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Apomorphine (APO-Go)

Apomorphine (APO-Go)

SUMMARY SHEET FOR (APO-go)

For the treatment of Parkinson's disease

Licensed indication are no longer effective or poorly tolerated, it may be necessary to use apomorphine. The treatment of disabling motor fluctuations in patients with Parkinson's disease which persist after treatment Dosage and administration with levodopa (with a peripheral decarboxylase inhibitor) Apomorphine is administered by the subcutaneous (SC) and/or other agonists.1,2 route. It is available as ampoules for injection and as a Apomorphine should be initiated in the controlled prefilled pen-injector, all of the same strength (10mg/ml). environment of a specialist clinic.1,2 The patient should Full details on initiating treatment are given in the be assessed/treatment supervised by a physician Summary of Product Characteristics (SPC).1,2 Prior to experienced in the treatment of Parkinson's disease. The initiating apomorphine treatment, patients should be patients’ treatment with levodopa and/or dopamine established on (usually 20mg three time a agonists should be optimised before starting apomorphine day) for at least 2 days. The optimum dose of treatment. apomorphine needs to be determined on an individual Background information patient basis. During continuing treatment the daily dose varies widely between patients and is typically within the Parkinson’s disease (PD) is a progressive neurological range 3-30mg, with each dose administered at the start of disorder characterised by , bradykinesia, rigidity 3 an 'off' episode. Individual bolus injections and the total and postural disturbances. The disease results from the daily dose should not exceed 10mg and 100mg degeneration of neurones in the substantia respectively. nigra of the midbrain. For patients whose overall control remains unsatisfactory Current treatment options using intermittent injections, or who require many and Diagnosis is made on clinical grounds and should be frequent injections (>10 per day), apomorphine can be undertaken by a specialist. Treatment of PD is administered as a continuous SC infusion. symptomatic, as there is insufficient evidence of the effect Patients selected for treatment with the pen-injector should 4 of any agent on disease progression. Treatment should be able to recognise the onset of their 'off' symptoms and be be started when there is significant functional disability capable of injecting themselves, or have a responsible carer affecting activities of daily living. able to inject for them when required. Levodopa, used in conjunction with a dopa-decarboxylase Clinical efficacy inhibitor has been the mainstay of treatment in PD although dopamine agonists are now being used in the There is a lack of good quality published trials for treatment of early disease,4 particularly in younger apomorphine in the treatment of motor fluctuations in patients. It is believed that use of dopamine agonists (e.g. Parkinson's disease. Several studies have been conducted , , pergolide) at this stage may in small groups of patients, most of which have been open, delay the long-term adverse effects of levodopa e.g. non-comparative investigations or observations with dyskinesias. subjective end points. These studies collectively recorded a reduction in 'off' time of 50-85% with apomorphine Traditional treatment with levodopa can be anticipated to administered for periods of 6 months to 2 years. 6,7 control symptoms throughout the day during the first few years of therapy. Within 3-5 years of initiating treatment Data from short-term randomised controlled studies, where at least half of patients develop fluctuations in response apomorphine was administered by intermittent SC with dyskinesia and end-of-dose akinesia or ‘wearing injection, show: off’.5 Additionally the swing from mobility to immobility · a >50% reduction in 'off' time with apomorphine (vs (the ‘on-off’ effect) can become more frequent and placebo)8 abrupt. · that a significantly greater proportion of 'off' episodes were aborted with apomorphine compared with As PD progresses, adjustment of medication by addition placebo (95% vs 23% p<0.001)9 of adjunctive agents (e.g. entacapone, dopamine agonists, ), or increasing the dose of levodopa, increasing Longer-term observational studies have also been the frequency of levodopa dosing, or using a slow release published, where apomorphine was administered by SC preparation of levodopa is usually required.3 In the later infusion during waking hours or by intermittent SC stages of the disease when levodopa and dopamine injection for periods of 3 months to 9 years.10-13 These data show that the reduction in the number of 'off' periods Parkinson's disease. Data from small, short-term or time in 'off' state was sustained over the longer term. randomised controlled studies show a ³50% reduction in In many patients levodopa dosage was reduced or 'off' time with apomorphine, which appears to be treatment withdrawn when concomitant apomorphine was maintained over the longer-term (observational data). introduced.11,13 Varying effects on patients' dyskinetic episodes were seen in these studies, from little if any The most common adverse effects seen with apomorphine overall change in intensity or duration of episodes,12 to are nausea, vomiting, and nodules or indurations at the reduced disability,11 or increasingly severe 'on' phase injection site. In some patients dyskinetic episodes may dyskinesia.10 occur which can be severe. Two small (n=6, 20) comparative studies with Careful introduction of apomorphine treatment is infusion have been published. These studies were too required, which necessitates hospital initiation. small to demonstrate any significant differences.14,15 References

