A UNIQUE COMPLEMENTARY APPROACH FOR T2DM1

Understanding the role of dopamine in your adult patients with T2DM

SNS hyperactivity SNS hyperactivity

Reduced brain dopamine activity in the morning potentiates SNS hyperactivity* and this neurophysiological state induces insulin resistance2-7

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Addressing reduced brain dopamine activity in patients with T2DM is associated with increased insulin sensitivity and glucose disposal1

SNS=sympathetic nervous system; T2DM=type 2 diabetes mellitus.

*Demonstrated predominantly in preclinical studies.4-7

Associated signs of elevated SNS activity8

Heart rate Heart rate

ELEVATED RESTING HEART RATE
(>80 BPM)9

Hypertension history Hypertension history

HISTORY OF HYPERTENSION (≥130/80 mm Hg)

ALONG WITH ELEVATED PLASMA

TRIGLYCERIDES (>150 mg/dL)10-12,†

BPM=beats per minute; mm Hg=millimeters of mercury; mg/dL=milligrams per deciliter.

†The American Association of Clinical Endocrinology recommends that blood pressure control be individualized; however, a target of <130/80 mm Hg is appropriate for most patients.12

Brain SNS activity Brain SNS activity

Morning administration of CYCLOSET®, as a D2 receptor agonist, helps improve insulin sensitivity and glucose disposal.1

A unique mechanism
of action1

CYCLOSET® offers a targeted mechanism of action as a complementary add-on therapy.1 CYCLOSET® is a go-to option in your treatment toolbox to help with your patient’s existing T2DM regimen.1

Patients should take CYCLOSET® once daily, in the morning with food, within 2 hours of waking up.1

Brain Brain

CYCLOSET® tablets work in the brain as the first and only dopamine D2 receptor agonist indicated, as an adjunct to diet and exercise, to improve glycemic control in adults with T2DM1,13

Micronized formulation Micronized formulation

CYCLOSET® is a uniquely micronized formulation of bromocriptine mesylate that helps reduce postprandial hyperglycemia without raising plasma insulin levels1,‡,§,||,¶

Adult patients with T2DM who have adequate insulin production and potential signs of elevated SNS activity may benefit from CYCLOSET® as an adjunct to diet and exercise.1,14

T2DM=type 2 diabetes mellitus.

‡Based on a pharmacodynamic study of postprandial glucose (PPG) and insulin response to a meal.1

§CYCLOSET® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2DM.1

||CYCLOSET® should not be used to treat type 1 diabetes or diabetic ketoacidosis. Limited efficacy data in combination with thiazolidinediones (TZDs).

Efficacy has not been confirmed in combination with insulin.1

CYCLOSET® should be taken orally once daily, in the morning, within 2 hours of waking, with food.1

DISCOVER CYCLOSET® EFFICACY

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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.
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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.

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.

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.

To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please click here for full Prescribing Information.

References: 1. CYCLOSET [prescribing information]. Tiverton, RI: VeroScience LLC; 2020. 2. Cincotta AH, Luo S, Liang Y. Hyperinsulinemia increases norepinephrine metabolism in the ventromedial hypothalamus of rats. Neuroreport. 2000;11(2):383-387. 3. Caravaggio F, Borlido C, Hahn M, et al. Reduced insulin sensitivity is related to less endogenous dopamine at D2/3 receptors in the ventral striatum of healthy nonobese humans. Int J Neuropsychopharmacol. 2015;18(7):pyv014. 4. Luo S, Zhang Y, Ezrokhi M, Li Y, Tsai TH, Cincotta AH. Circadian peak dopaminergic activity response at the biological clock pacemaker (suprachiasmatic nucleus) area mediates the metabolic responsiveness to a high-fat diet. J Neuroendocrinol. 2018;30(1):e12563. 5. Ter Horst KW, Lammers NM, Trinko R, et al. Striatal dopamine regulates systemic glucose metabolism in humans and mice. Sci Transl Med. 2018;10(442):eaar3752. 6. 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):113-148. 7. Defronzo RA. Bromocriptine: a sympatholytic, D2-dopamine agonist for the treatment of type 2 diabetes. Diabetes Care. 2011;34(4):789-794. 8. Tentolouris N, Argyrakopoulou G, Katsilambros N. Perturbed autonomic nervous system function in metabolic syndrome. Neuromolecular Med. 2008;10(3):169-178. 9. Chamarthi B, Vinik A, Ezrokhi M, Cincotta AH. Circadian-timed quick-release bromocriptine lowers elevated resting heart rate in patients with type 2 diabetes mellitus. Endocrinol Diabetes Metab. 2020;3(1):e00101. 10. American Diabetes Association. Standards of care in diabetes—2023. Diabetes Care. 2023;46(Suppl. 1):S1-S291. 11. Valensi P. Autonomic nervous system activity changes in patients with hypertension and overweight: role and therapeutic implications. Cardiovasc Diabetol. 2021;20(1):170. 12. Garber AJ, Handelsman Y, Grunberger G, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm–2020 executive summary. Endocr Pract. 2020;26(1):107-139. 13. Approved drug products with therapeutic equivalence evaluations: 41st Ed. U.S. Department of Health and Human Services; 2021. 14. 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.