Indacaterol Maleate

Pronunciation: IN-da-KA-ter-ol MAL-ee-ate
Class: Sympathomimetic

Trade Names

Arcapta Neohaler
- Capsules, powder for administration, oral inhalation 75 mcg

Pharmacology

Relaxes bronchial smooth muscles.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Absorption

T max is approximately 15 min. Absolute bioavailability after an inhaled dose is 43% to 45%.

Distribution

Vd is 2,361 to 2,557 L. Plasma protein binding is 95.1% to 96.2%.

Metabolism

Metabolized by UGT1A1 to a phenolic O-glucuronide and to a hydroxylated derivative by CYP3A4.

Elimination

Less than 2% excreted unchanged in the urine; 54% excreted unchanged in the feces. Renal Cl is 0.46 to 1.2 L/h; systemic Cl is 18.8 to 23.3 L/h. Half-life is 40 to 56 h.

Special Populations

Renal Function Impairment

Because of the low contribution of the urinary pathway to elimination of indacaterol, a study in renally impaired patients was not performed.

Hepatic Function Impairment

No relevant changes in C max , AUC, or protein binding were seen in patients with mild or moderate hepatic impairment. Studies were not performed in severe hepatic impairment.

Elderly

No dosage adjustment is necessary based on the effect of age on systemic exposure of indacaterol.

Gender

No dosage adjustment is necessary based on the effect of gender on systemic exposure of indacaterol.

Race

A population pharmacokinetic analysis did not suggest any difference between ethnic subgroups.

Weight

No dosage adjustment is necessary based on the effect of weight on systemic exposure of indacaterol.

Indications and Usage

For long-term, once-daily maintenance bronchodilator treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema.

Contraindications

Patients with asthma without use of a long-term asthma control medication.

Dosage and Administration

Adults

Oral inhalation 75 mcg once daily at the same time of day.

General Advice

  • For oral inhalation only. Advise patients to not swallow or take capsules by mouth. Administer only with supplied inhaler device.

Storage/Stability

Store in a dry place, between 59° and 86°F. Protect from light and moisture. Store capsules in the blister and only remove immediately before use.

Drug Interactions

Adrenergic drugs (eg, norepinephrine)

If additional adrenergic drugs are to be administered by any route, they should be used with caution because the sympathetic effects of indacaterol may be potentiated.

Beta-2 agonists (eg, formoterol)

Indacaterol should not be used with other long-acting beta-2 agonists. An overdose may result.

Beta-blockers (eg, propranolol)

Beta-blockers and indacaterol may interfere with each other's effects. Beta-blockers not only block the therapeutic effects of indacaterol, but may produce severe bronchospasm in COPD patients. Therefore, patients with COPD should not normally be treated with beta-blockers. However, under certain circumstances (eg, prophylaxis after MI), there may be no acceptable alternatives to the use of beta-blockers in patients with COPD. In this setting, cardioselective beta-blockers (eg, atenolol) could be considered, although they should be administered with caution.

Corticosteroids (eg, prednisone), xanthine derivatives (eg, theophylline)

Concomitant treatment with these agents may potentiate any hypokalemic effect of indacaterol. Use with caution and monitor serum potassium concentrations.

CYP3A4 inhibitors and P-glycoprotein efflux transporters (ie, erythromycin, ketoconazole, ritonavir, verapamil)

Drug interaction studies carried out using potent and specific inhibitors of CYP3A4 and P-glycoprotein (P-gp) suggest that indacaterol systemic Cl is influenced by modulation of both P-gp and CYP3A4 activities and that the increase in indacaterol AUC caused by a strong dual inhibitor (eg, ketoconazole) reflects the impact of maximal combined inhibition. No dose adjustment is warranted. Use with caution and monitor the clinical response to indacaterol.

Loop diuretics (eg, furosemide), thiazide diuretics (eg, hydrochlorothiazide)

Concomitant treatment with non–potassium-sparing diuretics (eg, loop diuretics, thiazide diuretics) may potentiate any hypokalemic effect of indacaterol. The ECG changes or hypokalemia that may result can be acutely worsened by indacaterol, especially when the recommended dose of indacaterol is exceeded. Coadminister with caution.

