1 門 診 處 方 討 論 Ropinirole 用於 Restless legs syndrome (RLS) 治療 98.9.24...
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Transcript of 1 門 診 處 方 討 論 Ropinirole 用於 Restless legs syndrome (RLS) 治療 98.9.24...
1
門 診 處 方 討 論 Ropinirole 用於 Restless legs syndrome (RLS) 治
療 98.9.24 黃怡君藥師
2處方 :
3
Outline
Ropinirole 的角色 ?
何謂 RLS (Restless legs syndrome) ? 如何治療 ?
Ropinirole 使用在 RLS 時用法是否合理 ?
Ropinirole 使用在 RLS 上健保是否給付 ?
其它治療 RLS 的藥物健保是否有核準 ?
4Restless legs syndrome (RLS)
Introduction Restless legs syndrome (RLS) refers to symptoms of spontaneous, continuous leg movements associated with unpleasant paresthesias. These sensations occur only at rest and are relieved by movement. The symptoms of this syndrome worsen in the evening and at night, leading to difficulty in sleeping. The abnormal feeling are typically deep seated and localized below the knees. Distribution is usually bilateral, but some asymmetry may occur and the arms can be affected in more severe cases.
5Pathogenesis In most cases RLS is a primary idiopathic
disorder, but it also can be associated with a variety of underlying medical disorders.
Primary RLS — The cause of primary
(or idiopathic) RLS is unknown.
6Pathogenesis Secondary RLS — RLS can occur secondary to a number of disorders including :
Iron deficiency End-stage renal disease (Uremic
polyneuropathy)- RLS is common among dialysis patients, with a reported incidence of 6 -60 %
Diabetes mellitus Rheumatic disease Venous insufficiency Others - Multiple sclerosis, Parkinson
disease, Pregnancy
7 Epidemiology
Mild symptoms of RLS occur in 5-15 % of the population
RLS symptoms occurred at least twice a week and were reported as moderately or severely distressing by 2.7 %
RLS occurs among people of all ages, and the prevalence generally increases with age.
RLS also occurs in children. A biologic parent with RLS symptoms was noted for >70% of children with RLS.
8Prevalence of restless legs syndrome (RLS)
by age and sex
9 Treatment – Nonpharmacologic therapy
Iron replacement therapy Serum ferritin level < 45-50 mcg/mL 給予 ferrous sulfate 325 mg tid/ da
y+ vitamin-C 100-200 mg. Ferritin levels should be checked after three to four months of therapy and then every three to six months until the serum ferritin level is greater than 50 mcg/mL and iron saturation is greater than 20 % .
Mental alerting activities such as video games or crossword puzzles
Avoidance of aggravating factors ex: Caffeine, nicotine and alcohol may aggravate RLS symptom
s. Antidepressants, dopamine-blocking antiemetics (ex:metoclopramide), antihistamines may contribute to RLS symptoms.
適度的運動、熱水澡、腿部按摩、熱敷或冰敷
10Drugs used to treat restless legs syndrome
AgentInitial dose
Recommended max. daily dose
Half-life in serum Common side effects
Dopaminergic agents
Levodopa (with carbidopa or benserazide)
50 mg 200 mg hs 1.5-2 hr Nausea or vomiting, orthostatic hypotension, hallucination, augmentation of symptoms, insomnia
Pergolide* 0.025 mg 0.5 mg bid-tid 12-16 hr Same as for levodopa, plus nasal congestion and fluid retention, Cardiac valve disease
Pramipexole*(Mirapex® )
0.125 mg 1.5 mg bid-tid 8-10 hr (possibly longer with renal dysfunction)
Same as for levodopa, plus nasal congestion and fluid retention
Ropinirole*(Requip®)
0.25 mg 4 mg bid-tid 6-8 hr (possibly longer with hepatic dysfunction)
Same as for levodopa, plus nasal congestion and fluid retention
11Drugs used to treat restless legs syndrome
AgentInitial dose
Recommended maximal daily
dose Half-life in serum Common side effects
Sedative-hypnotic agents
Clonazepam 0.25 mg 2 mg hs 30-40 hr
Tolerance, sedation
Oxazepam 10 mg 40 mg hs 5-10 hr
Zaleplon 5 mg 20 mg hs 1 hr (possibly longer with hepatic dysfunction)
Zolpidem 5 mg 20 mg hs 1.6 hr (possibly longer in elderly patients or with hepatic dysfunction)
Triazolam 0.125 0.5 mg hs 2-4 hr
Antiepileptic agents
Gabapentin 300 mg 3600 mg, tid or 1500 mg, hs
5-7 hr (possibly longer with renal dysfunction)
Sedation, dizziness, fatigue, somnolence, ataxia
12
Agent Initial dose
Recommendedmaximal daily
dose Half-life in serum Common side effects
Opiates
Propoxyphene 100-200 mg 600 mg bid-tid 6-12 hr (possibly longer with hepatic dysfunction) Sedation, pruritus,
constipation, nausea or vomiting, dry mouth, dependence
Hydrocodone 5 mg 20-30 mg bid-tid
3 hr (possibly longer with hepatic dysfunction)
Codeine 30 mg 180 mg bid-tid 2.5-3 hr (possibly longer with hepatic dysfunction)
Tramadol 50 mg 300 mg bid-tid 5-8 hr (possibly longer with hepatic or renal dysfunction)
Same as for propoxyphene and augmentation
Oxycodone 5 mg 20-30 mg, bid-tid
3 hr (possibly longer with renal dysfunction)
Sedation, pruritus, constipation, nausea or vomiting, dry mouth, dependence
Oxycodone-XR 10 mg 20-30 mg, bid-tid
12 hr (possibly longer with renal dysfunction)
Methadone* 2.5 mg 20 mg, bid-tid 16-22 hr (possibly longer with hepatic dysfunction or long-term use)
Morphine sulphate-XR
15 mg 30-45 mg, bid-tid
4 hr (possibly longer with hepatic dysfunction)
* Medication should be started at least two hours before bedtime or the anticipated onset of symptoms.
