CYCLOSET

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE CYCLOSET is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. CYCLOSET is an ergot derivative indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. ( 1 ) Limitations of Use: Should not be used to treat type 1 diabetes or diabetic ketoacidosis. ( 1 ) Limited efficacy data in combination with thiazolidinediones. ( 1 ) Efficacy has not been confirmed in combination with insulin. ( 1 ) Limitations of Use CYCLOSET should not be used to treat type 1 diabetes or diabetic ketoacidosis. Limited efficacy data in combination with thiazolidinediones. Efficacy has not been confirmed in combination with insulin. Dosage and administration 2 DOSAGE AND ADMINISTRATION Taken within two hours after waking in the morning with food ( 2.1 ) Initial dose is one tablet (0.8 mg) daily increased weekly by one tablet until maximal tolerated daily dose of 1.6 to 4.8 mg is achieved. ( 2.2 ) Limit dose to 1.6 mg daily during concomitant use of a moderate CYP3A4 inhibitor. Avoid concomitant use with strong CYP3A4 inhibitors. ( 2.3 ) 2.1 Recommended Dosing The recommended dose of CYCLOSET is 1.6 mg to 4.8 mg administered once daily within two hours after waking in the morning. CYCLOSET should be taken with food to potentially reduce gastrointestinal side effects such as nausea. If the morning dose is missed, instruct patients to take their usual dose the following morning. Doses of CYCLOSET should not be doubled the following morning. 2.2 Titration CYCLOSET should be initiated at one tablet (0.8 mg) and increased by one tablet per week until a maximum daily dose of 6 tablets (4.8 mg) or until the maximal tolerated number of tablets between 2 and 6 per day is reached. 2.3 Use with Concomitant Therapy CYCLOSET dose should not exceed 1.6 mg once daily during concomitant use of a moderate CYP3A4 inhibitor (e.g., erythromycin). Avoid concomitant use of CYCLOSET and strong CYP3A4 inhibitors (e.g., azole antimycotics, HIV protease inhibitors) and ensure adequate washout of the strong CYP3A4 inhibitor drug before initiating CYCLOSET treatment [see Drug Interactions (7) , Clinical Pharmacology (12.3) ] . Warnings and cautions 5 WARNINGS AND PRECAUTIONS Hypotension: Can cause orthostatic hypotension and syncope, particularly upon initiation or dose escalation. Use caution in patients taking antihypertensive medications. Assess orthostatic vital signs prior to initiation of CYCLOSET and periodically thereafter. Advise patients during early treatment to avoid situations that could lead to injury if syncope was to occur. ( 5.1 , 6.1 ) Psychosis: May exacerbate psychotic disorders or reduce the effectiveness of drugs that treat psychosis. Use in patients with severe psychotic disorders is not recommended. ( 5.2 ) Impulse control/compulsive behaviors: Ask patients or their caregivers about new or increased gambling urges, sexual urges, uncontrolled spending, or other urges while being treated with CYCLOSET. Consider dose reduction or stopping CYCLOSET if a patient develops such urges. Use of CYCLOSET in patients with impulse control/compulsive behaviors is not recommended. ( 5.3 , 6.2 ). Somnolence: May cause somnolence. Advise patients not to operate heavy machinery if symptoms of somnolence occur. ( 5.4 ) Interaction with dopamine antagonists: Concomitant use with dopamine antagonists such as neuroleptic agents may diminish the effectiveness of both drugs. Concomitant use is not recommended. ( 5.5 , 7 ) Other dopamine receptor agonists: Effectiveness and safety are unknown in patients already taking dopamine receptor agonists for other indications. Concomitant use is not recommended. ( 5.6 ) Risks in Postpartum Patients: Serious and life-threatening adverse reactions have been reported. ( 5.7 , 6.2 ) 5.1 Hypotension Hypotension, including orthostatic hypotension, can occur, particularly upon initiation of CYCLOSET therapy and with dose escalation. In a 52-week, randomized clinical trial of 3070 patients, hypotension was reported in 2.2% of patients randomized to CYCLOSET compared to 0.8% of patients randomized to placebo. Among CYCLOSET-treated patients reporting symptomatic hypotension, 98% were on at least one blood pressure medication compared to 73% on such medication in the total study population. In this trial, six CYCLOSET-treated patients (0.3%) reported orthostatic hypotension compared to 2 (0.2%) placebo-treated patients. All six patients were taking antihypertensive medications. Hypotension can result in syncope. In this trial, syncope due to any cause was reported in 1.6% of CYCLOSET-treated patients and 0.7% of placebo-treated patients [see Adverse Reactions (6.1) ] . As a precaution, assessment of orthostatic vital signs is recommended prior to initiation of CYCLOSET and periodically thereafter. Advise patients during early treatment with CYCLOSET to make slow postural