Apomorphine hydrochloride 5mg/ml solution for infusion

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
Apomorphine hydrochloride hemihydrate
Available from:
Pharmaceuticals Sales & Development Sweden AB (PharmSwed)
ATC code:
N04BC; N04BC07
INN (International Name):
Apomorphine hydrochloride hemihydrate
Dosage:
5 milligram(s)/millilitre
Pharmaceutical form:
Solution for infusion
Prescription type:
Product subject to prescription which may not be renewed (A)
Therapeutic area:
Dopamine agonists; apomorphine
Authorization status:
Not marketed
Authorization number:
PA1807/001/001
Authorization date:
2012-10-26

Package leaflet: Information for the user

Apomorphine hydrochloride 5 mg/ml, solution for infusion

apomorphine hydrochloride hemihydrate

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

important information for you.

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

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

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

even if their signs of illness are the same as yours.

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

effects not listed in this leaflet. See section 4.

What is in this leaflet

What Apomorphine hydrochloride is and what it is used for

What you need to know before you use Apomorphine hydrochloride

How to use Apomorphine hydrochloride

Possible side effects

How to store Apomorphine hydrochloride

Contents of the pack and other information

1.

What Apomorphine hydrochloride is and what it is used for

Apomorphine hydrochloride belongs to a group of medicines known as dopamine agonists which are

used to treat Parkinson’s disease. It helps to reduce the amount of time spent in an “off” or immobile

state in people who have previously been treated for Parkinson’s disease with levodopa and/or other

dopamine agonists.

Your doctor or nurse will help you to recognise the signs of when to use your medicine.

2.

What you need to know before you use Apomorphine hydrochloride

Do not use Apomorphine hydrochloride:

if you are allergic to apomorphine or any of the other ingredients of this medicine (listed in

section 6)

if you are under 18 years of age

if you have breathing difficulties or suffer from asthma

if you have dementia or Alzheimer’s disease

- if you suffer from confusion, hallucinations or any other similar problems

if you have liver problems

if you have severe overmobility, so called dyskinesia (involuntary movements), or abnormal

muscle tension (so called dystonia) on account of the treatment with levodopa

Warnings and precautions

Talk to your doctor before using Apomorphine hydrochloride

if you or someone in your family are known to have an abnormality of electrocardiogram

(ECG) called “long QT syndrome”.

if you have kidney problems

if you have lung problems

if you have heart problems

if you have low blood pressure or feel faint and dizzy when you stand

if you are taking any medicines to treat high blood pressure

if you feel sick or suffer from being sick

if you are elderly or weak

if you have any mental disorders when Apomorphine hydrochloride is started

if you are taking levodopa (another treatment for Parkinson’s disease) as well as apomorphine

your doctor should check your blood regularly.

Before you use Apomorphine hydrochloride, your doctor will obtain an ECG (electrocardiogram) and

will ask for a list of all other 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. 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,

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.

Tell your doctor if you or your family/carer notices that you are developing urges or cravings to

behave in ways that are unusual for you and you cannot resist the impulse, drive or temptation to carry

out certain activities that could harm yourself or others. These are called impulse control disorders

and can include behaviours such as addictive gambling, excessive eating or spending, an abnormally

high sex drive or an increase in sexual thoughts or feelings. Your doctor may need to adjust or stop

your dose.

Some patients develop addiction-like symptoms leading to craving for large doses of Apomorphine

hydrochloride and other medicines used to treat Parkinson’s disease.

If any of the above situations apply to you, please inform your doctor or nurse.

Other medicines and Apomorphine hydrochloride

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

medicines.

If you take Apomorphine hydrochloride in combination with other medicines (such as clozapine or

medicines to reduce your blood pressure or medicines for Parkinson’s disease) the effect of your

medicines may be altered. Your doctor will advise you if you need to adjust the dose of Apomorphine

hydrochloride or any of your other medicines.

