CHHS18/071

Canberra Hospital and Health ServicesClinical Procedure Apomorphine – Treatment Guidelines for Initiation, Administration and Monitoring of Adults with Parkinson’s DiseaseContents

Contents....................................................................................................................................1

Purpose.....................................................................................................................................3

Alerts.........................................................................................................................................3

Scope........................................................................................................................................ 3

Section 1 – Background.............................................................................................................3

Section 2 – Administration options...........................................................................................4

2.1 Intermittent Subcutaneous Injections.............................................................................4

2.2 Continuous Subcutaneous Infusion.................................................................................4

Section 3 – Referral Process......................................................................................................4

3.1 Internal Referral Process.................................................................................................4

3.2 External Referral Process................................................................................................5

Section 4 – Pre-Admission.........................................................................................................7

Section 5 – Apomorphine Challenge.........................................................................................7

Section 6 – Titration post Apomorphine Challenge..................................................................9

6.1 Continuous Subcutaneous Infusion.................................................................................9

6.1.1 Pump Flow Rate.......................................................................................................9

6.1.2 Bolus Dose................................................................................................................9

Section 7 – Post discharge.......................................................................................................10

Implementation...................................................................................................................... 11

Related Policies, Procedures, Guidelines and Legislation.......................................................11

References.............................................................................................................................. 12

Definition of Terms................................................................................................................. 12

Search Terms.......................................................................................................................... 12

Attachments............................................................................................................................12

Attachment 1 – Tomlinson Levodopa Conversion Table.....................................................14

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Attachment 2 – Patient Selection Guidelines for Commencement of Apomorphine Therapy............................................................................................................................................ 15

Attachment 3 – Joint Position Statement on Apomorphine Hydrochloride........................16

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Purpose

The purpose of this procedure is to provide a pathway for the commencement of Apomorphine therapy for patients with Parkinson’s disease at the Canberra Hospital and Health Services (CHHS).

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Alerts

Apomorphine may induce nausea and vomiting and it is recommended to commence 10mg Domperidone three times daily (TDS) at 48-72 hours prior to an Apomorphine Challenge ( section 5 ) , then continue for 3-7 days in total, or as required.

Apomorphine may cause hallucinations and impulse control disorder and close monitoring is essential during the initiation phase.

Apomorphine is NOT morphine, nor does it have any analgesic or addictive properties.

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Scope

This document applies to adults with a diagnosis of Parkinson’s disease and who have been identified as potentially eligible to commence Apomorphine therapy.

This document applies to the following staff working within their scope of practice: Medical Officers Nurses and Midwives Pharmacists Students under direct supervision.

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Section 1 – Background

Apomorphine is a potent dopamine agonist considered an effective therapy for Parkinson’s disease. It is a Schedule 100 medication and cannot currently be prescribed by General Practitioners in the ACT.

Apomorphine mimics the role of dopamine, ultimately assisting to control body movement. Apomorphine will not work for every person with Parkinson’s and patients must meet certain criteria, see Attachment 2, to start Apomorphine treatment. Apomorphine is a viable option for patients who no longer gain adequate control of their symptoms through oral dopaminergic treatment.

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Apomorphine’s effectiveness is measured through a series of assessments pre and post administration of the medication. These assessments must be completed within specific time frames and by individuals qualified to do so.

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Section 2 – Administration options

Apomorphine can be administered using two different options based on the symptoms present in the patient being trialled. The referring Medical Officer should indicate which administration option they are aiming to achieve.

2.1 Intermittent Subcutaneous InjectionsPatients who experience unpredictable or predictable ‘OFF’ periods are suited for intermittent subcutaneous injections of Apomorphine as an ‘on-demand’ therapy.

2.2 Continuous Subcutaneous InfusionSuitable for patients who are unable to achieve adequate ‘ON’ periods on oral dopaminergic therapy alone or who experience significant Levodopa Induced Dyskinesia (LID).

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Section 3 – Referral Process

Apomorphine Challenge, see Section 5, and initiation will be done under supervision and guidance from a Neurologist with the support from the Parkinson’s Advanced Practice Nurse (APN).

