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Yupelri

Generic Name: Revefenacin
Class: Antimuscarinics/Antispasmodics
Chemical Name: [1-[2-[[4-[(4-carbamoylpiperidin-1-yl)methyl]benzoyl]-methylamino]ethyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate
Molecular Formula: C35H43N5O4
CAS Number: 1211931-83-7

Medically reviewed by Drugs.com. Last updated on Nov 26, 2018.

Introduction

Revefenacin is an antimuscarinic agent.

Uses for Yupelri

Revefenacin has the following uses:

Revefenacin inhalation solution is an anticholinergic indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).1

Yupelri Dosage and Administration

General

Revefenacin is available in the following dosage form(s) and strength(s):

Inhalation solution in a unit-dose vial for nebulization. Each vial contains 175 mcg/3 mL solution.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

For oral inhalation use only. Do not swallow revefenacin.1

  • One 175 mcg vial (3 mL) once daily.1

  • For use with a standard jet nebulizer with a mouthpiece connected to an air compressor.1

Cautions for Yupelri

Contraindications

Revefenacin is contraindicated in patients with hypersensitivity to revefenacin or any component of this product.1

Warnings/Precautions

Deterioration of Disease and Acute Episodes

Revefenacin should not be initiated in patients during acutely deteriorating or potentially life-threatening episodes of COPD. Revefenacin has not been studied in subjects with acutely deteriorating COPD. The initiation of revefenacin in this setting is not appropriate.1

Revefenacin 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.1

COPD may deteriorate acutely over a period of hours or chronically over several days or longer. If revefenacin 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 revefenacin beyond the recommended dose is not appropriate in this situation.1

Paradoxical Bronchospasm

As with other inhaled medicines, revefenacin can produce paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs following dosing with revefenacin, it should be treated immediately with an inhaled, short-acting bronchodilator; revefenacin should be discontinued immediately and alternative therapy should be instituted.1

Worsening of Narrow-angle Glaucoma

Revefenacin 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 develop.1

Worsening of Urinary Retention

Revefenacin 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 develop.1

Immediate Hypersensitivity Reactions

Immediate hypersensitivity reactions may occur after administration of revefenacin. If such a reaction occurs, therapy with revefenacin should be stopped at once and alternative treatments should be considered. 1

Specific Populations

Pregnancy

Risk Summary: There are no adequate and well-controlled studies with revefenacin in pregnant women. Women should be advised to contact their physician if they become pregnant while taking revefenacin. 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). 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.1

Animal Data: In an embryofetal 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 embryofetal 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).1

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. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for revefenacin and any potential adverse effects on the breastfed infant from revefenacin or from the underlying maternal condition.1

Animal Data: In a PPND study, 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. 1

Pediatric Use

Revefenacin is not indicated for use in children. The safety and efficacy in pediatric patients have not been established.1

Geriatric Use

Based on available data, no adjustment of the dosage of revefenacin in geriatric patients is necessary. 1

Clinical trials of revefenacin 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.1

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 revefenacin has not been evaluated in COPD patients with mild-to-severe hepatic impairment. Revefenacin is not recommended in patients with any degree of hepatic impairment. 1

Renal Impairment

No dosage adjustment is required in patients with renal impairment. Monitor for systemic antimuscarinic adverse effects in COPD patients with severe renal impairment. 1

Common Adverse Effects

Most common adverse reactions (incidence greater than or equal to 2% and more common than with placebo) include cough, nasopharyngitis, upper respiratory tract infection, headache, and back pain.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

  • Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administration of revefenacin with other anticholinergic-containing drugs.1

  • Transporter-related drug interactions: Coadministration of revefenacin with organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 inhibitors (e.g., rifampicin, cyclosporine) may lead to an increase in exposure of the active metabolite. Therefore, coadministration with revefenacin is not recommended.1

Actions

Mechanism of Action

Revefenacin is a long-acting muscarinic antagonist, which is often referred to as an anticholinergic. It has similar affinity for muscarinic receptor subtypes M1 to M5. In the airways, it exhibits pharmacologic effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human- and animal-origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo models, prevention of methacholine- and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted longer than 24 hours. The clinical relevance of these findings is unknown. The bronchodilation following inhalation of revefenacin is predominantly a site-specific effect.1

Advice to Patients

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use) with each new prescription and refill.1

Inform patients that revefenacin is not meant to relieve acute symptoms of COPD and extra doses should not be used for that purpose. Advise patients to treat acute symptoms with an inhaled, short-acting beta2-agonist such as albuterol. Provide patients with such medicine and instruct them in how it should be used.1

Instruct patients to seek medical attention immediately if they experience any of the following: decreasing effectiveness of inhaled, short-acting beta2-agonists; need for more inhalations than usual of inhaled, short-acting beta2-agonists; or significant decrease in lung function as outlined by the physician. Tell patients they should not stop therapy with revefenacin without healthcare provider guidance since symptoms may recur after discontinuation.1

As with other inhaled medicines, revefenacin can cause paradoxical bronchospasm. If paradoxical bronchospasm occurs, instruct patients to discontinue revefenacin.1

Instruct patients to 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 healthcare provider immediately if any of these signs or symptoms develop.1

Instruct patients to be alert for signs and symptoms of urinary retention (e.g., difficulty passing urine, painful urination). Instruct patients to consult a healthcare provider immediately if any of these signs or symptoms develop. 1

It is important for patients to understand how to correctly administer revefenacin using a standard jet nebulizer. Instruct patients that revefenacin should only be administered via a standard jet nebulizer. Patients should be instructed not to inject or swallow the revefenacin solution. Patients should be instructed not to mix other medications with revefenacin.1

Patients should not inhale more than one dose at any one time. The daily dosage of revefenacin should not exceed one unit-dose vial. Inform patients to use the contents of one vial of revefenacin inhaled orally daily at the same time every day. Patients should throw the plastic dispensing vials away immediately after use. Due to their small size, the vials pose a danger of choking to young children.1

Additional Information

AHFSfirstRelease. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Revefenacin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral Inhalation

Solution

175 mcg /3 mL

Yupelri

Mylan Specialty L.P.

AHFS Drug Information. © Copyright 2020, Selected Revisions November 26, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Mylan Specialty L.P. YUPELRI (revefenacin) RESPIRATORY (INHALATION) prescribing information. 2018 Nov. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6dfebf04-7c90-436a-9b16-750d3c1ee0a6

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