The Use of

Apomorphine in
Parkinson’s
Disease

South East London

& Kent PDNS Team
Best Practice
Guidelines 2013.

This booklet has been produced following an educational

grant from Britannia Pharmaceuticals Ltd.
 South East London & Kent PD Nurse Specialist Team

This well-established and nationally respected nursing team is comprised of experienced

Parkinson’ Disease Nurse Specialist (PDNS) who work in the region. They are employed by a
variety of NHS Trusts in Primary, Secondary and Tertiary care. They work in a collaborative
manner to provide high quality, equitable care for people with Parkinson’s disease.

These best practice guidelines have been developed by the team to support the use of
Apomorphine in this region and are used in conjunction with local Clinical Commissioning
Group (CCG) shared care guidelines.

This document is supported by the following Trusts and Consultants:

King’s College Hospital Foundation Trust:

Prof K Ray Chaudhuri, Dr C Clough, Dr M Samuel. Anne Martin PDNS

Maidstone & Tunbridge Wells NHS Trust:

Dr R Hadden, Dr C Thom, Dr N Khan
Dr G Saldanha, Dr C Lloyd, Dr P Tsang, Dr P Reynolds.

Dartford & Gravesham NHS Trust:

Dr S Delamont, Dr E Fenandes, Dr M Toth.

Medway Maritime NHS Foundation Trust:

Dr S Chong, Dr C Ellis,

Queen Elizabeth Hospital NHS Trust:

Dr M Rose, Dr E Silber, Dr D Lorsardi

Bromley NHS Trust:

Dr Peter Brex, Dr J Quirk, Dr F Norwood, Dr B Kessel

East Kent NHS Trust:

Dr N. Munro, Dr M. Samuel, Dr A Heller, Dr J Hawkins,
Dr M Jenkinson

Oxleas NHS Foundation Trust:

Dr T Britton, Dr D Martino, Dr G Cocco.

University Hospital Lewisham NHS Trust:

Prof K Ray Chaudhuri

Other Health Professionals are welcome to use any part of this document,
but must acknowledge it as the work of the SE London & Kent PDNS Team.

Any comments or suggestions as to how these guidelines can be improved are always
welcome; please contact your local PDNS, who is -

2
 Foreword

The first edition of this document was adapted from UCL Hospitals NHS Trust’s publication
of the ‘Treatment of Parkinson’s Disease (PD) with Apomorphine, Shared Care Guidelines’
by kind permission from Dr A Lees and Kirsten Turner.

The South East London & Kent PDNS Team has reviewed this document to reflect the
changes in commissioning and service delivery. It is intended to be a source of information
and guidance to all health professionals sharing care directly with Kings College Hospital
NHS Foundation Trust and regional hospitals via this established nursing team. It aims to
identify the lines of communication between primary, secondary and tertiary care and to
explain the responsibilities of all those involved in the different aspects and stages of this
treatment, providing a smooth and seamless transition between primary, secondary and
tertiary care. It promotes best practice in the care of people receiving Apomorphine.

This document is for guidance only.  Responsibility for implementing any of the
recommendations for each patient remains with the supervising healthcare professional.

Introduction

These best practice guidelines provide information on the use of Apomorphine in patients
with PD who display one or more of the following symptoms; predictable or unpredictable
‘ON – OFF’ motor fluctuations, disabling biphasic or peak dose dyskinesia (unresponsive to
therapies such as levodopa, dopamine agonists and enzyme inhibitors), and dystonia.

Apomorphine is available as either an intermittent subcutaneous injection, via a prefilled pen,

or by continuous subcutaneous infusion, during waking hours (or in some individuals over 24
hours), using the Crono APO-go ambulatory pump.

Apomorphine is a dopamine agonist with NO opiate or addictive properties. Clinical effect is

poor when taken orally because it undergoes extensive first pass metabolism to an inactive
metabolite.
Following a single subcutaneous dose, Apomorphine has an onset of action of between 5 to
15 minutes, with duration of action of approximately 1 hour. Intermittent injections are used
for rapid relief from acute motor deficits (or “off-periods”).  Continuous subcutaneous

3
infusion is recommended for those patients who require exposure to apomorphine for
prolonged periods throughout the day.

Objectives

1. To provide general practitioners and primary care teams with information on the use of
Apomorphine therapy in the treatment of idiopathic Parkinson’s disease.

2. To provide a framework for co-operation and understanding between the primary care
team and the hospital, so that Apomorphine and other anti-Parkinsonism therapy can be
monitored and adjusted according to patients’ needs.

3. To establish clear lines of communication between general practitioners, community

pharmacists, district nurses other members of the multidisciplinary primary care team and
the hospital team

Background
Disabling motor fluctuations and dyskinesia are a common complication of drug treatment of
idiopathic Parkinson’s disease. Figures indicate that 45-50% patients develop troublesome
dyskinesias approximately 5 years after treatment with Levodopa. Affected patients develop
unpleasant ‘off’ period phenomena such as dystonia, depression, pain, sleep dysfunction,
bladder dysfunction and swallowing difficulties. Several open studies have shown that
Apomorphine significantly reduces and sometimes reverses these off period phenomena.

Many patients experience peak dose, interdose or biphasic dyskinesia, which can be equally,
or more disabling than an ‘OFF’ period. Over many years of experience, we have been able to
reduce, and in some cases, eliminate disabling dyskinesias by carefully reducing oral anti-
parkinsonian medication and introducing Apomorphine therapy. Drug regimes often become
complicated and confusing. Apomorphine can reduce the amount of oral dopaminergic drugs
taken by many patients and so reduce anxiety and risks associated with polypharmacy.

