하지불안증후군, restless legs syndrome, guideline

American academy of neurology(AAN) 가이드라인 요약본

 

1. moderate to severe restless legs syndrome(RLS) 일 때, RLS 증상 완화를 위해 약물학적 치료가 시도되어야 한다.

Strong Evidence	pramipexole, rotigotine, carbergoline*, gabapentin(level A).
Moderate Evidence	Ropinirole, pregabalin, and IV ferric carboxymaltose, and in patients with serum ferritin ≤ 75 mcg/l, ferrous sulfate with vitamin C (Level B).
Weak Evidence	Levodopa (Level C).
	Cabergoline* instead of levodopa (Level C).
Insufficient Evidence	Preferential use of pregabalin instead of pramipexole (Level U).
	Gabapentin, IV iron sucrose, oxycodone, clonazepam, bupropion, clonidine, selenium, rifaximin, botulinum neurotoxin, valproic acid, carbamazepine, or valerian in the treatment of RLS (Level U).

* Cabergoline is rarely used in clinical practice for RLS because of a risk of cardiac valvulopathy at higher doses

* IV ferric carboxymaltose(off-label) : gimi-drug.tistory.com/129?category=955633

철 결핍성 빈혈의 주사용 철분 보충제, IV iron. iron sucrose, ferric carboxymaltose, iron dextran

 

2. 다른 약제에 반응이 없는 RLS 환자의 치료

Weak Evidence

Prolonged-release oxycodone/naloxone (where available) (Level C), but potential benefits need to be weighed against known opioid risks.

 

3. psychiatric symptom을 동시에 고려해야하는 RLS 환자의 치료

Moderate Evidence	Ropinirole, in the context of anxiety (Level B).
	Gabapentin enacarbil, for overall mood (Level B).
Weak Evidence	Ropinirole, in the context of depression (Level C)
	Pramipexole, for depression and anxiety, in the context of moderate to severe RLS-related mood disturbance (Level C)

 

4. 증상 악화를 예방하기 위해 고려해야하는 사항

Weak Evidence	Pregabalin rather than pramipexole, when considering 52-week treatment in light of lower augmentation rates with pregabalin (Level C).
	Cabergoline rather than levodopa, when considering 30-week treatment in light of lower augmentation rates with cabergoline (Level C).
Insufficient Evidence	Which dopaminergic agents cause the least augmentation because augmentation rates are most commonly reported in long-term open-label Class IV studies (Level U). Results of these studies are summarized in this practice guideline but cannot support formal recommendations.

 

5. 말기신부전 환자/투석 환자에서의 이차 RLS의 치료

Moderate Evidence	Vitamin C and E supplementation (alone or in combination) (Level B).
Weak Evidence	Ropinirole, levodopa, or exercise (Level C).
Insufficient Evidence	Gabapentin or IV iron dextran in RLS associated with ESRD/HD (Level U). There is also insufficient evidence to support or refute the use of gabapentin or levodopa preferentially over the other in this population (Level U).

개별 약제

pramipexole

성분명	pramipexole
제형	Immediate-release tablet	Controlled-release tablet
식별/상품명/용량
용법 용량	IR 0.125 mg qd (취침2-3시간 전) response & tolerability에 맞춰 증량 가능 max 0.75 mg/day  증상 악화가 발생하는 경우, 더 일찍 복용하거나 용량을 나누어 복용하거나 대체치료로 전환하는 것을 고려	Parkinson disease에 ER형 사용 파킨슨 적응증에 사용 시 max dose 4.5 mg/day
부작용	orthostatic hypotension (3% to 53%) hallucination (5% to 17%; includes auditory, visual, and mixed hallucinations) extrapyramidal reaction (28%) nausea (PD and RLS: 11% to 28%), constipation (PD: 6% to 14%; RLS: 4%)
Time to peak, serum	Immediate release: ~2 hours	Extended release: 6 hours
대사	Negligible (<10%)
배설	Urine
신장애 시	Clearance is 75% lower with severe impairment (CrCl ~20 mL/min) and approximately 60% lower with moderate impairment (CrCl ~40 mL/min).
간장애 시	용량조절 불필요

 

Ropinirole

성분명	Ropinirole
제형	Immediate-release tablet	Controlled-release tablet
식별
용법 용량	IR 0.25 mg qd (취침1-3시간 전) response & tolerability에 맞춰 증량 가능 max 4 mg/day  증상 악화가 발생하는 경우, 더 일찍 복용하거나 용량을 나누어 복용하거나 대체치료로 전환하는 것을 고려	Parkinson disease에 ER형 사용 파킨슨 적응증에 사용 시 max dose : 24 mg/day
부작용	hypotension (RLS: ≤25%; PD: 2%) orthostatic hypotension (RLS: ≤25%; PD: 6%; extended release: 14%), hypertension (PD: 5%; extended release: 3% to 15%), syncope (PD: ≤12%; RLS: 1% to 2%; sometimes associated with bradycardia) drowsiness (PD: ≤40%; extended release: 8% to 15%; RLS: 12%), dizziness (PD: 40%; extended release: 6% to 10%; RLS: 11%), headache (PD, extended release: 5% to 15%), hallucination (PD: 5%) nausea (PD: 60%; RLS: 40%; extended release: 10% to 33%), vomiting (PD: 12%; extended release: 10%; RLS: 11%)
Time to peak, serum	Immediate release: ~1-2 hours	Extended release: 6-10 hours
대사	Extensively hepatic via CYP1A2 to inactive metabolites; first-pass effect
배설	Urine
신장애 시	Clearance of ropinirole was reduced by ~30% in patients with ESRD on dialysis
간장애 시	Patients with hepatic impairment may have higher plasma levels and lower clearance of ropinirole

 

Carbidopa and Levodopa

성분명	Carbidopa and Levodopa
제형	Immediate-release tablet	Controlled-release tablet
상품명	퍼킨 정 25/100 MG	시네메트 정 25/100 MG
식별
용법용량 (off label)	carbidopa/levodopa로써 12.5/50mg-25/100mg 필요시 저녁 혹은 자기전 혹은 RLS 증상으로 잠에서 깼을 때 복용 levedopa 용량 기준으로 200 mg/day 초과하지 않고 최소 3일 간격으로 복용	carbidopa/levodopa로써 25/100mg 필요시 RLS 증상으로 잠에서 깼을 때 복용 levedopa 용량 기준으로 200 mg/day 초과하지 않고 최소 3일 간격으로 복용
주의	오히려 증상 악화의 위험이 있기 때문에 주 2-3회로 횟수 제한이 필요함 prolonged immobility와 같은 특수한 상황에서 고려될 수 있음
신장애 시	용량조절 불필요
간장애 시	용량조절 불필요

 

 

reference :

(1) Practice Guideline: Treatment of Restless Legs Syndrome in Adults, American Academy of Neurology (AAN)(2016)

(2) Lexicomp

(3) 약학정보원