Talk to your doctor or pharmacist before you use this medicine if:

You use medicines that are known to affect how your heart beats. This includes medicines that are

used for heart rythm problems (such as quinidine and amiodarone), for depression (e.g. tricyclic

antidepressants such as amitriptyline and imipramine) and for bacterial infections (“macrolid

antibiotics” such as erythromycine, azithromycine and clarithromycine) and domperidone.

Apomorphine hydrochloride with food and drink

Food and drink do not affect Apomorphine hydrochloride.

Pregnancy and breast-feeding

Pregnancy

Apomorphine hydrochloride should not be used during pregnancy if it is not absolutely necessary.

Ask your doctor or nurse for advise before you use Apomorphine hydrochloride if you are pregnant,

think you may be pregnant or you are planning to become pregnant.

Breast-feeding

It is not known if Apomorphine hydrochloride is excreted in breast milk. Talk to your doctor if you

are breast-feeding or plan to breast-feed. Your doctor will explain to you if you should

continue/discontinue breast-feeding or continue/discontinue medication.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask

your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

Take special care when driving or operating machinery since apomorphine may cause sleepiness

including sudden sleep onset episodes (you must not drive or operate machinery if Apomorphine

hydrochloride makes you sleepy.)

Apomorphine hydrochloride contains sodium metabisulfite

Sodium metabisulfite may rarely cause severe hypersensitivity reactions and bronchospasm.

This medicinal product contains 3.3 mg sodium per ml. To be taken into consideration by

patients on a controlled sodium diet.

3.

How to use Apomorphine hydrochloride

Before you use Apomorphine hydrochloride, your doctor will ensure that you tolerate the medicine

and an antiemetic medicine that you need to use simultaneously.

The infusion is given subcutaneously (i.e. into the area under the skin).

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

or pharmacist if you are not sure.

Apomorphine hydrochloride has been designed for continuous infusion with an infusion pump. Your

doctor will decide which infusion pump and which dosage settings you should use. Follow the

instructions and advice given by your doctor how to use Apomorphine hydrochloride in an infusion

pump. Read the instruction leaflet for the infusion pump and follow it carefully.

Both the amount of Apomorphine hydrochloride that you should use and the total amount of time you

should receive your medicine each day, will depend upon your personal needs. Your doctor will tell

you how much of your medicine you should administer.

The dose that will work best for you have been determined on an initial evaluation at a specialist

clinic. Usual infusion dose per hour is between 1 mg and 4 mg apomorphine hydrochloride. This is

usually given when you are awake and generally stopped before sleeping. The amount of apomorphine

hydrochloride that you receive each day should not exceed 100 mg. Your doctor or nurse will decide

which dose is best for you.

A different site for your infusion should be used every 12 hours.

This medicine must not be administered into a vein. There is no need to dilute Apomorphine

hydrochloride before use. Apomorphine hydrochloride should not be mixed with other medicines.

Instructions for how to use Apomorphine hydrochloride

Clean the rubber stopper with a disinfectant swab

Insert the needle of the syringe into the vial through the centre of the rubber stopper

Turn the vial and syringe upside down

Draw the desired volume from the vial into the syringe

Remove the needle from the vial

Follow thereafter carefully the instructions that accompany your infusion pump

The treatment will be started by your doctor who will inform you thoroughly about how to use the

infusion pump, infusion technique and handling for administration of the medicine.

If you use more Apomorphine hydrochloride than you should

if you have received too much medicine or if e.g. a child has received the medicine by mistake

contact immediately doctor or hospital for risk evaluation and advice.

it is important to use the correct dose of Apomorphine hydrochloride and not to use more than the

amount recommended by your doctor. Higher doses may cause a slow heart rate, excessive

sickness, excessive sleepiness and/or difficulty breathing. You may also feel faint or dizzy

particularly when you stand up, due to low blood pressure. Lying down and raising your feet will

help to treat low blood pressure.

If you forget to use Apomorphine hydrochloride

take it when you next require it

do not take a double dose to make up for a forgotten dose

If you stop using Apomorphine hydrochloride

contact your doctor before stopping treatment and discuss whether this is appropriate or not.

