temptation to perform an action that could be harmful to you or others, which may include:
    - decreased or increased sexual arousal
    - increased need to gamble
    - compulsive eating, shopping or medication use
Blood related:
  • Reduction in blood platelets which can lead to bleeding or bruising
  • Reduction in red blood cells which can lead to pale yellow skin, weakness or breathlessness
Call your doctor straight away if you notice any of these serious side effects.

Very serious side effects

Serious side effectsWhat to do
Allergy related:
  • Shortness of breath
  • Wheezing or difficulty breathing
  • Swelling of the face, lips, tongue or other parts of the body
  • Rash, itching or hives of the skin
Nervous system or behaviour related:
  • Hallucinations (seeing, hearing or feeling things that are not there)
  • High fever, muscle cramps or stiffness, dizziness, severe headache, fast heartbeat, confusion, agitation, hallucinations, or if you are sweating a lot (symptoms relating to neuroleptic malignant syndrome)
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these very serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What MOVAPO PEN contains

Active ingredient
(main ingredient)
Apomorphine hydrochloride hemihydrate
Other ingredients
(inactive ingredients)
Sodium metabisulfite
Water for injections
Hydrochloric acid
Potential allergensSodium metabisulfite

Do not take this medicine if you are allergic to any of these ingredients.

What MOVAPO PEN look like

MOVAPO PEN is supplied as a disposable multiple dose pen injector system incorporating a clear glass cartridge. Each glass cartridge contains 3 mL of a sterile, clear, colourless solution (10 mg/mL), practically free from visible particles.

MOVAPO PEN 30 mg/3 mL is supplied in a box of 5 disposable pens (AUST R 275694).

Who distributes MOVAPO PEN

In Australia:

STADA Pharmaceuticals Australia Pty Ltd
Suite 2.04, 26 Rodborough Road
Frenchs Forest NSW 2086
Australia
www.stada.com.au

MOVAPO® is a registered trademark of Britannia Pharmaceuticals Limited.

This leaflet was prepared in January 2024.

Published by MIMS March 2024

BRAND INFORMATION

Brand name

Movapo Pen

Active ingredient

Apomorphine hydrochloride hemihydrate

Schedule

S4

 

1 Name of Medicine

Apomorphine hydrochloride hemihydrate.

2 Qualitative and Quantitative Composition

Each 3 mL injection cartridge contains 30 mg apomorphine hydrochloride hemihydrate, hence 1 mL of solution contains 10 mg apomorphine hydrochloride hemihydrate (10 mg/mL).
Sodium metabisulfite 1.37 mg/mL is included in the formulation as an antioxidant.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.
Movapo Pen is a sterile clear, colourless solution and practically free from visible particles.

4 Clinical Particulars

4.1 Therapeutic Indications

Movapo Pen 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 apomorphine 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

The optimal dosage of Movapo Pen has to be determined on an individual patient basis. Hospital admission under appropriate specialist supervision is advised when establishing a patient's therapeutic regime.
It is essential that the patient is established on the antiemetic domperidone for at least 48 - 72 hours prior to initiation of therapy.
If incremental dose adjustments smaller than 1 mg are required another product containing apomorphine should be used.

Patient selection.

For patients in whom conventional therapy has failed, Movapo Pen is only considered to be suitable for Parkinson's disease patients capable of recognising and anticipating 'off' phases in motor performance. Patients must be capable and motivated for Movapo Pen to be used effectively. Adult patients through all age ranges have been successfully managed with apomorphine injections. Movapo Pen is contraindicated in children and adolescents up to 18 years of age (see Section 4.3 Contraindications).
The elderly are well represented in the population of patients with Parkinson's disease and constitute a high proportion of those studied in clinical trials of apomorphine. The management of elderly patients treated with apomorphine has not differed from that of younger patients, except for the extra caution on commencing therapy, because of the risk of postural hypotension.
Patients who have shown a good 'on' period response during the initiation stage of apomorphine therapy, but whose overall control remains unsatisfactory using intermittent injections, or who require many and frequent injections, may be commenced on or transferred to continuous subcutaneous infusion by minipump and/or syringe driver.
The practical steps described below should be followed when commencing a patient on treatment:
pre-treat with domperidone;
discontinue all existing antiparkinsonian medication to provoke an 'off' phase in motor performance;
determine the threshold dose response to Movapo Pen that produces an unequivocal motor response;
re-establish other antiparkinsonian agents;
determine effective treatment regimen for Movapo Pen;
teach patient and/or carer how and when to administer;
discharge from hospital;
monitor frequently and adjust dosage regimen as appropriate;
full instructions are given below.