The rapid and reliable response to Apomorphine can be an advantage when oral doses of
Levodopa, combined with other dopaminergic drugs, become progressively less effective and
less predictable. The aim of treatment is to optimise the delicate balance between an effective
response and minimal side effects, promoting patient independence and reducing carer
burden.

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 FLOW CHART DEMONSTRATING THE USE OF APOMORPHINE IN PARKINSON’S DISEASE –
SHARED CARE PROTOCOL

GP referral – Patient selection by Consultant Local Parkinson’s Disease Nurse

Complex phase reached Neurologist/ Physician. Specialist

Apomorphine treatment and

guidelines discussed with GP
and Patient prior to initiation /
admission (SCG)

Agreement to initiate treatment

reached between patient, GP
and Consultant.

Liaison with Patient and Carers,

GP by coordinating PDNS

Start Domperidone 20-mg tds

three days prior to Apomorphine
challenge

Apomorphine challenge

If positive result, plan ongoing

treatment.

Intermittent Continuous ‘waking

Apomorphine hours’ infusion via
injection syringe driver

Liaison with GP, district nurses,

community pharmacist, local Training, assessment and
PDNS and multidisciplinary team information

Liaison with CCG & Community Discharge in to Primary Care

Nurse re provision of equipment.

GP to prescribe on – going drug Follow up:

Community pharmacist to supply therapy as agreed prior to  Regular outpatient appointments.
Apomorphine challenge  Optimisation of treatment
 Monitor and evaluate adverse
reactions - bloods
 Information to patient, carers and
Any problems Local PDNS primary care team
5
 Motor Fluctuations

More than 50% of Parkinsonian patients experience fluctuations in motor response after five
years of levodopa (L-dopa) treatment or combined therapy (Lees AJ, 1986). The most
common side effect of L-dopa therapy is 'end of dose deterioration', ‘ON-OFF’ phenomena
and peak dose or biphasic dyskinesias. Optimising treatment is difficult and complex for
many patients – these complications are often referred to as the ‘Complex phase’ of
Parkinson’s disease.

Initially, the ‘wearing off’ effect is predictable and occurs at the latter part of the dosing
interval. As the disease progresses, ‘wearing off’ becomes less predictable and can render
someone immobile in a matter of minutes.

The ‘ON-OFF’ phenomena is best described as a sudden and immobilising episode which can
transform a mobile person into a rigid, frozen and dependant one within a few moments. The
intensity and duration of these episodes are unpredictable and cannot always be accurately
related to the timing of oral medication. Off episodes may also affect cognition, mood and
communication.

Specialist Intervention

Initiation of Apomorphine therapy occurs mid to late disease and should be supported by
centres with experience in the management of complex Parkinson’s disease (Parkinson’s
disease National clinical guideline for diagnosis and management in primary and secondary
care.) The South East London and Kent Region have a team of Parkinson’s disease Nurse
Specialists who are experienced in all aspects of Parkinson’s disease management. Therefore,
where a PDNS is in post, people requiring Apomorphine therapy have access to local
services, thus admission to tertiary Hospital may not be necessary.

6
 Shared Care

The Apomorphine dose regime is individually titrated according to the patient’s symptom
management. This may range from 1-5 intermittent subcutaneous injections daily.
Continuous infusion dose may range from 50 to 100mg daily. In rare cases, doses of up to 250
mg daily have been used.

The specialist team provides the patient with information and advice, supported by written
and audio information if required, explaining the treatment and use of equipment. Only when
the patient and their family are satisfied with the process and the Primary care team have been
made aware of their funding obligation, will the treatment proceed. Successful Apomorphine
therapy is initiated and maintained in the primary care setting by sharing the responsibilities
for care between primary and secondary care. After a successful challenge, the initiation,
titration and adjustment of oral therapy will be the managed by the PDNS following
discussion with the Consultant and in accordance with the clinical management plan.

The primary care team accepts responsibility for the on going prescribing of Apomorphine
and will continue to act as the primary contact for general health care. The PDNS provides
training, support and advice for General Practitioners, community pharmacists and District
Nurses and the patient and family. It is recommended that D/Ns receive training in the use of
the Crono APO-go pump.

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 Presentation

Apomorphine is a colourless aqueous solution for injection, containing 10mg per ml of

apomorphine hydrochloride.

Available: Apomorphine Pre-filled syringe 5mg/ml (each syringe contains 10ml of

pre-diluted solution ready for use. 10ml solution contains 50mg
apomorphine).
Apomorphine 10mg/ml 2ml and 5ml Ampoules (these require dilution
50/50 with 0.9% saline for injection prior to use)
Apomorphine Pre-filled multiple dose Pen 10mg/ml (each pen contains
30mg apomorphine in 3ml)

Crono APO-go pump Pre-filled multiple dose pen

Apomorphine therapy

Apomorphine has been licensed since 1993 for use in patients with PD and disabling motor
fluctuations inadequately controlled by L-dopa or other dopamine agonists. The licence
covers intermittent subcutaneous injections and continuous subcutaneous infusions.
Funding arrangements should be agreed with the General Practitioner in advance of arranging
a challenge. So if the challenge is sucessful, treatment can be initiated.

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Apomorphine challenge
The Apomorphine challenge is performed to establish efficacy in a person with diagnosed
idiopathic Parkinson’s disease.
1. To determine whether a patient experiences a positive, safe response to treatment
2. To observe the patient for potential side effects, such as postural hypotension, confusion
and hallucinations. Such side effects may limit the potential for use.