1 Britannia Pharmaceuticals Ltd. APO-go ampoules. Summary of Adverse effects Product Characteristics 2000. 2 Britannia Pharmaceuticals Ltd. APO-go PEN 10mg/ml. Summary Nausea, vomiting and local indurations/nodules at of Product Characteristics 2001. subcutaneous injection sites are the most common side 3 Thomson F, Muir A, Stirton J, Macphee G, Hudson S. Parkinson's Disease. Pharm J 2001;267:600-12. effects. The local SC effects may be reduced in some cases 4 Bhatia K, Brooks DJ, Burn DJ, et al. Updated guidelines for the by rotation of injection sites, dilution of the solution with management of Parkinson's disease. Hospital 0.9% sodium chloride, and possibly the use of ultrasound to 2001;62:456-70. areas of nodularity and induration. 5 Quinn N. Drug treatment of Parkinsons's disease. BMJ 1995;310:575-9. Nausea, vomiting and local indurations/nodules at 6 Stibe CMH et al. Subcutaneous Apomorphine in Parkinsonian On- Off Oscillations Lancet 1988;i;403-406. subcutaneous injection sites are the most common side 7 Corboy DL, Wagner ML, Sage JI. Apomorphine for Motor effects. Dyskinesias can occur during 'on' periods which Fluctuations and Freezing in Parkinson's Disease Ann Pharmacother can be severe, leading to withdrawal of treatment in some 1995;29:282-8. patients. Other adverse events include neuropsychiatric 8 Ostergaard L, et al. Pen injected apomorphine against off phenomena in late Parkinson's disease: a double blind, placebo disturbances, transient sedation, and hypotension. controlled study. J Neurol Neurosurg Psychiatry 1995;58:681-7. 9 Dewey RB, et al. A randomized, double-blind, placebo-controlled trial of subcutaneously injected apomorphine for Parkinsonian off- Costs state events. Arch Neurol 2001;58:1385-92. 10 Hughes A.J. Subcutaneous Apomorphine in Parkinson's Disease: At current prices treatment with apomorphine 10mg/ml Response to Chronic Administration for up to Five Years. Movement costs: Disorders 1993;8:165-170. · £37.96 for 5x2ml ampoules 11 Colzi A, Turner K, Lees AJ. Continuous subcutaneous waking day apomorphine in the long term treatment of levodopa induced · £76.16 for 5x5ml ampoules interdose dyskinesias in Parkinson's disease. J Neurol Neurosurg · £123.91 for 5x3ml pens Psychiatry 1998;64:573-6. 12 Pietz K, Hagell P, Odin P. Subcutaneous apomorphine in late stage Summary Parkinson's disease: a long term follow up. J Neurol Neurosurg Psychiatry 1998;65:709-16. Apomorphine is a dopamine available as a 13 Gancher ST, et al. Apomorphine infusional therapy in Parkinson's parenteral preparation, used in the later stages of disease: clinical utility and lack of tolerance. Movement Disorders 1995;10:37-43. Parkinson's disease to treat disabling motor fluctuations 14 Stocci F et al. Apomorphine and lisuride infusion: a comparative which persist despite optimal treatment with levodopa chronic study. Adv Neurol 1993;60:653-5. and/or dopamine agonists. 15 Stibe C, Lees A, Stern G. Subcutaneous infusion of apomorphine and lisuride in the treatment of Parkinsonian on-off fluctuations. There is a paucity of good quality data on Lancet 1987;i:871. apomorphine for the treatment of motor fluctuations in

Date: November 2002 ©Midland Therapeutic Review & Advisory Committee, SS02/21 Department of Management (THIS SUMMARY SHEET REPLACES 95/03)

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