Pretreatment.

Domperidone is a peripherally acting dopamine receptor antagonist given by mouth to prevent nausea and vomiting. Domperidone is commenced 48 - 72 hours prior to the first dose of Movapo Pen. When patients are stabilised with respect to dosage of apomorphine, the dose of domperidone is reduced by 10 mg per day every week until mild nausea appears. The maintenance dose of domperidone is the lowest level which completely prevents nausea. Domperidone can usually be withdrawn after several weeks. Before the decision to initiate domperidone and apomorphine treatment, risk factors for QT interval prolongation in the individual patient should be carefully assessed to ensure that the benefit outweighs the risk (see Section 4.4 Special Warnings and Precautions for Use). The cardiovascular assessment should include an ECG and QT measurement. Patients with severe renal insufficiency will require the dosing interval of domperidone to be changed from three times a day to once or twice a day.
For further information regarding domperidone refer to the product information.

Provoking and assessing an 'off' phase.

After at least 3 days of hospitalisation, all antiparkinsonian therapy is withheld overnight to provoke an 'off' phase in motor performance and to undertake a baseline motor assessment as follows:
(a) Alternate, unilateral hand tapping for 30 seconds on mounted digital counters (preferably 20 cm apart).
(b) Time taken to walk 12 metres.
(c) Clinical assessment of tremor and dyskinesia according to a four point scale (0 = nil, 1 = mild, 2 = moderate, 3 = severe).
(d) Scoring on a modified Webster disability scale to assess 12 features of parkinsonism (maximum disability score of 36).

Determination of the threshold dose.

Following baseline motor assessment, the patient is challenged for Movapo Pen responsiveness according to the following schedule:
1.0 mg Movapo Pen (0.1 mL) is injected subcutaneously and the patient is observed over 30 minutes for motor responsiveness.
If no or poor response is obtained, a second dose of 3 mg Movapo Pen (0.3 mL) is given 40 minutes after the first dose, and the patient observed for a further 30 minutes.
The dosage is increased in an incremental fashion every 40 minutes and the patient observed carefully for an unequivocal motor response. The third dose is 5 mg SC, and the fourth dose is 7 mg SC. If the patient shows no response to the 7 mg dose then the patient must be classified as a non-responder to Movapo Pen and no further attempts to provoke a motor response should be made. If the patient shows only a mild response to the 7 mg dose, a maximum dose of 10 mg can be used to see if an unequivocal motor response is possible.
The lowest dose producing an unequivocal motor response is called the threshold dose. For the majority of patients the threshold dose is less than 7 mg Movapo Pen (0.7 mL), although very occasionally it can be up to 10 mg Movapo Pen (1.0 mL).
Motor responsiveness is judged to be positive if 2 or more of the following are seen:
(a) More than 15% increase in tapping score.
(b) More than 25% improvement in walking time.
(c) An improvement of at least 2 points of tremor score.
(d) An improvement of Webster's score of 3 or more.

Initiation of treatment.

Following establishment of an acceptable threshold dose of Movapo Pen, the patient should be restarted on conventional antiparkinsonian therapy.
A subcutaneous injection of the established threshold dose may then be given into the lower abdomen or outer thigh at the first signs of an 'off' phase. The patient should then be observed over the following hour and the quality of their 'on' phase noted. It may be appropriate to modify the dose of Movapo Pen according to the patient's response.
Close monitoring of therapeutic benefits and adverse reactions under specialist supervision is required after initiation of treatment.
Movapo Pen is administered by the subcutaneous route by intermittent bolus injection. Intermittent injection is either into the anterior abdominal wall or anterolateral thigh. The usual dosage range is 2.0 to 4.0 mg per injection; the maximum single dose being 6 mg and the maximum total daily dose being 50 mg.
The intermittent injection is given in an undiluted form. For microbiological reasons, the pen injector used for intermittent injections should be used within 48 hours of first use.
Patients who have shown a good 'on' phase response during the initiation stage, but whose overall control remains unsatisfactory using intermittent injections, or who require many and frequent injections (e.g. 8-10 injections per day), may be commenced on or transferred to continuous subcutaneous infusion by minipump.

Monitoring treatment.

Long term specialist supervision of patients is advised.
There is a high probability of adverse effects to Movapo Pen therapy. The frequency and severity of adverse events should be monitored carefully at regular intervals and a reassessment of the patient carried out if appropriate. Adjustments to the dosage or discontinuation may be necessary.

Instructions for use and handling.

