EVOXAC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EVOXAC (EVOXAC).
Cevimeline is a cholinergic agonist with affinity for muscarinic receptors, primarily M1 and M3 subtypes. Stimulation of these receptors increases exocrine gland secretion, including salivary and sweat glands.
| Metabolism | Primarily metabolized by CYP2D6 and CYP3A3/4; also undergoes N-oxidation and hydroxylation. |
| Excretion | Approximately 50% of a dose is excreted unchanged in urine via glomerular filtration and tubular secretion; the remaining 50% is metabolized by ester hydrolysis and excreted as inactive metabolites in urine. |
| Half-life | The terminal elimination half-life is approximately 1 hour. Due to its short half-life, multiple daily dosing is required for sustained pharmacological effect. |
| Protein binding | Approximately 50-60% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 6 L/kg, indicating extensive distribution into tissues beyond plasma water. |
| Bioavailability | Oral bioavailability is approximately 30% due to extensive first-pass metabolism. |
| Onset of Action | Oral administration: Onset of action occurs within 60 minutes, with peak effect typically observed at 2 hours. |
| Duration of Action | The duration of action is approximately 3 to 4 hours, corresponding to its half-life; clinical effect declines as drug levels fall. |
30 mg orally three times daily.
| Dosage form | CAPSULE |
| Renal impairment | For GFR <30 mL/min: not recommended due to increased systemic exposure. |
| Liver impairment | No adjustment required for mild to moderate hepatic impairment; not studied in severe impairment. |
| Pediatric use | Safety and efficacy not established; no recommended dose. |
| Geriatric use | No specific dose adjustment; monitor for increased anticholinergic effects due to age-related reduced clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EVOXAC (EVOXAC).
| Breastfeeding | Unknown if excreted in human breast milk. M/P ratio not available. Caution advised due to potential for cholinergic side effects in nursing infants. Consider discontinuing nursing or drug, taking into account importance of drug to mother. |
| Teratogenic Risk | Pregnancy Category C. No adequate studies in pregnant women. In animal studies, cevimeline (active ingredient) produced decreased fetal body weights and increased skeletal variations at doses 2-4 times the maximum recommended human dose. First trimester: Potential risk, use only if benefit justifies risk. Second trimester: Limited data, avoid unless necessary. Third trimester: No specific fetal risks identified, but monitor for maternal cholinergic effects. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Uncontrolled asthma","Narrow-angle glaucoma","Acute iritis","Hypersensitivity to cevimeline or any component","Concurrent use with certain anticholinergics (e.g., atropine) due to antagonistic effects"]
| Precautions | ["Cardiovascular effects: May cause bradycardia, AV block, hypotension; use caution in patients with cardiovascular disease.","Pulmonary effects: Can exacerbate asthma, chronic bronchitis, or COPD due to increased bronchial secretions.","Ophthalmic effects: May impair night vision or cause visual disturbances; caution when driving at night.","Renal impairment: Not recommended in severe renal impairment (CrCl <30 mL/min).","Hepatic impairment: Caution in moderate to severe hepatic disease.","Potential for sweating and dehydration: Monitor fluid intake.","Drug interactions: Concomitant use with beta-blockers or other cholinergic agents may increase risk of bradycardia."] |
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| Fetal Monitoring | Monitor for maternal cholinergic adverse effects (nausea, vomiting, diarrhea, excessive sweating, bradycardia). Assess fetal heart rate if maternal symptoms severe. No specific fetal monitoring required beyond routine prenatal care. |
| Fertility Effects | In animal studies, no adverse effects on fertility observed. Human data lacking. Theoretical risk of cholinergic effects on reproductive function. |