NICE Guidelines suggest challenge should not be used for differential diagnosis.
Prior to the challenge, Domperidone is commenced to manage the strong, but short-term

emetic effects of Apomorphine. The patient can have the challenge either as an inpatient or as
a day case – depending on the local set up and support of a Parkinson’s disease Nurse
Specialist. It is necessary that the challenge is performed in a safe, clinical environment with
medical support.
Prior to the challenge the GP may be asked to arrange an ECG and bloods- U&Es and FBC,
this is to eliminate any undiagnosed cardiac condition may contraindicate the use of
Apomorphine.

Procedure

1. Pre-treat with Domperidone 20 mg tds for 72 hours prior to the challenge. (30mg if PR
formulation used.)
2. The patient should not receive any oral anti-Parkinson medication for a minimum of four
to six hours prior to the challenge in order to provoke an ‘OFF’ state. The patient’s
mobility should be considered if the challenge is to be performed as a day case.
3. Using the Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 to assess motor
function of patient (‘OFF’) for a base line score. Including base line lying and standing
blood pressure and timed walk if possible. Non-motor symptoms should also be recorded.
4. Administer 1 mg Apomorphine subcutaneously and observe patients motor response 15
and 30 minutes post injection. Repeat baseline measurements.
5. If no or poor response, give a subsequent dose of 3 mg. Continue to assess and observe.
6. Increase the dose in incremental steps every 40 minutes thereafter (i.e. 1 mg to 3mg to 5
mg to 7mg. Dependent on patient’s general condition smaller increments can be made)
until a response is seen. If at 7 mg no response is seen, then the patient is a non-responder.
If some response is observed at 7mg, then the maximum dose of 10mg can be used with

9
 caution. Continue with incremental doses of 1 mg to a maximum 10mg until desired
response is achieved. Continue assessing the patient and review after the 10mg bolus
dose.

Positive Challenge

A challenge is positive if one or more of the following results are achieved:

1. An improvement in UPDRS score of 20% of baseline score

2. More than 25% improvement in walking time
3. Alleviation of specific symptoms, e.g. pain, dystonia, non-motor presentations such as
urinary retention, gastric disturbances, anxiety.

Treatment Strategy

Successful Apomorphine therapy in the community is achieved with effective shared care
between primary, secondary and or tertiary centres. Patients, families and healthcare
professionals must have access to specialist support.
A full range of educational materials, videos, DVDs and training is available free of charge.

Intermittent subcutaneous injections

Intermittent subcutaneous injections are used to reverse disabling ‘OFF’ periods in

conjunction with oral therapy. These are suitable for patients who experience unpredictable
‘OFF’ periods. ‘OFF’ symptoms can include pain, marked dystonia, freezing and immobility,
swallowing and speech problems. Some patients experience a range of non-motor symptoms
including depression, gastric and elimination problems.

10
 An individual therapeutic dose is established for each patient. A 10 year review of 161
patients at the Middlesex Hospital showed that once the correct dose has been established it
changes very little (Hughes, 1995).

Intermittent Subcutaneous Injection via a pre–filled multiple dose Pen

For ease of administration, Apomorphine comes in a pre-filled multiple dose Pen device.
The pen is discrete and easy to use. Patients and carers are trained to use the Pen and
administer the injection in the abdominal wall or outer aspects of the upper arms or thighs.

Continuous subcutaneous infusion using the Crono APO-go Pump

The continuous infusion pump is used when patients demonstrate a good ‘ON’ period
response to apomorphine, but whose overall motor control fluctuates between freezing and
dyskinesia. Existing patients using in excess of 6 bolus injections per day may benefit from
administration by continuous infusion. A continuous infusion allows for adjustment and /or
reduction of oral medication (associated with motor fluctuations and dyskinesia) to provide
more consistent symptom control.

Experience has found that managing this group of patients on a combination of Apomorphine
and oral dopamine agonists, and subsequently reducing or even stopping L-dopa, can
dramatically reduce dyskinesia. It is thought a 30% reduction in L-dopa can be made almost
immediately once an infusion is commenced.

11
The Crono APO-go syringe pump has been specifically designed for the purpose of delivering
Apomorphine. It permits:

1. Easy adjustment of the dose rate in small increments

2. Flow rate accuracy
3. Accurate bolus doses
4. It can be used with a 20ml syringe, which means, for most patients, a full days treatment
can be given without the need to change syringes. Syringes are supplied free of charge by
Britannia Pharmaceuticals and delivered to pharmacist for collection with the
Apomorphine prescription.
5. Neat, compact and lightweight
6. Time display, so the user knows exactly how much time the infusion will run for
7. Full alarm/error warning system complying with EU standards
8. Supplied on a permanent loan basis to the patient, 24-hour help line, provided by
Britannia Pharmaceuticals, is available.
District Nurses, patients and carers receive initial training in the use of the pump by their local
PDNS (where available) before a patient is established on a continuous infusion of
Apomorphine.
The Britannia Pharmaceuticals sales representative can arrange for the Health Care
Professional to receive training and training materials.
Pumps no longer required should be returned to Britannia Pharmaceuticals. Contact details
and help line number can be found in the back of these shared care guidelines.

Preparation of the infusion

Ideally, most patients should become independent of nursing support within a month after
initiation of therapy, eliminating the need for continued district nurse visits. However, on
occasions, a District Nurse will be required. See appendix. For care plan.

Storage and Stability

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Pre-filled syringes (PDFS) containing Apomorphine should be stored at room temperature (at
or below 25ºC) and protected from the light. The PFS has an unopened shelf life of 2 years
when stored within the recommended conditions.
Apomorphine turns green when exposed to oxygen and stains are difficult to remove. Lemon
juice can be effective if used immediately after spillage.

