Incruse Ellipta

Drug overview for INCRUSE ELLIPTA (umeclidinium bromide):

Generic name: UMECLIDINIUM BROMIDE (ue-ME-kli-DIN-ee-um)
Drug class: Anticholinergic Agents Long-Acting (Inhaled)
Therapeutic class: Respiratory Therapy Agents

Umeclidinium bromide, a synthetic quaternary ammonium antimuscarinic agent, is a long-acting orally inhaled bronchodilator.

No enhanced Uses information available for this drug.

DRUG IMAGES

INCRUSE ELLIPTA 62.5 MCG INH

The following indications for INCRUSE ELLIPTA (umeclidinium bromide) have been approved by the FDA:

Indications:
Bronchospasm prevention with COPD

Professional Synonyms:
COPD with bronchospasms prophylaxis

The following dosing information is available for INCRUSE ELLIPTA (umeclidinium bromide):

Dosing
Administration
INCRUSE ELLIPTA
Generic

Dosage of umeclidinium bromide is expressed in terms of umeclidinium.

Each foil-wrapped blister in the Incruse(R) Ellipta(R) inhaler device contains 74.2 mcg of umeclidinium bromide (equivalent to 62.5 mcg of umeclidinium). After the inhaler is activated, the powder within the blister is exposed and dispersed into the air stream created by the patient's inhalation.

Using standardized in vitro testing at a flow rate of 60 L/minute for 4 seconds, the inhaler delivered 55 mcg of umeclidinium per blister. The precise amount of drug delivered to the lungs with each activation of the inhaler device depends on factors such as the patient's inspiratory flow. The commercially available inhaler delivers 30 doses (or 7 doses from the sample or institutional package).

Umeclidinium bromide is administered by oral inhalation using a specific preloaded inhaler (Incruse(R) Ellipta(R)) that delivers powdered drug from foil-wrapped blisters. Umeclidinium should be administered once daily at the same time every day. Before first use of the Incruse(R) Ellipta(R) inhaler, the device should be removed from the foil tray and the enclosed desiccant should be discarded out of reach of children and pets.

The date the tray is opened and the discard date (6 weeks after opening) should be written on the inhaler label. The number of doses remaining in the inhaler is displayed on the counter located on the front of the device. The cover of the inhaler should not be opened until immediately before use; to avoid wasting doses, the inhaler cover should not be closed again until the dose has been inhaled.

When the cover of the inhaler is opened fully to expose the mouthpiece, a click should be heard. If the dose counter does not advance when the click is heard, the dose has not been properly prepared, and the patient should contact the clinician. Before inhaling the dose, the patient should exhale completely, but should not exhale into the mouthpiece of the inhaler.

The patient should then place the mouthpiece between the lips and inhale deeply through the inhaler with a steady, even breath; the patient should not inhale through the nose. The air vent on the inhaler should not be blocked while the dose is administered. The patient should remove the inhaler from the mouth, hold the breath for about 3-4 seconds (or as long as comfortable), and then exhale slowly and gently.

While some patients may taste or feel a dose of drug delivered from the inhaler, patients should be instructed not to use another dose even if they do not perceive that the dose has been delivered. After the dose is administered, the inhaler should be closed by sliding the cover up and over the mouthpiece as far as possible. The inhaler does not need to be cleaned after use.

However, if desired, the mouthpiece can be cleaned with a dry tissue. The inhaler should be discarded when every blister has been used or 6 weeks after removal of the inhaler from the foil tray, whichever comes first.

Dosing information for INCRUSE ELLIPTA
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
INCRUSE ELLIPTA 62.5 MCG INH	Maintenance	Adults inhale 1 puff (62.5 mcg) by inhalation route once daily at the same time each day

No generic dosing information available.

The following drug interaction information is available for INCRUSE ELLIPTA (umeclidinium bromide):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 1 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Pramlintide/Inhaled Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Pramlintide slows gastric emptying. Anticholinergics may result in additive or synergistic effects.(1) CLINICAL EFFECTS: Concurrent use of pramlintide and anticholinergics may result in additive or synergistic effects.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of pramlintide states that pramlintide therapy should not be considered in patients requiring the use of drugs that stimulate gastrointestinal motility or in patients taking drugs that alter gastrointestinal motility.(1) Patients receiving inhaled anticholinergics should be evaluated for signs of systemic effects, which may include constipation. DISCUSSION: Patients using drugs that alter gastrointestinal motility have not been studied in clinical trials for pramlintide.(1) Constipation has been reported as a side effect of inhaled anticholinergic agents such as ipratropium(2) and tiotropium.(3)	SYMLINPEN 120, SYMLINPEN 60

Drug Interaction

Drug Names

Pramlintide/Inhaled Anticholinergics

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Pramlintide slows gastric emptying. Anticholinergics may result in additive or synergistic effects.(1)

CLINICAL EFFECTS: Concurrent use of pramlintide and anticholinergics may result in additive or synergistic effects.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of pramlintide states that pramlintide therapy should not be considered in patients requiring the use of drugs that stimulate gastrointestinal motility or in patients taking drugs that alter gastrointestinal motility.(1) Patients receiving inhaled anticholinergics should be evaluated for signs of systemic effects, which may include constipation.

