Introduction
Yupelri (revefenacin) is an inhaled long-acting muscarinic antagonist (LAMA) approved for the maintenance treatment of chronic obstructive pulmonary disease (COPD). It represents the first once-daily nebulized LAMA formulation, providing a convenient option for patients who have difficulty using handheld inhaler devices.
Mechanism of Action
Revefenacin is a competitive antagonist of muscarinic receptors (specifically M1-M3 subtypes) in bronchial smooth muscle. By blocking acetylcholine binding at these receptors, it prevents bronchoconstriction and reduces airway tone. The drug's quaternary ammonium structure limits systemic absorption, resulting in primarily local pulmonary effects with minimal systemic anticholinergic activity.
Indications
Yupelri is indicated for the long-term maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.
Dosage and Administration
- Standard dosing: 175 mcg once daily via standard jet nebulizer
- Administration: Use with a standard jet nebulizer connected to an air compressor
- Preparation: Pour entire contents of one vial into nebulizer reservoir; administer until sputtering begins (approximately 8-10 minutes)
- Special populations: No dosage adjustment recommended for renal or hepatic impairment
- Geriatric patients: No dosage adjustment necessary
Pharmacokinetics
- Absorption: Low systemic absorption (absolute bioavailability <5%) due to quaternary ammonium structure
- Distribution: Minimal tissue distribution beyond lungs; plasma protein binding approximately 90%
- Metabolism: Primarily hydrolyzed by hydrolysis; minimal cytochrome P450 metabolism
- Elimination: Primarily excreted unchanged in feces (>80%); renal elimination minimal (<10%)
- Half-life: Approximately 22 hours
Contraindications
- Hypersensitivity to revefenacin or any component of the formulation
- History of hypersensitivity reactions to atropine or its derivatives
Warnings and Precautions
- Paradoxical bronchospasm: Discontinue immediately if occurs
- Worsening of narrow-angle glaucoma: Use with caution in patients with history of glaucoma
- Worsening of urinary retention: Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction
- Acute deterioration of COPD: Not for rescue therapy; ensure patients have access to short-acting bronchodilators
- Hypersensitivity reactions: Including anaphylaxis, urticaria, rash, and bronchospasm
- Cardiovascular effects: May increase heart rate; use with caution in patients with cardiovascular disorders
Drug Interactions
- Other anticholinergic medications: May potentiate anticholinergic adverse effects (avoid concomitant use)
- Beta-adrenergic agonists: Additive bronchodilator effects (monitor for cardiovascular effects)
- CYP450 inhibitors: Minimal interaction expected due to limited metabolism via this pathway
- QT-prolonging drugs: Theoretical risk of additive effects (clinical significance unknown)
Adverse Effects
Common (≥2% incidence):- Cough
- Headache
- Upper respiratory tract infection
- Dyspnea
- Back pain
- Paradoxical bronchospasm
- Worsening of narrow-angle glaucoma
- Worsening of urinary retention
- Hypersensitivity reactions
Monitoring Parameters
- Pulmonary function tests (spirometry) at regular intervals
- Symptom control and exacerbation frequency
- Signs/symptoms of anticholinergic effects (blurred vision, urinary retention)
- Ophthalmic exams in patients with history of glaucoma
- Cardiovascular monitoring in patients with pre-existing cardiac conditions
Patient Education
- Administration technique: Demonstrate proper nebulizer use; administer once daily
- Not for acute symptoms: Explain this is a maintenance medication, not for rescue use
- Back-up medication: Ensure patient has short-acting bronchodilator for acute symptoms
- Rinsing mouth: After administration to reduce potential systemic effects
- Device cleaning: Regular nebulizer cleaning per manufacturer instructions
- Side effects recognition: Educate about signs of worsening glaucoma, urinary retention, and allergic reactions
- Missed dose: Take as soon as remembered unless close to next dose; do not double dose
References
1. FDA Prescribing Information: YUPELRI (revefenacin) inhalation solution. 2018. 2. Donohue JF, et al. Efficacy and safety of revefenacin for nebulization in patients with chronic obstructive pulmonary disease. Adv Ther. 2020;37(7):3217-3232. 3. Ferguson GT, et al. Revefenacin: a once-daily, long-acting muscarinic antagonist for nebulized therapy of COPD. Expert Rev Respir Med. 2019;13(4):309-320. 4. Tashkin DP, et al. Long-term safety and efficacy of revefenacin in patients with moderate to very severe COPD. Respir Med. 2021;176:106247. 5. Gross NJ, et al. Efficacy and safety of revefenacin for the treatment of chronic obstructive pulmonary disease. Expert Opin Pharmacother. 2018;19(17):1945-1953.