The product is for individual patient use only. Do not use if the solution has turned green.
Discard each pen no later than 48 hours from first use.

Important.

Do not pull the red capped dial before you have set the dosage (see 'Selecting the correct dose').
Attaching the needle. (a) Before using Movapo Pen you will need some surgical wipes and one needle in its protective cone.
(b) Take the pen out of its box and remove the outer sleeve.
(c) Wipe the membrane of the pen with a surgical wipe.
(d) Peel off the paper from the needle cone.
(e) It is important to bring the needle to the pen in a straight line. If the needle is presented at an angle it may cause the pen to leak.
(f) Screw the cone clockwise onto the membrane until it is tight. This securely attaches the needle.
(g) Remove the protective cone, but do not throw it away. Do not remove the needle protector at this stage.
(h) Replace the pen's outer sleeve.
Selecting the correct dose. (i) Press the red capped dosage dial and whilst holding it down, turn the dial clockwise until the arrow points to the dose your doctor chose for you. Release the downward pressure on the red capped dial. The dose is now set and you do not need to redial for subsequent injections.

Important.

If you pass your prescribed dose while turning the dial, just continue pressing and turning in the same direction until the arrow points to the dose your doctor chose for you. Never pull and turn the red capped dosage dial at the same time.
If your dose is 1 mg, start by emptying a 1 mg dose onto a paper tissue and discarding it. This is called 'priming' and is important because it ensures you get a full dose the first time you use your pen. Then, set the dose you require for injection and inject it in the usual way (see "Injecting"). If the first dose required is more than 1 mg, you do not need to prime the pen.
Injecting. (j) Once you have set the dose, gently pull out the red capped dosage dial as far as it will go. Check the red scale on the plunger and inject only if the line that is just visible matches the intended dose.
(k) Using a surgical wipe, clean the area of skin where you plan to inject the medicine and around it.
(l) Remove the pen's outer sleeve.
(m) Remove the needle protector.
(n) Insert the needle into the skin as shown by your doctor.
(o) To inject, press the red capped dosage dial down as far as it will go, using your thumb if possible. Once the red capped dosage dial is fully depressed, count to three before withdrawing the needle.
(p) Replace the protective cone onto the used needle and push gently into place. Once secure, turn the needle anti-clockwise to unscrew it. Keep the needle in its protective cone and discard it in a "Sharps" container.
Preparing for the next injection. (q) Remove the outer sleeve of the pen and check there is enough apomorphine left in the cartridge for your next injection. If there is, put a new needle in place in the same way as before.
(r) If there is not enough apomorphine left for another injection, prepare another pen.
(s) Finally, replace the outer sleeve of your pen.

4.3 Contraindications

Movapo Pen is contraindicated in patients with a known hypersensitivity or allergy to apomorphine, morphine or chemically related products.
Movapo Pen 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.
Movapo Pen is also contraindicated in patients with inadequate renal or liver function, unstable coronary vascular disease, cerebrovascular disease, respiratory depression or CNS depression.
Movapo Pen is contraindicated for children and adolescents under 18 years of age.
Movapo Pen is contraindicated in patients with a known hypersensitivity to sodium metabisulfite.
Concomitant use with 5HT3 antagonists including antiemetics (for example ondansetron, granisetron, palonosetron) is contraindicated (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

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 Movapo Pen. Movapo Pen 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).
Movapo Pen contains sodium metabisulfite which may cause allergic type reactions, including anaphylactic symptoms and life threatening or less severe asthmatic episodes in susceptible people (see Section 4.3 Contraindications).
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 Movapo Pen 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 to areas of nodularity and induration (see Section 4.8 Adverse Effects (Undesirable Effects)).
Haemolytic anaemia and thrombocytopenia have been reported in patients treated with apomorphine. Haematology tests should be undertaken at regular intervals as with levodopa, when given concomitantly with apomorphine.
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.
Apomorphine has been associated with somnolence and episodes of sudden sleep onset, 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.
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 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).

Neuroleptic malignant syndrome.

Symptoms suggestive of neuroleptic malignant syndrome (characterised by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability) have been reported with abrupt withdrawal of dopaminergic therapy. Therefore, it is recommended to taper treatment (see Section 4.2 Dose and Method of Administration).

Dopamine agonist withdrawal syndrome.

Symptoms suggestive of dopamine agonist withdrawal syndrome (for example, apathy, anxiety, depression, fatigue, sweating, and pain) have been reported with abrupt withdrawal of dopaminergic therapy, therefore, it is recommended to taper treatment (see Section 4.2 Dose and Method of Administration).

