revefenacin (Rx)

1-10%

Cough (4%)

Nasopharyngitis (4%)

Headache (4%)

Upper respiratory tract infection (3%)

Back pain (2%)

Hypertension (1-2%)

Dizziness (1-2%)

Oropharyngeal pain (1-2%)

Bronchitis (1-2%)

Frequency Not Defined

Paradoxical bronchospasm

Worsening narrow-angle glaucoma

Worsening urinary retention

Immediate hypersensitivity reactions

Contraindications

Hypersensitivity

Cautions

Do not initiate during acutely deteriorating or life-threatening COPD episodes; intended as maintenance treatment and not for relief of acute symptoms

Inhalers can produce paradoxical bronchospasm that may be life-threatening; if this occurs, treat immediately with an inhaled, short-acting bronchodilator and discontinue revefenacin

Caution with narrow-angle glaucoma; instruct patients to contact physician if symptoms occur (eg, eye pain, blurred vision, visual halos, colored images, red eyes from congestion, corneal edema)

May worsen urinary retention, especially with history of prostatic hyperplasia or bladder-neck obstruction

Immediate hypersensitivity reported; discontinue drug immediately

Reevaluate COPD treatment immediately if

• Therapy no longer controls bronchoconstriction symptoms
• Inhaled short-acting beta2-agonist becomes less effective
• More inhalations of a short-acting beta2-agonist are needed or exceed recommended maximum dose

Drug interaction overview

• Avoid coadministration with other anticholinergic drugs, owing to additive effects
• OATP1B1 and OATP1B3 inhibitors may increase systemic exposure of revefenacin’s active metabolite; coadministration not recommended

Pregnancy

There are no available data regarding use in pregnant women

Advise women to contact their physician if they become pregnant while taking revefenacin

Lactation

Data are not available regarding presence of revefenacin in human milk, effects on breastfed infant, or effects on milk production

Present in milk of lactating rats following dosing during pregnancy and lactation

Consider the development and health benefits of breastfeeding along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Long-acting muscarinic antagonist (LAMA), which is often referred to as an anticholinergic; blocks action of acetylcholine at muscarinic receptors (M1 to M5); in the bronchial airways, it elicits pharmacologic effect by inhibiting M3 at the smooth muscle, leading to bronchodilation

Absorption

Absolute oral bioavailability: <3%

Peak plasma concentration: 0.16 ng/mL; 0.2 ng/mL (active metabolite)

AUC: 0.22 ng·hr/mL; 0.69 ng·hr/mL (active metabolite)

Steady-state achieved: Within 7 days

Distribution

Protein bound (IV): 71%; 42% (active metabolite)

Vd (IV): 218 L

Metabolism

Primarily metabolized via hydrolysis of the primary amide to a carboxylic acid forming its major active metabolite

Conversion to active metabolite occurred rapidly after inhalation, and plasma exposures of the active metabolite exceeded those of revefenacin by ~4- to 6-fold (based on AUC)

Elimination

Half-life: 22-70 hr

Excretion

• IV: 54% (19% active metabolite) feces; 27% urine
• PO: 88% feces; <5% urine
• Inhaled: <1% urine

Oral Inhalation

Do not swallow or inject solution

Orally inhale using a standard jet nebulizer connected to air compressor; safety and efficacy not established for administration via noncompressor nebulizer systems

Immediately before use, remove unit-dose vial from the foil pouch and open; discard vial and any residual content after use

Drug compatibility (physical and chemical), efficacy, and safety of revefenacin when mixed with other drugs in a nebulizer have not been established

Storage

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

Store in foil pouch until administered; protect from direct light