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 capsules 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.

WARNINGS Cardiovascular Disease: Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by EVOXAC ® . EVOXAC ® should be used with caution and under close medical supervision in patients with a history of cardiovascular disease evidenced by angina pectoris or myocardial infarction. Pulmonary Disease: Cevimeline can potentially increase airway resistance, bronchial smooth muscle tone, and bronchial secretions. Cevimeline should be administered with caution and with close medical supervision to patients with controlled asthma, chronic bronchitis, or chronic obstructive pulmonary disease. Ocular: Ophthalmic formulations of muscarinic agonists have been reported to cause visual blurring which may result in decreased visual acuity, especially at night and in patients with central lens changes, and to cause impairment of depth perception. Caution should be advised while driving at night or performing hazardous activities in reduced lighting.

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*=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% * n Is the total number of patients exposed to the dose at any time during the study. In addition, the following adverse events (≥3% incidence) were reported in the Sjögren’s clinical trials: Adverse Event Cevimeline 30 mg (tid) n*=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% * n is the total number of patients exposed to the dose at any time during the study. 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, dry mouth, vertigo, salivary gland pain, pruritus, influenza-like symptoms, eye infection, post operative pain, vaginitis, skin disorder, depression, hiccup, hyporeflexia, infection, fungal infection, sialoadenitis, otitis media, erythematous rash, pneumonia, edema, salivary gland enlargement, allergy, gastroesophageal reflux, eye abnormality, migraine, tooth disorder, epistaxis, flatulence, toothache, ulcerative stomatitis, anemia, hypoesthesia, cystitis, leg cramps, abscess, eructation, moniliasis, palpitation, increased amylase, xerophthalmia, allergic reaction. The following events were reported rarely in treated Sjögren’s patients (<1%): Causal relation is unknown: Body as a Whole Disorders : aggravated allergy, precordial chest pain, abnormal crying, hematoma, leg pain, edema, periorbital edema, activated pain trauma, pallor, changed sensation temperature, weight decrease, weight increase, choking, mouth edema, syncope, malaise, face edema, substernal chest pain Cardiovascular Disorders : abnormal ECG, heart disorder, heart murmur, aggravated hypertension, hypotension, arrhythmia, extrasystoles, t wave inversion, tachycardia, supraventricular tachycardia, angina pectoris, myocardial infarction, pericarditis, pulmonary embolism, peripheral ischemia, superficial phlebitis, purpura, deep thrombophlebitis, vascular disorder, vasculitis, hypertension Digestive Disorders : appendicitis, increased appetite, ulcerative colitis, diverticulitis, duodenitis, dysphagia, enterocolitis, gastric ulcer, gastritis, gastroenteritis, gastrointestinal hemorrhage, gingivitis, glossitis, rectum hemorrhage, hemorrhoids, ileus, irritable bowel syndrome, melena, mucositis, esophageal stricture, esophagitis, oral hemorrhage, peptic ulcer, periodontal destruction, rectal disorder, stomatitis, tenesmus, tongue discoloration, tongue disorder, geographic tongue, tongue ulceration, dental caries Endocrine Disorders : increased glucocorticoids, goiter, hypothyroidism Hem…