MAOIs (eg, phenelzine), QT prolonging drugs (eg, ziprasidone), tricyclic antidepressants (eg, amitriptyline)

Indacaterol should be administered with extreme caution to patients being treated with these agents because the action of indacaterol on the CV system may be potentiated.

Adverse Reactions

Cardiovascular

Increased heart rate, palpitations, tachycardia (postmarketing).

CNS

Headache (5%); dizziness (postmarketing).

Dermatologic

Pruritus, rash (postmarketing).

EENT

Nasopharyngitis (5%); oropharyngeal pain (2%).

GI

Nausea (2%).

Metabolic

Diabetes mellitus, hyperglycemia (more than 2%).

Respiratory

Cough (7%); sinusitis, upper respiratory tract infection (more than 2%).

Miscellaneous

Musculoskeletal pain, peripheral edema (more than 2%).

Precautions

Warnings

Asthma-related death

Long-acting beta-2 adrenergic agonists increase the risk of asthma-related death. Data from a large, placebo-controlled US study that compared the safety of another long-acting beta-2 adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of long-acting beta-2 adrenergic agonists, including indacaterol. The safety and efficacy of indacaterol in patients with asthma have not been established. Indacaterol is not indicated for the treatment of asthma.


Monitor

Monitor patient for worsening of COPD. Consider monitoring of pulse rate, BP, glucose levels, and potassium levels periodically during therapy.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Special Risk Patients

Use with caution in patients with convulsive disorders or thyrotoxicosis, and in patients unusually responsive to sympathomimetic amines.

Acute worsening or deterioration of COPD

Use of indacaterol in these conditions is not appropriate.

CV effects

Because indacaterol can produce clinically important CV effects, use with caution in patients with CV disorders, especially cardiac arrhythmia, coronary insufficiency, and hypertension.

Excessive use

Fatalities and clinically significant CV effects have been reported in association with excessive use of inhaled sympathomimetic drugs.

Metabolic effects

Significant hypokalemia may be produced, which has the potential to produce CV adverse reactions. Transient hyperglycemia and/or aggravation of preexisting diabetes mellitus and ketoacidosis may also occur.

Paradoxical bronchospasm

If paradoxical bronchospasm occurs, discontinue indacaterol and institute alternative therapy.

Overdosage

Symptoms

Angina, arrhythmias, cardiac arrest, death, dizziness, dry mouth, fatigue, headache, hyperglycemia, hypertension, hypokalemia, hypotension, insomnia, malaise, metabolic acidosis, muscle cramps, nausea, nervousness, palpitation, tachycardia, tremor.

Patient Information

  • Advise patients to read the Medication Guide before using product the first time and to reread with each refill.
  • Inform patients that long-acting beta-2 agonists may increase the risk of asthma-related death. Indacaterol is not indicated for the treatment of asthma.
  • Instruct patients on how to correctly administer indacaterol capsules using the Neohaler . Remind patients that capsules should only be used with the Neohaler inhaler and should not be swallowed. Instruct patient to always use the new Neohaler provided with each new prescription.
  • Educate patients that indacaterol is not meant to relieve acute symptoms or exacerbations of COPD and extra doses should not be used for that purpose. Advise patients that acute symptoms should be treated with an inhaled short-acting beta-2 agonist, such as albuterol.
  • Instruct patients who have been taking inhaled short-acting beta-2 agonists on a regular basis to discontinue the regular use of these products and use them only for the symptomatic relief of acute symptoms.
  • Instruct patients not to use other inhaled medications containing long-acting beta-2 agonists.
  • Instruct patients to notify their health care provider immediately if they experience worsening of symptoms, decreasing effectiveness of inhaled short-acting beta-2 agonists, a need for more inhalations than usual of inhaled short-acting beta-2 agonists, or a significant decrease in lung function as outlined by their health care provider.
  • Inform patients that treatment with beta-2 agonists may lead to adverse reactions that include chest pain, nervousness, palpitations, rapid heart rate, or tremor.
  • Instruct patients to take exactly as prescribed and not to change the dose or discontinue therapy unless advised by their health care provider. Advise patients that excessive use of sympathomimetics may cause significant CV effects and may be fatal.

Copyright © 2009 Wolters Kluwer Health.

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