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

4.

Possible side effects

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

doctor if you think your medicine is making you feel unwell or if you get any of the following:

Serious side effects:

An allergic reaction which may be serious may rarely occur, with symptoms such as:

difficulty breathing or tightness of the chest

puffiness of the eyelids, face or lips

swelling or redness of the tongue

Other side effects:

Very common (may affect more than 1 in 10 people)

hallucinations (seeing, hearing or feeling things that are not there), lumps under the skin at the site

of injection which are sore, troublesome and may be red and itchy. In order to avoid getting these

lumps, it is advisable to change the site of injection every time you insert the needle.

Common (may affect up to 1 in 10 people)

feeling sick or being sick, particularly when starting Apomorphine hydrochloride. Domperidone

should be started at least 2 days before Apomorphine hydrochloride to stop you feeling or being

sick. If you are taking domperidone and still feel sick, or if you are not taking domperidone and

have sickness, tell your doctor or nurse as soon as possible.

transient tiredness with each dose of Apomorphine hydrochloride at the start of therapy. This

usually resolves over the first few weeks of treatment.

feeling tired or excessive sleepiness

dizziness, light-headedness

confusion or hallucinations

yawning

Uncommon (may affect up to 1 in 100 people)

increased involuntary movements (so called dyskinesia, overmobility) or increased shakiness

during “on” periods (i.e. when the medicine is working).

haemolytic anaemia, abnormal degradation of red blood cells in vessels or in other parts of the

body, which can turn the skin weakly yellow and cause weakness and breathlessness, may occur

in patients also taking levodopa.

rashes

shortness of breath

a fall in blood pressure on standing up which causes dizziness, light-headedness or fainting

ulceration at the injection site

decreased count of platelets, which can increase the risk for bleeding and bruises.

the use of levodopa and apomorphine may affect the result of a certain laboratory test, called

Coombs test.

Rare (may affect up to 1 in 1,000 people)

eosinophilia, an unusually high count of white blood cells in the blood or tissues.

Not known: frequency cannot be estimated from the available data

fainting

swelling of legs, feet or fingers

inability to resist the impulse, drive or temptation to perform an action that could be harmful to

you or others, which may include:

strong impulse to gamble excessively despite serious personal or family consequences.

altered or increased sexual interest and behaviour of significant concern to you or to others,

for example, an increased sexual drive

uncontrollable excessive shopping or spending

binge eating (eating large amounts of food in a short time period) or compulsive eating (eating

more food than normal and more than is needed to satisfy your hunger)

aggression

agitation

Tell your doctor if you experience any of these behaviours; they will discuss ways of managing or

reducing the symptoms

Reporting of side effects

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

not listed in this leaflet. You can also report side effects directly via HPRA Pharmacovigilance,

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

www.hpra.ie; E-mail: medsafety@hpra.ie. By reporting side effects you can help provide more

information on the safety of this medicine.

5.

How to store Apomorphine hydrochloride

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

Do not use this medicine after the expiry date which is stated on the carton and vial label after EXP.

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

Keep the vial in the outer carton in order to protect from light.

Do not store above 25 ºC.

Once opened the vial should be used immediately. For single use only.

The product may be kept in the minipump and/or syringe pump and administered during/up to 24

hours without limitation of storage temperature. Other in-use storage times and conditions are the

responsibility of the user.

Discard any unused solution.

The solution should be inspected visually prior to use. Do not use Apomorphine hydrochloride if the

solution has turned green. Apomorphine hydrochloride should only be used if the solution is clear and

free of any visible particles.

Take care not to splash any of the solution onto yourself, or e.g. on textiles or household surfaces

since the solution may cause green discolouring. Any used needles and the vial should be discarded in

a sharp’s bin.

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

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

6.

Contents of the pack and other information

What Apomorphine hydrochloride contains

The active substance is apomorphine hydrochloride hemihydrate. 1 ml contains 5 mg

apomorphine hydrochloride hemihydrate. One vial with 20 ml solution contains 100 mg

apomorphine hydrochloride hemihydrate.