Reproduced with permission from: Earley, CJ. Restless legs syndrome. N Engl J Med 2003
13 Types of RLS
Intermittent RLS (Mild RLS ) — That is troublesome enough when present to require treatment but that is not sufficiently frequent to require regular daily medication use.
Daily RLS (Moderate to Severe RLS ) —That is frequent and troublesome enough to require daily treatment.
Refractory RLS — Refractory RLS is defined as daily RLS treated with a dopamine agonist but with a poor response.
14
Intermittent RLS (Mild RLS )
Treatment options include:
Nonpharmacologic therapy
Levodopa (first)
Dopamine agonists
Low potency opioids or opioid agonists
Benzodiazepines or benzodiazepine agonists
15
Daily RLS (Moderate to severe RLS )
Nonpharmacologic therapy
Dopamine agonists (first)
Gabapentin
Low potency opioids or opioid agonists
Treatment options include:
16 Refractory RLS
Change to gabapentin
Change to a different dopamine agonist
Add a second agent such as gabapentin, a benzodiazepine, or an opioid
Change to a high potency opioid or tramadol
2009 UpToDate , Inc.
Treatment options include:
17Ropinirole ( Requip® )
• A non-ergot dopamine agonist (D3> D2> D4)
• For the treatment of moderate to severe primary RLS.
• Dose titration: once daily 1-3 hrs at hs
0.25 mg for days 1 and 20.5 mg for days 3 to 71 mg for week 21.5 mg for week 32 mg for week 42.5 mg for week 53 mg for week 64 mg for week 7 Micromedex Last Modified April 21,2009
18
Ropinirole in Restless Legs Syndrome
• FDA Approval: Adult, yes; Pediatric, no
• Efficacy: Adult, Evidence favors efficacy
• Indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome
Reference: Micromedex Last Modified April 21,2009
19AASM Classification of Evidence
Recommendation Grades
Evidence Levels
Study Design
A I Large, well-designed, randomized and blinded controlled study with statistically significant conclusions on relevant variables .
B Ⅱ Smaller, well-designed, randomized and blinded controlled study with statistically significant conclusions on relevant variables
C Ⅲ Well-designed, non-randomized prospective study with control group
C Ⅳ Well-designed, large prospective study with historical controls or careful attention to confounding effects or small prospective study with control group.
C Ⅴ Small prospective study or case series without control groups .
AASM: The American Academy of Sleep Medicine
Sleep 2004;27(3):557-9
20AASM Levels of Recommendations
Term Definition
Standard This is a generally accepted patient-care strategy, which reflects a high degree of clinical certainty. The term standard generally implies the use of Level I Evidence, which directly addresses the clinical issue, or overwhelming Level II Evidence
Guideline This is a patient-care strategy, which reflects a moderate degree of clinical certainty. The term guideline implies the use of Level II Evidence or a consensus of Level III Evidence.
Option This is a patient-care strategy, which reflects uncertain clinical use. The term option implies either inconclusive or conflicting evidence or conflicting expert opinion.
Sleep 2004;27(3):557-9
21
Recommendations for treatment of RLS • Standard : Levodopa with decarboxylase inhibit
or and the dopamine agonist pergolide
• Guideline : The dopamine agonist pramipexole
• Option : The dopamine agonist ropinirole
Sleep 2004;27(3):557-9
22衛生署核准適應症
• 治療自發性帕金森氏症( Idiopathic Parki
nson’s Disease)
• 治療原發性腿部躁動症 (Primary Restless
Legs Syndrome)
23 全民健康保險藥品給付修正規定 97.7.1 生效• 1.3.4 帕金森氏症治療藥品 :
5. Pramipexole 及 Ropinirole 用於治療原發性腿部躁動症時需先排除腎衰竭、鐵缺乏症及多發性神經病變,且不得與 dopamine agonist 及 levodopa 併用
( 1 ) Pramipexole 每日最大劑量 0.75mg
( 2 ) Ropinirole 每日最大劑量為 4mg