Infusion Crono APO– go Pump Rate Settings

Infusion rates are based on a 50:50 dilution of apomorphine and saline, available ready
prepared in a pre-filled syringe.

mg Apomorphine per hour ml of diluted solution per hr

(Flow rate)
2.0 0.4
2.5 0.5
3.0 0.6
3.5 0.7
4.0 0.8
4.5 0.9
5.0 1.00
5.5 1.10
6.0 1.20
6.5 1.30
7.0 1.40
7.5 1.50
8.0 1.60
8.5 1.70

Side Effects

Possible side effects are divided into those derived from Apomorphine’s pharmacology and
those attributable to the mode of administration, i.e. localised reactions.

Pharmacological Side Effects

Pharmacological Mode of administration

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  Nausea and vomiting  Nodule formation at injection or
 Dyskinesias during ‘ON’ time infusion site
 Neuropsychiatric complications –  Local infection/abscess
Hallucinations, euphoria, /ulceration/scarring
increased libido, confusion,  Localised discomfort at injection or
personality changes, agitation, infusion site
restlessness, psychosis, sleep
disturbance.
 Sedation
 Orthostatic hypotension
 Light-headedness
 Haemolytic anaemia
(uncommon 0.1-1%)
 Eosinophilia

Where dyskinesia and sedation are experienced, the treatment will be reviewed, adjusted and
possibly discontinued. These side effects are more common when apomorphine is
administered in conjunction with relatively high levels of oral medication. Drug-induced
dyskinesias during ‘ON’ periods can be severe with intermittent injections. In contrast,
continuous subcutaneous infusions of Apomorphine as monotherapy can attenuate
dyskinesias.

Apomorphine is a strong, short term emetic, and all patients started on Domperidone prior to
challenge, will remain on 10-20 mg tds until established on Apomorphine therapy.
Domperidone is gradually withdrawn over several weeks on the advice of the PDNS or
supervising physician.

Transient, mild confusion and visual hallucinations have occurred; most commonly in patients
reporting previous Levodopa (as co-beneldopa or co-careldopa) and/or dopamine agonist
induced neuropsychiatric complications. Should these continue to develop, attempts should be
made to identify the contributing factor under the direct supervision of the hospital team.

Localised Reactions

14
 Nodule formation
 Redness, irritation and rarely ulceration.

Apomorphine induced nodules: how to reduce

incidence and discussion of possible treatments.

Cutaneous complications associated with continuous subcutaneous infusions are common,

ranging from mild nodule formation to painful hard nodules and rarely skin ulceration. It is
important to minimise the development of nodules as it is thought that they may reduce the
absorption of apomorphine, thus reducing the efficacy of the treatment.
Lines…..
How to reduce nodule formation

A clean technique is essential to minimise local reactions. It is important that patients, and
those who care for them, are taught the correct technique for managing the infusion prior to
initiation of Apomorphine therapy.

 It is important to use a 50:50 dilution of apomorphine (in PFS apomorphine is already

diluted)
 Daily rotation of injection sites
 The needle must be injected at a minimal angle of 45 degrees to the skin; if the needle is
inserted intra-dermally, the Apomorphine may irritate the skin and possibly cause
ulceration.
 Gentle massage of the injection sites on a daily basis, by hand or with a hand held massage
device, could help to reduce nodule formation. Massage promotes healthy skin by
encouraging good circulation to the adipose tissue whilst de-sloughing dead skin cells.
 Silicone gel patches can also help to reduce nodule formation and relieve itchiness. The
patches are placed over the nodules and left in place overnight. The patches can be used
many times if they are rinsed in warm water and dried carefully. Each packet contains
instructions for use. It is not fully understood how these patches work to reduce nodule
formation, although silica is known to exert a beneficial effect on scar tissue.
 There have been some anecdotal reports that therapeutic ultrasound may be used with
benefit on Apomorphine nodules. Some patients have received ultrasound treatment for

15
 many years and continue to maintain good skin quality and reduction in nodules. However,
ultrasound therapy has not been subject to any formal trials. There is no clinical evidence
to support its use or conversely to suggest that it is harmful.
 Patients with Deep Brain Stimulators in situ must not have ultra sound treatment.

Cost of Apomorphine therapy

Apomorphine is supplied in boxes of:

Pre-filled syringes (PFS) x 5
Ampoules, 2ml and 5ml, x 5
Multi-dose Pen x 5

(50mg in 10ml) x 5 PFS £73.11

(20mg in 2ml) x 5 ampoules £37.96
(50mg in 5ml) x 5 ampoules £73.11
(30mg in 3ml) x 5 Pens £123.91

The optimal daily dose of Apomorphine varies considerably between patients.

Intermittent subcutaneous apomorphine using APO-go Pens

Cost *
Daily Use Daily Dose Weekly Monthly Annually
½ 3ml Pen Up to 15mg £101.92 £436.80 £5314.40
1 x 3ml Pen Up to 30mg £203.84 £873.60 £10628.80

*The costs relate to one pre-filled multiple dose Pen. Each Pen must be used
within 48 hours of first opening.

Continuous subcutaneous Apomorphine using APO-go Pre-filled Syringe

16
 Cost **
Daily Use Daily Dose Weekly Monthly Annually
1 x Pre-filled Syringe Up to 50mg £120.26 £515.40 £6270.70
2 x Pre-filled Syringe Up to 100mg £240.52 £1030.80 £12541.40

** The costs relate to APO-go Pre-filled Syringes. Once opened the pre-filled
syringe should be used immediately.

Concomitant Domperidone treatment

Cost
Daily Dose Range Weekly Monthly Annually
10mg £1.06 £4.56 £55.52
three times a day
20mg £2.13 £9.13 £111.03
three times a day

Prices quoted are inclusive of VAT

Source: MIMS October 2006

APPENDIX
Further information, including references and documents developed by the team
are included in these guidelines. Colleagues are welcome to use any of the
documents but must acknowledge it as the work of the South East London &
Kent PDNS Team.

