Dosing and uses of Arcapta Neohaler (indacaterol inhaled)
Adult dosage forms and strengths
capsule, powder for inhalation
- 75mcg/capsule
COPD
Long-acting beta2-agonist indicated for long-term, once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema
75 mcg inhaled orally qDay; not to exceed once daily
Limitations of use
- Not indicated for acute deteriorations of COPD
- Not indicated for asthma
Administration
For oral inhalation only
Do not swallow the capsules for inhalation; if swallowed, intended effects on the lungs will not be obtained
For use with Neohaler inhaler device only
Administer qDay at the same time of the day by the oral inhalation route only
If a dose is missed, the next dose should be taken as soon as it is remembered
Not to exceed once daily administration
Store capsule in the blister pack it comes in until immediately before use
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
No dosage adjustment is required for geriatric patients, patients with mild-to-moderate hepatic impairment, or patients with renal impairment
Data are not available for severe hepatic impairment
Arcapta Neohaler (indacaterol inhaled) adverse (side) effects
>10%
Post-inhalation cough (24% compared with 7% on placebo)
1-10%
Cough (6.5%)
Nasopharyngitis (5.3%)
Headache (5.1%)
Nausea (2.4%)
Oropharyngeal pain (2.2%)
Postmarketing Reports
Hypersensitivity reactions
Paradoxical bronchospasm
Tachycardia/heart rate increase/palpitations
Pruritus/rash
Dizziness
Pruritus
Warnings
Black box warnings
Long-acting beta2-adrenergic agonists (LABAs) increase the risk of asthma-related death
Data from a large placebo-controlled US study that compared the safety of another long-acting beta2-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 LABA, 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
Contraindications
Hypersensitivity
All long-acting beta2-adrenergic agonists (LABAs) are contraindicated in patients with asthma without use of a long-term asthma control medication
Cautions
Do not initiate in acutely deteriorating COPD patients
Do not use for relief of acute symptoms; prescribe concomitant short-acting beta2-agonists for acute exacerbations
Do not exceed recommended daily dose; excessive doses may result in cardiovascular effects and may be fataL
Life-threatening paradoxical bronchospasm can occur; discontinue use immediately
Immediate hypersensitivity reactions reported; discontinue immediately and initiate alternate therapy
Data from a large placebo-controlled study in asthma patients showed that long-acting beta2-adrenergic agonists may increase the risk of asthma-related death (see Black box warnings)
Caution with CV disease, epilepsy, thyrotoxicosis, or sensitivity to sympathomimetics
Contains trace levels of milk protein
Tolerance to the effects of inhaled beta-agonists can occur with regularly-scheduled, chronic use
Increased sympathomimetic effects may occur if coadministered with other adrenergic drugs
May cause hypokalemia; this effect may be potentiated if coadministered with xanthine derivatives, corticosteroids, or diuretics
ECG changes or hypokalemia that may result from non-potassium sparing diuretics (eg, thiazides or loop diuretics) can be acutely worsened by beta-agonists, especially with high doses; use caution
Caution with coadministration of MOAIs, TCAs, and drugs that prolong QTc intervaL
Beta blockers may antagonize the effect of indacateroL
Strong dual inhibitors of CYP3A4 and P-gp (ie, ketoconazole, erythromycin, verapamil, ritonavir) may delay systemic clearance of indacaterol (AUC increased 1.9-fold); no dose adjustment is warranted with 75 mcg/day
Beta2 agonists may increase serum glucose; use caution in patients with diabetes mellitus
Use caution in patients with seizure disorders
Pregnancy and lactation
Pregnancy category: C
Beta-agonists are known to inhibit uterine contractility
Lactation: Unknown whether distributed in human breast milk; use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Arcapta Neohaler (indacaterol inhaled)
Mechanism of action
Long-acting beta2-adrenergic agonist; when inhaled, acts locally in the lung as a bronchodilator
Stimulates intracellular adenyl cyclase, causing conversion of ATP to cyclic AMP; increased cyclic AMP levels cause relaxation of bronchial smooth muscle
In vitro studies have shown that indacaterol has more than 24-fold greater agonist activity at beta2-receptors compared to beta1-receptors (selectivity profile is similar to formoterol)
Absorption
Bioavailability: 43-45% following inhalation (composite of pulmonary and intestinal absorption)
Peak Plasma Time: 15 min
Distribution
Protein Bound: 95% (after IV administration)
Vd: 2361-2557 L (after IV administration)
Metabolism
Metabolized by UGT1A1, CYP3A4 (predominant for hydroxylation), CYP1A1, CYP2D6
Low affinity for efflux pump P-gp
In vitro investigations indicated that indacaterol has negligible potential to cause metabolic interactions with medications (by inhibition or induction of cytochrome P450 enzymes, or induction of UGT1A1)
Elimination
Half-life (terminal): 45.5-126 hr, multiphasic half-life
Half-life (effective): 40-56 hr, calculated from accumulation after repeated dosing
Renal clearance: 0.46-1.2 L/hr
Total body clearance: 18.8-23.3 L/hr
Excretion: feces (54% unchanged, 23% hydroxylated metabolites), urine (<2%)
Pharmacogenomics
Pharmacokinetics were prospectively investigated in individuals with the UGT1A1 (TA)7/(TA)7 genotype (low UGT1A1 expression; also referred to as *28) and the (TA)6, (TA)6 genotype
Steady-state AUC and Cmax were 1.2-fold higher in the [(TA)7, (TA)7] genotype, suggesting no relevant effect of UGT1A1 genotype of indacaterol exposure