DISCUSSION: Patients using drugs that alter gastrointestinal motility have not been studied in clinical trials for pramlintide.(1) Constipation has been reported as a side effect of inhaled anticholinergic agents such as ipratropium(2) and tiotropium.(3)

SYMLINPEN 120, SYMLINPEN 60

There are 3 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Solid Oral Potassium Tablets/Inhaled Anticholinergics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concentrated potassium may damage the lining of the GI tract. Anticholinergics delay gastric emptying, resulting in the potassium product remaining in the gastrointestinal tract for a longer period of time.(1-16) CLINICAL EFFECTS: Use of solid oral dosage forms of potassium in patients treated with inhaled anticholinergics could potentially result in gastrointestinal erosions, ulcers, stenosis and bleeding.(1-16) PREDISPOSING FACTORS: Diseases or conditions which may increase risk for GI damage include: preexisting dysphagia, strictures, cardiomegaly, diabetic gastroparesis, elderly status, or insufficient oral intake to allow dilution of potassium.(1-10,21) Other drugs which may add to risk for GI damage include: nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, or tetracyclines.(21) PATIENT MANAGEMENT: Regulatory agency and manufacturer recommendations regarding this interaction: - In the US, all solid oral dosage forms (including tablets and extended release capsules) of potassium are contraindicated in patients receiving anticholinergics at sufficient dosages to result in systemic effects.(2-8) Patients receiving such anticholinergic therapy should use a liquid form of potassium chloride.(2) - In Canada, solid oral potassium is contraindicated in any patient with a cause for arrest or delay in tablet/capsule passage through the gastrointestinal tract and the manufacturers recommend caution with concurrent anticholinergic medications.(1,9-10) Evaluate each patient for predisposing factors which may increase risk for GI damage. In patients with multiple risk factors for harm, consider use of liquid potassium supplements, if tolerated. For patients receiving concomitant therapy, assure any potassium dose form is taken after meals with a large glass of water or other fluid. To decrease potassium concentration in the GI tract, limit each dose to 20 meq; if more than 20 meq daily is required, give in divided doses.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Patients should be instructed to immediately report any difficulty swallowing, abdominal pain, distention, severe vomiting, or gastrointestinal bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: In clinical trials, there was a higher incidence of gastric and duodenal lesions in patients receiving a high dose of a wax-matrix controlled-release formulation with a concurrent anticholinergic agent. Some lesions were asymptomatic and not accompanied by bleeding, as shown by a lack of positive Hemoccult tests.(1-17) Several studies suggest that the incidence of gastric and duodenal lesions may be less with the microencapsulated formulation of potassium chloride.(14-17) Constipation has been reported as a side effect of inhaled anticholinergic agents such as ipratropium(22) and tiotropium.(23)	KLOR-CON 10, KLOR-CON 8, KLOR-CON M10, KLOR-CON M15, KLOR-CON M20, POTASSIUM CHLORIDE, POTASSIUM CITRATE ER, UROCIT-K
Solid Oral Potassium Capsules/Inhaled Anticholinergics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concentrated potassium may damage the lining of the GI tract. Anticholinergics delay gastric emptying, resulting in the potassium product remaining in the gastrointestinal tract for a longer period of time.(1-16) CLINICAL EFFECTS: Use of solid oral dosage forms of potassium in patients treated with inhaled anticholinergics could potentially result in gastrointestinal erosions, ulcers, stenosis and bleeding.(1-16) PREDISPOSING FACTORS: Diseases or conditions which may increase risk for GI damage include: preexisting dysphagia, strictures, cardiomegaly, diabetic gastroparesis, elderly status, or insufficient oral intake to allow dilution of potassium.(1-10,21) Other drugs which may add to risk for GI damage include: nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, or tetracyclines.(21) PATIENT MANAGEMENT: Regulatory agency and manufacturer recommendations regarding this interaction: - In the US, all solid oral dosage forms (including tablets and extended release capsules) of potassium are contraindicated in patients receiving anticholinergics at sufficient dosages to result in systemic effects.(2-8) Patients receiving such anticholinergic therapy should use a liquid form of potassium chloride.(2) - In Canada, solid oral potassium is contraindicated in any patient with a cause for arrest or delay in tablet/capsule passage through the gastrointestinal tract and the manufacturers recommend caution with concurrent anticholinergic medications.(1,9-10) Evaluate each patient for predisposing factors which may increase risk for GI damage. In patients with multiple risk factors for harm, consider use of liquid potassium supplements, if tolerated. For patients receiving concomitant therapy, assure any potassium dose form is taken after meals with a large glass of water or other fluid. To decrease potassium concentration in the GI tract, limit each dose to 20 meq; if more than 20 meq daily is required, give in divided doses.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Patients should be instructed to immediately report any difficulty swallowing, abdominal pain, distention, severe vomiting, or gastrointestinal bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: In clinical trials, there was a higher incidence of gastric and duodenal lesions in patients receiving a high dose of a wax-matrix controlled-release formulation with a concurrent anticholinergic agent. Some lesions were asymptomatic and not accompanied by bleeding, as shown by a lack of positive Hemoccult tests.(1-17) Several studies suggest that the incidence of gastric and duodenal lesions may be less with the microencapsulated formulation of potassium chloride.(14-17) Constipation has been reported as a side effect of inhaled anticholinergic agents such as ipratropium(22) and tiotropium.(23)	POTASSIUM CHLORIDE
Methacholine/Beta-Agonists; Anticholinergics; Theophylline SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Beta-agonists, anticholinergics, and theophylline may inhibit the action of methacholine on the airway.(1) CLINICAL EFFECTS: The result of the methacholine challenge test may not be accurate.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The following drugs should be held before a methacholine challenge for the the duration indicated:(1) - short-acting beta-agonists: 6 hours - long-acting beta-agonists: 36 hours - short-acting anti-cholinergics: 12 hours - long-acting anti-cholinergics: at least 168 hours (7 days) - oral theophylline: 12-48 hours DISCUSSION: Beta-agonists, anticholinergics, and theophylline may inhibit the action of methacholine on the airway and cause inaccurate test results.	METHACHOLINE CHLORIDE, PROVOCHOLINE

