GREEN. Ropinirole Other PD treatments Benzodiazepines Opioids low potency Anticonvulsants Clonidine

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1 New Medicine Report (Adopted by the CCG until review and futher notice) Document Status Traffic Light Decision PRAMIPEXOLE For restless legs syndrome Post Suffolk D&TC GREEN Prescribers Rating Possibly helpful - 4 Date of Last Revision 04/01/06 Approved Name Trade Name Manufacturer Legal Status Indication Dosage Cost Possible Number of Suffolk Patients Number Needed to Treat Treatment Alternatives (NB Ropinirole has a licence others are off licence) Future Alternatives Possible Future Indications Pramipexole Not known Boehringer Ingelheim Not yet licensed for restless legs syndrome but under consideration Restless Legs Syndrome (RLS) Most information suggests between 0.125mg and 0.75mg per day Mirapexin (pramipexole) is currently available for the treatment of Parkinson s Disease The cost of this preparation is shown but the price of the RLS product may differ per 30 of 125mcg per 30 of 250mcg per 100 of 250mcg Up to 30,000 Not calculated Ropinirole Other PD treatments Benzodiazepines Opioids low potency Anticonvulsants Clonidine Gabapentin None known Not to be used for promotional purposes Page 1 of 7 May be freely copied by NHS agencies

2 Reviewer s Comments Restless legs syndrome (RLS) would appear to be a relatively common (5.5%) syndrome affecting patients in a number of ways. However it would appear that not many patients seek or receive treatment for it at present. A number of disease states may cause secondary RLS and it is important that any patient presenting is assessed carefully to exclude these prior to treatment. Pramipexole is an established medicine for Parkinson s Disease which would seem to give some relief from the symptoms of Restless Legs Syndrome. However it has a number of side effects, for example nausea and headache which may limit its use. It also has a number of drug interactions that may limit its use. It is not yet clear whether the dose used for RLS will have the same side effect profile as that found in the use of Mirapexin in PD. The expected level of uptake of the product is difficult to determine. The introduction of the product will no doubt lead to an increased awareness of the availability of treatment whilst the side effect profile may limit its use. It is possible that it will be seen as a medicine for intermittent use, for example use prior to a visit to the theatre, although there is no evidence to support its use in this manner. The product may be more expensive than some of the other available treatments although they are off licence products and care will need to be taken to ensure that expenditure on this is balanced by benefit to the patient. Evidence Reviewed Paper, Review, Abstract etc. Winkleman JW, Johnston L Augmentation and tolerance with long term pramipexole treatment of restless legs syndrome Sleep Medicine 5 (2004) 9-14 Ferini-Strambi L Restless legs syndrome augmentation and pramipexole treatment Sleep Medicine 3 (2002) S23-S25 Various Poster reports from 9 th International Congress of Parkinson s Disease and Movement Disorders Movement Disorders Vol 20 Suppl S58 S 59 Various Poster reports from 8 th International Congress of Level of evidence I I IV IV Not to be used for promotional purposes Page 2 of 7 May be freely copied by NHS agencies

3 Parkinson s Disease and Movement Disorders Movement Disorders Vol 19 Suppl S428 The National Horizon Scanning Centre University of Birmingham New & emerging technology briefing; Ropinirole for idiopathic restless legs syndrome Schapira AHV Restless Legs Syndrome an update on treatment options Drugs2004;64(2): Level of evidence adapted from Quick and Clean : authorative health technology assessment for local health care contracting Andrew Stevens, Duncan Collin-Jones & John Gabbay Health Trends Vol 27 No III III Review Restless legs syndrome (RLS) may be characterised by four diagnostic elements 1- A desire to move the limbs, often associated with paresthesia or dysesthesia 2- Symptoms exacerbated by rest and relieved by activity 3- Motor restlessness 4- Nocturnal worsening of symptoms Most patients experience vague, non-painful, bilateral discomfort in their limbs using terms such as crawling, tingling, burning, itching and aching to describe the sensation which is relieved by movement of the limbs. All patients experience a worsening of symptoms at night and may suffer sleep disturbance leading to a possible loss of quality of life due to the subsequent tiredness. In most cases RLS is idiopathic and may be familial. However RLS may develop as a result of other conditions and these need to be excluded before a correct diagnosis can be made. Factors which may contribute to secondary RLS include deficiency in iron, folate or magnesium, polyneuropathy of many causes, Parkinson s Disease, COPD, caffeine, alcohol, nicotine, medicines (including phenytoin, antidepressants, paroxetine, lithium etc), hypo/hyper thyroidism and others. There is a paucity of published papers to support the use of pramipexole in the treatment of RLS. However several posters have been published and these are described below. Poster 1255 from the 8 th International Congress of Parkinson s Disease and Movement Disorders reported on 234 patients who received a prescription for pramipexole for more than one year (range 12 to 63 months). All patients Not to be used for promotional purposes Page 3 of 7 May be freely copied by NHS agencies

