Yupelri
(revefenacin)Dosage & Administration
For oral inhalation use only. Do not swallow YUPELRI.
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Yupelri Prescribing Information
YUPELRI is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).
The recommended dosage is 175 mcg YUPELRI (one 175 mcg unit‑dose vial) administered by oral inhalation once daily by nebulizer using a mouthpiece.
Administration Overview
YUPELRI should be administered by the orally inhaled route via a standard jet nebulizer connected to an air compressor (See Instructions for Use). The safety and efficacy of YUPELRI have been established in clinical trials when administered using the PARI LC® Sprint nebulizer with a mouthpiece and the PARI Trek® S compressor. The safety and efficacy of YUPELRI delivered from non‑compressor based nebulizer systems have not been established.
The YUPELRI unit-dose vial should only be removed from the foil pouch and opened IMMEDIATELY BEFORE USE. The vial and any residual content should be discarded after use.
No dosage adjustment is required for geriatric patients, or patients with renal impairment [see Use in Specific Populations (8.5, 8.7) and Clinical Pharmacology (12.3)].
The drug compatibility (physical and chemical), efficacy, and safety of YUPELRI when mixed with other drugs in a nebulizer have not been established.
Inhalation solution: 175 mcg of revefenacin in 3 mL of sterile, clear, colorless, aqueous solution in unit dose vials.
Pregnancy
Risk Summary
There are no adequate and well-controlled studies with YUPELRI in pregnant women. Women should be advised to contact their physician if they become pregnant while taking YUPELRI. In animal reproduction studies, subcutaneous administration of revefenacin to pregnant rats and rabbits during the period of organogenesis produced no evidence of fetal harm at respective exposures approximately 209 times the exposure at the maximum recommended human dose (MRHD) (on an area under the curve [AUC] basis) (see Data).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data
Animal Data
In an embryo‑fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 6 to 17, revefenacin was not teratogenic and did not affect fetal survival at exposures up to 209 times the MRHD (based upon summed AUCs for revefenacin and its active metabolite at maternal subcutaneous doses up to 500 mcg/kg/day).
In an embryo‑fetal development study in pregnant rabbits dosed during the period of organogenesis from gestation days 7 to 19, revefenacin was not teratogenic and did not affect fetal survival at exposures up to 694 times the MRHD (based upon summed AUCs for revefenacin and its active metabolite at maternal subcutaneous doses up to 500 mcg/kg/day).
Placental transfer of revefenacin and its active metabolite was observed in pregnant rabbits.
In a pre- and postnatal development (PPND) study in pregnant rats dosed during the periods of organogenesis and lactation from gestation day 6 to lactation day 20, revefenacin had no adverse developmental effects on pups at exposures up to 196 times the MRHD (based upon summed AUCs for revefenacin and its active metabolite at maternal subcutaneous doses up to 500 mcg/kg/day).
Lactation
Risk Summary
There is no information regarding the presence of revefenacin in human milk, the effects on the breastfed infant, or the effects on milk production. However, revefenacin was present in the milk of lactating rats following dosing during pregnancy and lactation (see Data).
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for YUPELRI and any potential adverse effects on the breastfed infant from YUPELRI or from the underlying maternal condition.
Data
Animal Data
In a PPND study [see Pregnancy (8.1)], revefenacin and its active metabolite were present in milk of lactating rats on lactation day 22. Milk-to-plasma concentration ratios were up to 10 for revefenacin and its active metabolite.
Pediatric Use
The safety and effectiveness of YUPELRI have not been established in pediatric patients. YUPELRI is not indicated for use in children.
Geriatric Use
Based on available data, no adjustment of the dosage of YUPELRI in geriatric patients is necessary.
Clinical trials of YUPELRI included 441 subjects aged 65 years and older, and of those, 101 subjects were aged 75 years and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Hepatic Impairment
The systemic exposure of revefenacin is unchanged while that of its active metabolite is increased in subjects with moderate hepatic impairment. The safety of YUPELRI has not been evaluated in COPD patients with mild-to-severe hepatic impairment. YUPELRI is not recommended in patients with any degree of hepatic impairment. [see Clinical Pharmacology (12.3)].
Renal Impairment
No dosage adjustment is required in patients with renal impairment. Monitor for systemic antimuscarinic side effects in COPD patients with severe renal impairment. [see Clinical Pharmacology (12.3)].
YUPELRI is contraindicated in patients with hypersensitivity to revefenacin or any component of this product.
Deterioration of Disease and Acute Episodes
YUPELRI should not be initiated in patients during acutely deteriorating or potentially life-threatening episodes of COPD. YUPELRI has not been studied in subjects with acutely deteriorating COPD. The initiation of YUPELRI in this setting is not appropriate.
YUPELRI is intended as a once-daily maintenance treatment for COPD and should not be used for relief of acute symptoms, i.e. as rescue therapy for the treatment of acute episodes of bronchospasm, and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.
COPD may deteriorate acutely over a period of hours or chronically over several days or longer. If YUPELRI no longer controls symptoms of bronchoconstriction, the patient's inhaled, short-acting beta2-agonist becomes less effective, or the patient needs more inhalations of a short-acting beta2-agonist than usual, these may be markers of deterioration of disease. In this setting, a re-evaluation of the patient and the COPD treatment regimen should be undertaken at once. Increasing the daily dose of YUPELRI beyond the recommended dose is not appropriate in this situation.
Paradoxical Bronchospasm
As with other inhaled medicines, YUPELRI can produce paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs following dosing with YUPELRI, it should be treated immediately with an inhaled, short-acting bronchodilator; YUPELRI should be discontinued immediately and alternative therapy should be instituted.
Worsening of Narrow-Angle Glaucoma
YUPELRI should be used with caution in patients with narrow-angle glaucoma. Prescribers and patients should be alert for signs and symptoms of acute narrow-angle glaucoma (e.g. eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). Instruct patients to consult a physician immediately if any of these signs or symptoms develops.
Worsening of Urinary Retention
YUPELRI should be used with caution in patients with urinary retention. Prescribers and patients should be alert for signs and symptoms of urinary retention (e.g. difficulty passing urine, painful urination), especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to consult a healthcare provider immediately if any of these signs or symptoms develops.
Immediate Hypersensitivity Reactions
Immediate hypersensitivity reactions may occur after administration of YUPELRI. If such a reaction occurs, therapy with YUPELRI should be stopped at once and alternative treatments should be considered.