CYCLOSET ACTS IN THE BRAIN
TO HELP CONTROL GLUCOSE1,2

CYCLOSET helped patients use the insulin in their body more effectively2

CYCLOSET is the only micronized bromocriptine formulation, and it provides dopaminergic activity when dosed orally in the morning with food1,2

 

 

PROPOSED MECHANISM OF ACTION OF HOW CYCLOSET MAY BENEFIT PATIENTS WITH T2DM

T2DM

Type 2 diabetes can be characterized by decreased dopamine D2 receptor activity at the biological clock in the morning.1

Decreased morning brain
dopamine D2 receptor activity

With reduced D2 receptor activity at the clock in the morning, other neurotransmitters (such as serotonin and norepinephrine) may become elevated, contributing to increased sympathetic nervous system activity. Overactivity of the sympathetic nervous system can cause detrimental effects such as insulin resistance, hyperglycemia, hypertension, and increased risk of cardiovascular disease.1,3-6

Increased sympathetic tone

High sympathetic tone is associated with multiple systemic defects, including increased plasma free fatty acids and elevated cortisol levels, which can interrupt insulin activity in cells.3,5,7

Decreased insulin sensitivity

Postprandial glucose levels are important because data show that high postmeal glucose can contribute to increased risk of microvascular complications and cardiovascular events in patients with type 2 diabetes.10-12

Postprandial hyperglycemia

Mannequin

T2DM + CYCLOSET

CYCLOSET is a unique micronized formulation of bromocriptine, a potent dopamine D2 agonist, that facilitates a rapid increase of dopamine D2 receptor activity in the brain. Taken in the morning, when it is most needed in type 2 diabetes patients, CYCLOSET is thought to help reestablish the morning surge in dopamine D2 receptor activity.1,2,6

Reestablished morning brain
dopamine D2 receptor activity

By activating D2 receptors, CYCLOSET helps reduce the activity of inappropriately elevated levels of neurotransmitters such as serotonin and norepinephrine, leading to a reduction of elevated sympathetic tone, a driver of insulin resistance and dysglycemia.1

Reduced sympathetic tone

The sympatholytic activity of CYCLOSET may help modulate the multiple systemic defects associated with increased sympathetic tone, helping to decrease tissue and plasma norepinephrine, free fatty acid, and cortisol levels. This effect may help restore insulin activity in cells.1,2,3,7,9

Increased insulin sensitivity

CYCLOSET helps reduce postmeal plasma glucose levels without raising plasma insulin and may lower HbA1c.2

Improved postprandial
hyperglycemia

Mannequin

CYCLOSET MAY help unlock the brain’s potential to increase insulin sensitivity for improved glycemic control2

INDICATION

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.

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.

IMPORTANT SAFETY INFORMATION

Contraindications
CYCLOSET is contraindicated in:

Patients with hypersensitivity to ergot-related drugs, bromocriptine or to any of the excipients in CYCLOSET.

Patients with syncopal migraines. May precipitate hypotension.

Postpartum patients. Serious and life-threatening adverse reactions have been reported.

Lactating patients. CYCLOSET contains bromocriptine which inhibits lactation.

Orthostatic Hypotension/Syncope

CYCLOSET can cause orthostatic hypotension and syncope, particularly upon initiation or dose escalation. Use caution in patients taking antihypertensive 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.

Psychotic Disorders

The use of CYCLOSET in patients with severe psychotic disorders is not recommended.

Impulse Control/Compulsive Behaviors

Consider dose reduction or discontinuation of CYCLOSET if a patient develops intense urges to gamble, increased sexual urges, intense urges to spend money uncontrollably and/or other intense urges.

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 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.

Risks in Postpartum Patients

CYCLOSET is contraindicated in postpartum patients. Serious and life-threatening adverse reactions have been reported in postpartum women who were administered bromocriptine for inhibition of lactation. These risks may be higher in postpartum patients with cardiovascular disease. The indication for use of bromocriptine for inhibition of postpartum lactation was withdrawn from bromocriptine-containing products and is not approved for CYCLOSET.

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.

Drug Interactions

May increase the unbound fraction of highly protein-bound therapies, altering their effectiveness and safety profiles.

May increase ergot-related side effects or reduce ergot effectiveness for migraines if co-administered within 6 hours of ergot-related drugs.

