Incruse Ellipta Drug Information

INCRUSE ELLIPTA is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).

• The recommended dosage of INCRUSE ELLIPTA for maintenance treatment of COPD is 1 actuation (umeclidinium 62.5 mcg) once daily by oral inhalation.
• INCRUSE ELLIPTA should be used at the same time every day. Do not use INCRUSE ELLIPTA more than 1 time every 24 hours.
• No dosage adjustment is required for geriatric patients, patients with renal impairment, or patients with moderate hepatic impairment.
• For oral inhalation only.
• Maintenance treatment of COPD: 1 actuation of INCRUSE ELLIPTA once daily administered by oral inhalation.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. In a 12-month, randomized, double-blind, placebo-controlled, long-term safety trial, 227 subjects received umeclidinium 125 mcg for up to 52 weeks. Table 1.

Adverse Reactions with INCRUSE ELLIPTA with ≥1% Incidence and More Common than Placebo in Subjects with Chronic Obstructive Pulmonary Disease Other adverse reactions with INCRUSE ELLIPTA observed with an incidence <1% but more common than placebo included atrial fibrillation. The demographic and baseline characteristics of the long-term safety trial were similar to those of the efficacy trials described above. Adverse reactions that occurred with a frequency ≥1% in subjects receiving umeclidinium 125 mcg that exceeded that in placebo in this trial were: nasopharyngitis, upper respiratory tract infection, urinary tract infection, pharyngitis, pneumonia, lower respiratory tract infection, rhinitis, supraventricular tachycardia, supraventricular extrasystoles, sinus tachycardia, idioventricular rhythm, headache, dizziness, sinus headache, cough, back pain, arthralgia, pain in extremity, neck pain, myalgia, nausea, dyspepsia, diarrhea, rash, depression, and vertigo.

Adverse reactions that occurred with INCRUSE ELLIPTA in combination with an ICS/LABA were similar to those reported with INCRUSE ELLIPTA as monotherapy. In addition to the umeclidinium monotherapy adverse reactions reported above, adverse reactions occurring with INCRUSE ELLIPTA in combination with an ICS/LABA, at an incidence of ≥1% and exceeding ICS/LABA alone, were oropharyngeal pain and dysgeusia.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of INCRUSE ELLIPTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to INCRUSE ELLIPTA or a combination of these factors.

Eye Disorders Eye pain, glaucoma, vision blurred. Immune System Disorders Hypersensitivity reactions, including anaphylaxis, angioedema, pruritus, and urticaria. Renal and Urinary Disorders Dysuria, urinary retention.

Respiratory, Thoracic and Mediastinal Disorders Dysphonia, oropharyngeal pain.

Anticholinergics There is potential for an additive interaction with concomitantly used anticholinergic medicines. Therefore, avoid coadministration of INCRUSE ELLIPTA with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects.

Pregnancy Risk Summary There are insufficient data on the use of umeclidinium in pregnant women to inform a drug‑associated risk. Umeclidinium administered via inhalation or subcutaneously to pregnant rats and rabbits was not associated with adverse effect on embryofetal development at exposures approximately 50 and 200 times, respectively, the human exposure at the maximum recommended human daily inhaled dose (MRHDID). (See Data.) The estimated risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.

Data Animal Data: In separate embryofetal developmental studies, pregnant rats and rabbits received umeclidinium during the period of organogenesis at doses up to approximately 50 and 200 times the MRHDID, respectively (on an AUC basis at maternal inhalation doses up to 278 mcg/kg/day in rats and at maternal subcutaneous doses up to 180 mcg/kg/day in rabbits). No evidence of teratogenic effects was observed in either species. In a perinatal and postnatal developmental study in rats, dams received umeclidinium during late gestation and lactation periods with no evidence of effects on offspring development at doses up to approximately 26 times the MRHDID (on an AUC basis at maternal subcutaneous doses up to 60 mcg/kg/day).

Pediatric Use The safety and effectiveness of INCRUSE ELLIPTA have not been established in pediatric patients. INCRUSE ELLIPTA is not indicated for use in pediatric patients.

• INCRUSE ELLIPTA is contraindicated in the following conditions:
• Severe hypersensitivity to milk proteins
• Hypersensitivity to umeclidinium or any of the excipients
• Hypersensitivity to any ingredient.

High doses of umeclidinium may lead to anticholinergic signs and symptoms. Treatment of overdosage consists of discontinuation of INCRUSE ELLIPTA together with institution of appropriate symptomatic and/or supportive therapy.