4 underwent a telephone interview to assess efficacy and side effects of pramipexole. The results showed that 82% of patients were still taking the medication. Of those who had discontinued treatment 20 did so due to side effects, 6 due to lack of efficacy, 6 for both and 11 for other reasons. Overall patients reported a mean decrease in RLS symptom severity of 80.9% and 96% of patients reported a decrease of 50% or more. A majority of patients reported improvement in nocturnal sleep (92.7%) and quality of life (94%). None of the patients reported sudden onset of sleep and morning rebound was present in 4% of patients with 32% reporting worsening of symptoms in the afternoon or earlier in the evening. Poster 191 from the 9 th International Congress of Parkinson s Disease and Movement Disorders reported on a double blind placebo controlled trial of 345 patients in 37 centres over a 6 week period. Patients underwent dose titration in weeks 1 to 4 and remained on that dose for the following 2 weeks. The mean improvement in RLSRS score was for the treatment arm vs for the placebo arm. In addition 64.4% of the patients receiving active treatment were CGI-I responders (much/very much improved) vs. 34.3% of the placebo group. Poster 193 also reports on a group of 345 patients over a 6 week period. It is not showed that night-time RLS symptoms rated on a visual scale gave an alteration from baseline of for the treatment group vs for the placebo group. In addition the severity of symptoms during the day gave an alteration from baseline of for the treatment group vs for the placebo group. Poster 194 also reports on a group of 345 patients over a 6 week period. It is not showed that 31.2% of patients in the treatment arm showed a Patient Global Impression (PGI) response of much or very much improved after 1 week of treatment vs. 7.5% of those receiving placebo. This response persisted in 19.8% of the treated patients vs. 3.74% of the placebo patients at 6 weeks. Poster 195 also reports on a group of 345 patients over a 6 week period. It is not showed that patient mood improved with the use of pramipexole whereas most antidepressants worsen the RLS. Not to be used for promotional purposes Page 4 of 7 May be freely copied by NHS agencies

5 Poster 196 also reports on a group of 345 patients over a 6 week period. It is not showed a reduction in RLS when getting to sleep (-31.1 vs on a 10cm visual scale) and an improved satisfaction with the sleep. In the paper by Winkelman a retrospective analysis of 59 patients treated with prampexole for at least 6 months (mean duration 21.2 ±11.4 months) showed that augmentation (need for earlier administration of the same dose of pramipexole) occurred in 32% of patients and tolerance (need for an increase in dose) occurred in 46% of patients Adverse Effects etc. The medication has been available for some years for the treatment of Parkinson s Disease and its side effect profile is well known. Please refer to the SPC for full information. Economic Information GSK have carried out a large unpublished study, which suggests that the prevalence of RLS in the adult (15+) population is about 5.5%. Other studies have suggested that it might be as high as 15%. Prevalence increases with age and is higher in women. Using this data the following population estimates can be made Table 1 Mediplus data quoted by the National Horizon Scanning Centre suggests that the majority of these patients are currently not receiving treatment to control their symptoms. Indeed they suggest that only 7,000 to 12,000 patients out of the expected total for England and Wales of 2.32million patients are currently treated. Thus it can be seen that only 0.44% of patients are currently being treated. Table 1 To show the estimated numbers of patients with RLS in Suffolk. PCT 5.5% of the population aged 15 years or over Cost ( ) assuming average dose of 2mg once daily at for 84 tablets Central 4,423 1,953,224 Ipswich 6,290 2,777,948 Suffolk Coastal 4,451 1,965,916 Suffolk West 9,607 4,242,884 Waveney 5,487 2,423,144 Total for Suffolk 15,164 6,697,088 Not to be used for promotional purposes Page 5 of 7 May be freely copied by NHS agencies

6 East Total for Suffolk 30,257 13,363,116 An additional confounding factor in estimating the number of patients likely to benefit from and use the medicine is that many patients may wish to not take it, given the side effect profile, on a regular basis but may wish to take it before, say, a trip to the cinema or on an aeroplane. This would alter the uptake figures dramatically. SUFFOLK DRUG AND THERAPEUTICS COMMITTEE New Drug Bulletin Pramipexole for Restless Legs Syndrome SUFFOLK DRUG AND THERAPEUTICS COMMITTEE RECOMMENDATION: Suffolk D&T Prescriber s Rating Grade 4 - Possibly Helpful - the product has minimal additional value, and should not change prescribing habits except in rare circumstances.* The traffic light placing is Green Hospital initiated, GP prescribed Licensed indication: Dosage: day Restless Legs Syndrome (RLS) Most information suggests between 0.125mg and 0.75mg per Not to be used for promotional purposes Page 6 of 7 May be freely copied by NHS agencies

7 Cost: Mirapexin (pramipexole) is currently available for the treatment of Parkinson s Disease The cost of this preparation is shown but the price of the RLS product may differ per 30 of 125mcg per 30 of 250mcg per 100 of 250mcg Further Comments: Local consultants commented that the drug should not be used first line, and that the evidence for its efficacy was not good. The Committee noted that although restless legs syndrome is common, people do not frequently request treatment for it. It may be a problem for people with renal failure, but is then generally treated by renal physicians. It was noted that the Drug and Therapeutics Bulletin had published a Treatment Note (No 31) on restless legs syndrome in August 2004, available from More information is available from - the notes can be ordered from dtb@which.net. Pramipexole for restless legs syndrome carries a black triangle in common with all new drugs. All suspected adverse reactions should be reported to the CSM on a yellow card. *Suffolk D&T s Prescriber s Rating ranges from Grade 1: Bravo! The drug is a major therapeutic advance in an area where previously no treatment was available to Grade 7 Not acceptable. Product without evident benefit but with potential or real disadvantages. Paul Berry Prescribing Medical Advisor January 2006 These notes are only intended to provide brief guidance. Please refer to the latest Summary of Product Characteristics (Data Sheet) for full prescribing details. Not to be used for promotional purposes Page 7 of 7 May be freely copied by NHS agencies