Appendix one: References for further reading.

Appendix two: Admission information sheet.
Appendix three: Apomorphine challenge; ward information
Appendix four: Infusion record, records adjustment in doses.
Appendix five: Training and competency statement for registered nursed.
Appendix six: Training for care home staff.

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Appendix seven: Care Home Assessment: PD information.
Appendix eight: Apomorphine infusion care plan.
Appendix nine: Apomorphine challenge record.

REFERENCES

Ahlskog, J.J., Muenter, M.D. (2001) Frequency of Levodopa related dyskinesias and
motor fluctuations estimated from cumulative literature. Movement Disorders (2001)
vol.16: 448 – 458.

Chaudhuri, K.R., Critchley, P., Abbott, R.J., Pye, I.F., Millac, P.A.H. (1988) Subcutaneous
Apomorphine for On – Off oscillations in Parkinson’s disease. Lancet 1988; ii (8622) :
1260.

Clarke, C.E. (2002) Parkinson’s Disease in Practice. The Royal Society of Medicine Press
Ltd.

Colzi, A., Turner,K., Lees, A.J. (1998) Continuous subcutaneous waking day
apomorphine in long term treatment of Levodopa induced interdose dyskinesias in
Parkinson’s disease. Journal Neurology, Neurosurgery & Psychiatry 1998; Vol. 64: 573 –
576.

Dewey, R.B., Hutton, T., LeWitt, A., Factor, S.A. (2001) A randomised, double blind,
placebo – controlled trial of subcutaneously injected Apomorphine for Parkinsonian Off
state events. Arch. Neurology 2001; 58: 1385 – 1392.

Gervason, C.L., Pollak, P.R., Limousin, P., Perret, J.E. (1993). Reproducability of motor
effects induced by successive subcutaneous Apomorphine injections in Parkinson’s
disease. Clinical Neuropharmachology 1993; 16: 113 –119.

Grancher, S.T., Woodward, W.R., Gliessman, P., Boucher, B., Nutt, J.G. (1990) The short
duration response to Apomorphine: Implications for the dopaminergic effects in
Parkinsonism. Ann. Neurology 1990; 27: 660 – 665.

Grancher, S.T., Nutt, J.D., Woodward, W.R. (1995) Apomorphine infusional therapy in
Parkinson’s Disease : Clinical utility and lack of tolerance. Movement Disorders 1995 10:
37 –43.

Hughes, A.J., Bishop, S., Stern, G.M., Lees, A.J.(1991) The motor response to repeated
apomorphine injections in Parkinson’s disease. Clinical Neuropharmacology 1991; 14 :
209 – 213.

Hughes, A.J., Bishop, S., Kleedorfer, B., Turjanski, N., Fernandez, W., Lees, A.J., Stern,
G.M. (1993) Subcutaneous Apomorphine in Parkinson’s disease: Response to chronic
administration for up to five years. Movement Disorders 1993; 8: 165 –170.

Kanovsky, P., Kubora, D., Bares, M., Hortora, H., Streitova, H., Rektor, I., Znojil,V. (2002)
Levodopa induced dyskinesias and continuous subcutaneous infusions apomorphine :
Results of a two year, prospective follow-up. Movement Disorders 2002; 17: 188 –191.

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Lees, A. Turner, K. (2002) Apomorphine for Parkinson’s Disease. Practical Neurology 2002;
2: 280 – 286.

Morgante, l., Basile, G., Epifanio, A., Spina,E., Antonini, A., Stocchi, F., DiRosa, E., Martin,
O.G., Marconi,R., LaSpina, P., Nicita-Mauro,V., DiRosa, A.E. (2004) Continuous
apomorphine infusion and neuropsychiatric disorders in patients with advanced

Parkinson’s disease : a follow-up of 2 years. Archives of Gerontological Geriatrics 2004 38

(suppl) : 291-296.

National Institute for Health and Clinical Excellence (2006) Parkinson’s Disease :
Diagnosis and management in primary and secondary care. Department of Health, London.

Pietz,K., Hagell,P., Odin,P. (1998) Subcutaneous apomorphine in late stage Parkinson’s

disease : A long term follow-up. Journal of Neurology, Neurosurgery & Psychiatry 1998; 65 :
709-716.

Stocchi,F., Vacca,L., DePandis,M.F., Barbato,L., Valente,M., Ruggieri,S. ( ) Subcutaneous

continuous Apomorphine infusion in fluctuating patients with Parkinson’s disease :
Longterm results. Neurol. Sci; 22 : 93-94.

19
 Apomorphine Therapy: Admission information.

This person uses Apomorphine as therapy to relieve symptoms of

Parkinson’s disease. It is used when the more usual oral
medications are no longer effective or predictable.

It is NOT MORPHINE, but a derivative,

It is not addictive.
It is not a controlled drug.

Unless there are very strong MEDICAL reasons this drug should not be
discontinued.

The person or their family will usually be knowledgeable and independent in

the use of this medication and associated equipment. Please do not ignore
their information.

They will also have the contact details of a health professional that supervises
the use of Apomorphine, please contact this person if you would like help and
advice.

The Crono APO-go pump is the property of Britannia Pharmaceuticals and is

on loan to the NAMED PATIENT, it is NOT NHS PROPERTY.

