Approved May 5, 2009

BROMOCRIPTINE MESYLATE
(FDA Category 3S)

CYCLOSET(R) (VeroScience LLC), is an ergot derivative that is a dopamine receptor agonist .

DOSING INFORMATION: Bromocriptine mesylate should be initiated at 0.8 milligrams (mg) and increase by 0.8 mg per week until the maximal tolerated dose between 1.6 to 4.8 mg per day is reached. The recommended dose is 1.6 mg to 4.8 mg once daily taken with food within two hours after waking in the morning.

PHARMACOKINETICS: When given orally, approximately 93% of bromocriptine mesylate is absorbed and undergoes first-pass metabolism and the remaining 7% reaches the systemic circulation. Peak plasma levels occur approximately 53 minutes after administration under fasting conditions and 90 to 120 minutes after a standard high-fat meal. Bromocriptine mesylate is 90% to 96% bound to plasma proteins. Metabolism is extensive in the gastrointestinal tract and liver and primarily through the CYP3A4 metabolic pathway. The elimination half-life of bromocriptine mesylate is about 6 hours with the major route of excretion in the bile and the remaining 2% to 6% in the urine.

CAUTIONS: Contraindicated in patients with hypersensitivity to ergot-related drugs, bromocriptine, or to any of the excipients in the tablets. Do not use bromocriptine mesylate in patients with syncopal migraines as this may precipitate hypotensive episode and the risk for syncope. Do not use in nursing women as bromocriptine mesylate may inhibit lactation. Further, postmarketing reports of stroke have been documented in nursing women on bromocriptine mesylate although causality not proven. Bromocriptine mesylate is not recommended for use in patients with severe psychotic disorders. Concomitant use of dopamine receptor agonist and antagonists, including neuroleptic drugs, is not recommended. The most common adverse events include nausea, fatigue, dizziness, vomiting, and headache.

FDA APPROVED INDICATIONS: Bromocriptine mesylate is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus; not indicated for type 1 diabetes or diabetic ketoacidosis.