CYCLOSET HAD A
WELL ESTABLISHED TOLERABILITY PROFILE1

IN PHASE 3 CLINICAL TRIALS, THE MOST COMMONLY REPORTED ADVERSE EVENTS (AEs) WITH CYCLOSET WERE NAUSEA, FATIGUE, DIZZINESS, VOMITING, AND HEADACHE

Most commonly reported AEs (including nausea) usually occurred during initial titration and lasted a median of 14 days

None of the reports of nausea or vomiting were described as serious

Most common adverse events in 52-week safety study
(≥5% of patients and numerically more frequent than placebo)

   

ADVERSE EVENTS

CYCLOSET

(n=2054) 1.6 mg to 4.8 mg
% (n)

 

PLACEBO

(n=1016) % (n)

NAUSEA
32.2% (661/2054)
7.6% (77/1016)
DIZZINESS
14.8% (303/2054)
9.2% (93/1016)
FATIGUE
13.9% (285/2054)
6.7% (68/1016)
HEADACHE
11.4% (235/2054)
8.3% (84/1016)
VOMITING
8.1% (167/2054)
3.1% (32/1016)
DIARRHEA
8.1% (167/2054)
8.0% (81/1016)
CONSTIPATION
5.8% (119/2054)
5.1% (52/1016)

Postmarketing reports with higher doses of bromocriptine used for other indications include psychotic disorders, hallucinations, and fibrotic complications.

IN THE 52-WEEK SAFETY TRIAL, THERE WAS NO DIFFERENCE BETWEEN CYCLOSET AND PLACEBO GROUPS IN THE OCCURRENCE OF ALL-CAUSE SERIOUS ADVERSE EVENTS

Hazard ratio: The hazard ratio quantifies the probability of an event happening within a specified time interval. In the CYCLOSET Safety Trial, the time period was 52 weeks. For all-cause serious adverse events, the hazard ratio of 1.02 shows that the probability of an event happening during the 52-week study to a CYCLOSET patient was not statistically different from an event happening to a placebo patient.1,2 1.02, upper bound of one-sided 96% confidence interval: 1.27

Hypoglycemia rate was not statistically different from placebo

6.9% (142/2054) of CYCLOSET patients vs 5.3% (54/1016) of placebo patients

Weight gain was similar to placebo

+0.2 kg for CYCLOSET patients vs +0.1 kg for placebo patients

Study Design: A 52-week, randomized, double-blind, placebo-controlled safety study of 3070 patients. Patients were treated with diet or no more than 2 anti-diabetic medications (metformin, insulin secretagogues such as sulfonylurea, thiazolidinediones, alpha glucosidase inhibitors, and/or insulin). The primary endpoint of the 52-week CYCLOSET Safety Trial was the occurrence of all-cause serious adverse events (SAEs). SAEs occurred in 8.5% (176/2054) of CYCLOSET patients vs 9.6% (98/1016) of placebo-treated patients.1

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. 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.