REQUIP XL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REQUIP XL (REQUIP XL).
Ropinirole is a non-ergoline dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D2 subfamily of dopamine receptors, binding with higher affinity to D3 than to D2 or D4 receptor subtypes. The relevance of D3 receptor binding in Parkinson's disease is unknown.
| Metabolism | Extensively metabolized by CYP1A2 (major pathway) and to a lesser extent by CYP3A4. Major metabolites are N-despropyl and hydroxylated derivatives, which are excreted in urine. |
| Excretion | Renal: 60% (mainly metabolites, <10% unchanged); fecal/biliary: 20%; total excretion accounts for >80% of dose. |
| Half-life | Approximately 6 hours (range 4-8 hours) for ropinirole; terminal half-life in elderly or hepatic impairment may be prolonged up to 10-12 hours. Clinically, steady-state achieved within 2 days of dosing. |
| Protein binding | Approximately 40% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Approximately 7 L/kg (range 5-10 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral immediate-release: 55% (due to first-pass metabolism); extended-release: approximately 60-70% relative to immediate-release, with reduced peak-to-trough fluctuation. |
| Onset of Action | Oral immediate-release: 1-2 hours; extended-release (REQUIP XL): onset of clinical effect typically within 1-2 weeks of therapeutic dosing, with some benefit seen as early as 1-2 hours post-dose due to initial drug release. |
| Duration of Action | Immediate-release: dosing every 8 hours; extended-release: once-daily dosing provides sustained plasma levels over 24 hours. Clinical effect duration correlates with plasma concentration above therapeutic threshold (~2 ng/mL). |
Initial: 2 mg orally once daily for weeks 1-2, then titrate as needed; maintenance: 8-24 mg orally once daily.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | No specific adjustment recommended; caution in severe renal impairment (CrCl < 30 mL/min) due to limited data. |
| Liver impairment | Child-Pugh Class A/B: No adjustment; Child-Pugh Class C: Avoid use due to increased exposure. |
| Pediatric use | Not approved for pediatric use. |
| Geriatric use | Initiate at low end of dosing range (2 mg/day); titrate slowly due to increased sensitivity and risk of adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REQUIP XL (REQUIP XL).
| Breastfeeding | Excretion into human breast milk is unknown. M/P ratio not available. Caution advised; consider risk vs. benefit. |
| Teratogenic Risk | Pregnancy Category C. First trimester: No adequate studies in humans; animal studies show fetal harm at high doses. Second and third trimesters: Limited human data; potential for neonatal withdrawal or extrapyramidal symptoms if used near term. |
| Fetal Monitoring |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to ropinirole or any excipients"]
| Precautions | ["May cause sudden onset of sleep and somnolence, including daytime sleepiness","May cause hypotension, orthostatic hypotension, and syncope","May cause hallucinations","May cause impulse control disorders (e.g., pathological gambling, hypersexuality)","May cause dyskinesias","May cause melanoma risk (monitor for skin lesions)","May cause fibrotic complications (e.g., pleural effusion, pulmonary fibrosis) - rare","May cause augmentation and rebound in RLS (immediate-release only)","May cause withdrawal symptoms upon discontinuation (e.g., hyperpyrexia, confusion)"] |
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| Monitor for maternal hypotension, sedation, and extrapyramidal symptoms. Neonatal monitoring for withdrawal symptoms (irritability, abnormal movements) if used near delivery. |
| Fertility Effects | In animal studies, decreased implantation and increased post-implantation loss observed at high doses. Human fertility effects unknown. |