Dosing and uses of Requip, Requip XL (ropinirole)
Adult dosage forms and strengths
tablet
- 0.25mg
- 0.5mg
- 1mg
- 2mg
- 3mg
- 4mg
- 5mg
tablet, extended release
- 2mg
- 4mg
- 6mg
- 8mg
- 12mg
Parkinson Disease
Immediate release
- 0.25 mg PO q8hr for 1 week initially, then increased weekly by 0.25 mg q8hr; if necessary, after week 4, may be increased weekly by 1.5 mg/day up to 9 mg/day, then increased weekly by 3 mg/day up to 24 mg/day
- See Administration for discontinuation instructions
Extended release
- 2 mg/day PO initially for 1-2 weeks; increased by 2 mg/day at intervals >1 week; not to exceed 24 mg/day
- See Administration for discontinuation instructions
Restless Legs Syndrome (Moderate-Severe)
Immediate release: 0.25 mg/day PO 1-3 hours before bedtime; after day 2, may be increased to 0.5 mg/day PO; at end of week 1, increased to 1 mg/day, then increased weekly by 0.5 mg/day up to 4 mg/day
See Administration for discontinuation instructions
Dosing Modifications
Renal impairment
- CrCl 30-50 mL/min: Dose adjustment not necessary
- CrCl <30 mL/min: Safety and efficacy not established; use with caution; use of ropinirole XL not studied
- End-stage renal disease on hemodialysis: Maximum recommended dose is 18 mg/day in Parkinson disease and 3 mg/day in restless legs syndrome
Hepatic impairment
- Safety and efficacy not established; use with caution
Pediatric dosage forms and strengths
Safety and efficacy not established
Requip, Requip XL (ropinirole) adverse (side) effects
>10%
Nausea (40-60%)
Dizziness (6-40%)
Somnolence (11-40%)
Syncope (1-12%)
Vomiting (12%)
Fatigue (8-11%)
Viral infection (11%)
Dyspepsia (10%)
1-10%
Hypertension (5%)
Flushing (3%)
Orthostasis (1-6%)
Chest pain (4%)
Palpitation (3%)
Extrasystoles (2%)
Tachycardia (2%)
Hyperhidrosis (3%)
Abnormal pain (3-7%)
Anorexia (4%)
Flatulence (3%)
Malaise (3%)
Hypoesthesia (4%)
Urinary tract infection (5%)
Impotence (3%)
Alkaline phosphatase (3%)
Abnormal vision (6%)
Xerophthalmia (2%)
Increased diaphoresis (3-6%)
<1%
Agitation
Aneurysm
Aphasia
Bradycardia
Cardiac arrest
Valvulopathy
Cellulitis
Colitis
Delusion
Delirium
Diaphoresis
Dyspnea
Ulceration
Glaucoma
Psychotic-like behavior
Impulse control/compulsive behavior
Withdrawal-emergent hyperpyrexia and confusion
Melanoma
Fibrotic complications
Warnings
Contraindications
Known hypersensitivity/allergic reaction (including urticaria, angioedema, rash, pruritus) to ropinirole or to any of the excipients
Cautions
Risk of somnolence associated with use for restless legs syndrome, as well as (rare) risk of syncope, hypotension, and hallucinations
May cause psychotic-like behavior; abnormal thinking and behavior can consist of one or more of a variety of manifestations including paranoid ideation, delusions, hallucinations, confusion, disorientation, aggressive behavior, agitation, and delirium; risk may be increased in the elderly
Risk of orthostatic hypotension with extended-release formulation
Possible risk of erratic behavior associated with dopamine agonists, compulsive behavior including urge to gamble and increased sexual urges
Dyskinesia seen with concurrent use of levodopa
Increased risk of melanoma development and pleural retroperitoneal fibrosis reported, but causation not established; monitoring warranted
Use caution in patients with history of hepatic/renal impairment, psychotic disorders, dyskinesias, restless leg syndrome
Abrupt withdrawal or significant dosage reduction associated with syndrome resembling neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability); see Administration section for how to gradually discontinue drug
Augmentation and rebound in restless leg syndrome
- Augmentation is a phenomenon in which dopaminergic medication causes a worsening of symptom severity above and beyond the level at the time the medication was started
- Augmentation symptoms may include earlier onset of symptoms in the evening (or even the afternoon), increase in symptoms, and spread of symptoms to involve other extremities
- Rebound refers to new onset of symptoms in the early morning hr
Pregnancy and lactation
Pregnancy: There are no adequate data on the developmental risk associated with therapy in pregnant women; background risk of major birth defects and miscarriage is unknown
Lactation: Unknown if excreted in milk; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on the breastfed infant from ropinirole or from underlying maternal condition
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Requip, Requip XL (ropinirole)
Mechanism of action
Potent nonergoline dopamine agonist specific for D2 and D3 subtypes, possibly within caudate putamen in brain
Absorption
Bioavailability: 55%
Peak plasma time: Immediate release, 1-2 hr; extended release, 6-10 hr
Distribution
Protein bound: 40%
Vd: 525 L
Metabolism
Metabolized in liver by CYP1A2
Elimination
Half-life: 6 hr (extended release)
Total body clearance: 47 L/hr
Excretion: Urine
Administration
Oral Administration
May take with or without food
If a significant interruption in therapy has occurred, retitration of the drug is warranted
Conversion from immediate-release to extended-release formulation
- Choose extended-release strength that most closely matches total daily dose of immediate-release formulation
Discontinuation
- Abrupt withdrawal or significant dosage reduction associated with syndrome resembling neuroleptic malignant syndrome (see Cautions)
- Parkinson disease: Discontinued gradually over a 7-day period; administration frequency should be reduced from TID to BID for 4 days, and then once daily for the remaining 3 days prior to completely withdrawing the drug
- Restless leg syndrome: Gradually reduce the daily dose
