South East London & Kent PDNS Team

Best Practice Guidelines 2013.

This booklet has been produced following an educational grant from Britannia Pharmaceuticals Ltd.

The Use of Apomorphine in

Parkinson’s Disease

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

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.

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

Foreword

Introduction

3

infusion is recommended for those patients who require exposure to apomorphine for

prolonged periods throughout the day.

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

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.

Objectives

Background

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

GP referral –Complex phase reached

Patient selection by Consultant Neurologist/ Physician.

Apomorphine treatment and guidelines discussed with GP and Patient prior to initiation /

admission (SCG)

Agreement to initiate treatment reached between patient, GP

and Consultant.

Local Parkinson’s Disease Nurse Specialist

Liaison with Patient and Carers, GP by coordinating PDNS

Start Domperidone 20-mg tds three days prior to Apomorphine

challenge

Apomorphine challenge

Intermittent Apomorphine

injection

Continuous ‘waking hours’ infusion via

syringe driver

If positive result, plan ongoing treatment.

Training, assessment and information

Discharge in to Primary Care

Liaison with GP, district nurses, community pharmacist, local

PDNS and multidisciplinary team

GP to prescribe on – going drug therapy as agreed prior to

challengeCommunity pharmacist to supply

Apomorphine

Liaison with CCG & Community Nurse re provision of equipment.

Any problems

Follow up: Regular outpatient appointments. Optimisation of treatment Monitor and evaluate adverse

reactions - bloods Information to patient, carers and

primary care teamLocal PDNS

5

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.

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.

Specialist Intervention

Motor Fluctuations

6

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.

Shared Care

7

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 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.

Apomorphine therapy

Presentation

8

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

Apomorphine challenge

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.

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.

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 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.

Positive Challenge

Intermittent subcutaneous injections

Treatment Strategy

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).

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.

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.

Intermittent Subcutaneous Injection via a pre–filled multiple dose Pen

Continuous subcutaneous infusion using the Crono APO-go Pump

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.

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

Preparation of the infusion

12

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 SettingsInfusion 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

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 EffectsPharmacological Mode of administration

Side Effects

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Nausea and vomiting

Dyskinesias during ‘ON’ time

Neuropsychiatric complications –

Hallucinations, euphoria,

increased libido, confusion,

personality changes, agitation,

restlessness, psychosis, sleep

disturbance.

Sedation

Orthostatic hypotension

Light-headedness

Haemolytic anaemia

(uncommon 0.1-1%)

Eosinophilia

Nodule formation at injection or

infusion site

Local infection/abscess

/ulceration/scarring

Localised discomfort at injection or

infusion site

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.

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

Apomorphine induced nodules: how to reduce incidence and discussion of possible treatments.

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.

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

Daily Dose

Cost *

Daily Use 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

Cost of Apomorphine therapy

16

Daily Dose

Cost **

Daily Use 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

Daily Dose Range

Cost

Weekly Monthly Annually

10mg

three times a day

£1.06 £4.56 £55.52

20mg

three times a day

£2.13 £9.13 £111.03

Prices quoted are inclusive of VAT

Source: MIMS October 2006

APPENDIXFurther 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.

Appendix seven: Care Home Assessment: PD information.

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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.

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

18

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 knowa) Number of milligrams per hour of Apomorphine requiredb) 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 dressingsSilgel patch, if used.Contact number of PDNS or DN Blue District Nurses folder, don’t forget to bring this home again!

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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.

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.

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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.

Date

Syringe setting10ml / 20ml

ApomorphineTotal mg in syringe

0.9% sodium chloride

ml in syringe or PFS

Apomorphine dosemg per hour

Bolus dosed setting

Flow rateF setting

Signature

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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

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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.

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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 MedicationAfter 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 Pen3) 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.

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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 time

Current Symptom Yes No Usual time

Bradykinesia HallucinationsRigidity Confusion/memoryTremor Sleep issuesFreezing Loss of appetiteDizziness/giddiness Loss of weightBalance problems Difficulty swallowingWeakness DribblingDystonia NauseaCramp VomitingDyskinesias CoughOn/off problems Urinary problemsEnd of dose Sexual dysfunctionAnxiety/worry Bowel problemsBreathlessness Menopausal/HRTDepression Speech problems

Swallow problemsAnything 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.

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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 needlesPre filled Syringes or Apomorphine ampoules and 0.9% saline ampoulesSyringe driver and syringes Infusion lines Film dressings

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

DATE No. PROBLEM GOAL NURSING PLAN SIGNATURE REVIEW DATE

Uncontrolled Parkinson’s disease.

Motor fluctuations and sustained unpredictable ‘OFF’ periods, resulting in poor quality ‘OFF’ time.

To maximise ‘ON’ time

Safe administration of Apomorphine

Improve quality of life

Ensure Apomorphine is prescribed correctly. 50mg = 1 x 10ml syringe, 100mg = 2 x 10ml To be given during waking hours / over night Ensure Domperidone 20 mg tds is prescribed 72 hours

before starting apomorphine If using a 10ml volume ensure the spacer is attached to

the APO-go pump. Slide plunger up/down to loosen. Unscrew the syringe plunger, leaving black bung at the

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!

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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

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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.

PROTOCOLA. 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 challengeD. 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 bandCheck patients understanding of procedureHas 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

Base line motor scale of Unified Parkinson’s Disease Rating ScaleHas Apomorphine or Levodopa been prescribed correctly

T R P BP BP

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Handwriting sample pre and post challenge

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

Procedure for Apomorphine challenge

Suggested Intervals / time

Intervention Comments (monitor BP)

Signature

00.00 Administer 1.0mg Apo15 mins Reassess UPDRS part III30 mins Administer 3mg Apo45 mins Reassess UPDRS part III60 mins Administer 5mg Apo1hr 15 mins Reassess UPDRS part III1hr 30 mins Administer 7mg Apo1hr 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 (monitor BP)

Signature

00.00 Administer 275mg Sinemet, or250mg Madopar dispersible

30 mins Reassess UPDRS part III1hr Reassess UPDRS part III1hr 30mins Reassess UPDRS part III2 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.

PRE POST

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UNIFIED PARKINSON’S DISEASE RATING SCALE / MOTOR FUNCTION LEVODOPA / APOMORPHINE CHALLENGE

I-dopa / ApomorphineTimeSpeechFacial expressionTremor: head, jaw, mouthHands RightHands LeftFeet RightFeet LightAction tremor / hands RAction tremor / hands LRigidity: neckArms RightArms LeftLegs RightLegs LeftFinger Taps RightFinger Taps LeftHand Grips RightHand Grips LeftHand pronate/ supinate RHand pronate/ supinate LHeel / toe taps RightHeel / toe taps LeftArise from chairPosturePostural stabilityGaitBody bradykinesiaTotal pointstimed 12m Walk

To calculate the percentage improvement:

1) calculate the point improvement, i.e. starting score 87 last score 5187 – 51 = 36 point improvement

2) transform to a percentage:point improvement x 100 = %starting scoretherefore: 36 x 100 = 41% improvement

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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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