The other ingredients are:

Sodium chloride

Sodium metabisulfite (E223)

Hydrochloric acid for pH adjustment

Water for injections

What Apomorphine hydrochloride looks like and contents of the pack

Apomorphine hydrochloride is a solution for infusion. The solution is clear and practically colourless.

Apomorphine hydrochloride is supplied in glass vials

with bromobutyl rubber stoppers and

aluminium caps

. Each pack contains 5 vials with 20 ml (5x20).

Marketing Authorisation Holder:

Pharmaceuticals Sales & Development Sweden AB

Tullvaktsvägen 2

115 56 Stockholm

Sweden

Manufacturer:

Apotek Produktion och Laboratorier AB (APL)

Box 3076

903 03 Umeå

Sweden

This medicinal product is authorised in the Member States of the EEA under the following

names:

Sweden

Apomorfin PharmSwed

Denmark

Apomorfin PharmSwed

Norway

Apomorfin PharmSwed

Iceland

Apomorfin PharmSwed

Netherlands

Apomorfine hydrochloride PharmSwed 5 mg/ml, oplossing voor infusie

Germany

Apomorphinhydrochlorid PharmSwed 5 mg/ml Infusionslösung

Apomorphine hydrochloride 5 mg/ml solution for infusion

Ireland

Apomorphine hydrochloride 5 mg/ml solution for infusion

This leaflet was last revised in July 2019

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Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Apomorphine hydrochloride 5mg/ml solution for infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml contains 5 mg apomorphine hydrochloride hemihydrate.

One 20 ml vial contains 100 mg apomorphine hydrochloride hemihydrate.

Excipient with known effect: Sodium metabisulfite 1 mg per ml.

Contains sodium 3.3mg per ml.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Solution for infusion

Clear and practically colourless solution

pH 2.6 – 4.0

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Treatment of motor fluctuations ('on-off' phenomena) in patients with Parkinson’s disease which are not sufficiently controlled

by oral anti-Parkinson medication.

4.2 Posology and method of administration

Posology

Patients Suitable for Apomorfin PharmSwed

Patients selected for treatment with Apomorfin PharmSwed be capable of inserting the needle s.c. themselves or else have a

responsible carer able to insert the needle s.c. for them when required.

Patients treated with apomorphine will usually need to start domperidone at least two days prior to initiation of therapy. The

domperidone dose should be titrated to the lowest effective dose and discontinued as soon as possible. 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).

Apomorphine treatment should be initiated in a controlled environment of a specialist clinic. The treatment should be

managed by a physician experienced in the treatment of Parkinson’s disease (e.g. neurologist). The patient’s treatment with

levodopa, with or without dopamine agonists, should be optimised before starting Apomorfin PharmSwed treatment.

Establishment of treatment

Alterations in dosage may be made according to the patient’s response.

The optimal dosage of apomorphine hydrochloride varies between individuals but, once established, it remains relatively

constant for the individual patient.

Precautions on continuing treatment

The daily dose of Apomorfin PharmSwed varies widely between patients, typically within the range of 3-30 mg.

The total daily dose of apomorphine hydrochloride should not exceed 100 mg.

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In clinical studies it has usually been possible to make a slight reduction in the dose of levodopa. This varies however

considerably between patients and must be carefully managed by an experienced physician.

Once treatment has been established domperidone therapy may be gradually reduced in some patients. Only in a few patients

domperidone may be completely discontinued without any vomiting or hypotension as a result.

Paediatric population

Apomorfin PharmSwed 5 mg/ml, solution for infusion, is contra-indicated for children and adolescents under 18 years of age

(see Section 4.3).

Elderly

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 hydrochloride. The treatment with apomorphine hydrochloride has been the

same in elderly and younger patients. Special caution is however recommended during initiation of therapy in elderly patients

due to the risk of postural hypotension.