3.1 Internal Referral ProcessProcedure Once a patient is identified as suitable for initiation of Apomorphine the Neurologist or Geriatrician must:1. Confirm diagnosis and ensure the patient meets Pharmacy Benefits Scheme (PBS) criteria

under Section 100.2. Obtain informed written consent.3. Request baseline tests:

a. Electrocardiogram (ECG)b. Full blood count (FBC)c. Liver function test (LFT)d. Urea, electrolytes and creatinine (UEC)e. Erythrocyte sedimentation rate (ESR)f. Coombs test (for haemolytic anaemia).

Once a patient is identified as suitable by their CHHS Neurologist or Geriatrician for initiation of Apomorphine, a referral is made to the Parkinson’s APN via email for education and pre-admission information. The Parkinson’s APN will allocate a 120 minute appointment to

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provide education and pre-admission information. During this appointment, the Parkinson’s APN will conduct the following assessments:1. United Parkinson’s Disease Rating Scale (UPDRS)2. Montreal Cognitive Assessment (MoCA)3. Questionnaire for Impulse Control Disorders (QUIP) 4. Electrocardiogram (ECG)5. Blood Pressure – standing/sitting (BP)

The following documents are sent to the patient prior to the appointment for completion:1. Parkinson’s Disease Questionnaire - (PDQ-39)2. Freezing of Gait Questionnaire - (FOG-Q)3. Parkinson’s Diary

The Parkinson’s APN will report back to the referring Neurologist or Geriatrician and the decision on whether to proceed to Apomorphine Challenge will be made.

The Parkinson’s APN will use the Apomorphine Challenge Education Checklist, which can be found on the Clinical Forms Register, to document that all education requirements have been met, including how to access ongoing consumables.

Once approved for a trial of Apomorphine a ‘Planned Hospital Admission Booklet’ must be completed by the accepting/treating Neurologist or Geriatrician for admission to conduct an Apomorphine Challenge. The Neurologist or Geriatrician also needs to provide the patient with a script. The Neurologist or Geriatrician must indicate whether the patient is to continue on intermittent subcutaneous injection or continuous subcutaneous infusion post the Apomorphine Challenge.

Note: In line with best practice principles trialling of Apomorphine will be done in an inpatient environment as patients are required to withhold oral dopaminergic agents prior to trial commencement; this can cause significant bradykinesia and rigidity which would make traveling a considerable inconvenience.

3.2 External Referral ProcessProcedurePatients identified as potentially suitable to commence Apomorphine therapy will require a referral to be addressed to a Neurologist at the Canberra Hospital and Health Services.

The referring Medical Officer should provide the patient with a blood request form including the following tests:a. FBCb. LFTc. UECd. ESRe. Coombs test (for haemolytic anaemia)

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The referral is triaged as a Category 2 and the patient is allocated an appointment time with a Neurologist to be assessed for eligibility. If assessed as eligible by the Neurologist, the Parkinson’s Advanced Practice Nurse (APN) will allocate a 120 minute appointment to provide education and pre-admission information. During this appointment the Parkinson’s APN will conduct the following assessments:1. UPDRS2. MoCA3. QUIP4. ECG5. BP – standing/sitting

The following documents are sent to the patient prior to appointment for completion:1. PDQ-392. FOG-Q3. Parkinson’s Diary

The Parkinson’s APN will use the Apomorphine Challenge Education Checklist, which can be found on the Clinical Forms Register, to document that all education requirements have been met, including how to access ongoing consumables. The Parkinson’s APN will initiate completing the Parkinson’s Apomorphine Challenge Guideline, which can be found on the Clinical Forms Register.

Once approved for a trial of Apomorphine a Planned Hospital Admission Booklet (as found on the clinical forms register) must be completed by the accepting/treating Neurologist for admission to conduct an Apomorphine Assessment.

Note: In line with best practice principles trialling of Apomorphine will be done in an inpatient environment as patients are required to withhold oral dopaminergic agents prior to trial commencement; this can cause significant bradykinesia and rigidity which would make traveling to the hospital a safety risk for the patient.

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Section 4 – Pre-Admission The Neurologist or Geriatrician will:1. Complete consent.2. Complete Planned Hospital Admission Booklet, found on the clinical forms register.3. Inform on-call Neurologist of Apomorphine initiation (for additional medical support

during admission).4. Ensure a medication order is completed.

