IN CLINICAL TRIALS, THE EFFICACY RESULTS DEMONSTRATED THAT CYCLOSET LOWERED HbA1c1
HbA1c AT WEEK 241
CYCLOSET patients achieved HbA1c ≤7.0% vs placebo1,c
CYCLOSET OR PLACEBO + 1 OR 2 OTHER ORAL ANTIDIABETIC AGENTS
AT WEEK 24 (52-WEEK SAFETY TRIAL)1
aStudy Design (CYCLOSET Monotherapy): A 24-week, multicenter, double-blind, placebo-controlled study. CYCLOSET monotherapy n=80, placebo n=79.2 At baseline and Week 24, study subjects received standardized meals at 7 AM (breakfast), 12 PM (lunch), and 5 PM (dinner). Blood samples were taken prior to and 1 and 2 hours following each meal and analyzed for insulin and glucose concentrations. Premeal plasma glucose levels at Week 24: fasting: CYCLOSET=-2 mg/dL, placebo=+28 mg/dL; lunch: CYCLOSET=-16 mg/dL, placebo=+15 mg/dL; dinner: CYCLOSET=-2 mg/dL, placebo=+13 mg/dL.3,4
bStudy Design (CYCLOSET + Sulfonylurea): Two 24-week, multicenter, placebo-controlled, double-blind studies.1 The primary endpoint was reduction in HbA1c relative to placebo.3 Study K: CYCLOSET n=114; placebo n=122. Study L: CYCLOSET n=114; placebo n=123. Intent to-treat population using last observation carried forward between-group change from baseline in HbA1c.1
cStudy Design (CYCLOSET + 1-2 OADs): A 52-week, randomized, double-blind, multicenter, placebo-controlled safety study with subgroup efficacy assessments at Week 24. CYCLOSET or placebo + 1 or 2 oral antidiabetic (OAD) medications n=376; placebo n=183. CYCLOSET + metformin + sulfonylurea n=177, placebo n=90.1 CYCLOSET + TZD +/- OAD n=78; placebo n=44.5 Patients in the “metformin + sulfonylurea” and “TZD +/- OAD” subgroups are also counted in the “adjunct to 1-2 OAD” subgroup.1 OADs included metformin, sulfonylurea, thiazolidinedione (TZD), alpha-glucosidase inhibitor, meglitinide, phenylalanine derivative, or oral combination therapy formulated as 1 pill.1,4,6-8 Doses of background antidiabetic medications could be adjusted at any time during the trial, and additional antidiabetic medications were permitted after Week 12, if needed to maintain ideal glycemic control.1
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.
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 for CYCLOSET.
References: 1. CYCLOSET [prescribing information]. Tiverton, RI: VeroScience LLC; 2020. 2. Misbin, Robert I. CYCLOSET Drug Approval Package: Medical Review(s). NDA 20866 Clinical Review. US Food and Drug Administration Center for Drug Evaluation Research. January 16, 2009. Accessed June 1, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/020866Orig1s000MedR.pdf 3. Data on file, Salix Pharmaceuticals. 4. 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. 5. 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 Metab. 2011;2(7):1-8. doi:10.4172/2155-6156.1000142. 6. Vinik AI, Cincotta AH, Scranton RE, Bohannon N, Ezrokhi M, Gaziano JM. Effect of bromocriptine-QR on glycemic control in subjects with uncontrolled hyperglycemia on one or two oral anti-diabetes agents. Endocr Pract. 2012;18(6):931-943. 7. Scranton RE, Gaziano JM, Rutty D, Ezrokhi M, Cincotta A. A randomized, double-blind, placebo-controlled trial to assess safety and tolerability during treatment of type 2 diabetes with usual diabetes therapy and either Cycloset™ or placebo. BMC Endocr Disord. 2007;7(1):3. doi:10.1186/1472-6823-7-3. 8. Gaziano JM, Cincotta AH, Vinik A, Blonde L, Bohannon N, Scranton R. Effect of bromocriptine-QR (a quick-release formulation of bromocriptine mesylate) on major adverse cardiovascular events in type 2 diabetes subjects. J Am Heart Assoc. 2012;1(5):e002279. doi:10.1161/JAHA.112.002279.
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.
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 for CYCLOSET.