Impulse control disorders.

Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including apomorphine. Dose reduction/tapered discontinuation should be considered if such symptoms develop.
Dopamine dysregulation syndrome (DDS) is an addictive disorder resulting in excessive use of Movapo Pen seen in some patients treated with apomorphine. Before initiation of treatment, patients and caregivers should be warned of the potential risk of developing DDS.

Use in debilitated patients.

Extra caution is also recommended in debilitated patients, since they may show an increased susceptibility or be more sensitive to the respiratory depressant effects of apomorphine.

Use in the elderly.

Extra caution is also recommended in geriatric patients, since they may show an increased susceptibility or be more sensitive to the respiratory depressant effects of apomorphine. Extra caution is recommended during initiation of therapy in elderly patients because of the risk of postural hypotension.

Paediatric use.

Movapo Pen is contraindicated for children and adolescents under 18 years of age.

Effects on laboratory tests.

Positive Coombs' tests have been reported for patients receiving apomorphine.

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.
Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, the concomitant use of apomorphine with 5HT3 antagonists including antiemetics (for example ondansetron, granisetron, palonosetron) is contraindicated (see Section 4.3 Contraindications).

Antihypertensive and cardiac active medicinal drugs.

Even when co-administered with domperidone, apomorphine may potentiate the antihypertensive effects of antihypertensive and cardiac active medicinal products.
It is recommended to avoid the administration of apomorphine with other drugs known to prolong the QT interval.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In a fertility study in male rats, fertility was decreased at 2 mg/kg/day SC, one tenth that of the maximum recommended human dose (based on body surface area). Effects on female fertility have not been determined.
(Category B3)
The safety of using apomorphine during pregnancy has not been established in either human or animal studies. Movapo Pen should therefore not be used in pregnant women, or those likely to become pregnant.
It is not known whether apomorphine is excreted in breast milk although problems in humans have not been documented. Nevertheless, because many drugs are excreted in human milk and because of the potential for serious adverse drug reactions due to apomorphine in breastfed infants, a decision should be made either to discontinue breastfeeding or the drug, taking into account the importance of the drug to the mother.

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%).

Most patients experience injection site reactions, particularly with continuous use. These may include subcutaneous nodules, induration (see Section 4.4 Special Warnings and Precautions for Use), erythema, tenderness and panniculitis. Various other local reactions (such as irritation, itching, bruising, fibrosis and pain) may also occur (see Section 4.4 Special Warnings and Precautions for Use). Care should be taken to ensure that areas of ulceration do not become infected.
Hallucinations have been reported.

Common (1-10%).

Gastrointestinal side effects including nausea and vomiting appear to be the most prevalent adverse effects, however tolerance to these effects develops rapidly. Pre-treatment with domperidone may reduce or prevent these effects (see Section 4.2 Dose and Method of Administration).
Apomorphine is associated with somnolence. Drowsiness and sedation occur in most patients on initial treatment but these effects largely subside with repeated dosing, although in some patients these effects may persist. Tachyphylaxis to postural related faintness or syncope also occurs rapidly.
Neuropsychiatric disturbances (including confusion and visual hallucinations) have occurred during apomorphine therapy.
Yawning has been reported during apomorphine therapy.

Uncommon (0.1-1%).

Apomorphine may induce dyskinesias during 'on' periods, which can be severe in some cases, and in a few patients may result in cessation of therapy. Apomorphine has been associated with sudden sleep onset episodes (see Section 4.4 Special Warnings and Precautions for Use).
Postural hypotension is seen infrequently and is usually transient (see Section 4.4 Special Warnings and Precautions for Use).
Breathing difficulties have been reported.
Local and generalised rashes have been reported. Injection site necrosis and ulceration have been reported.
Haemolytic anaemia and thrombocytopenia have been reported in patients treated with apomorphine.

Rare (0.01-0.1%).

Eosinophilia has rarely occurred during treatment with apomorphine.
Due to the presence of sodium metabisulfite, allergic reactions (including anaphylaxis and bronchospasm) may occur.

Not known (cannot be estimated from available data).

Impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including apomorphine (see Section 4.4 Special Warnings and Precautions for Use).
Aggression and agitation have also been reported.
Headache has been reported.
Peripheral oedema has been reported.
Dopamine agonist withdrawal syndrome (apathy, anxiety, depression, fatigue, sweating and pain), see Section 4.4 Special Warnings and Precautions for Use.
Neuroleptic malignant syndrome (see Section 4.4 Special Warnings and Precautions for Use).
Other adverse reactions to apomorphine that have been reported infrequently include transient rises in serum prolactin, stomatitis, transient metallic taste, rhinorrhoea, increased lacrimation, reduced facial hair growth, loss of libido and spontaneous penile erection.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

Symptoms.