Renal impairment

A dose schedule similar to that recommended for adults and the elderly can be followed for patients with renal impairment

(see Section 4.4).

Method of administration

Apomorfin PharmSwed 5 mg/ml, solution for infusion, is intended for use without dilution as a continuous subcutaneous

infusion by minipump and / or syringe pump (infusion pump).

Apomorphine must not be used via the intravenous route.

Do not use if the solution has turned green. The solution should be visually inspected prior to use. Only clear and particle free

solutions should be used. See Section 6.6.

Continuous Infusion

Patients who have shown a good ‘on period’ response during an initial apomorphine injection, but whose overall control

remains unsatisfactory using intermittent injections, or who require many and frequent injections (more than 10 per day), may

be commenced on or transferred to continuous subcutaneous infusion by minipump and / or syringe pump as follows:

The choice of which minipump and / or syringe pump to use, and dosage settings required will be determined by the physician

in accordance with the particular needs of the patient.

The threshold dose for continuous infusion should be determined as follows:

Continuous infusion is started at a rate of 1 mg apomorphine hydrochloride (0.2 ml) per hour. The dose can thereafter be

increased according to the patient’s response during that particular day. Increases in the infusion rate should not exceed 0.5

mg at intervals of not less than 4 hours. Hourly infusion rates may range between 1 mg and 4 mg (0.2 ml and 0.8 ml),

equivalent to 0.014 - 0.06 mg/kg/hour. Infusions should run for waking hours only. Unless the patient is experiencing severe

night-time problems, 24 hour infusions are not recommended. Tolerance to the therapy does not seem to occur as long as

there is an overnight period without treatment of at least 4 hours. The infusion site should be changed every 12 hours.

Where appropriate and as advised by a physician, the continuous infusion may need to be supplemented with intermittent

bolus doses.

A reduction in dosage of other dopamine agonists may be considered during continuous infusion treatment.

4.3 Contraindications

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

Respiratory depression, dementia, psychotic diseases or hepatic insufficiency.

Apomorphine hydrochloride treatment must not be administered to patients who develop severe dyskinesia or dystonia as

response to levodopa.

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Apomorfin PharmSwed must not be given to children and adolescents under 18 years of age.

4.4 Special warnings and precautions for use

Apomorphine hydrochloride should be given with caution to patients with renal, pulmonary or cardiovascular disease and

persons prone to nausea and vomiting.

Special caution is recommended during initiation of therapy in elderly and/or debilitated patients.

Since apomorphine may produce hypotension, even when given with domperidone, care should be exercised in patients with

cardiac disease or in patients taking vasoactive medicinal products such as antihypertensives, and especially in patients with a

history of postural hypotension.

Since apomorphine, especially at high dose, 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 reactions. These may sometimes be reduced by switching injection site or

possibly by using ultra-sound (if this is available) on areas with nodularity and induration.

Haemolytic anaemia has been reported in patients treated with levodopa and 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).

Neuropyschiatric 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 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 must refrain from driving or operating machines. Furthermore a

reduction of dosage or termination of therapy may be considered.

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 and hyper

sexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine

agonists including Apomorfin PharmSwed. Dose reduction/tapered discontinuation should be considered if such symptoms

develop.

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Dopamine dysregulation Syndrome (DDS) is an addictive disorder resulting in excessive use of the product seen in some

patients treated with apomorphine. Before initiation of treatment, patients and caregivers should be warned of the potential

risk of developing DDS.

Apomorfin PharmSwed 5 mg/ml, solution for infusion, contains sodium metabisulfite which may rarely cause severe

hypersensitivity reactions and bronchospasm.

This medicinal product contains 3.3 mg sodium per ml. To be taken into consideration by patients on a controlled sodium diet.

4.5 Interaction with other medicinal products and other forms of interactions

Patients selected for treatment with apomorphine hydrochloride are almost certain to be taking concomitant medicinal

products for their Parkinson’s disease. In the initial stages of apomorphine hydrochloride therapy the patient should be

monitored for unusual undesirable effects or signs of potentiation of effect.

