Description of Cevimeline
Cevimeline is a quinuclidine derivative of acetylcholine and acts as a cholinergic agonist. Cevimeline improves the symptoms of dry mouth (xerostomia) in patients with Sjogren’s syndrome. Prior to the approval of cevimeline, pilocarpine was the only other agent approved for this indication; however, significant advantages of cevimeline over pilocarpine have yet to be determined. In studies comparing cevimeline at various dosages per day, there was no difference between the 180 mg/day and 90 mg/day dosages; however, the 90 mg/day dosage was preferred by patients over the 45 mg/day dosage. An increase in salivary flow was reported at all dosages. Animal studies suggest potential usefulness of cevimeline in patients with xerostomia secondary to radiation therapy of the head or neck area. As a cholinergic agonist, cevimeline is in Phase III trials to study its usefulness as an adjunct in the treatment of Alzheimer’s disease. The FDA approved cevimeline in January 2000.
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Mechanism of Action of Cevimeline
Cevimeline is a muscarinic receptor agonist. Muscarinic receptors occur in cardiovascular, exocrine gland, gastrointestinal, ocular, pulmonary, and urinary tissues. Effects of muscarinic agonists on these tissues may include bradycardia or other alterations in cardiac conduction, vasodilation, secretion from lacrimal, salivary and sweat glands, increased GI motility, miosis and accommodation, increased bronchial secretions and bronchoconstriction, and biliary or urinary tract contraction. It has partial direct M1-receptor agonist activity in the CNS and has high binding affinity for muscarinic M3 receptors on lacrimal and salivary gland epithelium. Binding to other muscarinic receptor subtypes has been reported to varying degrees depending upon the tissue and assay used. As a muscarinic receptor agonist, cevimeline increases secretion of exocrine glands, such salivary and sweat glands and increases tone of the smooth muscle in the gastrointestinal tract and urinary tract.
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Pharmacokinetics
Cevimeline is administered orally. It has a high volume of distribution with little protein binding, suggesting high binding to tissues; however, specific tissue binding sites are not known. It is metabolized by liver cytochrome P450 isoenzymes (CYP) 2D6 and 3A4. It has no induction or inhibitory effects on any CYP isoenzymes. The mean half-life is 5 hours and it is mostly excreted in the urine.
Affected cytochrome P450 isoenzymes: CYP2D6, CYP3A4
Route-Specific Pharmacokinetics
Oral Route
Following oral administration of cevimeline, Tmax occurs within 1.5—2 hours. When it is administered with food the Tmax increases to 2.86 hours and the Cmax is decreased by 17.3%.
Generic Name
Cevimeline Hydrochloride
- Evoxac
- Central Nervous System Agent
- Cholinergic System
- Sjogren’s syndrome – Xerostomia: Adult
- Dermatologic: Diaphoresis (18.7% )
- Gastrointestinal: Diarrhea (10.3% ), Excessive salivation (2.2% ), Nausea (13.8% ), Vomiting (4.6% )
- Renal: Urinary tract infectious disease (6.1% )
- Respiratory: Bronchitis (4.1% ), Cough (6.1% ), Rhinitis (11.2% ), Sinusitis (12.3% ), Upper respiratory infection (11.4% )
- Evoxac: Oral Capsule: 30 MG
- Oral Capsule: 30 MG
- Sjogren’s syndrome – Xerostomia: 30 mg orally 3 times a day
- General Dosage Information: Safety and efficacy have not established in pediatric patients .