INDICATIONS AND USAGE

REQUIP®  XLTM is an orally administered, non-ergoline dopamine agonist indicated for the treatment of signs and symptoms of idiopathic Parkinson’s disease. (1.1)

DOSAGE AND ADMINISTRATION

• REQUIP XL Tablets are taken once daily, with or without food. Tablets must be swallowed whole and must not be chewed, crushed, or divided. (2.1)

• The starting dose is 2 mg taken once daily for 1 to 2 weeks, followed by increases of 2 mg/day at 1 week or longer intervals as appropriate, depending on therapeutic response and tolerability, up to a maximally recommended dose of 24 mg/day. Patients should be assessed for therapeutic response and tolerability at a minimal interval of 1 week or longer after each dose increment. Caution should be exercised during dose titration because too rapid a rate of titration can lead to dose selection that does not provide additional benefit, but that increases the risk of adverse reactions. (2.2, 14.2)

• Patients may be switched directly from immediate-release ropinirole to REQUIP XL. The initial switching dose of REQUIP XL should most closely match the total daily dose of immediate-release ropinirole, see Table 1. (2.3)

• If REQUIP XL must be discontinued, it should be tapered gradually over a 7-day period. (2.2)

DOSAGE FORMS AND STRENGTHS

Tablets: 2 mg, 4 mg, and 8 mg (3)

CONTRAINDICATIONS

None

WARNINGS AND PRECAUTIONS

• Falling asleep during activities of daily living may occur, including the operation of motor vehicles, which sometimes resulted in accidents. Sudden onset of sleep may occur without apparent warning or daytime drowsiness. Sedating medications (such as alcohol or CNS depressants), the presence of sleeping disorders, or other medications that increase plasma levels of ropinirole, may increase the risk of somnolence or falling asleep while engaged in activities of daily living. Before initiating treatment, patients should be advised of the potential of sudden onset of sleep or to develop drowsiness and asked about risk factors they may have. If a patient develops sudden onset of sleep during activities that require active participation (e.g., conversations, eating, etc.) and/or cannot avoid high-risk activities in the future, REQUIP XL should ordinarily be discontinued. (5.1)

• Syncope, sometimes associated with bradycardia, may occur. (5.2)

• Symptomatic hypotension (including postural/orthostatic hypotension) may occur, especially during dose escalation. (5.3)

• Elevation of blood pressure and changes in heart rate may occur. (5.4)

• Hallucination may occur. (5.5)

• Dyskinesia may be caused or exacerbated. Decreasing the L-dopa dose may lessen or eliminate this side effect. (5.6)

ADVERSE REACTIONS

• Most common adverse reactions (incidence ≥5% and greater than placebo) in advanced Parkinson’s disease with concomitant L-dopa were dyskinesia, nausea, dizziness, hallucination, somnolence, abdominal pain/discomfort, and orthostatic hypotension. (6.1)

• Most common adverse reactions (incidence ≥5%) in early Parkinson’s disease without L-dopa were nausea, somnolence, abdominal pain/discomfort, dizziness, headache, and constipation. (6.1)

DRUG INTERACTIONS

• CYP1A2 is the major enzyme responsible for the metabolism of ropinirole. Thus inhibitors (e.g., ciprofloxacin, fluvoamine) or inducers (e.g., omeprazole or smoking) of CYP1A2 may alter the clearance of ropinirole. Adjustment of dosage of REQUIP XL may be required. (7.1)

• Higher doses of estrogens, usually associated with hormone replacement therapy (HRT), reduced oral clearance of ropinirole. Starting or stopping HRT treatment may require adjustment of dosage of REQUIP XL. (7.3)

• Dopamine antagonists, such as neuroleptics (e.g., phenothiazines, butyrophenones, thioxanthenes) or metoclopramide, may diminish effectiveness of ropinirole. (7.4)

USE IN SPECIFIC POPULATIONS

Pregnancy: REQUIP XL should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. (8.1)

Revised: June 2008

RXL:2PI