Revefenacin

Approved Indications:

• Maintenance treatment of chronic obstructive pulmonary disease (COPD):
• Indicated for the long-term, once-daily maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and emphysema.
• Not indicated for acute bronchospasm or asthma.

Off-label / Clinically Accepted Uses:

• May be considered for patients with COPD who have difficulty using handheld inhalers or require nebulized therapy.
• Use in COPD patients with moderate to severe airflow limitation who benefit from LAMA therapy.

Adults:

• Recommended dose: 175 mcg (1 vial) inhaled once daily via a standard jet nebulizer.
• Administer as a nebulized solution with a mouthpiece or facemask.

Pediatrics:

• Safety and efficacy not established; not recommended.

Elderly:

• No dosage adjustment necessary; use standard adult dose.

Renal Impairment:

• No dosage adjustment needed for mild to moderate impairment.
• Use with caution in severe impairment due to lack of data.

Hepatic Impairment:

• No dosage adjustment recommended for mild or moderate impairment.
• Use caution in severe hepatic impairment; insufficient data.

Administration Notes:

• Use once daily at approximately the same time each day.
• Do not use more than one vial per day.
• Rinse mouth after use to reduce risk of oral candidiasis.

Revefenacin is a long-acting muscarinic antagonist (LAMA) that selectively blocks M3 muscarinic receptors on airway smooth muscle. By competitively inhibiting these receptors, it prevents acetylcholine-induced bronchoconstriction, leading to bronchodilation and improved airflow in the lungs. Its prolonged receptor binding provides sustained bronchodilatory effects suitable for once-daily dosing in COPD maintenance therapy.

• Absorption:
• Systemic absorption after nebulized administration is low to moderate.
• Peak plasma concentrations occur approximately approximately 6 to 9 minutes post-dose.
• Distribution:
• High plasma protein binding (~71%).
• Volume of distribution not extensively reported.
• Metabolism:
• Primarily metabolized by hydrolysis to an active metabolite (THRX-195518), which has ~10-fold lower potency than parent drug.
• Minor CYP450 involvement.
• Elimination:
• Eliminated mainly via feces (biliary excretion) and urine.
• Parent drug has a terminal half-life of approximately 22 to 70 hours.
• Active metabolite has a longer half-life (~50 hours).

Pregnancy:

• No adequate, well-controlled studies in pregnant women.
• Animal studies have not shown direct teratogenic effects at clinically relevant exposures.
• Use only if potential benefits outweigh risks.

Lactation:

• Unknown if inhaled revefenacin is excreted in human milk.
• Caution advised when administered to breastfeeding women; monitor infant for adverse effects.

• Primary Class: Bronchodilator
• Subclass: Long-acting muscarinic antagonist (LAMA), anticholinergic bronchodilator

• Known hypersensitivity to revefenacin or any of its excipients
• Hypersensitivity to other anticholinergic agents (caution)
• Not indicated for acute bronchospasm or asthma treatment

• Paradoxical bronchospasm:
• Discontinue immediately if it occurs.
• Narrow-angle glaucoma:
• Use with caution as anticholinergics may increase intraocular pressure.
• Urinary retention:
• Use cautiously in patients with urinary retention or prostatic hypertrophy.
• Cardiovascular effects:
• Monitor patients with cardiovascular disease as anticholinergic drugs may cause tachycardia.
• Hypersensitivity reactions:
• Rare but may include rash, urticaria, angioedema.

Common Adverse Effects:

• Cough
• Nasopharyngitis
• Headache
• Upper respiratory tract infection
• Back pain

Less Common/Rare:

• Paradoxical bronchospasm
• Hypersensitivity reactions
• Urinary retention
• Increased intraocular pressure or glaucoma symptoms

Timing:

• Side effects usually occur within the first weeks of therapy; ongoing monitoring recommended.

• Minimal CYP450 metabolism reduces potential for significant interactions.
• Caution when used concomitantly with other anticholinergic drugs (additive anticholinergic effects).
• No significant drug-food or drug-alcohol interactions reported.

• GOLD 2024 guidelines recommend LAMA agents including nebulized options like revefenacin for maintenance therapy in COPD patients with moderate to severe disease, especially those with difficulty using handheld inhalers.
• No new major safety warnings or dosing changes reported in the past 2 years by FDA or EMA.
• Ongoing monitoring recommended for long-term safety.

• Store at 20°C to 25°C (68°F to 77°F)
• Protect from freezing and excessive moisture
• Keep vial in original packaging until use
• Use immediately after opening vial; discard any unused portion