VA Class:AU900
Cevimeline hydrochloride is a cholinergic agonist that binds to muscarinic receptors.1, 2
Dry Mouth Secondary to Sjögren Syndrome
Cevimeline hydrochloride is used for the symptomatic treatment of dry mouth (xerostomia) in patients with Sjögren syndrome.1, 2, 10, 15, 16 Sjögren syndrome is a chronic, progressive autoimmune disease characterized by lymphocytic infiltration of the exocrine glands.4, 8, 9 In most patients, the salivary and lacrimal glands are affected, resulting in symptoms of xerostomia and dry eyes.4, 8, 9 Muscarinic agonists (cevimeline and pilocarpine) have been shown to substantially increase salivary flow and improve symptoms of dry mouth in patients with Sjögren syndrome.2, 6, 7, 16
Efficacy of cevimeline in alleviating symptoms of dry mouth in patients with Sjögren syndrome was established in 2 randomized, double-blind, placebo-controlled studies.1, 2, 15, 16 Patient assessment of symptoms of dry mouth was used to evaluate global improvement.1, 15, 16 A cevimeline dosage of 30 mg 3 times daily for 6 or 12 weeks was substantially more effective than placebo in global improvement evaluations in these studies.1, 2, 15, 16 In one of the studies, no additional clinical benefit was observed with a dosage of 60 mg 3 times daily.1, 15 In the other study, a dosage of 15 mg 3 times daily was not associated with substantial benefit in global improvement evaluations relative to placebo, although a substantial increase in salivary flow was observed.1, 16 In a third study of 12 weeks' duration, no substantial effect on global improvement scores was observed at dosages of 15 or 30 mg 3 times daily when compared with placebo; however, a higher placebo response was noted in this study compared with the previous studies.1 A substantial improvement in salivary flow was observed at a dosage of 30 mg 3 times daily in this study.1, 2
There are few comparative studies of cevimeline and pilocarpine.6, 7 Although both drugs are effective in improving symptoms of xerostomia in patients with Sjögren syndrome, adverse effects may differ based on differences in muscarinic receptor selectivity and affinity.6, 7 (See Description.) In an observational study comparing the tolerability and adverse effect profiles of the drugs in patients with primary Sjögren syndrome, the discontinuance rate due to adverse effects was higher with pilocarpine than with cevimeline.6 Severe sweating was the most frequent adverse effect leading to cessation of therapy in both groups, and occurred at a higher incidence in patients receiving pilocarpine compared with those receiving cevimeline.6
Cevimeline hydrochloride is administered orally 3 times daily.1 Although food may decrease the rate of absorption, no clinically important effects have been demonstrated and the manufacturer makes no specific recommendations for administering the drug with regard to meals. 1, 5
Dosage of cevimeline hydrochloride is expressed in terms of cevimeline.1
The recommended adult dosage of cevimeline for treatment of dry mouth secondary to Sjögren syndrome is 30 mg 3 times daily.1 Safety and efficacy of dosages exceeding 90 mg daily have not been established.1
The manufacturer makes no special population dosage recommendations at this time.1 The effects of renal impairment, hepatic impairment, or ethnicity on the pharmacokinetics of cevimeline have not been investigated.1
Known hypersensitivity to cevimeline hydrochloride, uncontrolled asthma, and when miosis is undesirable (e.g., acute iritis, angle-closure glaucoma).1
Cevimeline may alter cardiac conduction and/or heart rate.1 Patients with clinically important cardiovascular disease may be unable to compensate for transient changes in hemodynamics or heart rhythm induced by cevimeline.1
Cevimeline should be used with caution and under close medical supervision in patients with a history of cardiovascular disease (e.g., angina pectoris, myocardial infarction).1
Cevimeline may increase bronchial smooth muscle tone, bronchial secretions, and airway resistance.1 The drug should be used with caution and under close medical supervision in patients with controlled asthma, chronic bronchitis, or chronic obstructive pulmonary disease (COPD).1
Ophthalmic formulations of muscarinic agonists have been associated with blurred vision, which may result in impairment of depth perception and decreased visual acuity, especially at night and in patients with central lens changes.1 (See Advice to Patients.)
Cevimeline may cause adverse effects related to exaggeration of parasympathomimetic effects, including headache, visual disturbance, lacrimation, sweating, respiratory distress, GI spasm, nausea, vomiting, diarrhea, AV block, tachycardia, bradycardia, hypotension, hypertension, shock, mental confusion, cardiac arrhythmia, and tremors.1
Sweating is the most common adverse effect of cevimeline and was reported in approximately 19% of patients receiving the drug in clinical studies.1 Excessive sweating may cause dehydration.1 (See Advice to Patients.)
Cevimeline should be used with caution in patients with history of cholelithiasis.1 Contraction of gallbladder or biliary smooth muscle could precipitate complications (e.g., cholecystitis, cholangitis, biliary obstruction).1
Cevimeline should be used with caution in patients with history of nephrolithiasis.1 Increased ureteral smooth muscle tone theoretically could precipitate renal colic or ureteral reflux in patients with nephrolithiasis.1
Cytochrome P-450 (CYP) 2D6 Deficiency
Patients known or suspected to be deficient in CYP2D6 activity may be at a higher risk of adverse effects because of decreased cevimeline metabolism.1 (See Drug Interactions: Drugs Affecting Hepatic Microsomal Enzymes.)
