Cevimeline for the treatment of dry mouth in patients with Sjogren's syndrome

Abstract

Sjogren's Syndrome (SS) is a chronic autoimmune disease characterized by the presence of xerostomia and xerophthalmia and by the dysfunction of salivary and lacrimal glands. The disease is frequently associated with other systemic manifestations, including vasculitis, pulmonary interstitial disorders and lymphoma. SS constitutes the primary cause of disability and xerostomia can represent an obstacle to deglutition and to oral hygiene, making it difficult for these patients to talk, eat, and swallow. In addition, it can cause tooth decay and recurring candidosis of the oral cavity, as well as premature teeth loss. The treatment of SS is based on the use of artificial tears, saliva substitutes, and lubricants to control the symptoms, and is usually associated with muscarinic agonist drugs such as pilocarpine, especially in cases of severe dryness. Pilocarpine has been proven to increase the secretion of saliva, but its use in clinical practices is highly limited to the short duration of its action, less than 3 hours, which considerably reduces its compliance. There have recently been studies of a new muscarinic receptor agonist, Cevimeline, which has a longer half-life than Pilocarpine (about 5 hours), and has already been commercialised in some countries. The purpose of this article is to review the published literature regarding the pharmacological and clinical properties of this drug, as well as its efficacy, tolerability, and safety in the treatment of xerostomia in patients suffering from primary and secondary SS.

Drug Permeability: From the Blood–Brain Barrier to the Peripheral Nerve Barriers

“…Pirenzepine prevents gastrointestinal spasm, cevimeline increases salivation to treat dry mouth, and succinylcholine is a neuromuscular blocking agent commonly used as a muscle relaxant. [189][190][191][192][193][194][195] Another common drug, epinephrine, acts on peripheral nerves to constrict blood vessels. [196,197] These drugs can be administered orally, via intramuscular injection, or intravenously.…”

Systematic review of randomized controlled trials in the treatment of dry eye disease in Sjogren syndrome

“…Cevimeline is a parasympathomimetic drug that acts like pilocarpine, except that it has a longer serum half-life. [ 30 ] Two RCTs [ 22 , 28 ] showed that treatment with cevimeline compared to placebo improved symptoms (Visual analog scale) and signs (Schirmer I) of dry eye. Oral cevimeline (15 mg) thrice daily is superior to placebo in terms of symptoms and signs of dry eye.…”

S-Oxidation of Thiazolidinedione with Hydrogen Peroxide, Peroxynitrous Acid, and C4a-Hydroperoxyflavin: A Theoretical Study

“…Sulfur-containing drugs (Figure ) like Methimazole, Cimetidine, Artemiside, , Ranitidine, ,, Thioridazine, , 7-(1,3-thiazolidin-2-methyl) theophylline, (+)- cis -3,5-dimethyl-2-(3-pyridyl)-thiazolidin-4-one, Sulindac sulfide, etc., are reported to undergo change in metabolic state through sulfur oxidation process. The S-oxidized metabolites may be excreted as such (e.g., sulfoxide and sulfone metabolite of tazarotenic acid, cevimeline), may be therapeutically active (e.g., albendazole, flosequinan), may be toxic (e.g., fenthion sulfoxide), or may have reduced activity as compared to the original substrate (e.g., omapatrilat, sulindac sulfide, S -carboxymethyl cysteine, ziprasidone, chlorpromazine). Thorough understanding of the sulfur oxidation process at the molecular level is an essential first step in the prediction of the complex pathway of metabolite generation and its action.…”