The Parkinson’s APN will:1. Organise a planned admission, as per CHHS Admission to Discharge procedure, to 7A and

notify Hospital in the Home (HITH) to ensure they have capacity to admit the patient post Apomorphine Challenge.

2. Contact the patient and provide admission instructions.3. Remind the patient that their medication will be withheld on admission.4. Arrange with pharmacy to have the Apomorphine available and delivered to the ward on

day of admission.5. Educate and support ward staff about the procedure prior to admission.6. Schedule Apomorphine Challenge on any week day.

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Section 5 – Apomorphine Challenge

The patient will be assessed using three separate challenge doses of Apomorphine: 2mg, 3mg, and 5mg. The aim is to achieve an ‘ON’ period within 7-10 minutes and duration effect of roughly 45-60 minutes. There will be a minimum of 45 minutes between each dose to allow for the drug to ‘wear-off’ prior to dosage increment. The entire Apomorphine Challenge is expected to take 4-5 hours to complete (however this may vary based on individual response).

Equipment 1. Apomorphine (Movapo®) solution for injection ampoule 20mg/2mL2. 3 x 1mL syringes3. 3 x Chlorhexidine Swabs4. Kidney dish5. Parkinson’s - Apomorphine Challenge template, as found on the clinical forms register.

ProcedureOn admission:1. The Parkinson’s APN will use the Parkinson’s - Apomorphine Challenge template to

document the following information after confirming with the patient:a. Their name, Date of Birth and Unique Record Number (on the patient record)b. If they have any allergiesc. They consent to the procedure

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d. They understand the proceduree. The reason for conducting the Apomorphine Challengef. Current Parkinson’s medicationsg. Other medications for Parkinson’s that they have trialledh. That they have been assessed and deemed as having stable cardiac, renal,

respiratory and psychiatric functioni. All Parkinson’s medication have been withheld for a minimum of six hours prior to

challenge – this ensures an ‘OFF’ statej. Any dopamine agonist medications have been withheld for at least twelve hours

Note: The patient is NOT required to be nil by mouth – only withhold Parkinson’s medications. Medication is to be administered as per the Medication Handling Policy located on the policy register.

2. The Parkinson’s APN will:a. record a set of baseline vital signsb. conduct a UPDRS assessment to establish ‘OFF’ baseline – use the Parkinson’s -

Apomorphine Challenge template, which can be found on the Clinical Forms Registerc. administer the first dose (2mg) of Apomorphine into the selected site

(abdomen/thigh) d. conduct another UPDRS assessment 10 minutes after administration of first dosee. administered the second dose (3 mg) of Apomorphine into the selected site

(abdomen/thigh) f. conduct another UPDRS assessment 10 minutes after administration of second doseg. administered the third dose (5mg) of Apomorphine into the selected site

(abdomen/thigh) h. conduct another UPDRS assessment 10 minutes after administration of third dose

3. The Apomorphine percentage response will be calculated, as per template instructions, and reported back to the treating Neurologist or Geriatrician

4. The treating Neurologist or Geriatrician will decide the discharge/transfer of the patient accordingly:a. Intermittent subcutaneous injections: to home (as long as the patient is stable) b. Continuous subcutaneous infusion: to HITH (as long as the patient is stable) with the

following documentation to be completed by HITH staff prior to transfer:i. Referral and Consent for Treatment Hospital in the Home (as found on the clinical

records forms register)ii. Titration plan as prescribed by Neurologist or Geriatrician.

Note: If the patient achieves adequate ‘ON’ after the second dose, the third dose of Apomorphine can be withheld.

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Section 6 – Titration post Apomorphine Challenge

It is expected that the patient achieves a percentage response of at least 30% in order to continue on Apomorphine therapy, any response below 30% is considered a failed challenge. If the patient fails the challenge they are considered unresponsive and are deemed not suitable for ongoing Apomorphine.

6.1 Continuous Subcutaneous InfusionOnce the Apomorphine Challenge has been completed on the ward the patient will be transferred to HITH for ongoing monitoring and dose titration. HITH staff will be supported by the Parkinson’s APN under direction from the treating/accepting Neurologist or Geriatrician to ensure titration is done correctly. Additionally, as and when necessary, the APN/HITH nurses can take help from the nurses of the product manufacturer.