Apomorphine can be administered through any syringe driver that you

are trained to use.

You need to know

a) Number of milligrams per hour of Apomorphine required
b) Ensure the Apomorphine is diluted 50/50 with 0.9% saline (unless
using a pre-diluted pre-filled syringe)

Patients, families & care homes.

Please remember to take the following into hospital, many units will not be
familiar with your treatment or have all the necessary equipment.
Pens and needles.
Crono APO-go pump and blue case with spare battery and instruction book.
Weeks supply of syringes.
Weeks supply of Apomorphine. (Pre-filled syringe or ampoules)
1 or 2 infusion lines “butterfly”
1 or 2 clear dressings
Silgel patch, if used.

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Contact number of PDNS or DN
Blue District Nurses folder, don’t forget to bring this home again!

Apomorphine challenge: Information for wards/ departments .

Patient.

Date of admission.

Ward.

Dear colleagues,

This is to provide Nursing and Medical staff with information about caring for a
person under going an Apomorphine challenge. This could be to aid diagnosis or with
a view to treatment.

This procedure is to test a person’s responsiveness to Apomorphine for reversing

their “off-periods” which they experience with their Parkinson’s disease.  For the
purposes of the test only, an “OFF” is induced by withholding their usual PD
medication for a number of hours. This means their symptoms will be at their worst
and they will be much less mobile and independent than usual. 

Having established an effective dose, the person would then take their oral
medications (where prescribed) and use apomorphine to relieve their “OFF” periods
as appropriate.  Patients experience “off-periods” when their conventional oral
medications are no longer effective or the response to them is unpredictable.

Apomorphine is NOT morphine and has no narcotic properties.

It is not addictive.
It is not a controlled drug.

Medical Team.
 Please clerk and examine the patient; an ECG is also recommended.
 Prescribe the patients usual medications, including DOMPERIDONE 20mg tds,
(The patient should have started this pre admission)
 Please prescribe Apomorphine for challenge, as variable dose 1 – 8mg s/c,
frequency ½ hourly.
 PD medication should be stopped 6 hours prior to challenge so the patient is in
an OFF state, i.e. overnight for an a.m. challenge. But must continue to have
domperidone.

Nursing Team.
 Please ask the patient about their symptoms and difficulties when they are OFF,
what help will they need?
 They DO NOT need to be nil by mouth, but will require plenty of fluids and a light
diet.
 Please obtain the Apomorphine from pharmacy.
 After the challenge they can have their normal PD medication.

21
For further information about this procedure a copy of the shared care guidelines has
been provided, but please do ask the PDNS if you have any questions about this
admission.

22
RECORD OF CHANGES IN DOSE: APOMORPHINE INFUSION PLEASE BRING TO CLINIC.
(Using Crono APO-go pump)

Patient Details.

Name. GP. Contact number.

D.O.B. PD Nurse. Contact number.
Consultant.

Dat Syringe setting Apomorphine 0.9% sodium Apomorphine dose Bolus dose Flow rate Signature
e 10ml / 20ml Total mg in syringe chloride mg per hour d setting F setting
ml in syringe or PFS

23
Registered Nurse Competency Statement:

For: Crono APO-go Pump

Patient:

Questions to ask yourself.

1. Have I completed formal training for this device OR am I an experienced user?

2. Am I aware of the indications & limitations of the piece of equipment?
3. Can I recognise if the equipment is ready to use?
4. Can I assemble the equipment and it’s accessories?
5. Do I know what accessories are compatible with this pump?
6. Can I carry out relevant safety checks?
7. Am I aware of any relevant acceptable operating ranges?
8. Can I use the equipment with a patient, effectively and with minimal
discomfort?
9. Can I adjust and set up the equipment?
10. Can I recognise if the equipment is operating normally?
11. Would I recognise a fault?
12. Do I know what to do if something goes wrong?
13. Am I aware of the procedures to clean or decontaminate the equipment?
14. Do I know where to put it when I have finished?

If you are unable to answer “yes” to all the above questions, do not use the
equipment unsupervised and arrange for further training.

Having read the above, I confirm that I am competent to use a Crono APO-go pump
in the care of this patient.

NAME (print) DATE SIGNATURE

24
 The use of Apomorphine & Crono APO-go Pump by Registered Nurses

Apomorphine is an injectable drug used to relieve the symptoms of Parkinson's

disease. It may be used as an intermittent injection by pre-filled Pen or as a
continuous subcutaneous infusion via a pump. Apomorphine must not be given by
the intravenous route.

It is vital that all staff caring for a person using Apomorphine are competent to do so.
The following is a suggested training programme for experienced registered nurses,
both hospital and community based. Sessions could be completed in educational
opportunity. Training should be provided by an experienced PD Nurse Specialist. A
Britannia Pharmaceuticals Representative can arrange for the Health Care
Professional to receive training and training materials.

Session one:
After this session staff should be able to:

1) Describe the signs and symptoms of advanced PD

2) Have a basic understanding of types of medications and how they work.
3) Recognise common side effects of medication.
4) Recognise when medication is working and when it is not.
5) Understand the importance of recording & reporting changes in response to
treatment.

Session Two: Apomorphine explained.

After this session staff should be able to:

1) Describe what Apomorphine is and why is it used.

2) Explain when to use an APO-go Pen (if applicable)
3) Demonstrate safe use of APO-go Pen (if applicable)

Session Three: Apomorphine continuous infusions.

After this session staff should be able to:

1) Understand why Apomorphine is given by infusion.

