Is Monitoring Required?

Shared Care Protocol

Shared Care Guideline for Reference Number Apomorphine use in Parkinson’s Disease

Version: 3.1 Replaces: 3 Issue date: 12/09/2017 Author(s)/Originator(s): (please state author name and To be read in conjunction department) with the following Carol Miller, Emma Wilson and Chris Kobylecki documents: Salford Royal Hospital Current Summary of Product Neurology Department characteristics (http://www.medicines.org.uk) BNF

Date approved by Interface Prescribing Group: Date approved by Greater Manchester 12/05/2016 Medicines Management Group: 16/06/2016 Date approved by Commissioners: Review Date: dd/mm/yyyy 01/01/2018 Please complete all sections 1. Name of Drug, Brand Apomorphine (APO-go®) 10mg/ml Solution for Injection in 3ml PEN or 5mg/ml Solution for Name, Form and Infusion in Pre-Filled Syringe in 10ml syringe (PFS) Strength 2. Licensed Indications The treatment of disabling motor fluctuations (“on-off” phenomena) in patients with Parkinson's disease which persist despite individually titrated treatment with levodopa (with a peripheral decarboxylase inhibitor) and/or other dopamine agonists 3. Criteria for shared Prescribing responsibility will only be transferred when care  Treatment is for a specified indication.  Treatment has been initiated and established by the secondary care specialist.  The patient’s initial reaction to and progress on the drug is satisfactory.  The GP has agreed in each individual case that shared care is appropriate.  The patient’s general physical, mental and social circumstances are such that he/she would benefit from shared care arrangements

4. Patients excluded  Unstable disease state from shared care  Patient does not consent to shared care  Patient does not meet criteria for shared care

5. Therapeutic use & Parkinson’s disease is a progressive degenerative neurological condition that affects background nerve cells in the substantia nigra and basal ganglia (the parts of the brain controlling movement). Parkinson’s disease is caused by idiopathic degeneration of dopamine producing cells in this area. Three ‘cardinal signs’ of Parkinson’s disease are resting tremor, cogwheel rigidity and bradykinesia. Postural instability, typically a late finding in Parkinson’s disease is the fourth main symptom. Parkinson’s disease is characterised by a good symptomatic response to levodopa. Parkinson’s disease is one of the commonest neurological conditions to affect older people. It is estimated to affect 160 per 100,000 of the general population. Version: 3.1 Shared Care Guideline for Apomorphine Page 1 of 4 Date: 12/09/2017 Apomorphine treatmentuse in is Parkinson’s to be initiated, Disease and doses optimised by the hospital specialist Review: 1st Jan 2018 team. ContinuationCurrent ofversion the therapyis held on requiresGMMMG Websiteco-operation between the hospital and Primary Care teamsCheck with with theirinternet roles that thisdefined printed by copy the of shared the latest care issue protocol. Apomorphine is a directly acting dopaminergic agonist, licensed for use in patients with Parkinson’s disease who have frequent and/or severe akinesia (“off periods”) not controlled by levodopa or other dopamine agonists

Apomorphine is a dopamine agonist, which acts directly on D1 and D2 receptors, Appendix 1 – Local Contact Details

Commissioner contact information Name: [insert text here]

Email: [insert text here]

Contact number: [insert text here]

Organisation: [insert text here]

Secondary care contact information If stopping medication or needing advice please contact:

Dr [insert text here]

Contact number: [insert text here]

Fax Number: [insert text here]

Hospital: [insert text here]

Version: 3.1 Shared Care Guideline for Apomorphine Page 2 of 4 Date: 12/09/2017 use in Parkinson’s Disease Review: 1st Jan 2018 Current version is held on GMMMG Website Check with internet that this printed copy of the latest issue Shared Care Guideline Summary: APOMORPHINE for the treatment of PARKINSON’S DISEASE

Drug Apomorphine (APO-go®) 10mg/ml Solution for Injection in 3ml PEN or 5mg/ml Solution for Infusion in Pre-Filled Syringe in 10ml syringe (PFS) Indication The treatment of disabling motor fluctuations (“on-off” phenomena) in patients with Parkinson's disease which persist despite individually titrated treatment with levodopa (with a peripheral decarboxylase inhibitor) and/or other dopamine agonists. Overview Apomorphine is a dopamine agonist, which acts directly on D1 and D2 receptors, stimulating areas of the brain where dopamine works. It produces a similar effect to levodopa, that is, the ability to prevent and reverse disabling “off” periods. Despite its name it has no opiate or addictive properties. Apomorphine cannot be used orally because it undergoes extensive first pass metabolism (in the liver) to an inactive metabolite; for this reason it is administered subcutaneously. Apomorphine may be administered as a “rescue therapy” with intermittent subcutaneous bolus injections given via a prefilled Apomorphine Pen: 10mg/ml Solution for Injection in a 3ml Pen (Apomorphine Pen) Patients selected for treatment with Apomorphine should be able to recognise the onset of their ‘off’ symptoms and be capable of injecting themselves or else have a responsible carer able to inject for them when required For those patients who experience more complex motor fluctuations, including dyskinesias, a continuous subcutaneous infusion using an ambulatory Apomorphine pump may be used with the Apomorphine PFS. Specialist’s Initial investigations: Assess suitability of patient for treatment. Discuss benefits and side-effects of Responsibilities treatment with the patient. Undertake baseline investigations (BP, Hb, Reticulocyte count). Carefully consider whether the benefits of concomitant apomorphine and domperidone treatment outweigh the small increased risk of cardiac side effects as per MHRA Drug Safety Update.

