Cevimeline

199.31

199.31

DTXSID2023777

N - Nervous system

37.8

log Kow = 1.22 /Estimated/

1.2±0.1 g/cm3

195-197ºC

140.4±27.9 °C

1.586

In water, 4.1X10+4 mg/L at 25 °C /Estimated/

Store between 15 and 30 °C (59 and 86 °F), in a tight container.

Henry's Law constant =1.6X10-9 atm-cu m/mole @ 25 °C /Estimated/

pKa= 9.78 /Estimated/

Hydroxyl radical reaction rate constant = 1.5X10-10 cu cm/molec-sec @ 25 °C /Estimated/

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl cevimeline hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Cevimeline Hydrochloride/

In prelicensure trials of cevimeline, serum enzyme elevations were no more frequent than with placebo and there were no reports of acute liver injury. Since licensure and more wide scale use, cevimeline has remained free of association with instances of clinically apparent liver injury.

Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Drugs with parasympathomimetic effects administered concurrently with cevimeline can be expected to have additive effects. Cevimeline might interfere with desirable antimuscarinic effects of drugs used concomitantly. Drugs which inhibit CYP2D6 and CYP3A3/4 also inhibit the metabolism of cevimeline. Cevimeline should be used with caution in individuals known or suspected to be deficient in CYP2D6 activity, based on previous experience, as they may be at a higher risk of adverse events.

Cevimeline is an orally available cholinergic agonist that is used to treat symptoms of dry mouth in patients with keratoconjunctivitis sicca (Sjögren syndrome). Cevimeline has not been linked to serum enzyme elevations during therapy or to instances of clinically apparent liver injury.

Sjögren Syndrome Agents

Cevimeline is indicated for the treatment of symptoms of dry mouth commonly associated with Sjogren's syndrome. /Included in US product labeling/

FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./|The safety and efficacy of cevimeline for the treatment of dementia of Alzheimer's disease has not been established.|Excessive perspiration can occur when using cevimeline, and may cause dehydration. In the event that this occurs, patients should drink extra water and consult with their physician.|Risk of altered cardiac conduction and/or heart rate. Patients with clinically important cardiovascular disease may be unable to compensate for transient changes in hemodynamics or heart rhythm induced by cevimeline. Use with caution and under close medical supervision in patients with a history of cardiovascular disease (e.g., angina pectoris, myocardial infarction).|For more Drug Warnings (Complete) data for CEVIMELINE (14 total), please visit the HSDB record page.

Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate. (See all compounds classified as Muscarinic Agonists.)|Drugs that mimic the effects of parasympathetic nervous system activity. Included here are drugs that directly stimulate muscarinic receptors and drugs that potentiate cholinergic activity, usually by slowing the breakdown of acetylcholine (CHOLINESTERASE INHIBITORS). Drugs that stimulate both sympathetic and parasympathetic postganglionic neurons (GANGLIONIC STIMULANTS) are not included here. (See all compounds classified as Parasympathomimetics.)

Elimination: Urine: 97%. Feces: 0.5%.|It is not known whether this drug is secreted in human milk.|After administration of a single 30 mg capsule, cevimeline was rapidly absorbed with a mean time to peak concentration of 1.5 to 2 hours. No accumulation of active drug or its metabolites was observed following multiple dose administration. When administered with food, there is a decrease in the rate of absorption, with a fasting T MAX of 1.53 hours and a T MAX of 2.86 hours after a meal; the peak concentration is reduced by 17.3%. Single oral doses across the clinical dose range are dose proportional. Cevimeline has a volume of distribution of approximately 6L/kg and is <20% bound to human plasma proteins. This suggests that cevimeline is extensively bound to tissues; however, the specific binding sites are unknown.|After 24 hours, 84% of a 30 mg dose of cevimeline was excreted in urine. After seven days, 97% of the dose was recovered in the urine and 0.5% was recovered in the feces.

The pharmacokinetics and metabolism cevimeline were investigated in six healthy volunteers after a single oral administration of 14(C)-cevimeline. ... The mean recoveries of the metabolites in urine at 24 hr after administration were 16.0% for cevimeline, 35.8% for cevimeline trans-sulfoxide, 8.7% for cevimeline cis-sulfoxide, 4.1% for cevimeline N-oxide, furthermore, two unknown metabolites, UK-1 and UK-2, were detected 14.6% and 7.7%, respectively. LC/MS analysis and hydrolysis studies revealed that UK-1 and UK-2 were glucuronic acid conjugates of cevimeline and cevimeline trans-sulfoxide, respectively.|Isozymes CYP2D6 and CYP3A3/4 are responsible for the metabolism of cevimeline. After 24 hours, 86.7% of the dose was recovered (16.0% unchanged, 44.5% as cis and trans-sulfoxide, 22.3% of the dose as glucuronic acid conjugate and 4% of the dose as N-oxide of cevimeline). Approximately 8% of the trans-sulfoxide metabolite is then converted into the corresponding glucuronic acid conjugate and eliminated. Cevimeline did not inhibit cytochrome P450 isozymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4.|Cevimeline has known human metabolites that include Cevimeline Sulfoxide.

Elimination: Approximately 5 hours.|The mean half-life of cevimeline is 5+/-1 hours.

Cevimeline hydrochloride, a quinuclidine derivative of acetycholine, is a cholinergic agonist that bind to muscarinic receptors. In sufficient dosages, muscarinic agonists may cause increased exocrine (eg sweat, salivary) gland secretion and increased GI and urinary tract smooth muscle tone. Cevimeline exhibits a higher affinity for muscarinic receptors on lacrimal and salivary gland epithelium than for those on cardiac tissues. Cevimeline is structurally unrelated to other currently available drugs but is pharmacologically similar to pilocarpine, another oral cholinergic agonist that exerts predominantly muscarinic action. Both drug stimulate residual salivary gland tissues that are still functioning despite damage.

Treatment of overdose: Note: It is not known whether cevimeline is dialyzable. Specific treatment: Treatment of signs and symptoms of cevimeline toxicity should occur in a manner consistent with that indicated for other muscarinic, cholinergic agonists. If medically indicated, atropine, an anti-cholinergic agent, may be of value as an antidote for emergency use. If medically indicated, epinephrine may also be of value in the presence of severe cardiovascular depression or bronchoconstriction. Supportive care: General supportive measures should be initiated. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.

/SIGNS AND SYMPTOMS/ Toxicity is characterized by exaggeration of parasympathomimetic effects. These may include headache, visual disturbance, lacrimation, sweating, respiratory distress, GI spasm, nausea, vomiting, diarrhea, atrioventricular block, tachycardia, bradycardia, hypotension, shock, mental confusion, cardiac arrhythmias, and tremors.|/SIGNS AND SYMPTOMS/ Risk of altered cardiac conduction and/or heart rate. Patients with clinically important cardiovascular disease may be unable to compensate for transient changes in hemodynamics or heart rhythm induced by cevimeline. Use with caution and under close medical supervision in patients with a history of cardiovascular disease (e.g., angina pectoris, myocardial infarction).|/SIGNS AND SYMPTOMS/ Risk of increased bronchial smooth muscle tone, bronchial secretions, and airway resistance. Use with caution and under close medical supervision in patients with controlled asthma, chronic bronchitis, or chronic obstructive pulmonary disease (COPD).

2-methyspiro(1,3-oxathiolane-5,3)quinuclidine

Oral: Capsules 30 mg (of cevimeline) Evoxac (Daiichi). /Cevimeline hydrochloride/

Information available in 2004 indicated that Cevimeline was used in the manufacture of pharmaceutical preparations in the following countries: Japan, USA (1,2)