Neuroleptic medicinal products may have an antagonistic effect if used with apomorphine.

There is a potential interaction between clozapine and apomorphine. Clozapine may however also be used to reduce the

symptoms of neuropsychiatric complications.

If neuroleptics have to be used in patients with Parkinson’s disease treated by dopamine agonists, a gradual reduction in

apomorphine dose may be considered when administration is by minipump and / or syringe pump (symptoms suggestive of

neuroleptic malignant syndrome have been reported rarely with abrupt withdrawal of dopaminergic therapy).

The possible effects of apomorphine on the plasma concentrations of other medicinal products have not 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 products

Even when co-administered with domperidone, apomorphine may potentiate the antihypertensive effects of these medicinal

products (see Section 4.4).

It is recommended to avoid the administration of apomorphine with other drugs known to prolong the QT interval.

4.6 Fertility, pregnancy and lactation

Pregnancy

There is no experience of apomorphine usage in pregnant women.

Reproduction studies in animals do not indicate any teratogenic effect, but in rats, dosages that are toxic to the mother may

cause respiratory failure in the newborn offspring. The potential risk for humans is unknown. Apomorfin PharmSwed should

therefore be used during pregnancy only when considered absolutely necessary.

Breast-feeding

It is not known whether apomorphine is excreted in breast milk. Decision whether breast -feeding should be continued/

discontinued or if Apomorfin PharmSwed treatment should be continued/discontinued should be taken after consideration of

the advantages of breast-feeding the child and the advantages of Apomorfin PharmSwed treatment for the mother.

4.7 Effects on ability to drive and use machines

Apomorphine hydrochloride has minor or moderate influence on 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 (see also Section 4.4).

4.8 Undesirable effects

Very common (≥1/10)

Common (≥1/100 to <1/10)

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Uncommon (≥1/1,000 to <1/100)

Rare (≥1/10,000 to <1/1,000)

Very rare (<1/10,000)

Not known (cannot be estimated from the available data)

Blood and lymphatic system disorders

Uncommon

Rare

Haemolytic anaemia, thrombocytopenia

Eosinophilia

Immune system disorders

Rare

Allergic reactions due to the presence of sodium metabisulfite

(including anaphylaxis and bronchospasm)

Psychiatric disorders

Very common

Common

Not known

Hallucinations

Neuropsychiatric disturbances (including transient mild confusion and

visual hallucinations)

Impulse control disorders: pathological gambling, increased libido and

hyper sexuality, compulsive spending or buying, binge eating and

compulsive eating can occur in patients treated with dopamine agonists

including Apomorfin PharmSwed (see Section 4.4)

Aggression, agitation

Nervous system disorders

Common

Uncommon

Not known

Transient sedation with each dose of apomorphine hydrochloride at the

start of therapy may occur. This usually resolves over the first few weeks.

Somnolence.

Dizziness / lightheadedness

Apomorphine may induce dyskinesia during 'on periods', which can be

severe in some cases, and in a few patients may result in cessation of

therapy.

Syncope

Vascular disorders

Uncommon

Postural hypotension (see Section 4.4).

Respiratory, thoracic and mediastinal disorders

Common

Uncommon

Yawning

Breathing difficulties

Gastrointestinal disorders

Common

Nausea and vomiting, particularly when apomorphine treatment is first

initiated, usually as a result of not using domperidone (see Section 4.2).

Skin and subcutaneous tissue disorders

Uncommon

Local and generalised rash

General disorders and administration site conditions

Very common

Uncommon

Not known

In most patient's injection site reactions develop, particularly with

continuous use. These may include subcutaneous nodules, induration,

erythema, tenderness and panniculitus. A number of other local

reactions (such as irritation, pruritus, bruising and pain) may also occur.