2) Explain what information and support materials are available.
3) Safely draw up prescribed drug and set up Crono APO-go pump.
4) Safely site the infusion and start pump.
5) Monitor infusion, recognise problems with pump or site and take appropriate
action.
6) Discontinue infusion, dismantle and reset pump, care for site.

25
The use of Apomorphine by staff in care homes.

Apomorphine is an injectable drug used to relieve the symptoms of Parkinson's

disease. It may be used as an intermittent injection by pre-filled Pen or as a
continuous subcutaneous infusion via a syringe driver.

Most people with PD are independent in the use of this treatment or may require
some help from a spouse/partner or carer. On rare occasions some ongoing input is
need from a Community Nurse. Training and support for all involved is provided by
the PDNS until competent, confident and independent in the use of the drug and
equipment.

Apomorphine therapy can provide patients with respite from disabling motor
fluctuations, and most patients can be safely treated in a care-home environment if;

a) Care staff are willing to take on this responsibility

b) Managers agree it is reasonable to expand the staff role in this way.
c) Sufficient training and support is provided by a PDNS.
d) Competency can be established and skills and knowledge maintained.

Staff should have experience of caring for people with PD. They do not have to be
registered nurses but should be recommended and supported by their manager

Session one: PD Medication

After this session staff should be able to:

1) Describe the signs and symptoms of both early and advanced PD

2) Have a basic understanding of types of medications and how they work.
3) Recognise common side effects of medication.
4) Recognise when medication is working and when it is not.
5) Understand the importance of recording & reporting changes in response to
treatment.

Session Two: Apomorphine explained.

After this session staff should be able to

1) Describe what Apomorphine is and why is it used.

2) Explain when to use an APO-go Pen
3) Demonstrate safe use of APO-go Pen.

Session Three: Apomorphine continuous infusions.

After this session staff should be able to

Understand why Apomorphine is given by infusion.

Explain what information and support materials are available.
Safely draw up prescribed drug and set up Crono APO-go pump.
Safely site the infusion and start pump.
Monitor infusion, recognise problems with pump or site and take appropriate action.
Discontinue infusion, dismantle and reset pump, care for site.

26
 Care Home Assessment: Parkinson’s disease Information.

We understand Parkinson’s symptoms and treatment can be very individual. In order

to provide the highest standard of care and support during your stay, the staff would
be grateful if you could provide the following additional information.

Please remember to bring with you sufficient supplies of anything you may need such
as incontinence pads / pants, sheaths or catheters, drainage bags, colostomy bags
and medication, inc. creams, drops lotions etc

Current Medication
Don’t forget any non-prescription items you may take. i.e. vitamins etc.
If you also use Apomorphine, please record the details on reverse.

Name of Drug Dose Times

Common symptoms or problems

Symptoms Yes No Usual Current Symptom Yes No Usual

time time
Bradykinesia Hallucinations
Rigidity Confusion/memory
Tremor Sleep issues
Freezing Loss of appetite
Dizziness/giddiness Loss of weight
Balance problems Difficulty swallowing
Weakness Dribbling
Dystonia Nausea
Cramp Vomiting
Dyskinesias Cough
On/off problems Urinary problems
End of dose Sexual dysfunction
Anxiety/worry Bowel problems
Breathlessness Menopausal/HRT
Depression Speech problems
Swallow problems
Anything else we may need to know? If you have a particular pattern to your day,
times when you are better than others please fill in the enclosed diary if you wish .

27
Apomorphine.

How long have you been using Apomorphine?

Do you administer your Apomorphine Independently

or need assistance (please tick)

Do you use Pens?….. Infusion? …..

Type of syringe driver? Crono APO-go Graseby other

Who provides support? Name and contact numbers please.

PD Nurse Specialist

District Nurse

Others.

PENS.

Dose in mg……….. Approx. number of doses needed in the day…… ,at

night…….

Comments.

INFUSION.

When used (please tick) only daytime only at night both day and night.

Syringe setting 10ml / 20ml

Amount of Apomorphine 50mg/5ml 100mg/10ml

Apomorphine dose Day ……mg per hour Night……mg per hour

Pump setting Day F . Night F .

Bolus dose …….. mg pump setting d .

Comments.

Don’t forget.
You will need to bring with you sufficient supplies for the duration of your stay.

Apomorphine Pens and needles

Pre filled Syringes or Apomorphine ampoules and 0.9% saline ampoules
Syringe driver and syringes
Infusion lines Film dressings

28
NAME: D.O.B Hospital no. Consultant:

DATE No. PROBLEM GOAL NURSING PLAN SIGNATURE REVIEW

DATE
 Uncontrolled  To maximise ‘ON’  Ensure Apomorphine is prescribed correctly.
Parkinson’s time  50mg = 1 x 10ml syringe, 100mg = 2 x 10ml
disease.  Safe  To be given during waking hours / over night
 Motor fluctuations administration of  Ensure Domperidone 20 mg tds is prescribed 72 hours
and sustained Apomorphine before starting apomorphine
unpredictable  Improve quality of  If using a 10ml volume ensure the spacer is attached to
‘OFF’ periods, life the APO-go pump.
resulting in poor  Slide plunger up/down to loosen.
quality ‘OFF’  Unscrew the syringe plunger, leaving black bung at the
time. top.
 Attach the syringe to the pump by firmly pressing the
syringe onto the pump and clicking the syringe wings
into place under the clips (by twisting the syringe).
Stand pump in its rest on the tray.
 Attach the connecting tube to the syringe.
 Using the pre filled syringe add 10ml or 20ml to the
APO-go syringe (see instruction sheet)
 Remove the connecting tube.
 Attach the butterfly needle with extension tubing to the
leur lock of the syringe.
 Turn the pump ON by pressing and holding the red
ON/OFF button.
 Check the pump settings:
 Ensure the small 10 or 20 in the left-hand corner of the
pump display match the correct volume of infusion.
Refer to the instruction manual if it doesn’t.
 Check the pump reads the following settings:
d . F . . The pump will then read a number,
this is the amount of time in hours and minutes the
infusion will run for. It does not have to run for this
length of time!

