Initial pharmacotherapy for chronic persistent restless legs syndrome (RLS) in adults

	Initial daily dose	Minimum interval to assess effect before increasing dose	Usual effective daily dose range*	Metabolism and clearance
Gabapentinoids (alpha-2-delta calcium channel ligands)
Gabapentin (IR)	100 to 300 mg 2 hours before bedtime	5 to 7 days	900 to 2400 mg as a single dose or in two divided doses (eg, one-third an hour before symptoms start and two-thirds before bed)	>95% renally excreted as unchanged drug Dose adjustment is needed in renal impairment^¶
Gabapentin enacarbil (ER)	300 to 600 mg in early evening (eg, ~5 PM)	5 to 7 days	600 mg^Δ	>95% renally excreted as unchanged drug Dose adjustment is needed in renal impairment^¶
Pregabalin (IR)	50 to 75 mg 1 to 3 hours before bedtime	5 to 7 days	150 to 450 mg	>95% renally excreted as unchanged drug Dose adjustment is needed in renal impairment^¶
Dopamine agonists
Pramipexole (IR)	0.125 mg 2 to 3 hours before bedtime	2 to 3 days	0.25 to 0.50 mg	>90% renally excreted as unchanged drug Use longer titration interval (ie, 14 days) in moderate to severe renal impairment and in older adults
Ropinirole (IR)	0.25 mg 1 to 3 hours before bedtime	2 to 3 days	2 to 4 mg	~90% metabolized, primarily by CYP1A2 Not studied in moderate to severe hepatic impairment; increased levels are likely Use with caution in severe renal impairment (maximum 3 mg daily in dialysis-dependent patients)
Rotigotine transdermal patch	1 mg per 24 hour patch	5 to 7 days	2 to 3 mg per 24 hour patch	Hepatic metabolism (multiple substrates) and glucuronidation No dose adjustments recommended in renal impairment for the dose ranges provided Use with caution in severe hepatic impairment

IR: immediate release; ER: extended release; US FDA: US Food and Drug Administration.
* Long-term use of dopaminergic drugs for RLS can result in augmentation. To decrease risk, use lowest effective dose and do not exceed upper dose range. Refer to UpToDate topic review for details.
¶ Specific dose adjustment recommendations for patients with impaired kidney function are provided in the Lexicomp drug specific monographs included within UpToDate.
Δ Doses up to 1200 mg have been used, although doses ≥600 mg provided no additional benefit in clinical trial for RLS.

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