additional
Safety results1

Cardiovascular (CV) findings

Prespecified composite CV endpoint (composite of myocardial infarction, stroke, coronary revascularization, hospitalization for angina, and hospitalization for congestive heart failure) occurred in 1.5% of CYCLOSET patients vs 3.0% of placebo patients

CV data disclaimer CV data disclaimer CV data disclaimer The hazard ratio quantifies the probability of an event happening within a specified time interval.5 In the CYCLOSET Safety Trial, the time period was 52 weeks. For the prespecified composite CV endpoint, the hazard ratio of 0.58 shows that the probability of an event happening to a CYCLOSET patient was 0.58 vs 1.0 for a placebo patient during the 52-week study, or a 42% relative decrease in the risk for having an adverse cardiovascular event. The upper bound of the confidence interval being less than 1.0 signifies a statistically significant difference in the outcome.1,2

CHANGES IN BLOOD PRESSURE AND LIPIDS2,3

Although CYCLOSET is not indicated to reduce blood pressure or plasma lipids, reductions were observed in the clinical trials

Blood Pressure Lipids Blood Pressure Lipids Blood Pressure Lipids

*A secondary endpoint of the 52-week safety trial was the occurrence of the composite of myocardial infarction, stroke, coronary revascularization, hospitalization for angina, and hospitalization for congestive heart failure.1

†Secondary endpoint of the 52-week safety trial.4

‡Secondary endpoint of the two 24-week efficacy studies as adjunct to stable sulfonylurea.4

Hypotension, including orthostatic hypotension, can occur, particularly upon initiation of CYCLOSET and with dose escalation. Use caution in patients taking anti-hypertensive medications.

INDICATION FOR CYCLOSET

CYCLOSET (bromocriptine mesylate) 0.8 mg tablets is a dopamine receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

IMPORTANT LIMITATIONS OF USE

CYCLOSET should not be used to treat type 1 diabetes or diabetic ketoacidosis.

There are limited efficacy data in combination with thiazolidinediones.

Efficacy has not been confirmed in combination with insulin.

IMPORTANT SAFETY INFORMATION FOR CYCLOSET

Contraindications

Do not use CYCLOSET in patients with hypersensitivity to ergot-related drugs, bromocriptine or to any of the excipients in CYCLOSET.

Do not use CYCLOSET in patients with syncopal migraines. May precipitate hypotension.

Do not use CYCLOSET in nursing women. May inhibit lactation. There have been postmarketing reports of stroke with bromocriptine in this patient population, although causality has not been proven. Based on CYCLOSET clinical trials, there is no evidence of increased risk for stroke when CYCLOSET is used to treat type 2 diabetes.

Orthostatic Hypotension/Syncope

CYCLOSET can cause orthostatic hypotension and syncope, particularly upon initiation or dose escalation. Use caution in patients taking anti-hypertensive medications. Orthostatic vital signs should be assessed prior to initiation of CYCLOSET and periodically thereafter.

Advise patients during early treatment to avoid situations that could lead to injury if syncope were to occur, and to make slow postural changes.

Exacerbation of Mental Illness

Pathological gambling and exacerbation of psychotic disorders have been reported with bromocriptine generally given in higher doses than what is approved for diabetes treatment. There have been no reported cases of psychoses or pathological gambling among CYCLOSET-treated patients in clinical trials. The use of CYCLOSET in patients with severe psychotic disorders is not recommended.

Somnolence

CYCLOSET may cause somnolence, particularly when initiating therapy. Advise patients not to drive or operate heavy machinery if symptoms of somnolence occur.

Concomitant Use of Dopamine Antagonists or Agonists

Concomitant use with other dopamine antagonists, such as neuroleptic agents, may diminish the effectiveness of both drugs and is not recommended.

Effectiveness and safety are unknown in patients already taking dopamine receptor agonists for other indications and concomitant use is not recommended.

Macrovascular Effects

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with CYCLOSET. CYCLOSET has not been associated with increased risk of macrovascular events.

Safety and Effectiveness in Pediatrics

The safety and effectiveness of CYCLOSET in pediatric patients have not been established.

