Indacaterol

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Inhalation:

Arcapta Neohaler: 75 mcg [contains lactose monohydrate, milk protein]

Pharmacology

Mechanism of Action

Relaxes bronchial smooth muscle by selective action on beta₂-receptors with little effect on heart rate; acts locally in the lung.

Pharmacokinetics/Pharmacodynamics

Absorption

Systemic: Inhalation: 43% to 45% bioavailable

Metabolism

Hepatic; hydroxylated via CYP3A4, CYP2D6, and CYP1A1

Excretion

Feces (>90%; 54% as unchanged drug [after oral administration]); urine (<2% as unchanged drug)

Onset of Action

5 minutes; Peak effect: 1-4 hours

Time to Peak

Serum: ~15 minutes

Duration of Action

24 hours

Half-Life Elimination

40-56 hours

Protein Binding

~95%

Use: Labeled Indications

Chronic obstructive pulmonary disease (maintenance): Long-term maintenance treatment of airflow obstruction in chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema

Contraindications

Hypersensitivity to indacaterol or any component of the formulation; monotherapy (without use of a concomitant inhaled corticosteroid) in the treatment of asthma.

Dosage and Administration

Dosing: Adult

Chronic obstructive pulmonary disorder (maintenance): Dry powder inhaler: Oral inhalation: Contents of 1 capsule (75 mcg) inhaled once daily via approved inhalation device

Note: A dose of 75 to 300 mcg once daily is recommended by the 2018 GOLD Guidelines.

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral inhalation: Dry powder inhaler: Administer via oral inhalation at the same time each day using Neohaler inhaler (US labeling) or Onbrez Breezhaler (Canadian labeling) only. Do not swallow capsules. Use the new inhaler included with each prescription. Do not remove capsule from blister until immediately before use. Place one capsule into inhaler capsule chamber and close until it clicks. Pierce capsule by pressing both red buttons once on sides of device. If powder is left within capsule, repeat inhalation procedure. Do not wash mouthpiece; inhalation device should be kept dry. Discard any capsules that are exposed to air and not used immediately.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light and moisture. Remove capsule from blister pack immediately before use; discard if not used immediately.

Drug Interactions

AtoMOXetine: May enhance the tachycardic effect of Beta2-Agonists. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Atosiban: Beta2-Agonists may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

Beta2-Agonists (Long-Acting): May enhance the adverse/toxic effect of other Beta2-Agonists (Long-Acting). Avoid combination

Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Monitor therapy

Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination

Betahistine: May diminish the therapeutic effect of Beta2-Agonists. Monitor therapy

Caffeine and Caffeine Containing Products: May enhance the adverse/toxic effect of Indacaterol. Caffeine and Caffeine Containing Products may enhance the hypokalemic effect of Indacaterol. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

Corticosteroids (Systemic): Indacaterol may enhance the hypokalemic effect of Corticosteroids (Systemic). Monitor therapy

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Loop Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination

Methacholine: Beta2-Agonists (Long-Acting) may diminish the therapeutic effect of Methacholine. Management: Hold long-acting beta₂ agonists for 36 hours before methacholine use. Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Theophylline Derivatives: May enhance the adverse/toxic effect of Indacaterol. Theophylline Derivatives may enhance the hypokalemic effect of Indacaterol. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tricyclic Antidepressants: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

Adverse Reactions

>10%: Respiratory: Cough (post-inhalation 7% to 24%)

1% to 10%:

Central nervous system: Headache (5%)

Gastrointestinal: Nausea (2%)

Respiratory: Nasopharyngitis (5%), oropharyngeal pain (2%)

<1%, postmarketing, and/or case reports: Dizziness, hypersensitivity reaction, palpitations, paradoxical bronchospasm, pruritus, skin rash, tachycardia

Warnings/Precautions

Concerns related to adverse effects:

