Cevimeline

Cevimeline is a synthetic quinuclidine derivative and direct muscarinic agonist with relative selectivity for M1 and M3 receptors. Its only established indication is dry mouth in Sjögren syndrome. It is not stocked in many markets, including much of East Africa, where oral pilocarpine is the usual alternative.

Classification. Direct acting cholinergic agonist; muscarinic M1 and M3 selective.

Mechanism. Stimulates M3 receptors on salivary and lacrimal acinar cells, increasing secretion from residual functional tissue.

Pharmacodynamics. Increased saliva within 1 to 2 hours; may also improve dry eye symptoms. Systemic muscarinic effects include sweating and gastrointestinal hypermotility.

Pharmacokinetics. Rapid oral absorption, peak 1.5 to 2 hours; food slows absorption. Metabolised by CYP2D6 and CYP3A4; elimination half life about 5 hours; mainly renal excretion of metabolites.

Dry mouth in Sjögren syndrome, adult.

• Cevimeline 30 mg orally three times daily.

• Maximum 90 mg daily; higher doses add adverse effects without benefit.

• No loading dose or titration.

• Review benefit at 6 to 12 weeks; stop if no symptomatic gain.

Children. Not established; not advised.

Choice against pilocarpine. Both drugs need residual gland function. Cevimeline has a longer half life and some patients tolerate it better; neither has been shown clearly superior.

Contraindications. Uncontrolled asthma; acute iritis; angle closure glaucoma; hypersensitivity.

Warnings. Caution in controlled asthma, chronic bronchitis, chronic obstructive pulmonary disease, significant cardiovascular disease (conduction changes, angina), cholelithiasis and nephrolithiasis. Miosis impairs night vision. Caution in known CYP2D6 poor metabolisers, who have higher exposure.

Adverse effects. Sweating, nausea, rhinitis, diarrhoea, abdominal pain, sinusitis, headache, urinary frequency, dizziness; uncommonly bradycardia, hypotension and bronchospasm.

Interactions. CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) and CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) raise concentrations; use with caution. Beta blockers increase conduction risk. Anticholinergics oppose the effect.

Special groups.

• Pregnancy: no adequate human data; avoid.

• Breastfeeding: no data; avoid.

• Older adults: no adjustment; watch for hypotension and dehydration.

• Kidney and liver impairment: not studied; use with caution and monitor tolerance.

Overdose and reversal. Atropine reverses muscarinic toxicity; give 0.6 to 1.2 mg IV in adults and repeat as needed. Supportive care for dehydration from sweating.

Formulation. Capsules 30 mg.

Administration. Oral, with or without food; taking with food reduces nausea. Maintain fluid intake, especially in hot conditions.

Baseline. Confirm residual salivary flow, review asthma and cardiac history, list interacting drugs.

Monitoring. Symptom response, sweating and hydration, heart rate in cardiac disease, respiratory symptoms in airway disease.

Stopping. Stop if no benefit by 12 weeks or adverse effects outweigh benefit.