Extensively metabolized by CYP3A4. Limit CYCLOSET dose to 1.6 mg/day during concomitant use of moderate CYP3A4 inhibitors. Avoid concomitant use of CYCLOSET with strong CYP3A4 inhibitors.

References: 1. Defronzo R. Bromocriptine: a sympatholytic, D2-dopamine agonist for the treatment of type 2 diabetes. Diabetes Care. 2011;34(4):789-794. 2. CYCLOSET [prescribing information]. Tiverton, RI: VeroScience, LLC. 3. Cincotta A. Hypothalamic role in insulin resistance and insulin resistance syndrome. In: Hansen B, Shafrir E, eds. Frontiers in Animal Diabetes Research Series. London, UK: Taylor and Francis; 2002:271-312. 4. Jamerson KA, Julius S, Gudbrandsson T, Andersson O, Brant DO. Reflex sympathetic activation induces acute insulin resistance in the human forearm. Hypertension. 1993;21(5):618-623. 5. Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58(4):773-795. 6. Cincotta AH, Meier AH, Cincotta M Jr. Bromocriptine improves glycaemic control and serum lipid profile in obese Type 2 diabetic subjects: a new approach in the treatment of diabetes. Expert Opin Investig Drugs. 1999;8(10):1683-1707. 7. Peng K, Pan Y, Li J, et al. 11ß-Hydroxysteroid Dehydrogenase Type 1(11ß-HSD1) mediates insulin resistance through JNK activation in adipocytes. Sci Rep. 2016;6:37160. 8. Florez H, Scranton R, Farwell WR, et al. Randomized clinical trial assessing the efficacy and safety of bromocriptine-QR when added to ongoing thiazolidinedione therapy in patients with type 2 diabetes mellitus. J Diabetes Metabol. 2011;2(7):1-8. 9. Raskin P, Cincotta AH. Bromocriptine-QR therapy for the management of type 2 diabetes mellitus: developmental basis and therapeutic profile summary. Expert Rev Endocrinol Metab. 2016;11(2):113-149. 10. DECODE Study Group, the European Diabetes Epidemiology Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med. 2001;16(3):397-405. 11. Takao T, Suka M, Yanagisawa H, Iwamoto Y. Impact of postprandial hyperglycemia at clinic visits on the incidence of cardiovascular events and all-cause mortality in patients with type 2 diabetes. J Diabetes Investig. 2017;8(4):600-608. 12. Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c). Diabetes Care. 2003;26(3):881-885.

INDICATION

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.

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.

IMPORTANT SAFETY INFORMATION

Contraindications
CYCLOSET is contraindicated in:

Patients with hypersensitivity to ergot-related drugs, bromocriptine or to any of the excipients in CYCLOSET.

Patients with syncopal migraines. May precipitate hypotension.

Postpartum patients. Serious and life-threatening adverse reactions have been reported.

Lactating patients. CYCLOSET contains bromocriptine which inhibits lactation.

Orthostatic Hypotension/Syncope

CYCLOSET can cause orthostatic hypotension and syncope, particularly upon initiation or dose escalation. Use caution in patients taking antihypertensive 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.

Psychotic Disorders

The use of CYCLOSET in patients with severe psychotic disorders is not recommended.

Impulse Control/Compulsive Behaviors

Consider dose reduction or discontinuation of CYCLOSET if a patient develops intense urges to gamble, increased sexual urges, intense urges to spend money uncontrollably and/or other intense urges.

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 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.

Risks in Postpartum Patients

CYCLOSET is contraindicated in postpartum patients. Serious and life-threatening adverse reactions have been reported in postpartum women who were administered bromocriptine for inhibition of lactation. These risks may be higher in postpartum patients with cardiovascular disease. The indication for use of bromocriptine for inhibition of postpartum lactation was withdrawn from bromocriptine-containing products and is not approved for CYCLOSET.

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.

Drug Interactions

May increase the unbound fraction of highly protein-bound therapies, altering their effectiveness and safety profiles.

May increase ergot-related side effects or reduce ergot effectiveness for migraines if co-administered within 6 hours of ergot-related drugs.

Extensively metabolized by CYP3A4. Limit CYCLOSET dose to 1.6 mg/day during concomitant use of moderate CYP3A4 inhibitors. Avoid concomitant use of CYCLOSET with strong CYP3A4 inhibitors.