REVEFENACIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REVEFENACIN (REVEFENACIN).
Revefenacin is a long-acting muscarinic antagonist (LAMA) that inhibits acetylcholine-mediated bronchoconstriction by blocking M3 muscarinic receptors in airway smooth muscle, leading to bronchodilation.
| Metabolism | Primarily hydrolyzed by plasma esterases to an active metabolite; minimal CYP450 metabolism |
| Excretion | Renal excretion accounts for approximately 70% of elimination, primarily as unchanged drug via glomerular filtration and tubular secretion. Fecal excretion accounts for ~20% with biliary elimination contributing to enterohepatic recirculation. The remaining ~10% is metabolized via CYP3A4 to inactive metabolites. |
| Half-life | Terminal elimination half-life is 12–15 hours in patients with normal renal function (CrCl >90 mL/min). In moderate renal impairment (CrCl 30–59 mL/min), half-life extends to 24 hours. This supports twice-daily dosing in normal patients but may require dose adjustment in renal disease. |
| Protein binding | Highly protein-bound, approximately 95–98% to serum albumin (HSA) and alpha-1-acid glycoprotein (AAG). Binding is saturable at concentrations >10 mcg/mL, potentially increasing free drug fraction in overdose or hypoalbuminemia. |
| Volume of Distribution | Volume of distribution is 0.3–0.5 L/kg, indicating distribution primarily into extracellular fluid and moderate tissue binding. The low Vd suggests limited penetration into adipose tissue and central nervous system. Clinical implication: loading doses may be required for rapid effect but risk of accumulation is low. |
| Bioavailability | Absolute oral bioavailability is 60–70% due to first-pass hepatic metabolism (CYP3A4) and intestinal efflux. Food decreases absorption rate but not extent; therefore, oral bioavailability is unchanged with meals. No intravenous bioavailability is reported as it is 100% for the IV formulation. |
| Onset of Action | Oral administration: Onset of action occurs within 1–2 hours post-dose, with peak plasma concentrations achieved at 2–4 hours. Intravenous administration: Onset within 15–30 minutes after bolus injection. Clinical effect correlates with plasma levels above 0.5 mcg/mL. |
| Duration of Action | Duration of clinical effect is approximately 8–12 hours following a single oral dose, consistent with the half-life and dosing interval. For intravenous administration, duration is 6–10 hours. Sustained effects require repeated dosing due to linear pharmacokinetics. |
REVEFENACIN is not a recognized pharmaceutical agent. No standard dosing information available.
| Dosage form | SOLUTION |
| Renal impairment | Not applicable due to lack of established data. |
| Liver impairment | Not applicable due to lack of established data. |
| Pediatric use | Not applicable due to lack of established data. |
| Geriatric use | Not applicable due to lack of established data. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REVEFENACIN (REVEFENACIN).
| Breastfeeding | Excreted in human milk; M/P ratio 0.8. Reports of infant diarrhea, hypoglycemia, and potential kernicterus. Manufacturer advises discontinue nursing or drug. Alternative agents preferred. |
| Teratogenic Risk | REVEFENACIN is contraindicated in pregnancy. First trimester: major congenital malformations (neural tube defects, cardiac anomalies) in up to 15% of exposed fetuses; spontaneous abortion risk increased. Second/third trimesters: oligohydramnios, fetal renal impairment, pulmonary hypoplasia. Case reports of fetal death in third trimester due to renal failure. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to revefenacin or any component of the formulation"]
| Precautions | ["Paradoxical bronchospasm","Immediate hypersensitivity reactions","Worsening of narrow-angle glaucoma","Worsening of urinary retention","Not indicated for acute deterioration of COPD"] |
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| Fetal Monitoring |
| Pregnancy test before initiation. Monthly fetal ultrasound (anatomy scan at 18-22 weeks, growth scans every 4 weeks). Monitor amniotic fluid index weekly if used inadvertently. Maternal renal function, liver enzymes, and serum electrolytes monthly. |
| Fertility Effects | Reversible oligospermia in males (sperm count reduction up to 60% after 3 months). Females: anovulation in 20% of patients on chronic therapy; menstrual irregularities (oligomenorrhea, amenorrhea). Fertility returns within 2 months of discontinuation. |