Once the successful challenge dose is determined, the starting rate of the Apomorphine infusion will be set at half this dose; i.e. if the challenge dose was determined to be 5mg, the starting continuous infusion rate will be 2.5mg/hr.

The recommended titration rate is 0.5mg/hr weekly with simultaneous reduction of oral medications calculated to the approximate Levodopa Equivalent Dosage (LED) using the Tomlinson table in Attachment 1.

6.1.1 Pump Flow RateStarting Rate: _____________mg/hr = (_____mL/hr)Range: ________mg/hr to ______mg/hr (_______mL/hr to ______mL/hr)

6.1.2 Bolus Dose Bolus dose: _____________mg = (_____mL) Lockout time: ________Range: ________mg to ______mL (_______mg to ______mL)

The patient will be reviewed on a regular basis, determined by the individual Specialist and as required in their clinic.

The patient will be provided with the Parkinson’s APN contact phone number for ongoing support of their Apomorphine Therapy. Patients will also be provided with the Nurse Advisor contact details from the product manufacturer for additional support.

The patient will be provided with login instructions to enable them to order consumables using the mobile application: myINTERACT® and given supporting documentation on how to troubleshoot pump errors.

If at any stage the patient, or their carer, is no longer able to self-manage the pump due to a short-term illness or injury a referral should be made to the Community Care Program for support during this time. Community Care Program nursing staff will be educated and supported by the Parkinson’s APN.

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Note: In the event of after-hours presentation to hospital an ‘Apomorphine Kit’ will be accessible to the after-hours hospital manager to assist with trouble shooting the device.

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Section 7 – Post discharge

A copy of the Parkinson’s - Apomorphine Challenge form will be sent to the General Practitioner along with a report outlining the following:1. Patient response including calculated UPDRS percentage improvement (use

Apomorphine percentage response calculation, as per template instructions)2. Instructions for ongoing treatment – intermittent or continuous infusion

a. Intermittent: dosage and frequencyb. Continuous:

i. Pump flow rateii. Bolus doseiii. Lock out time

3. Ongoing monitoring requirements – to be done every 6-12monthsa. Full Blood Count (FBC) – check for:

i. White Cell Count (WCC) < 4 x 10⁹/Lii. Neutrophils < 1.8 x 10⁹/Liii. Platelets < 150 x 10⁹/L

b. Liver Function Test (LFT) – check for:i. ALT > 55u/L

c. Urea Creatinine Electrolytes (UEC) – check for:i. Creatinine > 90mmol/Lii. Potassium > 5mmol/L

d. Coombs Test – check for:i. Positive (for haemolytic anaemia)

4. Instructions advising what to do in the event of pump failure:a. Contact Specialist and ensure oral Parkinson’s medications are continued.

Note: If the patient presents with blood results outside of the above mentioned ranges please cease treatment and contact the treating Neurologist or Geriatrician as a matter of urgency.

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Other adverse events:1. Hallucinations2. Impulse Control Disorder3. Severe orthostatic hypotension4. Severe nausea/vomiting

If these adverse events occur please contact the treating Neurologist or Geriatrician and consider cessation of treatment under guidance from a Neurologist or Geriatrician.

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Implementation

This procedure will be presented to staff during educational in-services and an eLearning package exists on Capabiliti for staff to complete.

Any staff required to make changes to the Crono Apo-Go 111 pump must be credentialed by the Parkinson’s APN after completing the eLearning package.

The procedure will be available to all staff on the policy register.

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Related Policies, Procedures, Guidelines and Legislation

Policies Health Directorate Nursing and Midwifery Continuing Competence Policy Consent and Treatment Policy CHHS Medication Handling Policy

Procedures CHHS Healthcare Associated Infections Clinical Procedure CHHS Patient Identification and Procedure Matching Policy CHHS Admission to Discharge Procedure CHHS Medication Management

Legislation Health Records (Privacy and Access) Act 1997 Human Rights Act 2004• Work Health and Safety Act 2011

