REQUIP XL
Clinical safety rating
cautionComprehensive 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). |
| Molecular Weight | 296.38 |
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 | Human data are limited. Based on animal studies, there is evidence of reproductive toxicity, including fetal malformations and embryotoxicity at maternally toxic doses. Use only if potential benefit justifies risk. |
| 2nd trimester | Human data are limited. Animal studies show developmental delays and skeletal variations. Consider maternal benefit vs. fetal risk. |
| 3rd trimester | May cause uterine contractions or peripartum complications. Use only if clearly needed and benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for REQUIP XL (REQUIP XL).
| Placental transfer | Ropinirole crosses the placenta in animal studies; human placental transfer is likely given molecular size and lipophilicity. The extent is not quantified in humans. |
| Breastfeeding | Ropinirole is excreted in human milk. The amount is low (relative infant dose estimated ~1-3% of maternal weight-adjusted dose). However, effects on the nursing infant are unknown. Monitor for excessive sedation, irritability, or feeding problems. |
| Lactation Rating | L3 (Moderately Safe) |
| 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 | 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. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to ropinirole or any component of the formulation
| 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) |
| Food/Dietary | Take with or without food. High-fat meals may reduce peak concentration but do not affect overall absorption. Avoid grapefruit juice as it may inhibit CYP1A2 and increase ropinirole levels. Alcohol can potentiate sedative effects and orthostatic hypotension. |
| Clinical Pearls | REQUIP XL (ropinirole extended-release) is a non-ergoline dopamine agonist used primarily for Parkinson's disease. Initiate with 2 mg once daily for 1-2 weeks, then titrate by 2 mg/day every 1-2 weeks. Maximum dose is 24 mg/day. Avoid abrupt discontinuation to prevent dopamine agonist withdrawal syndrome. Monitor for impulse control disorders, orthostatic hypotension, and hallucinations. Coadministration with strong CYP1A2 inhibitors (e.g., ciprofloxacin) or inducers (e.g., smoking) may require dose adjustment. |
| Patient Advice | Take once daily at approximately the same time each day, with or without food. Do not crush, chew, or divide the tablet. · Do not stop taking this medication suddenly; taper slowly under medical supervision to avoid withdrawal symptoms such as fever, confusion, muscle stiffness, or sudden sleep episodes. · Be aware of potential sudden onset of sleep during daily activities (e.g., driving, operating machinery). Avoid these activities until you know how the drug affects you. · Report any new or worsening urges (gambling, spending, eating, sexual urges) to your doctor immediately. · Rise slowly from sitting or lying down to minimize dizziness from low blood pressure. · If you miss a dose, skip the missed dose and take the next dose at the regular time. Do not double the dose. · Avoid alcohol consumption as it may increase side effects such as drowsiness and dizziness. |
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