Cevimeline

Cevimeline is a muscarinic agonist marketed under the brand name Evoxac. It is approved by the FDA for the stimulation of saliva production in patients with dry mouth (xerostomia), most commonly seen in Sjögren’s syndrome.

This medication is primarily used to treat dry mouth symptoms by targeting the salivary glands. It can also improve tear secretion in some patients. Cevimeline binds selectively to M1 and M3 muscarinic receptors in glandular tissue.

By activating these receptors, cevimeline increases intracellular calcium, which enhances secretion from salivary and lacrimal glands. The result is improved lubrication in the mouth and eyes, reducing discomfort and risk of dental issues.

The primary gene involved in cevimeline metabolism is CYP2D6, a liver enzyme responsible for breaking down many drugs. CYP2D6 activity determines how quickly or slowly cevimeline is processed and cleared from the body.

Genetic variations in CYP2D6 can classify individuals into metabolizer types (e.g., ultrarapid, normal, intermediate, poor). Metabolizer status affects drug levels: fast metabolizers may clear the drug too quickly, reducing efficacy, while slow metabolizers may accumulate higher levels, increasing risk of side effects.

Depending on CYP2D6 phenotype, patients may experience normal response (normal metabolizers), reduced efficacy (ultrarapid metabolizers), or higher exposure and risk of adverse reactions (poor metabolizers). Intermediate metabolizers fall between normal and poor, with modest changes in drug levels. If genotype is unknown, standard dosing with clinical monitoring is recommended.

Ultrarapid Metabolizer

• Effect on drug levels: Decreased plasma levels due to rapid clearance
• Clinical consequence: Potential for reduced efficacy and symptom relief
• Side effects: Fewer cholinergic effects; mild or infrequent

Normal Metabolizer

• Effect on drug levels: Expected therapeutic levels with standard dosing
• Clinical consequence: Adequate symptom control
• Side effects: Typical cholinergic events (e.g., sweating, nausea); usually mild to moderate

Intermediate Metabolizer

• Effect on drug levels: Slightly increased exposure compared to normal
• Clinical consequence: Generally adequate control, possible mild increased effect
• Side effects: Possible mild to moderate cholinergic symptoms; occasional

Poor Metabolizer

• Effect on drug levels: Increased plasma levels due to slow clearance
• Clinical consequence: Higher risk of excessive cholinergic activity
• Side effects: Sweating, diarrhea, abdominal cramps; moderate severity; more frequent

Indeterminate / Not Available

• Effect: Unknown
• Clinical consequence: No specific guidance; follow standard dosing with clinical monitoring
• Side effects: As per standard population; monitor for cholinergic effects

CYP2D6 Dosing Guideline

Examples of alternative approaches include pilocarpine (Salagen), another muscarinic agonist, and non-pharmacological measures such as artificial saliva substitutes, sugar-free lozenges, or increased water intake. These are examples only; treatment should be individualized by a healthcare professional.

• FDA – Table of Pharmacogenetic Associations