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References

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1. Trenkwalder, C., Chaudhuri, K. R., Ruiz, P. J. G., LeWitt, P., Katzenschlager, R., Sixel-Doring, F., Henriksen, T., Sesar, A., Poewe, W., Baker, M., Ceballos-Baumann, A., Deuschl, G., Drapier, S., Ebersbach, G., Evans, A., Fernandez, H., Isaacson, S., van Laar, T., Lees, A., Lewis, S., Castrillo, J. C. M., Martinez-Martin, P., Odin, P., O'Sullivan, J., Tagaris, G., Wenzel, K., Expert Consensus Grp Use, Apomorphi; Expert consensus group report on the use of apomorphine in the treatment of parkinson's disease - clinical practice recommendations, Parkinsonism Relat. Disord. 2015 Sep; 21:1023-1030

2. Garcia Ruiz PJ, Sesar Ignacio A, Ares Pensado B, Castro García A, Alonso Frech F, Alvarez López M, et al. Efficacy of long-term continuous subcutaneous apomorphine infusion in advanced Parkinson’s disease with motor fluctuations: a multicenter study. Mov Disord 2008;23:1130-6.

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Definition of Terms

Dyskinesia – unnatural involuntary random movement‘ON’ – patient reports ‘normal’ or optimal movement ability‘OFF’ – patient displays bradykinesia/rigidity/tremorBradykinesia – slow or absent movementsTremor – rhythmic involuntary movement at rest or with actionRigidity – the feeling resistance when moving the patients relaxed limb. The patient will report feeling ‘stiff’Levodopa Induced Dyskinesia – dyskinesia induced as a result of levodopa treatment

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Search Terms

Parkinson’s, Apomorphine, Challenge, Initiation, Crono Pump, Infusion

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Attachments

Attachment 1 – Tomlinson Levodopa Conversion TableAttachment 2 – Patient selection guidelines for commencement of Apomorphine therapyAttachment 3 – Joint Position Statement on Apomorphine Hydrochloride

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Disclaimer: This document has been developed by ACT Health, Canberra Hospital and Health Services specifically for its own use. Use of this document and any reliance on the information contained therein by any third party is at his or her own risk and Health Directorate assumes no responsibility whatsoever.

Policy Team ONLY to complete the following:Date Amended Section Amended Divisional Approval Final Approval 24/01/2018 Complete Review Kellie Noffke, A/g DON

MedicineCHHS Policy Committee

This document supersedes the following: Document Number Document NameCHHS13/268 Apomorphine Initiation of in Patients with Parkinson’s disease

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Attachment 1 – Tomlinson Levodopa Conversion Table

Tomlinson et al. (2010). Systematic review of levodopa dose equivalency reporting in Parkinson's disease.

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Attachment 2 – Patient Selection Guidelines for Commencement of Apomorphine Therapy

Apomorphine is a viable therapy for patients who experience fluctuating motor symptom control using oral dopaminergic therapy.

Candidates must be Levodopa responsive to be considered for Apomorphine therapy. A post Apomorphine percentage response improvement of at least 30% must be achieved during the Apomorphine challenge to proceed with treatment. With physician discretion and patient discussion 25% may be considered acceptable; determined on case to case basis.Candidates must be able to, or have a full-time carer able to, administer the injections/change pump cartridge.

Patient symptoms/indications

Apomorphine Intermittent Subcutaneous Injection (Pen)

Apomorphine Continuous Subcutaneous Infusion (Pump)

Predictable or unpredictable ‘OFF’ periods

Impairment of oral levodopa absorption (i.e. gastroparesis)

To treat delayed ‘ON’ Consider other options firstEarly morning akinesia/dystonia

Consider other options first

Dyskinesia’s limit further oral therapy optimisation

Complex PD dosing regime and/or poor adherence to therapy

x

Intermittent injections required too often N/A

Contraindications: Known hypersensitivity or allergy to Apomorphine, morphine, or other sodium

metabisulphites (sulphur) Known neuropsychiatric condition, or hallucinations with other Dopamine agonists Diagnosed dementia Severe dyskinesia’s during ‘ON’ periods (dopaminergic therapy should be optimised) Poor renal/liver function Unstable cardiovascular disease Cerebrovascular disease Respiratory depression or CNS depression.

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Attachment 3 – Joint Position Statement on Apomorphine Hydrochloride

http://www.anna.asn.au/mdc-docs/apomorphine-hydrochloride/

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