APO-GO PEN

Main information

  • Trade name:
  • APO-GO PEN
  • Available from:
  • Genus Pharmaceuticals Limited
  • Dosage:
  • 10 Mg/Ml
  • Pharmaceutical form:
  • Solution for Injection
  • Medicine type:
  • Human

Documents

Localization

  • Available in:
  • APO-GO PEN
    Ireland
  • Language:
  • English

Other information

Status

  • Source:
  • IMB
  • Authorization date:
  • 25-01-2010
  • Last update:
  • 23-04-2015

Summary of Product characteristics


Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

APO-go PEN 10 mg/ml Solution for Injection

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

1ml contains 10mg apomorphine hydrochloride

Excipients: Also contains sodium bisulphite 0.93 mg per ml.

For a full list of excipients see section 6.1

3 PHARMACEUTICAL FORM

Solution for injection.

Solution is clear and colourless.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

The treatment of disabling motor fluctuations (‘on-off’ phenomena) in patients with Parkinson’s disease which persist

despite individually titrated treatment with levodopa (with a peripheral decarboxylase inhibitor) and/or other dopamine

agonists.

4.2 Posology and method of administration

APO-go Pen 10 mg/ml Solution for Injection is for subcutaneous use by intermittent bolus injection. See section 4.4

Dosage

Adults

Administration

Selection of patients suitable for APO-go injections:

Patients selected for treatment with APO-go should be able to recognise the onset of their ‘off’ symptoms and be

capable of injecting themselves or else have a responsible carer able to inject for them when required.

It is essential that the patient is established on domperidone, usually 20 mg three times daily for at least two days

prior to initiation of therapy.

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

supervised by a physician experienced in the treatment of Parkinson’s disease (e.g. Neurologist). The patient’s

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Determination of the threshold dose.

The appropriate dose for each patient is established by incremental dosing schedules. The following schedule is

suggested:-

1mg of apomorphine HCl (0.1 ml), that is approximately 15-20 micrograms/kg, may be injected subcutaneously during

a hypokinetic, or ‘off’ period and the patient is observed over 30 minutes for a motor response.

If no response, or an inadequate response, is obtained a second dose of 2 mg of apomorphine HCl (0.2 ml) is injected

subcutaneously and the patient observed for an adequate response for a further 30 minutes.

The dosage may be increased by incremental injections with at least a forty minute interval between succeeding

injections, until a satisfactory motor response is obtained.

Establishment of treatment.

Once the appropriate dose is determined a single subcutaneous injection may be given into the lower abdomen or outer

thigh at the first signs of an ‘off’ episode. It cannot be excluded that absorption may differ with different injection sites

within a single individual. Accordingly, the patient should then be observed for the next hour to assess the quality of

their response to 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, remains relatively

constant for each patient.

Precautions on continuing treatment.

The daily dose of APO-go varies widely between patients, typically within the range of 3-30mg, given as 1-10

injections and sometimes as many as 12 separate injections per day.

It is recommended that the total daily dose of apomorphine HCl should not exceed 100 mg and that individual bolus

injections should not exceed 10 mg.

In clinical studies it has usually been possible to make some reduction in the dose of levodopa; this effect varies

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

Once treatment has been established domperidone therapy may be gradually reduced in some patients but successfully

eliminated only in a few, without any vomiting or hypotension.

Children and adolescents:

APO-go Pen 10mg/ml Solution for Injection is contra-indicated for children and adolescents under 18 years of age (see

section 4.3 Contraindications).

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 APO-go. The management of elderly patients treated with APO-go has not differed

from that of younger patients.

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 Special warnings and precautions for use).

4.3 Contraindications

In patients with respiratory depression, dementia, psychotic diseases or hepatic insufficiency.

Intermittent apomorphine HCl treatment is not suitable for patients who have an ‘on’ response to levodopa which is

marred by severe dyskinesia or dystonia.

APO-go should not be administered to patients who have a known hypersensitivity to apomorphine or any excipients of

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APO-go is contraindicated for children and adolescents under 18 years of age.

4.4 Special warnings and precautions for use

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

persons prone to nausea and vomiting.

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

Since apomorphine may produce hypotension, even when given with domperidone pretreatment, care should be

exercised in patients with pre-existing cardiac disease or in patients taking vasoactive medicinal products such as

antihypertensives, and especially in patients with pre-existing 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.

