Cevimeline Hydrochloride

Class: Parasympathomimetic (Cholinergic) Agents
VA Class: AU900
Chemical Name: cis-2′-Methyl-spiro[1-azabicyclo[2.2.2]octane-3,5′-[1,3]oxathiolane] hydrate hydrochloride
Molecular Formula: C10H17NOS•ClH•½H2O
CAS Number: 153504-70-2
Brands: Evoxac

Introduction

Cholinergic agonist; binds to muscarinic receptors.1 2

Uses for Cevimeline Hydrochloride

Sjögren’s Syndrome

Treatment of symptoms of dry mouth in patients with Sjögren’s syndrome.1 2

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Cevimeline Hydrochloride Dosage and Administration

Administration

Oral Administration

Administer orally 3 times daily.1

Manufacturer makes no specific recommendations for administering the drug with regard to meals; food may decrease rate of absorption, but no clinically important effects demonstrated.1 5

Dosage

Available as cevimeline hydrochloride; dosage is expressed in terms of cevimeline.1

Adults

Sjögren’s Syndrome
Oral

30 mg 3 times daily.1

Prescribing Limits

Adults

Sjögren’s Syndrome
Oral

Safety and efficacy of dosages >90 mg daily not established.1

Cautions for Cevimeline Hydrochloride

Contraindications

  • Known hypersensitivity to cevimeline.1

  • Uncontrolled asthma.1

  • Patients in whom miosis is undesirable (e.g., those with acute iritis, angle-closure glaucoma).1

Warnings/Precautions

Warnings

Cardiovascular Effects

Risk of altered 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

Use with caution and under close medical supervision in patients with a history of cardiovascular disease (e.g., angina pectoris, MI).1

Pulmonary Effects

Risk of increased bronchial smooth muscle tone, bronchial secretions, and airway resistance.1

Use with caution and under close medical supervision in patients with controlled asthma, chronic bronchitis, or COPD.1

Ocular Effects

Blurred vision reported with ophthalmic formulations of muscarinic agonists.1 May result in impaired depth perception and decreased visual acuity, especially at night and in patients with central lens changes; may impair ability to drive at night or perform hazardous activities in reduced lighting.1

General Precautions

Parasympathomimetic Effects

Possible exaggeration of parasympathomimetic effects (e.g., headache, visual disturbance, lacrimation, sweating, respiratory distress, GI spasm, nausea, vomiting, diarrhea, AV block, tachycardia, bradycardia, hypotension, hypertension, shock, mental confusion, cardiac arrhythmia, tremors).1

Biliary Effects

Contraction of gallbladder or biliary smooth muscle could precipitate complications (e.g., cholecystitis, cholangitis, biliary obstruction) in patients with cholelithiasis.1

Use with caution in patients with a history of cholelithiasis.1

Renal Effects

Increased ureteral smooth muscle tone theoretically could precipitate renal colic or ureteral reflux in patients with nephrolithiasis.1

Use with caution in patients with a history of nephrolithiasis.1

Fluid and Electrolyte Effects

Possible dehydration secondary to excessive sweating.1

CYP2D6 Deficiency

Possible increased risk of adverse effects due to decreased cevimeline metabolism in patients with known or suspected deficiency in CYP2D6 activity.1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether cevimeline is distributed into milk; discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in children.1 5

Geriatric Use

Response in patients ≥65 years of age does not appear to differ from that in younger adults; 1 5 however, use with caution due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.1

Common Adverse Effects

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, pain.1

Interactions for Cevimeline Hydrochloride

Metabolized by CYP2D6, 3A3, and 3A4.1 Does not inhibit CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 in vitro.1

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (decreased cevimeline metabolism) with inhibitors of CYP2D6, 3A3, or 3A4.1

Specific Drugs

Drug

Interaction

Antimuscarinic agents

Potential for antagonism of antimuscarinic effects1

β-Adrenergic blocking agents

Possible cardiac conduction disturbances1

Parasympathomimetic agents

Possible additive effects1

Cevimeline Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration, with peak concentrations achieved within 1.5–2 hours.1

Food

Food decreases rate of absorption; time to peak concentration under fasting conditions and after a meal were 1.53 and 2.86 hours, respectively.1 Following administration after a meal, peak cevimeline concentrations decreased by approximately 17%.1

Distribution

Extent

Appears to be extensively bound to tissues; however, specific binding sites are not known.1

Not known whether cevimeline is distributed into milk.1

Plasma Protein Binding

<20%.1

Elimination

Metabolism

Metabolized by CYP2D6, 3A3, and 3A4.1

Elimination Route

Excreted principally in urine, with 97 and 0.5% of a 30-mg dose recovered in urine and feces, respectively, after 7 days.1

Half-life

Approximately 5 hours.1

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).1

Actions

  • In sufficient dosages, may cause increased exocrine (e.g., salivary, sweat) gland secretion and increased GI and urinary tract smooth muscle tone.1

  • Exhibits a higher affinity for muscarinic receptors on lacrimal and salivary gland epithelium than for those on cardiac tissues.3

  • Stimulates residual salivary gland tissues that are still functioning despite damage.2

  • Structurally unrelated to other currently available drugs but pharmacologically similar to pilocarpine.1 2 3 5

Advice to Patients

  • Risk of blurred vision, especially at night; may impair ability to drive an automobile safely or perform hazardous activities in reduced lighting.1

  • Risk of dehydration if excessive sweating occurs; 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, as well as any concomitant illnesses.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.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Cevimeline Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

30 mg (of cevimeline)

Evoxac

Daiichi

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Evoxac 30MG Capsules (DAIICHI PHARMACEUTICAL CORP): 30/$95.99 or 90/$268.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions May 1, 2004. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Yamanouchi Pharma Technologies, Inc. Evoxac (cevimeline hydrochloride) capsules prescribing information. Norman, OK; 2002 Nov.

2. Anon. Cevimeline (Evoxac) for dry mouth. Med Lett Drugs Ther. 2000; 42:70. [PubMed 10932302]

3. MGI Pharma. Salagen (pilocarpine hydrochloride) tablets prescribing information (dated 1998 Feb). In: Physicians’ desk reference. 54th ed. Montvale, NJ: Medical Economics Company Inc; 2000:1924-6.

4. Moutsopoulos HM. Sjögren’s syndrome. In: Fauci AS, Braunwald E, Isselbacher KJ et al, eds. Harrison’s principles of internal medicine. l4th ed. New York: McGraw-Hill Company; 1998:1901-3.

5. Daiichi Pharmaceutical Corp., Montvale, NJ: Personal communication.

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