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. |
| Molecular Weight | 675.78 |
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 | Insufficient human data; animal studies show no teratogenic effects at exposures up to 240 times the maximum recommended human dose. Use only if benefit outweighs risk. |
| 2nd trimester | Insufficient human data; animal studies show no fetotoxicity at exposures up to 240 times MRHD. Use only if benefit outweighs risk. |
| 3rd trimester | Insufficient human data; animal studies show no adverse effects on parturition or offspring development at exposures up to 240 times MRHD. Use only if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for YUPELRI (YUPELRI).
| Placental transfer | Unknown in humans; animal studies indicate placental transfer in rats and rabbits. |
| Breastfeeding | No human data on presence in breast milk; animal studies show excretion in rat milk at concentrations similar to plasma. Caution should be exercised due to potential for adverse effects in nursing infants. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to revefenacin or any excipient
| 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. |
| Food/Dietary | No specific food interactions have been identified with YUPELRI. It is not known to interact with food or beverages. However, patients should avoid grapefruit juice if taking other medications that interact with CYP3A4, though this is not specific to YUPELRI. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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). |
| Clinical Pearls | YUPELRI (revefenacin) is a long-acting muscarinic antagonist (LAMA) for maintenance treatment of COPD. Administer via standard jet nebulizer; do not mix with other drugs. Patients should be warned about paradoxical bronchospasm and anticholinergic effects like urinary retention and narrow-angle glaucoma. No dose adjustment needed for hepatic or renal impairment. |
| Patient Advice | Use YUPELRI exactly as prescribed, once daily, at the same time each day. · Do not swallow the solution; use only with a nebulizer, not a metered-dose inhaler. · Avoid getting the solution in your eyes; if contact occurs, rinse with water and seek medical advice if symptoms persist. · Seek immediate medical help if you experience sudden chest tightness, wheezing, or trouble breathing after use. · Inform your doctor if you have glaucoma, trouble urinating, or an enlarged prostate. |