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. |
| Molecular Weight | 508.55 |
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 | Insufficient human data; based on animal studies, potential risk of fetal harm cannot be ruled out. Use only if benefit outweighs risk. |
| 2nd trimester | Insufficient human data; based on animal studies, potential risk of fetal harm cannot be ruled out. Use only if benefit outweighs risk. |
| 3rd trimester | Insufficient human data; based on animal studies, potential risk of fetal harm cannot be ruled out. Use only if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for INCRUSE ELLIPTA (INCRUSE ELLIPTA).
| Placental transfer | Umeclidinium is a quaternary ammonium compound; placental transfer is expected to be limited due to its high polarity and molecular weight. Animal studies show low fetal exposure but transfer occurs. |
| Breastfeeding | It is not known whether umeclidinium is excreted in human milk; however, based on its physicochemical properties (high molecular weight, low oral bioavailability), excretion into breast milk is likely minimal. Caution is advised; consider the developmental and health benefits of breastfeeding along with the mother's clinical need. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to umeclidinium or any component of the product
| 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 |
| Food/Dietary | No specific food interactions reported. Avoid grapefruit juice? Not known; no contraindications with food. |
| Clinical Pearls |
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| Lactation Rating | L3 (Moderately Safe) |
| 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 | 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. |
| INCRUSE ELLIPTA (umeclidinium) is a long-acting muscarinic antagonist (LAMA) for maintenance treatment of COPD. Not for acute bronchospasm. Administer once daily via ELLIPTA inhaler; no priming needed. Rinse mouth after use to minimize anticholinergic side effects (dry mouth, urinary retention). Caution in patients with narrow-angle glaucoma or prostatic hyperplasia. |
| Patient Advice | Use one inhalation once daily at the same time each day. · Do not use for sudden breathing problems; have a rescue inhaler available. · Rinse mouth with water after each dose (do not swallow) to reduce dry mouth and throat irritation. · Store at room temperature (20-25°C) in a dry place away from heat and moisture. · Do not open the inhaler tray until ready to use; discard 6 weeks after opening the foil pouch. |