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) to areas of nodularity and induration.

APO-go Pen 10mg/ml Solution for Injection contains sodium bisulphite which may rarely cause severe allergic

reactions and bronchospasm.

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).

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 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.

Pathological gambling, increased libido and hypersexuality have been reported in patients treated with dopamine

agonists for Parkinson’s disease, including apomorphine.

This medicinal product contains less than 1 mmol sodium (23 mg) per 3ml, i.e. essentially “sodium-free”.

4.5 Interaction with other medicinal products and other forms of interaction

Patients selected for treatment with apomorphine HCl are almost certain to be taking concomitant medications for their

Parkinson’s disease. In the initial stages of apomorphine HCl therapy the patient should be monitored for unusual side-

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, however clozapine may also be used to reduce the symptoms of

neuropsychiatric complications.

The possible effects of apomorphine on the plasma concentrations of other drugs have not been studied. Therefore

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Antihypertensive and Cardiac Active Medicinal Drugs

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

drugs. (See section 4.4 Special warnings and precautions for use).

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

4.6 Fertility, pregnancy and lactation

There is no experience of apomorphine usage in pregnant women.

Animal reproduction studies do not indicate any teratogenic effects, but doses given to rats which are toxic to the

mother can lead to failure to breathe in the newborn. The potential risk for humans is unknown. See Section 5.3.

APO-go should not be used during pregnancy unless clearly necessary.

It is not known whether apomorphine is excreted in breast milk. A decision on whether to continue/discontinue

breastfeeding or to continue/discontinue therapy with APO-go should be made taking into account the benefit of breast-

feeding to the child and the benefit of APO-go to the woman.

4.7 Effects on ability to drive and use machines

Apomorphine may have a sedative effect and patients affected should not drive or operate machinery.

Patients being treated with apomorphine and presenting with somnolence 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 unless patients have overcome such experiences of somnolence (see also Section 4.4 Special

warnings and precautions for use).

4.8 Undesirable effects

Blood and lymphatic system disorders

Uncommon:

Haemolytic anaemia and thrombocytopenia have been reported in patients treated with apomorphine.

Rare:

Eosinophilia has rarely occurred during treatment with apomorphine HCl.

Immune system disorders

Rare:

Very common ( 1/10)

Common ( 1/100 to <1/10)

Uncommon ( 1/1,000 to <1/100)

Rare ( 1/10,000 to <1/1,000)

Very rare (<1/10,000)

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Psychiatric disorders

Common:

Neuropsychiatric disturbances are common in parkinsonian patients. APO-go should be used with special caution in

these patients. Neuropsychiatric disturbances (including transient mild confusion and visual hallucinations) have

occurred during apomorphine HCl therapy.

Not known:

Patients treated with dopamine agonists for treatment of Parkinson's disease, including apomorphine, especially at high

doses, have been reported as exhibiting signs of pathological gambling, increased libido and hypersexuality; generally

reversible upon reduction of the dose or treatment discontinuation.

Nervous system disorders

Common:

Transient sedation with each dose of apomorphine HCl at the start of therapy may occur; this usually resolves over the

first few weeks.

Apomorphine is associated with somnolence.

Dizziness / light-headedness have also been reported.

Uncommon:

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.

Vascular disorders

Uncommon:

Postural hypotension is seen infrequently and is usually transient (See Section 4.4).

Respiratory, thoracic and mediastinal disorders

Common:

Yawning has been reported during apomorphine therapy.

Uncommon:

Breathing difficulties have been reported.

Gastrointestinal disorders

Common:

Nausea and vomiting, particularly when apomorphine treatment is first initiated, usually as a result of the omission of

domperidone (See Section 4.2).

Skin and subcutaneous tissue disorders

Uncommon:

Local and generalised rashes have been reported.

General disorders and administration site conditions

Very common:

Most patients experience injection site reactions, particularly with continuous use. These may include subcutaneous

nodules, induration, erythema, tenderness and panniculitis. Various other local reactions (such as irritation, itching,

bruising and pain) may also occur.

Uncommon:

Injection site necrosis and ulceration have been reported.