• Asthma-related deaths: Monotherapy with a long-acting beta-2-agonist (LABA) is contraindicated in the treatment of asthma. In a large, randomized, placebo-controlled US clinical trial (SMART [Nelson] 2006), salmeterol was associated with an increase in asthma-related deaths (when added to usual asthma therapy); risk is considered a class effect among all LABAs. When LABAs are used in a fixed-dose combination with inhaled corticosteroids, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to inhaled corticosteroids alone. Current guidelines recommend the use of an inhaled corticosteroid before adding a LABA (GINA 2015; NIH/NHLBI 2007). In a more recent multicenter, randomized, double-blinded trial, the use of salmeterol and an inhaled corticosteroid (ie, fluticasone) combined in a single inhaler in a large number of children, adolescent, and adult patients with persistent asthma (non-life threatening and stable) did not increase the risk of serious asthma-related events compared with fluticasone alone; in addition, patients receiving fluticasone/salmeterol had fewer severe asthma exacerbations compared with patients receiving fluticasone alone (Peters 2016; Stempel 2016a; Stempel 2016b). Indacaterol is not indicated for the treatment of asthma. Available data do not suggest an increased risk of death with use of LABA in patients with chronic obstructive pulmonary disorder (COPD).
• Bronchospasm: Paradoxical bronchospasm that may be life-threatening may occur with use of inhaled bronchodilating agents; this reaction should be distinguished from inadequate response. Discontinue immediately if paradoxical bronchospasm occurs and institute alternative therapy.
• Hypersensitivity: Immediate hypersensitivity reactions (difficulty in breathing or swallowing; swelling of tongue, lips, and face; urticaria; skin rash) have been reported; discontinue therapy immediately if patient develops an allergic reaction.
• Serious effects/fatalities: Do not exceed recommended dose or frequency or use with other medications containing LABAs; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease (arrhythmia, coronary insufficiency, hypertension); beta-agonists may cause elevation in blood pressure and heart rate. Beta-2-agonists have been reported to produce ECG changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression.
• Appropriate use: Do not use for acute bronchospastic episodes of COPD. Do not initiate in patients with significantly worsening or acutely deteriorating COPD. Data are not available to determine if LABA use increases the risk of death in patients with COPD. Available data do not suggest an increased risk of death with use of LABA in patients with COPD.
• Diabetes: Use with caution in patients with diabetes mellitus; beta-2-agonists may increase serum glucose and aggravate preexisting diabetes mellitus and ketoacidosis.
• Hyperthyroidism: Use with caution in patients with hyperthyroidism; may stimulate thyroid activity.
• Hypokalemia: Use with caution in patients with hypokalemia; beta-2-agonists may decrease serum potassium (transient).
• Seizures: Use with caution in patients with seizure disorders; beta-2-agonists may result in CNS stimulation/excitation.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions for more detailed information.

Special populations:

• Pediatric: LABAs, when used as monotherapy, may increase the risk of asthma-related hospitalization in pediatric and adolescent patients. When LABAs are used in a fixed-dose combination with inhaled corticosteroids, data from large clinical trials in adolescents do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to inhaled corticosteroids alone.

Dosage form specific issues:

• Lactose: Product may contain lactose; allergic reactions possible in patients with severe milk protein allergy.

Other warnings/precautions:

• Patient information: Patients using inhaled, short-acting beta-2-agonists should be instructed to discontinue routine use of these medications prior to beginning treatment. Short-acting agents should still be provided to patients; however, use should be reserved for symptomatic relief of acute symptoms. Patients must be instructed to seek medical attention in cases where acute symptoms are not relieved or a previous level of response is diminished. The need to increase frequency of use of short-acting beta-2-agonists may indicate deterioration of COPD, and medical evaluation must not be delayed.
• Tolerance/tachyphylaxis: Tolerance to the bronchodilator effect, measured by FEV₁, has been observed in studies.

Monitoring Parameters

FEV₁, FVC, and/or other pulmonary function tests; serum potassium, serum glucose; blood pressure, heart rate; CNS stimulation. Monitor for increased use of short-acting beta₂-agonist inhalers; may be marker of a deteriorating condition.

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. Beta-agonists may interfere with uterine contractility if administered during labor.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience sore throat, stuffy nose, nausea, or cough. Have patient report immediately to prescriber signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), chest pain, fast heartbeat, abnormal heartbeat, severe anxiety, passing out, vision changes, severe headache, severe dizziness, tremors, wheezing, cough, or difficulty breathing (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.