There are no adequate and well-controlled studies of cevimeline in pregnant women; in animal studies, a reduced number of implantations, possibly due to maternal toxicity was observed when the drug was administered to pregnant rats.1
Cevimeline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.1
It is not known whether cevimeline is distributed into milk; a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.1
Safety and efficacy of cevimeline have not been established in children.1, 5
Response in patients 65 years of age and older does not appear to differ from that of younger adults.1, 5 However, the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly should be considered.1
Adverse effects occurring in 3% or more of patients receiving cevimeline include excessive sweating, headache, nausea, sinusitis, upper respiratory tract infection, rhinitis, diarrhea, dyspepsia, abdominal pain, urinary tract infection, cough, pharyngitis, vomiting, injury, back pain, rash, conjunctivitis, dizziness, bronchitis, arthralgia, surgical intervention, fatigue, and pain.1
Drugs Affecting Hepatic Microsomal Enzymes
Cevimeline hydrochloride is metabolized by cytochrome P-450 (CYP) isoenzymes 2D6, 3A3, and 3A4.1 Drugs that inhibit these isoenzymes may decrease metabolism and increase plasma concentrations of cevimeline.1
Cevimeline does not inhibit CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 in vitro.1
Beta-Adrenergic Blocking Agents
Because of the potential for cardiac conduction disturbances, caution is advised when cevimeline is used concomitantly with β-adrenergic blocking agents.1
Cevimeline may antagonize the effects of antimuscarinic agents (e.g., atropine, ipratropium) if used concomitantly.1
Concomitant administration of cevimeline and drugs with parasympathomimetic effects may result in additive pharmacologic effects.1
Cevimeline hydrochloride, a quinuclidine derivative of acetylcholine, is a cholinergic agonist that binds to muscarinic receptors.1, 2, 7 In sufficient dosages, muscarinic agonists can increase exocrine (e.g., salivary, sweat) gland secretion and increase GI and urinary tract smooth muscle tone.1
Cevimeline is pharmacologically similar to pilocarpine, another oral cholinergic agonist that exerts predominantly muscarinic action.2, 3, 5 Both drugs stimulate residual salivary gland tissues and have been shown to substantially increase salivary flow.2, 7 However, the adverse effect profile of the drugs may differ based on differences in selectivity and affinity for specific muscarinic receptor subtypes.7 Cevimeline is a more selective muscarinic agonist than pilocarpine and exhibits a 40-fold greater affinity for M3 muscarinic receptors in the lacrimal and salivary glands than for M2 receptors in cardiac tissue.3, 7, 15
Cevimeline is rapidly absorbed following oral administration; peak plasma concentrations are reached in approximately 1.5-2 hours.1 Cevimeline is metabolized by cytochrome P-450 (CYP) isoenzymes 2D6, 3A3, and 3A4.1 In an in vitro study, CYP isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 were not inhibited by cevimeline.1 The drug is excreted principally in urine, with 97 and 0.5% of a 30-mg dose recovered in urine and feces, respectively, after 7 days.1
Risk of visual disturbances, especially at night; importance of advising patients to use caution when driving at night or performing hazardous activities in reduced lighting.1
Risk of dehydration if excessive sweating occurs while receiving cevimeline; increase water intake and consult a clinician if this occurs.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 30 mg (of cevimeline)* | Cevimeline Hydrochloride Capsules | |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions January 7, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Daiichi Sankyo. Evoxac® (cevimeline hydrochloride) capsules prescribing information. Basking Ridge, NJ; 2018 May.
2. Anon. Cevimeline (Evoxac) for dry mouth. Med Lett Drugs Ther . 2000; 42:70. [PubMed 10932302]
3. Eisai. Salagen® (pilocarpine hydrochloride) film-coated tablets prescribing information. Woodcliff Lake, NJ; 2018 Jun.
4. Moutsopoulos HM and Tzioufas AG. Sjögren's syndrome. In: Kasper DL, Fauci AS, Hauser SL et al, eds. Harrison's principles of internal medicine. 19th ed. New York: McGraw-Hill Education; 2015:2166-9
5. Daiichi Pharmaceutical Corp., Montvale, NJ: Personal communication.
6. Noaiseh G, Baker JF, Vivino FB, et al. Clin Exp Rheumatol. Comparison of the discontinuation rates and side-effect profiles of pilocarpine and cevimeline for xerostomia in primary Sjögren's syndrome. 2014 Jul-Aug;32(4):575-7.
7. Braga MA, Tarzia O, Bergamaschi CC, et al. Comparison of the effects of pilocarpine and cevimeline on salivary flow. Int J Dent Hyg . 2009 May;7(2):126-30.
8. Mariette X, Criswell LA. Primary Sjögren's Syndrome. N Engl J Med . 2018; 378:931-939. [PubMed 29514034]
9. Ramos-Casals M, Tzioufas AG, Stone JH et al. Treatment of primary Sjögren syndrome: a systematic review. JAMA . 2010; 304:452-60. [PubMed 20664046]
10. Vivino FB, Carsons SE, Foulks G et al. New Treatment Guidelines for Sjögren's Disease. Rheum Dis Clin North Am . 2016; 42:531-51. [PubMed 27431353]
15. Fife RS, Chase WF, Dore RK et al. Cevimeline for the treatment of xerostomia in patients with Sjögren syndrome: a randomized trial. Arch Intern Med . 2002; 162:1293-300. [PubMed 12038948]
16. Petrone D, Condemi JJ, Fife R et al. A double-blind, randomized, placebo-controlled study of cevimeline in Sjögren's syndrome patients with xerostomia and keratoconjunctivitis sicca. Arthritis Rheum . 2002; 46:748-54. [PubMed 11920411]