Moderate List
Angle-closure glaucoma
Benign prostatic hyperplasia
Bladder outflow obstruction
Urinary retention

The following adverse reaction information is available for INCRUSE ELLIPTA (umeclidinium bromide):

Overview
Severe
Less Severe

Adverse reaction overview.

Adverse events occurring in 2% or more of patients with COPD receiving umeclidinium and at an incidence greater than placebo include nasopharyngitis, upper respiratory tract infection, cough, and arthralgia.

There are 8 severe adverse reactions.

More Frequent	Less Frequent
None.	Urinary retention

Rare/Very Rare
Abnormal ECG Anaphylaxis Angioedema Atrial fibrillation Ocular hypertension Secondary angle-closure glaucoma Supraventricular premature beats

There are 25 less severe adverse reactions.

More Frequent	Less Frequent
Arthralgia Cough Pharyngitis Upper respiratory infection	Chest pain Constipation Diarrhea Dyspepsia Lower respiratory infection Myalgia Neck pain Toothache Upper abdominal pain Urinary tract infection

Rare/Very Rare
Blurred vision Conjunctivitis Dysgeusia Dysuria Ocular pain Pain in oropharynx Pruritus of skin Sinusitis Urticaria Voice change Xerostomia

The following precautions are available for INCRUSE ELLIPTA (umeclidinium bromide):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of umeclidinium have not been established in children. The drug is not indicated for use in pediatric patients.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

There are insufficient data on the use of umeclidinium in pregnant women to inform a drug-associated risk. When administered via inhalation or subcutaneously to pregnant rats and rabbits, umeclidinium was not associated with adverse effects on embryofetal development at exposures approximately 50 and 200 times, respectively, the human exposure at the maximum recommended human daily inhaled dose.

Umeclidinium may be distributed into milk in rats; it is not known whether the drug is distributed into milk in humans or whether the drug has any effects on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for umeclidinium and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition..

No dosage adjustment required in geriatric patients. When the total number of patients studied in clinical trials of umeclidinium is considered, about 49% were 65 years of age or older, while 11% were 75 years of age or older. Although no overall differences in efficacy or safety were observed between geriatric and younger patients in clinical trials, and other clinical experience revealed no evidence of age-related differences, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out. Dosage adjustment is not necessary in geriatric patients.

Bronchospasm prevention with COPD
J44	Other chronic obstructive pulmonary disease
J44.8	Other specified chronic obstructive pulmonary disease
J44.89	Other specified chronic obstructive pulmonary disease
J44.9	Chronic obstructive pulmonary disease, unspecified