The clinical features of overdose of Movapo Pen are an extension of the pharmacological effects of the drug. They include nausea and persistent vomiting, dyskinesias, hypotension and acute circulatory failure, cardiac arrest, respiratory depression, drowsiness and central nervous system depression or stimulation, euphoria, restlessness and hallucinations and possibly coma and death.
Concomitant use of domperidone may exacerbate the clinical features of overdose.

Treatment.

An opioid antagonist such as naloxone may be given to treat excessive vomiting, central nervous system depression and respiratory depression due to Movapo Pen overdose. Excessive vomiting may also be treated with domperidone. Atropine may be also used to treat bradycardia. To treat hypotension, appropriate measures should be taken e.g. raising the foot of the bed.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Apomorphine is a directly acting dopamine receptor agonist, structurally related to dopamine. Apomorphine has high in vitro binding affinity for the dopamine D4 and D5 receptor (Ki: 4 and 14 nanoM respectively), moderate affinity (Ki: 26 to 130 nanoM) for the dopamine D2 and D3, adrenergic α1D, α2B, α2C receptors, serotonin 5HT1A, 5HT2A, 5HT2B, and 5HT2C receptors and low affinity for the dopamine D1 receptor (Ki: 370 nanoM). Apomorphine exhibits no affinity for the adrenergic β1 and β2 or histamine H1 receptors.
The effect of apomorphine as an antiparkinsonian agent is believed to be the result of direct stimulation of postsynaptic D2 dopamine receptors, but stimulation of presynaptic D2 dopamine receptors and antagonism of α2 adrenergic receptors may also be important. Apomorphine reduces the tremor, rigidity and bradykinesia in patients receiving levodopa. Apomorphine induces vomiting by direct stimulation of the medullary chemoreceptor trigger zone.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

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

Absorption.

Following intramuscular or subcutaneous administration, apomorphine is reported to be well absorbed. Peak plasma concentration occurs as early as three minutes following subcutaneous bolus injection. The rapid and complete absorption from subcutaneous tissues and rapid clearance is believed to correlate with the rapid onset and brief duration of action respectively. Antiparkinsonian effects are observed within five minutes following subcutaneous bolus administration.

Distribution.

The distribution half-life of apomorphine was found to be five minutes. The volume of distribution, plasma clearance and half-life were similar for subcutaneous injection, subcutaneous infusion and intravenous infusion.
Apomorphine reaches a concentration in the brain up to eight times higher than that in plasma, due to high lipid solubility which allows rapid equilibration between blood and tissue compartments.

Metabolism.

Apomorphine is metabolised in the liver. Routes of metabolism in humans include sulfation, N-demethylation, glucuronidation and oxidation to norapomorphine by CYP 2B6, CYP 2C8 and CYP 3A4. The major metabolite in humans after sublingual administration was apomorphine sulfate.

Excretion.

Apomorphine is cleared rapidly. The elimination half-life (t1/2) is about 33 minutes.

5.3 Preclinical Safety Data

Genotoxicity.

In vitro genotoxicity studies demonstrated mutagenic and clastogenic effects, most likely due to products formed by oxidation of apomorphine. Apomorphine was not genotoxic in vivo in a mouse micronucleus test or in a rat unscheduled DNA synthesis test.

Carcinogenicity.

No carcinogenicity studies have been performed.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium metabisulfite.
Water for injections.
Hydrochloric acid may also be included in the formulation to adjust the pH. The pH of the injection is 2.5 to 4.0.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

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.
For microbiological reasons, the pen injector used for intermittent injections should be used within 48 hours of first use.

6.4 Special Precautions for Storage

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

6.5 Nature and Contents of Container

Movapo Pen, apomorphine hydrochloride hemihydrate 30 mg/3 mL is a disposable multiple dose pen injector system incorporating a clear glass (type I) cartridge containing a clear solution for injection. The glass cartridge is sealed at one end with a bromobutyl rubber piston, and at the other end with a bromobutyl rubber/aluminium membrane.
Each cartridge contains 3 mL of solution for injection.
Packs contain 5 x 3 mL pens in a moulded plastic tray in an outer cardboard carton.

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

Chemical structure.


CAS number.

The CAS registry number of apomorphine hydrochloride hemihydrate is 41372-20-7.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes