Cevimeline Hydrochloride (2 brand names, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- CEVIMELINE HYDROCHLORIDE
- EVOXAC
Indications and Usage
Cevimeline is indicated for the treatment of symptoms of dry mouth in patients with Sjögren’s Syndrome.
Dosage and Administration
The recommended dose of Cevimeline Hydrochloride is 30 mg taken three times a day. There is insufficient safety information to support doses greater than 30 mg tid. There is also insufficient evidence for additional efficacy of Cevimeline Hydrochloride at doses greater than 30 mg tid.
Contraindications
Cevimeline is contraindicated in patients with uncontrolled asthma, known hypersensitivity to cevimeline, and when miosis is undesirable, e.g., in acute iritis and in narrow-angle (angle-closure) glaucoma.
Adverse Reactions
Cevimeline was administered to 1777 patients during clinical trials worldwide, including Sjögren’s patients and patients with other conditions. In placebo-controlled Sjögren’s studies in the U.S., 320 patients received cevimeline doses ranging from 15 mg tid to 60 mg tid, of whom 93% were women and 7% were men. Demographic distribution was 90% Caucasian, 5% Hispanic, 3% Black and 2% of other origin. In these studies, 14.6% of patients discontinued treatment with cevimeline due to adverse events. The following adverse events associated with muscarinic agonism were observed in the clinical trials of cevimeline in Sjögren’s syndrome patients: Adverse Event Cevimeline 30 mg (tid) n n is the total number of patients exposed to the dose at any time during the study.= 533 Placebo (tid) n = 164 Excessive sweating 18.7% 2.4% Nausea 13.8% 7.9% Rhinitis 11.2% 5.4% Diarrhea 10.3% 10.3% Excessive salivation 2.2% 0.6% Urinary frequency 0.9% 1.8% Asthenia 0.5% 0.0% Flushing 0.3% 0.6% Polyuria 0.1% 0.6% In addition, the following adverse events (≥3% incidence) were reported in the Sjögren’s clinical trials: Adverse Event Cevimeline 30 mg (tid) n n is the total number of patients exposed to the dose at any time during the study.=533 Placebo (tid) n =164 Headache 14.4% 20.1% Sinusitis 12.3% 10.9% Upper respiratory Tract Infection 11.4% 9.1% Dyspepsia 7.8% 8.5% Abdominal pain 7.6% 6.7% Urinary Tract Infection 6.1% 3.0% Coughing 6.1% 3.0% Pharyngitis 5.2% 5.4% Vomiting 4.6% 2.4% Injury 4.5% 2.4% Back pain 4.5% 4.2% Rash 4.3% 6.0% Conjunctivitis 4.3% 3.6% Dizziness 4.1% 7.3% Bronchitis 4.1% 1.2% Arthralgia 3.7% 1.8% Surgical intervention 3.3% 3.0% Fatigue 3.3% 1.2% Pain 3.3% 3.0% Skeletal pain 2.8% 1.8% Insomnia 2.4% 1.2% Hot flushes 2.4% 0.0% Rigors 1.3% 1.2% Anxiety 1.3% 1.2% The following events were reported in Sjögren’s patients at incidences of <3% and ≥1%: constipation, tremor, abnormal vision, hypertonia, peripheral edema, chest pain, myalgia, fever, anorexia, eye pain, earache,
Drug Interactions
Drug Interactions: 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. In an in vitro study, cytochrome P450 isozymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 were not inhibited by exposure to cevimeline.
Overdosage
Management of the signs and symptoms of acute overdosage should be handled in a manner consistent with that indicated for other muscarinic agonists: general supportive measures should be instituted. If medically indicated, atropine, an anti-cholinergic agent, may be of value as an antidote for emergency use in patients who have had an overdose of cevimeline. If medically indicated, epinephrine may also be of value in the presence of severe cardiovascular depression or bronchoconstriction. It is not known if cevimeline is dialyzable.