Adverse Reactions

In clinical trials, the most common adverse reactions reported in ≥5% of patients treated with CYCLOSET, and reported more commonly than in patients treated with placebo, included nausea, fatigue, dizziness, vomiting, and headache. Postmarketing reports with higher doses of bromocriptine used for other indications include psychotic disorders, hallucinations, and fibrotic complications.

References: 1. CYCLOSET [prescribing information. Tiverton, RI: VeroScience, LLC. 2. Scranton R, Ezrohki M, Farwell W, Gaziano JM, Cincotta A. Quick release bromocriptine (Cycloset) a novel treatment for type 2 diabetes also demonstrates improvements in blood pressure. Presented at the 20th World Diabetes Congress; October 18-22, 2009; Montreal, Canada. 3. Scranton R, Cincotta A. Bromocriptine – unique formulation of a dopamine agonist for the treatment of type 2 diabetes. Expert Opin Pharmacother. 2010;11(2): 269-279. 4. Data on file, Salix Pharmaceuticals, Inc. 5. Spruance SL, Reid JE, Grace M, Samore M. Hazard ratio in clinical trials. Antimicrob Agents Chemother. 2004;48(8):2787-2792.

INDICATION FOR CYCLOSET

CYCLOSET (bromocriptine mesylate) 0.8 mg tablets is a dopamine receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

IMPORTANT LIMITATIONS OF USE

CYCLOSET should not be used to treat type 1 diabetes or diabetic ketoacidosis.

There are limited efficacy data in combination with thiazolidinediones.

Efficacy has not been confirmed in combination with insulin.

IMPORTANT SAFETY INFORMATION FOR CYCLOSET

Contraindications

Do not use CYCLOSET in patients with hypersensitivity to ergot-related drugs, bromocriptine or to any of the excipients in CYCLOSET.

Do not use CYCLOSET in patients with syncopal migraines. May precipitate hypotension.

Do not use CYCLOSET in nursing women. May inhibit lactation. There have been postmarketing reports of stroke with bromocriptine in this patient population, although causality has not been proven. Based on CYCLOSET clinical trials, there is no evidence of increased risk for stroke when CYCLOSET is used to treat type 2 diabetes.

Orthostatic Hypotension/Syncope

CYCLOSET can cause orthostatic hypotension and syncope, particularly upon initiation or dose escalation. Use caution in patients taking anti-hypertensive medications. Orthostatic vital signs should be assessed prior to initiation of CYCLOSET and periodically thereafter.

Advise patients during early treatment to avoid situations that could lead to injury if syncope were to occur, and to make slow postural changes.

Exacerbation of Mental Illness

Pathological gambling and exacerbation of psychotic disorders have been reported with bromocriptine generally given in higher doses than what is approved for diabetes treatment. There have been no reported cases of psychoses or pathological gambling among CYCLOSET-treated patients in clinical trials. The use of CYCLOSET in patients with severe psychotic disorders is not recommended.

Somnolence

CYCLOSET may cause somnolence, particularly when initiating therapy. Advise patients not to drive or operate heavy machinery if symptoms of somnolence occur.

Concomitant Use of Dopamine Antagonists or Agonists

Concomitant use with other dopamine antagonists, such as neuroleptic agents, may diminish the effectiveness of both drugs and is not recommended.

Effectiveness and safety are unknown in patients already taking dopamine receptor agonists for other indications and concomitant use is not recommended.

Macrovascular Effects

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with CYCLOSET. CYCLOSET has not been associated with increased risk of macrovascular events.

Safety and Effectiveness in Pediatrics

The safety and effectiveness of CYCLOSET in pediatric patients have not been established.

Adverse Reactions

In clinical trials, the most common adverse reactions reported in ≥5% of patients treated with CYCLOSET, and reported more commonly than in patients treated with placebo, included nausea, fatigue, dizziness, vomiting, and headache. Postmarketing reports with higher doses of bromocriptine used for other indications include psychotic disorders, hallucinations, and fibrotic complications.