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. |
| Molecular Weight | 394.46 |
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 | Insufficient human data; animal studies show no teratogenicity at therapeutic doses. Use only if clearly needed. |
| 2nd trimester | No known fetal risk in animal studies; limited human data. Consider risk-benefit. |
| 3rd trimester | Avoid near term due to potential for adverse effects on neonatal hepatic function. |
Clinical note
Comprehensive clinical and safety monograph for REVEFENACIN (REVEFENACIN).
| Placental transfer | Animal studies indicate placental transfer; molecular weight suggests possible human transfer. |
| Breastfeeding | Excretion into breast milk is unknown; however, due to low molecular weight, it may be present. Monitor infant for diarrhea or rash. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to revefenacinSevere hepatic impairment (Child-Pugh class C)
| Precautions | Paradoxical bronchospasm, Immediate hypersensitivity reactions, Worsening of narrow-angle glaucoma, Worsening of urinary retention, Not indicated for acute deterioration of COPD |
| Food/Dietary | Avoid grapefruit juice as it may increase drug levels. High-fat meals may delay absorption but not overall effect. Limit sodium intake to reduce fluid retention. Avoid excessive caffeine. |
| Clinical Pearls |
Loading safety data…
| L3 (Moderately Safe) |
| 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. |
| 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. |
| REVEFENACIN is a non-steroidal anti-inflammatory drug (NSAID) with selective COX-2 inhibition. Monitor renal function and blood pressure regularly. Avoid use in patients with severe heart failure, active GI bleeding, or history of allergic reactions to NSAIDs. Use lowest effective dose for shortest duration. Combine with proton pump inhibitor in high-risk GI patients. Caution in elderly and those with renal impairment (CrCl <30 mL/min contraindicated). |
| Patient Advice | Take with food or milk to reduce stomach upset. · Avoid alcohol while taking this medication. · Report any signs of stomach bleeding (black stools, vomit with coffee grounds). · Do not take with other NSAIDs or aspirin unless directed. · Swallow tablet whole; do not crush or chew. · Store at room temperature away from moisture and heat. |