Necrosis and ulceration at the injection site

Periferal edema

Investigations

Uncommon

Positive Coombs' tests for patients receiving levodopa and

apomorphine

Reporting of suspected adverse reactions

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Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued

monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected

adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517,

Website: www.hpra.ie, e-mail: medsafety@hpra.ie

4.9 Overdose

There is limited clinical experience of overdose with apomorphine by subcutaneous administration. Symptoms of overdose

may be treated empirically as suggested below:

Excessive emesis may be treated with domperidone.

Respiratory depression may be treated with naloxone.

Hypotension: appropriate measures should be taken, e.g. raising the foot of the bed.

Bradycardia may be treated with atropine.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Dopamine agonists, ATC code: N04BC07

Apomorphine is a direct stimulant of dopamine receptors. Even if it is possessing both D1 and D2 receptor agonist properties it

does not share transport or metabolic pathways with levodopa.

Although in intact experimental animals, administration of apomorphine suppresses the rate of firing of nigro-striatal cells and

in low dose has been found to produce a reduction in locomotor activity (thought to represent pre-synaptic inhibition of

endogenous dopamine release) its actions on parkinsonian motor disability are likely to be mediated at post-synaptic receptor

sites. This biphasic effect is also seen in humans.

5.2 Pharmacokinetic properties

After subcutaneous injection of apomorphine its pharmacokinetics can be described by a two-compartment model, with a

distribution half-life of 5 (±1.1) minutes and an elimination half-life of 33 (±3.9) minutes. Clinical response correlates well with

levels of apomorphine in the cerebrospinal fluid. Apomorphine is rapidly and completely absorbed from subcutaneous tissue,

correlating with the rapid onset of clinical effects (4-12 minutes). The brief duration of clinical action of apomorphine (about 1

hour) is explained by its rapid clearance. The metabolism of apomorphine is by glucuronidation and sulphonation to at least

ten per cent of the total; other pathways have not been described.

5.3 Preclinical safety data

Repeat dose subcutaneous toxicity studies reveal no special hazard for humans, beyond the information included in other

sections of the SmPC.

In vitro genotoxicity studies demonstrated mutagenic and clastogenic effects, most likely due to products formed by oxidation

of apomorphine. However, apomorphine was not genotoxic in in vivo studies.

The effect of apomorphine on reproduction has been studied in rats. Apomorphine was not teratogenic in this species, but it

was observed that toxic doses to the mother can result in impaired maternal attention and respiratory failure in the newborn

offspring.

No carcinogenicity studies have been performed.

Health Products Regulatory Authority

13 March 2020

CRN009DYX

Page 7 of 8

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium chloride

Sodium metabisulfite (E223)

Hydrochloric acid (for pH adjustment)

Water for Injections

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

2 years.

Once opened the vial must be used immediately.

From a microbiological point of view, once opened, the product should be used immediately. The product may be kept in the

minipump and / or syringe pump and administered during/up to 24 hours without limitation of storage temperature. Other

in-use storage times and conditions are the responsibility of the user.

6.4 Special precautions for storage

Keep in the outer carton in order to protect from light.

Do not store above 25 ºC.

For storage conditions after first opening of the medicinal product, see section 6.3.

6.5 Nature and contents of container

Vial (type I glass) with bromobutyl rubber stopper and aluminium cap.

1 pack contains 5 vials of 20 ml, stored in a cardboard box.

6.6 Special precautions for disposal and other handling

For single use only.

Do not use if the solution has turned green. The solution should be visually inspected prior to use. Only clear and particle free

solutions should be used. See Section 4.2.

After use, vials and syringes and any unused contents should be discarded.

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

7 MARKETING AUTHORISATION HOLDER

Pharmaceuticals Sales & Development Sweden AB (PharmSwed)

Tullvaktsvägen 2

115 56 Stockholm

Sweden

8 MARKETING AUTHORISATION NUMBER

PA1807/001/001

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Health Products Regulatory Authority

13 March 2020

CRN009DYX

Page 8 of 8

Date of first authorisation: 26

October 2012

Date of last renewal: 16

July 2015

10 DATE OF REVISION OF THE TEXT

March 2020

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