Initial regimen: The optimal dosage of Apomorphine has to be determined on an individual patient basis and the threshold dose is determined by the specialist using incremental dosing schedules. Once the optimal dose for an individual patient has been determined and the patient is stable, the dose is likely to remain relatively constant. The daily dose of Apomorphine varies widely between patients.

Clinical & Safety monitoring: Monitoring for response and adverse drug reactions (ADRs) during initiation period. Evaluating ADRs raised by the GP and evaluating any concerns arising from reviews undertaken by GP.

Prescribing details: Initiate treatment including domperidone. To stop the drug or provide GP with advice on when to stop this drug.

Documentation: The consultant team will write formally to the GP to request shared care using the GMMMG agreed process. Patients will only be transferred to the GP once the GP has agreed. Provide GP with diagnosis, relevant clinical information, treatment plan, duration of treatment with 14 days of seeing the patient or inform GP if the patient does not attend appointment. GP’s Maintenance prescription: Prescribe apomorphine and domperidone in accordance with the Responsibilities specialist’s recommendations. Maximum recommended dose as per BNF. Clinical monitoring: To report to and seek advice from the specialist on any aspect of patient care which is of concern to the GP and may affect treatment. Safety monitoring: FBC – 6 monthly Duration of treatment: Stop treatment on advice of specialist team. Re-referral criteria: Seek urgent advice from secondary care if:  Toxicity is suspected  The patient becomes pregnant

Version: 3.1 Shared Care Guideline for Apomorphine Page 3 of 4 Date: 12/09/2017 use in Parkinson’s Disease Review: 1st Jan 2018 Current version is held on GMMMG Website Check with internet that this printed copy of the latest issue  Non-compliance is suspected  The GP feels a dose change is required  There is marked deterioration in the patient’s condition  The GP feels the patient is not benefiting from the treatment Documentation: GPs should reply to request for shared care to either accept or decline within 14 days. A form is available on the GMMMG website to facilitate this, if you so wish. Adverse Events Adverse events Action Localised discomfort at needle site Assessment by nurse. Nodule formation at needle or infusion site. Usually Rotate injection site. asymptomatic but may persist in patients on high Massage to injection sites is recognised to reduce doses. Severe nodule formation may lead to nodule formation. Ultrasound therapy has been worsening of symptoms due to erratic absorption of anecdotally said to alleviate severe nodule formation. Apomorphine Anecdotally Hirudoid cream can be used on nodules Nausea & vomiting. Usually transient and resolved Treatment with Domperidone 10-20mg oral TDS daily, within 6-8 weeks 48 hours before and during Apomorphine therapy is essential . Once treatment has been established Domperidone* therapy may be gradually reduced and can be successfully discontinued in most patients within 6-8 weeks * please refer to latest recommendations for Domperidone Where Domperidone is contraindicated, consider requesting secondary care to prescribe Ondansetron Allergic reactions including bronchospasm and Withhold and discuss with Consultant/PDNS anaphylaxis (due to sodium bisulphate) Light-headedness Discuss with Consultant /PDNS Postural hypotension is seen infrequently and is Care should be exercised in patients with pre-existing usually transient cardiac disease or in patients taking vasoactive medicinal products such as antihypertensives, and in patients with pre-existing postural hypotension. Dyskinesias during ‘On’ periods Discuss with Consultant /PDNS Coombs positive Haemolytic anaemia Coombs’ test is carried out at baseline (if deemed appropriate). If positive, the patient should have a further blood screen of the same parameters after one month’s treatment and then have FBC and reticulocyte count at 6 monthly hospital visits from then on but no requirement to keep doing Coombs’ tests provided FBC remains normal Eosinophilia in up to 10% of patients Discuss with Consultant /PDNS Dopamine dysregulation, Discuss with Consultant /PDNS neuropsychiatric complications – hallucinations, euphoria, increased libido, confusion, personality changes, agitation, restlessness, psychosis, sleep disturbances, pathological gambling and over eating Sedation. Usually transient Advise patients not to drive / operate machinery if affected. If persists discuss with Consultant / PDNS Contra-indications Please refer to the BNF and/or SPC for information Cautions Please see the MHRA drug safety alert for domperidone with apomorphine: Drug Interactions https://www.gov.uk/drug-safety-update/apomorphine-with-domperidone-minimising-risk-of- cardiac-side-effects Other Information APO-go® Information is available for both patients and healthcare professionals at www.apo- go.co.uk An APO-go Helpline is available for patients and healthcare professionals 24/7, 365 days a year, tel: 0844 880 1327. Contact Details Name: [insert text here] Address: [insert text here] Telephone: [insert text here]

Version: 3.1 Shared Care Guideline for Apomorphine Page 4 of 4 Date: 12/09/2017 use in Parkinson’s Disease Review: 1st Jan 2018 Current version is held on GMMMG Website Check with internet that this printed copy of the latest issue