Not known:

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Investigations

Uncommon:

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

4.9 Overdose

There is little clinical experience of overdose with apomorphine by this route of 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

Pharmatherapeutic group: Dopamine agonists

ATC Classification: N04B C07

Apomorphine is a direct stimulant of dopamine receptors and while possessing both D1 and D2 receptor agonist

properties 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 fate 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; the drug distribution being best described by a two- compartment

model. Apomorphine is rapidly and completely absorbed from subcutaneous tissue, correlating with the rapid onset of

clinical effects (4-12 minutes), and that the brief duration of clinical action of the drug (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 the in vivo studies performed.

The effect of apomorphine on reproduction has been investigated in rats. Apomorphine was not teratogenic in this

species, but it was noted that doses which are toxic to the mother can cause loss of maternal care and failure to breathe

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No carcinogenicity studies have been performed.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

6.2 Incompatibilities

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

6.3 Shelf life

Unopened: 2 years

After opening: 48 hours

6.4 Special precautions for storage

Do not store above 25°C.

Store in the original container.

6.5 Nature and contents of container

Cartridge.

APO-go Pen 10 mg/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 pen contains 3ml of solution for injection.

Packs containing 1, 5, or 10 x 3ml pens in a moulded plastic tray in an outer cardboard carton.

Not all pack sizes may be marketed

6.6 Special precautions for disposal and other handling

APO-go PEN

Do not use if solution has turned green.

Discard each pen no later than 48 hours from first use.

Sodium bisulphite (E222)

Hydrochloric Acid (37%), concentrated

(to adjust pH to 3.0 –4.0)

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HOW TO USE YOUR APO-go PEN

Read these instructions carefully

DO NOT PULL THE RED DIAL BEFORE YOU HAVE SET THE DOSAGE (See f)

(see attached diagram)

ATTACHING THE NEEDLE

(a) Before using your pen system you will need a surgical wipe and one needle in its protective cone (see 9). Take the

pen out of its box and remove the outer sleeve (see 8).

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(c) Peel off the paper from the needle cone (see 10), and screw the cone clockwise onto the membrane. This will attach

needle securely.

PLEASE NOTE

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

may cause the Pen to leak. This will attach the needle securely.

(d) Remove the protective cone, but do not throw it away. Do not remove the needle protector at this stage (see 7).

(e) Replace the pen’s outer sleeve.

HOW TO SELECT YOUR CORRECT DOSAGE

(see attached diagram)

(f) Press the red dosage dial (see 1) and turn the dial clockwise until the arrow points to your prescribed dosage (see

2,3). Then release downward pressure on the red dial. The dose is now set, and you do not need to redial for

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Important; If you pass your prescribed dose while turning the dial, just continue pressing and turning in the same

direction until you arrive at it again. Never pull and turn the red dosage dial at the same time.

If your prescribed dose is 2mg or less, it is necessary to “prime” the pen before injecting the first dose. Do this by

emptying the first 2mg dose onto a paper tissue and discard. Then, set the dose you require for injection and inject in

the usual way (see below under “INJECTING”). If the first dose required is more than 2mg, then it is not necessary to

“prime” the pen.

INJECTING

(see attached diagram)

(g) Pull out the red dosage dial as far as it will go. Check the white scale on the plunger and inject only if the highest

number visible corresponds to the intended dose.

(h) Using a surgical wipe, clean the area of skin around the proposed site of injection.

Remove the pen’s outer sleeve.

(i) Remove the needle protector (see 7).

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To inject, press the red dosage dial down as far as it will go, using your thumb if possible. Once the red dosage dial is

fully depressed, count to three before withdrawing the needle.

(k) Remove and discard the needle, using the protective cone (see 9). This is done by replacing the protective cone

onto the used needle, and pushing it gently into place. Once secure, you can unscrew the needle anti-clockwise.

Discard the needle in a safe place.

Important: Each needle can only be used once.

PREPARING FOR THE NEXT INJECTION:

Check that there is enough apomorphine left in the cartridge for the next injection (see 4). If there is, put a new needle

in place, following the same procedure as before. (Remember not to throw away the protective cone).

If there is not enough apomorphine left for another injection, prepare another pen.

Finally, replace the outer sleeve of the pen.

7 MARKETING AUTHORISATION HOLDER

Genus Pharmaceuticals Limited

Park View House

65 London Road

Newbury

Berkshire RG14 1JN

UK

8 MARKETING AUTHORISATION NUMBER

PA 1496/2/2

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 6 th

April 2001

Date of last renewal: 31 st

March 2009

10 DATE OF REVISION OF THE TEXT

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There are no safety alerts related to this product.

There are no news related to this product.