indication

For the treatment of symptoms of dry mouth in patients with Sjögren's Syndrome.

pharmacology

Cevimeline is a cholinergic agonist which binds to muscarinic receptors. Muscarinic agonists in sufficient dosage can increase secretion of exocrine glands, such as salivary and sweat glands and increase tone of the smooth muscle in the gastrointestinal and urinary tracts.

mechanism of action

Muscarinic agonists such as cevimeline bind and activate the muscarinic M1 and M3 receptors. The M1 receptors are common in secretory glands (exocrine glands such as salivary and sweat glands), and their activation results in an increase in secretion from the secretory glands. The M3 receptors are found on smooth muscles and in many glands which help to stimulate secretion in salivary glands, and their activation generally results in smooth muscle contraction and increased glandular secretions. Therefore, as saliva excretion is increased, the symptoms of dry mouth are relieved.

biotransformation

Primarily hepatic, isozymes CYP2D6 and CYP3A4 are responsible for the metabolism of cevimeline. Approximately 44.5% of the drug is converted to cis and trans-sulfoxide, 22.3% to glucuronic acid conjugate, and 4% to N-oxide of cevimeline. Approximately 8% of the trans-sulfoxide metabolite is then converted into the corresponding glucuronic acid conjugate.

absorption

Rapidly absorbed with peak concentration after 1.5 to 2 hours

half life

5 ± 1 hours

route of elimination

After 24 hours, 84% of a 30 mg dose of cevimeline was excreted in urine.

drug interactions

Conivaptan: Conivaptan may increase the serum concentration of CYP3A4 substrates such as cevimeline. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.

Tacrine: The acetylcholinesterase inhibitor, Tacrine, may increase the adverse/toxic effects of Cevimeline, a cholinergic agonist. Monitor for increased cholinergic effects and toxicity.