Cevimeline Hydrochloride

Pronunciation: seh-vih-MEH-leen
Class: Cholinergic agent

Trade Names

Evoxac
- Gelatin capsules 30 mg

Pharmacology

Cevimeline is a cholinergic agonist that binds to muscarinic receptors. Muscarinic agonists in sufficient dosage can increase secretion of exocrine glands, such as salivary and sweat glands, and increase tone of the smooth muscle in the GI and urinary tracts.

Slideshow: Grapefruit and Medicines: A Possible Deadly Mix?

Grapefruit and grapefruit juice can react adversely with over 85 prescription medications.

Pharmacokinetics

Absorption

Cevimeline is rapidly absorbed. T max is 1.5 to 2 h. Food decreases the rate of absorption and C max (by 17.3%).

Distribution

Vd is about 6 L/kg. Cevimeline is less than 20% protein bound. It is extensively bound to tissues.

Metabolism

Cevimeline is metabolized by CYP2D6 and CYP3A3/4.

Elimination

After 24 h, 84% is excreted in the urine (16% as unchanged drug). The t ½ is about 5 h.

Indications and Usage

Relieves dry mouth in patients with Sjogren syndrome.

Contraindications

Patients with uncontrolled asthma, hypersensitivity to cevimeline, or any condition in which miosis could be harmful (eg, acute iritis, narrow-angle glaucoma).

Dosage and Administration

Dry Mouth with Sjogren Syndrome
Adults

PO 30 mg 3 times daily.

Dosage Adjustments
Adults

PO Because cevimeline is eliminated extensively in the urine, dosage adjustments may be required for patients with severe renal failure. However, specific recommendations are not established.

Storage/Stability

Store at room temperature.

Drug Interactions

Anticholinergic medications (eg, atropine, ipratropium bromide, phenothiazines, tricyclic antidepressants)

Cevimeline antagonizes the pharmacologic effects of these medications.

Beta-adrenergic blockers (eg, levobunolol)

Cardiac conduction disturbances possible. Use caution during concomitant therapy.

CYP-450 system

Drugs that inhibit CYP2D6 and CYP3A3/4 also inhibit the metabolism of cevimeline. Use with caution in individuals known or suspected to be deficient of CYP2D6.

Drugs that induce CYP3A3/4 (eg, aminoglutethimide, barbiturates, carbamazepine, dexamethasone, griseofulvin, modafinil, nafcillin, phenytoin, primidone, rifabutin, rifampin)

Increased cevimeline metabolism; reduced cevimeline concentrations and efficacy possible.

Drugs that inhibit CYP2D6 (eg, amiodarone, fluoxetine, paroxetine, quinidine, ritonavir) or CYP3A3/4 (eg, diltiazem, erythromycin, itraconazole, ketoconazole, verapamil)

Reduced cevimeline metabolism; increased cevimeline concentrations and toxicity possible.

Food

Absorption of cevimeline is decreased when administered with food.

Parasympathomimetics (eg, bethanecol, donepezil, galantamine, neostigmine, physostigmine, pilocarpine, pyridostigmine, rivastigmine, tacrine)

Additive pharmacologic effects and increased toxicity possible.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Dizziness; fatigue.

Dermatologic

Excessive sweating.

GI

Nausea; vomiting; diarrhea; dyspepsia.

Genitourinary

UTI.

Musculoskeletal

Back pain; arthralgia.

Respiratory

Sinusitis; upper respiratory tract infection; rhinitis; cough.

Special Senses

Conjunctivitis; excessive salivation; blurred vision; decreased visual acuity; impaired depth perception.

Miscellaneous

Drugs that inhibit CYP2D6 and CYP3A3/4 also inhibit the metabolism of cevimeline. Use with caution in individuals known or suspected to be deficient of CYP2D6 activity.

Precautions

Monitor

Improvement

Monitor patient for signs of improvement after therapy is started.

Adverse reactions

Monitor patient for excessive parasympathomimetic, GI, respiratory, CNS, and general body adverse reactions. Notify health care provider if noted and significant.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Exercise special care when cevimeline treatment is initiated in an elderly patient, considering the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in the elderly.

Biliary tract

Administer with caution to patients with a history of nephrolithiasis.

CV

Cevimeline can potentially alter cardiac conduction or heart rate. Use with caution in patients with a history of CV disease evidenced by angina pectoris or MI.

Ocular

Ophthalmic formulations of muscarinic agonists have been reported to cause visual blurring that may result in decreased visual acuity (especially at night and in patients with central lens changes) and impairment of depth perception. Advise caution while driving at night or performing hazardous activities in reduced lighting.

Pulmonary

Cevimeline can potentially increase airway resistance, bronchial smooth muscle tone, and bronchial secretions. Administer with caution to patients with asthma, chronic bronchitis, or COPD.

Renal colic

Administer with caution to patients with a history of nephrolithiasis.

Overdosage

Symptoms

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.

Patient Information

  • Inform patient that cevimeline may cause visual disturbances, especially at night, that could impair their ability to drive safely.
  • If a patient sweats excessively while taking cevimeline, consult health care provider and advise the patient to drink extra water as dehydration may develop.

Copyright © 2009 Wolters Kluwer Health.

Hide
(web4)