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Apomorphine

  • This is a dopamine agonist used for the management of motor symptoms of Parkinson's disease (PD). 1
  • It has several different characteristics which mark it out from the rest of the dopamine agonist group used in the management of PD.
  • It is given subcutaneously.
  • It is structurally similar to dopamine and its use results in a rapid improvement in motor symptoms of PD by stimulation of dopaminergic receptors in substantia nigra.
Indications2,3
  • It is suitable for patients with advanced disease which is difficult to manage with levodopa. Age and disease duration does not affect efficacy.
  • As a rescue agent to provide rapid but short-lived benefit for sudden, severe 'Off' episodes, to establish whether further benefit can be obtained by increasing the dose of oral agents.
  • In patients unable to take oral medication due to acute illness or chronic dysphagia.
  • In cases of diagnostic difficulty.
Cautions, contra-indications2,4
  • The population in whom apomorphine can to most good is ironically the same in whom it can do most harm - i.e. elderly patients, who often have multisystem disease.
  • It is specifically contraindicated in neuropsychiatric conditions, dementia, or if 'On' response to levodopa is marred by severe dyskinesia, hypotonia or psychiatric effects.
  • Monitoring for hepatic, renal, cardiovascular complications, and haemolytic anaemia is required.

See drug monograph for full list.

Adverse Effects2,4

Mainly nausea, vomiting and postural hypotension.

Main Interactions

Apomorphine is antagonised by antipsychotics and methyldopa; it is enhanced by entacapone, memantine. See drug monograph for full list.

The Apomorphine Challenge Test. 2
WARNING: The onset of postural hypotension in patients challenged with apomorphine can be severe and unpredictable. It should only be attempted in clinical setting where such emergency can be dealt with - i.e. access to full resuscitative facilities and expertise.

Purpose

To check:


  • Whether the patient responds to the medication.
  • Optimal dose - (efficacy vs adverse effects).
  • Educate patient/carers in delivery method.
  • Assess whether patient likely to respond to further dopaminergic stimulation if already on oral medication - the decision may then be to either commence therapy to increase oral medication rather than start apomorphine.

Protocol


  • Prescribe domperidone 20mg t.d.s to be started 3 days prior to challenge.
  • Perform a routine ECG to rule out cardiac disease.
  • Provide information and obtain informed consent.
  • Advise the patient to have an early light breakfast, as the test can take several hours.
  • The patient needs to be in the 'Off' phase, so morning medication is usually omitted. This may vary depending on mobility needs of patient.
  • Perform challenge first thing in morning to minimise patient discomfort.
  • Perform a baseline motor examination using the Unified Parkinson's Disease Rating Scale (UPDRS).5 Time a 6 or 12m walk.
  • Administer single increasing subcutaneous doses of apomorphine (e.g.1.5mg, 3mg, 4.5mg, 6mg, 7mg) at 45 minute to one hour intervals until a response is seen. If there is a mild response at 7mg, some clinics use 10mg.
  • Recheck motor assessment 20 minutes after each dose using UPDRS - e.g. walking, time in seconds required to tap index finger right or left hand 20 times between 2 points placed 12 inches apart.

Interpretation of Results and Further Action

A challenge is positive if there is:


  • A decrease in the UPDRS motor score by at least 20%
  • At least a 20% improvement in either timed hand tests or timed walking

If there is a positive challenge, consider whether to increase levodopa dose (as test proves that condition is responsive to dopaminergic stimulation) or to institute apomorphine.

Methods of Delivery6,7,8,9
  • Intermittent Subcutaneous Injections
    • These are used as rescue therapy for disabling 'Off' periods in patients taking oral therapy.
    • The 'Off' period can be averted or reversed within 10-15 minutes and can last for up to one hour.
    • They are suitable for patients who have short 'Off' periods less than six times a day. For more frequent episodes, continuous infusion should be considered.
    • Injections need to be given no later than the beginning of the 'Off' period.
    • Most patients can be taught to self-administer. Injection should be to lower abdominal wall below umbilicus, upper outer aspect thighs, or outer aspect top of arms.
    • Patients should be advised to rotate the injection site, and gently massage after administration, to avoid nodule formation.
    There are two ways to administer apomorphine. Choice governed by patient preference, condition and cost.
    • Pre-filled penject device (APO-go Pen®) - 30mg in 3 ml, needs to be discarded every 48 hours but needle needs changing after each injection
    • Insulin-type syringe - patient prepares syringe using 2ml (10mg/ml) amp apomorphine, prepared on daily basis, discard unused syringe after 24 hours.
  • Continuous Infusion
    • Indicated for patients with advanced disease who experience frequent unpredictable and disabling motor fluctuations and dyskinesias despite maximal oral therapy
    • Can be given as adjunct or monotherapy
    • Benefits comparable to deep brain stimulation of subthalamic nucleus
    • Most patients only need infusion during waking hours, a few need 24 hour therapy
    • Mean daily dosage range 50-100mg per day
    • Initiation requires hospital admission to educate patient and monitor for side effects
    • Titration in community required, may take several months to obtain optimal dose and response
    • Used to be administered only by Sims -Graseby syringe driver
    • APO-go pump now available
    • Choice depends on patient preference and cost

Document references
  1. Summary of Product Characteristics - APO-go® PFS 5mg/ml Solution for Infusion in Pre-filled Syringe (apomorphine) Britannia Pharmaceuticals Limited updated Oct 2005; electronic Medicines Compendium.
  2. Sharma JC, Macnamara L, Hasoon M, et al; Diagnostic and therapeutic value of apomorphine in Parkinsonian patients.; Int J Clin Pract. 2004 Nov;58(11):1028-32. [abstract]
  3. Cotzias GC, Papavasiliou PS, Tolosa ES, et al; Treatment of Parkinson's disease with aporphines. Possible role of growth hormone.; N Engl J Med. 1976 Mar 11;294(11):567-72. [abstract]
  4. Colzi A, Turner K, Lees AJ; Continuous subcutaneous waking day apomorphine in the long term treatment of levodopa induced interdose dyskinesias in Parkinson's disease.; J Neurol Neurosurg Psychiatry. 1998 May;64(5):573-6. [abstract]
  5. Unified Parkinson's Disease Rating Scale; MD Virtual University
  6. Kempster PA, Frankel JP, Stern GM, et al; Comparison of motor response to apomorphine and levodopa in Parkinson's disease.; J Neurol Neurosurg Psychiatry. 1990 Nov;53(11):1004-7. [abstract]
  7. Swinn LA, James CR, Quinn NP et al, Shared Care Guidelines 2005: Treatment of Parkinson's Disease with Apomorphine
  8. Esteban Munoz J, Marti MJ, Marin C, et al; Long-term treatment with intermitent intranasal or subcutaneous apormorphine in patients with levodopa-related motor fluctuations.; Clin Neuropharmacol. 1997 Jun;20(3):245-52. [abstract]
  9. Katzenschlager R, Hughes A, Evans A, et al; Continuous subcutaneous apomorphine therapy improves dyskinesias in Parkinson's disease: a prospective study using single-dose challenges.; Mov Disord. 2005 Feb;20(2):151-7. [abstract]
Internet and further reading AcknowledgementsEMIS is grateful to Dr Laurence Knott for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2008.
DocID: 277
Document Version: 3
DocRef: bgp26035
Last Updated: 10 Jul 2007
Review Date: 9 Jul 2008

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