YUPELRI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for YUPELRI (YUPELRI).
YUPELRI (revefenacin) is a long-acting muscarinic antagonist (LAMA) that inhibits acetylcholine at M3 receptors in bronchial smooth muscle, leading to bronchodilation.
| Metabolism | Metabolized by esterases and cytochrome P450 enzymes (CYP2D6 and CYP3A4) to inactive metabolites. |
| Excretion | Primarily non-renal elimination via biliary/fecal routes (up to 60% as unchanged drug and metabolites). Renal excretion accounts for approximately 20% of the dose. |
| Half-life | Terminal elimination half-life is 15-22 hours after intravenous administration, supporting once-daily dosing in clinical use. |
| Protein binding | Approximately 60% bound to human plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 150 L (about 2.1 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Inhalation: Absolute bioavailability is approximately 13-16% of the delivered dose, with minimal systemic absorption. |
| Onset of Action | Inhalation: Bronchodilation is observed within 15 minutes, with peak effect at 1-2 hours post-dose. |
| Duration of Action | Duration of bronchodilation is approximately 24 hours, allowing once-daily dosing in COPD maintenance therapy. |
175 mcg orally inhaled once daily via a standard jet nebulizer with a mouthpiece.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment, including end-stage renal disease. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B); not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not approved for pediatric use; safety and efficacy in patients <18 years have not been established. |
| Geriatric use | No dose adjustment recommended based on age; monitor for anticholinergic effects as elderly patients may be more sensitive. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for YUPELRI (YUPELRI).
| Breastfeeding | Unknown if excreted in human milk. No data on M/P ratio. In lactating rats, revefenacin was excreted in milk. Consider developmental and health benefits of breastfeeding along with mother's clinical need for YUPELRI and potential adverse effects on breastfed infant. |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. Animal studies: In rats and rabbits, intravenous administration of revefenacin during organogenesis resulted in increased postimplantation loss at doses ≥0.4 mg/kg/day (rat) and ≥0.01 mg/kg/day (rabbit); no structural abnormalities were observed. In rats, administration during late gestation and lactation increased pup mortality at doses ≥0.4 mg/kg/day. Human risk cannot be excluded; YUPELRI should be used during pregnancy only if potential benefit justifies potential risk to fetus. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to revefenacin or any component of the formulation."]
| Precautions | ["Worsening of narrow-angle glaucoma may occur; use with caution.","Urinary retention may occur; monitor patients with prostatic hyperplasia or bladder neck obstruction.","Immediate hypersensitivity reactions including anaphylaxis have been reported.","Paradoxical bronchospasm, which may be life-threatening, can occur; discontinue therapy if it occurs."] |
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| Fetal Monitoring | Monitor for signs of bronchospasm, such as paradoxical bronchospasm, worsening of COPD, or acute asthma-like symptoms. In pregnant women, monitor fetal growth and well-being during third trimester if used chronically, given limited safety data. |
| Fertility Effects | In animal fertility studies, no adverse effects on fertility or reproductive performance were observed in male or female rats at intravenous doses up to 0.4 mg/kg/day (approximately 20 times the MRHDID on AUC basis). |