29
  Prime the line by pressing and holding the BLUE d
button. Repeat this until the line is fully primed. Turn the
pump OFF, red button.
 Attach the butterfly needle to the abdomen, inserting it
at a 45 -60 degree angle. Secure firmly using a film
dressing.
 THE PUMP IS RUNNING WHEN THE TIME
REMAINING IS DISPLAYED

CARE PLAN FOR APO-Go Pump CONTINUED

TO DISCONTINUE THE INFUSION

 Turn the pump OFF by pressing and holding the

RED ON/OFF button.
 Remove the butterfly needle carefully from the
abdomen and place in sharps box.
 Press and hold BOTH THE BLUE AND GREY
BUTTONS TOGETHER until the display reads
End.
 The pump will then return the plunger back to its
original setting. This can take a couple of minutes.
Carry out skin care & massage
 The syringe can now be removed from the pump
and placed in the sharps box.
 Leave the pump reading OFF until the next infusion
is due.
 DO NOT CHANGE EITHER THE FLOW RATE OR
THE BOLUS DOSE.
 When the pump is reading OFF it is in battery
saving mode

30
31
 LEVODOPA AND APOMORPHINE CHALLENGE PROTOCOL

NAME: CONSULTANT:

DATE OF BIRTH:

UNIT No: PDNS:

REFERRAL REC:

AIM OF APOMORPHINE CHALLENGE

To provide a safe and controlled environment in which to establish the correct dose of Apomorphine to induce
an ‘ON’ phase in the patient (within 5 – 10 mins), which is equivalent in quality to that of Levodopa and lasts for
40 to 45 mins.

PROTOCOL
A. Arrange pre challenge counselling and provide written information.
B. Arrange date, time and venue for challenge.
C. Arrange for Domperidone 20mg tds to be given for at least three days prior to challenge
D. Arrange for the patient to be clerked, prescription written and Apomorphine obtained from the pharmacy.
E. Ensure all PD medication has been stopped for a minimum of four to six hours to induce an OFF state. Be
aware some PD medication may need to be stopped for longer.
F. The patient DOES NOT have to be nil by mouth.

Patient’s main problems:

Checklist CHALLENGE RECORD

Check patient details, provide a name band
Check patients understanding of procedure
Has Domperidone been taken for three days?
Has PD medication been stopped for six hours or longer?
Base line vital signs including lying and standing BP

T R P BP BP
Base line motor scale of Unified Parkinson’s Disease Rating Scale
Has Apomorphine or Levodopa been prescribed correctly

32
 Handwriting sample pre and post challenge

PRE POST

Copy this design and write a sentence Copy this design and write a sentence

Procedure for Apomorphine challenge

Suggested Intervals / Intervention Comments Signature

time (monitor BP)
00.00 Administer 1.0mg Apo
15 mins Reassess UPDRS part III
30 mins Administer 3mg Apo
45 mins Reassess UPDRS part III
60 mins Administer 5mg Apo
1hr 15 mins Reassess UPDRS part III
1hr 30 mins Administer 7mg Apo
1hr 45 mins Reassess UPDRS part III

If no response is seen at 7mg, then the patient is a non-responder. If a mild response is noted at 7mg then the
maximum dose of 10mg can be used with extreme caution.

Procedure for Levodopa challenge

Intervals / time Intervention Comments Signature

(monitor BP)
00.00 Administer 275mg Sinemet, or
250mg Madopar dispersible
30 mins Reassess UPDRS part III
1hr Reassess UPDRS part III
1hr 30mins Reassess UPDRS part III
2 hr Reassess UPDRS part III

A greater than 20% in motor function as assessed by the UPDRS part III indicates a positive
challenge in both Apomorphine and Levodopa.
33
UNIFIED PARKINSON’S DISEASE RATING SCALE / MOTOR FUNCTION LEVODOPA / APOMORPHINE
CHALLENGE
I-dopa / Apomorphine
Time
Speech
Facial expression
Tremor: head, jaw,
mouth
Hands Right
Hands Left
Feet Right
Feet Light
Action tremor / hands
R
Action tremor / hands
L
Rigidity:
neck
Arms Right
Arms Left
Legs Right
Legs Left
Finger Taps Right
Finger Taps Left
Hand Grips Right
Hand Grips Left
Hand pronate/ supinate
R
Hand pronate/ supinate
L
Heel / toe taps Right
Heel / toe taps Left
Arise from chair
Posture
Postural stability
Gait
Body bradykinesia
Total points
timed 12m Walk

To calculate the percentage improvement:

1) calculate the point improvement, i.e. starting score 87 last score 51

87 – 51 = 36 point improvement

2) transform to a percentage:
point improvement x 100 =%
starting score
therefore: 36 x 100 = 41% improvement
87
34
 Conclusion
………………………………………………………………………………………………………………………………………...

………………………………………………………………………………………………………………………………………...

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………………………………………………………………………………………………………………………………………...

………………………………………………………………………………………………………………………………………...

Follow up:

Confirm outcome with Consultant:

Arrange training sessions with patient and carer:

Letter to GP:

Contact District Nurse:

Other Information
………………………………………………………………………………………………………………………………………...

………………………………………………………………………………………………………………………………………...

………………………………………………………………………………………………………………………………………...

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