Yupelri

— THERAPEUTIC CATEGORIES —
  • Asthma/COPD
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Yupelri Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Revefenacin 175mcg/3mL; soln for inh.

    Pharmacological Class

    Long-acting anticholinergic.

    How Supplied

    Vials (3mL)—7, 30

    Storage

    Store Yupelri in the protective foil pouch; should only be opened immediately before use.

     

    Store at room temperature from 68°F to 77°F (20°C to 25°C); excursions permitted from 59°F to 86°F (15°C to 30°C).

     

    Protect from direct sunlight and excessive heat.

     

    The vial and any residual content should be discarded after use.

    Manufacturer

    Mylan Specialty L.P. and Theravance Biopharma

    Generic Availability

    NO

    Mechanism of Action

    Revefenacin is a long-acting muscarinic antagonist, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological 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.

    Yupelri Indications

    Indications

    Maintenance treatment of COPD.

    Yupelri Dosage and Administration

    Adult

    Administer by the orally inhaled route via standard jet nebulizer connected to an air compressor. Inhale 1 vial (175mcg) once daily (using a mouthpiece).

    Children

    Not established.

    Administration

    Administer via a standard jet nebulizer connected to an air compressor with an adequate airflow, and equipped with a mouthpiece. Treatment should be administered at the same time every day.

    Safety and efficacy have been established in clinical trials using the PARI LC® Sprint nebulizer with a mouthpiece and the PARI Trek® S compressor. The mean delivered dose from the mouthpiece was approximately 62mcg (35% of label claim), at a mean flow rate of 4 LPM. Mean nebulization time was 8 minutes.

    Yupelri vial should only be removed from the foil pouch and opened immediately before use. Discard any residual content after use.

    Drug compatibility, efficacy, and safety of Yupelri when mixed with other drugs in a nebulizer have not been established.

    Nursing Considerations

    Yupelri vial should only be removed from the foil pouch and opened immediately before use. Discard any residual content after use.

    Drug compatibility, efficacy, and safety of Yupelri when mixed with other drugs in a nebulizer have not been established.

    Yupelri Contraindications

    Not Applicable

    Yupelri Boxed Warnings

    Not Applicable

    Yupelri Warnings/Precautions

    Warnings/Precautions

    Do not initiate during acutely deteriorating or potentially life-threatening COPD episodes. Not for treating acute symptoms. ­Prescribe a short-acting β2-agonist for acute symptoms; monitor for increased need. Do not exceed recommended dose. Discontinue immediately and treat if paradoxical bronchospasm or immediate hypersensitivity reactions occur; use alternative therapy. Narrow-angle glaucoma. Urinary retention. Prostatic hyperplasia. Bladder-neck obstruction. Hepatic impairment: not recommended. Severe renal impairment: monitor. Pregnancy. Nursing mothers.

    Pregnancy Considerations

    There are no adequate and well-controlled studies with Yupelri in pregnant women.

    Nursing Mother Considerations

    There is no information regarding the presence of revefenacin in human milk, the effects on the breastfed infant, or the effects on milk production. Consider the benefits to the mother vs the potential for adverse effects on the breastfed infant.

    Pediatric Considerations

    Yupelri is not indicated for children; safety and effectiveness have not been established in this population.

    Geriatric Considerations

    Clinical trials included 441 patients aged 65 years and older (101 patients were aged 75 years and older). No overall differences in safety or effectiveness were observed between older and younger patients. No dosage adjustment in geriatric patients is necessary.

    Renal Impairment Considerations

    No dosage adjustment is required in patients with renal impairment.

    Severe renal impairment: Monitor for systemic antimuscarinic side effects.

    Hepatic Impairment Considerations

    Yupelri is not recommended in patients with any degree of hepatic impairment.

    Systemic exposure of the active metabolite of revefenacin is increased in patients with moderate hepatic impairment.

    Yupelri Pharmacokinetics

    Absorption

    Following inhaled administration, Cmax of revefenacin and its active metabolite occurred at the first postdose sampling time which ranged from 14 to 41 minutes after start of nebulization.

    Distribution

    Protein binding of revefenacin and its active metabolite in human plasma was on average 71% and 42%, respectively. 

    Metabolism

    Primarily metabolized via hydrolysis of the primary amide to a carboxylic acid forming its major active metabolite. Plasma exposures of the active metabolite exceed those of revefenacin by approximately 4- to 6-fold. The active metabolite is formed by hepatic metabolism and possesses activity at target muscarinic receptors that could potentially contribute to systemic antimuscarinic effects at therapeutic doses.

    Elimination

    Terminal half-life of revefenacin and its active metabolite after once-daily is 22 to 70 hours.

    Yupelri Interactions

    Interactions

    Additive effects with concomitant other anticholinergic-containing drugs; avoid. Concomitant OATP1B1 and OATP1B3 inhibitors (eg, rifampicin, cyclosporine): not recommended.

    Yupelri Adverse Reactions

    Adverse Reactions

    Cough, nasopharyngitis, upper respiratory tract infection, headache, back pain; paradoxical bronchospasm.

    Yupelri Clinical Trials

    Clinical Trials

    Yupelri was evaluated in 2 dose-ranging trials, 2 replicate 12-week, phase 3 confirmatory trials, and a 52-week safety trial. In the 2 replicate 12-week, phase 3 placebo-controlled trials (N=1229), patients aged ≥40 years with moderate to very severe COPD were randomly assigned to receive Yupelri 175mcg once daily or placebo. The primary endpoint was the change from baseline in trough FEV1 at day 85. 

    Treatment with Yupelri showed significant improvement in lung function vs placebo. In Trial 1 (ClinicalTrials.gov Identifier: NCT02459080), the least square mean change in trough FEV1 was 127mL and -19mL in the Yupelri and placebo groups, respectively (treatment difference 146, 95% CI, 103.7-188.8). 

    In Trial 2 (ClinicalTrials.gov Identifier: NCT02512510) , the least square mean change in trough FEV1 was 102mL and -45mL in the Yupelri and placebo groups, respectively (treatment difference 147, 95% CI, 97.0-197.1). 

    In addition, the mean peak FEV1 (within the first 2 hours after dosing) improvement on day 1 relative to placebo was 133mL and 129mL in Trials 1 and 2, respectively.

    In Trial 1, the St. Georges Respiratory Questionnaire (SGRQ) responder rate (defined as an improvement in score of ≥4 as threshold) on day 85 was 49% for the Yupelri arm vs 34% for placebo (odds ratio [OR] 2.11, 95% CI 1.14-3.92). In Trial 2, the SGRQ responder rate was 45% vs 39%, respectively (OR  1.31, 95% CI, 0.72-2.38).

    Yupelri Note

    Not Applicable

    Yupelri Patient Counseling

    Patient Counseling

    Yuperli should only be administered via a standard jet nebulizer; do not mix with other medications.

    Yupelri is not meant to relieve acute symptoms of COPD; extra doses should not be used for that purpose.

    Yupelri can cause paradoxical bronchospasm; discontinue treatment if this occurs.

    Be alert for signs and symptoms of acute narrow-angle glaucoma (eg, eye pain or discomfort, blurred vision, visual halos, or colored images in association with red eyes from conjunctival congestion and corneal edema).

    Be alert for signs and symptoms of urinary retention (eg, difficulty passing urine, painful urination).

    Cost Savings Program

    Yupelri Savings Card

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