INCRUSE ELLIPTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INCRUSE ELLIPTA (INCRUSE ELLIPTA).
Umeclidinium is a long-acting muscarinic antagonist (LAMA). It competitively inhibits M3 muscarinic receptors in the airways, reducing acetylcholine-induced bronchoconstriction and mucus secretion.
| Metabolism | Primarily metabolized by cytochrome P450 (CYP) 2D6 and to a lesser extent by CYP3A4. |
| Excretion | Umeclidinium is eliminated primarily by hepatic metabolism and biliary excretion; after oral administration, approximately 58% of the dose is excreted in feces (mostly as parent drug) and about 22% in urine. Renal excretion of unchanged drug is minimal (<1%). |
| Half-life | Terminal elimination half-life is approximately 11 hours (range 10–13 hours) after inhalation, supporting once-daily dosing. |
| Protein binding | Approximately 89% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | The apparent volume of distribution is large, approximately 100–150 L, indicating extensive tissue distribution. Given typical body weight, this corresponds to roughly 1.4–2.1 L/kg. |
| Bioavailability | Inhalation: Absolute bioavailability is estimated at 13% (range 9–18%) due to lung deposition and absorption; oral bioavailability is <5% due to poor absorption and first-pass metabolism. |
| Onset of Action | Inhalation: Onset of bronchodilation occurs within 30 minutes, with peak effect at 1–3 hours. |
| Duration of Action | Inhalation: Bronchodilation is sustained for 24 hours after a single dose, allowing once-daily administration. |
Inhalation: 1 inhalation (62.5 mcg umeclidinium) once daily.
| Dosage form | POWDER |
| Renal impairment | No dosage adjustment required for renal impairment. |
| Liver impairment | No dosage adjustment required for mild or moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not approved for use in pediatric patients (<18 years). |
| Geriatric use | No dosage adjustment required for elderly patients, but monitor for anticholinergic effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INCRUSE ELLIPTA (INCRUSE ELLIPTA).
| Breastfeeding | Excreted in rat milk; unknown in humans. M/P ratio not established. Caution in nursing mothers; weigh benefits against potential infant exposure. |
| Teratogenic Risk | Pregnancy Category C. Inadequate studies in pregnant women. Animal studies show fetal harm at high doses. Use only if potential benefit justifies risk to fetus. First trimester: unknown risk; avoid if possible. Second/third trimesters: may cause preterm labor or low birth weight due to beta-adrenergic receptor agonism. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to umeclidinium or any component of the formulation","Not for initial treatment of acute bronchospasm or acute exacerbations of COPD"]
| Precautions | ["Not for acute bronchospasm or acute episodes of COPD","Paradoxical bronchospasm may occur","Worsening of narrow-angle glaucoma may occur","Worsening of urinary retention may occur","Immediate-type hypersensitivity reactions including anaphylaxis have been reported","Use with caution in patients with severe hepatic impairment"] |
Loading safety data…
| Monitor fetal growth and uterine activity. Assess for preterm labor symptoms. Monitor maternal respiratory status and signs of systemic beta2-agonist effects (tachycardia, hyperglycemia). |
| Fertility Effects | No specific human data. Animal studies show no impairment of fertility at clinically relevant doses. Theoretical risk due to beta2-adrenergic receptor modulation on reproductive tissues. |