Bromocriptine Mesylate Tablets (Cycloset™)
July 30, 2009 4 minutes read
Pharmacology Update
Bromocriptine Mesylate Tablets (Cycloset™)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationship to this field of study.
Bromocriptine, a dopamine receptor agonist initially approved in 1978 as Parlodel®, has been approved for the treating type 2 diabetes mellitus. The drug is marketed as a quick release formulation by VeroScience LLC as Cycloset™.
Indications
Bromocriptine is indicated as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes.1
Dosage
The initial recommended dose is 0.8 mg taken with food within 2 hours of awakening in the morning. The dose should be increased by 0.8 mg weekly until the maximal tolerated dose of 1.6 mg to 4.8 mg.1
Bromocriptine is available as 0.8 mg tablets.
Potential Advantages
Bromocriptine represents a new agent that improves glycemic control without increasing insulin level. In animal models, the drug acts centrally to reduce resistance to insulin-mediated suppression of release of glucose from the liver and tissue disposal of glucose.2
Potential Disadvantages
Orthostatic hypotension and syncope have been associated with bromocriptine. It may also exacerbate psychotic disorders or reduce the effectiveness of drugs that treat psychosis.1 Common adverse events (> 10%) include nausea (32.5%), rhinitis (13.8%), headache (12.5%), asthenia (12.5%), dizziness (12.5%), and constipation (11.3%).1
Comments
Bromocriptine is a sympatholytic dopamine D2 receptor agonist that has been shown in animal studies and phase II studies to reduce insulin resistance and glucose intolerance.2 Resetting central (hypothalamic) circadian organization of monoamine neuronal activities has been proposed as the mechanism of action.3 The efficacy of bromocriptine was shown in a pooled 24-week placebo-controlled trial (n = 159), two 24-week add-on-to-a-sulfonylurea trials (n = 245, n = 249), and a 52-week add-on-to-various-diabetic-drugs trial (n = 3070).1,4 As monotherapy, bromocriptine (1.6-4.8 mg) improved placebo-adjusted mean change in HbA1c by -0.4% from a mean baseline of 9.0% (bromocriptine) and 8.8% (placebo). Mean adjusted change in fasting plasma glucose was -23 mg/dL (baseline 215 mg/dL and 205 mg/dL, respectively). Bromocriptine added to a sulfonylurea showed a placebo-adjusted mean difference of -0.5 and -0.6% (baseline 9.3%-9.4%). The primary endpoint of the 52-week trial was to compare add-on therapy with bromocriptine compared to placebo in all-cause rate of serious adverse events. A subset of subjects (n = 559) with baseline HbA1c ≥ 7.5% on 1-2 oral anti-diabetic drugs or metformin plus sulfonylurea showed a mean placebo-adjusted change of -0.5%. The study has been completed but the safety results have not been published. VeroScience reported at the recent ADA meeting that none of the serious adverse events grouped by System Organ Class occurred more than 0.3% more frequently with bromocriptine than with placebo.5 In pooled phase III studies (n = 2298 bromocriptine; n = 1266 placebo), 24% of subjects on bromocriptine discontinued participation due to adverse events compared to 9% for those who received placebo, driven mainly by nausea.1,2
Clinical Implications
Bromocriptine, with a novel mechanism of action, offers a treatment option for type 2 diabetes. As monotherapy, the reduction in HbA1c was less than that typically reported with metformin or a sulfonylurea (average 1%-2%).6 In addition, current drugs are likely better tolerated, as bromocriptine is associated with orthostatic hypotension and exacerbation of psychosis, as well as other adverse events (e.g., nausea, headache, dizziness, asthenia).
References
1. Cycloset Product Information. Tiverton, RI: VeroScience LLC; April 2009.
2. Cincotta AH, et al. 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;8:1683-1707.
3. Luo S, et al. Association of the antidiabetic effects of bromocriptine with a shift in the daily rhythm of monoamine metabolism within the suprachiasmatic nuclei of the Syrian hamster. Chronobiol Int 2000; 17:155-172.
4. Scranton RE, et al. 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;7:3.
5. VeroScience presents data on newly FDA approved drug Cycloset at American Diabetes Association. Available at: www.allbusiness.com/medicine-health/diseases-disorders-endocrine/12355689-1.html. Accessed July 2, 2009.
6. Krentz AJ, Bailey CJ. Oral antidiabetic agents: Current role in type 2 diabetes mellitus. Drugs 2005;65:385-411.
Bromocriptine, a dopamine receptor agonist initially approved in 1978 as Parlodel®, has been approved for the treating type 2 diabetes mellitus. The drug is marketed as a quick release formulation by VeroScience LLC as Cycloset™.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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