indacaterol, inhaled/glycopyrrolate inhaled (Utibron Neohaler)
Classes: Respiratory Inhalant Combos; Anticholinergics, Respiratory; Beta2 Agonists; COPD Agents
Dosing and uses of Utibron Neohaler (indacaterol, inhaled/glycopyrrolate, inhaled)
Adult dosage forms and strengths
indacaterol/glycopyrrolate
inhalation powder
- (27.5mcg/15.6mcg)/capsule
Chronic Obstructive Pulmonary Disease (COPD)
Combination inhalant containing long-acting muscarinic antagonist (LAMA) plus a long-acting beta2-agonist (LABA) indicated for the long-term, maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema
Orally inhale contents of 1 capsule PO q12hr using the Neohaler device
Dosage modifications
No dosage adjustment is required for geriatric patients, patients with mild and moderate hepatic impairment, or patients with mild-to-moderate renal impairment
Severe renal or hepatic impairment: Not studied
Dosing Considerations
Limitations of use: Not indicated for the relief of acute bronchospasm or for the treatment of asthma
Pediatric dosage forms and strengths
Safety and efficacy not established
Utibron Neohaler (indacaterol, inhaled/glycopyrrolate, inhaled) adverse (side) effects
1-10%
Nasopharyngitis (4.1%)
Hypertension (2%)
Back pain (1.8%)
Oropharyngeal pain (1.6%)
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 LABA (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 all LABAs, including indacateroL
Safety and efficacy of indacaterol/glycopyrrolate in patients with asthma have not been established
Not indicated for the treatment of asthma
Contraindications
Hypersensitivity
All LABAs are contraindicated in patients with asthma without use of a long-term asthma control medication Indacaterol/glycopyrrolate is not indicated for the treatment of asthma
Cautions
Data from a large placebo-controlled US study in asthma patients showed that LABAs may increase the risk of asthma-related death (see Black box warnings)
Should not be initiated in patients with acutely deteriorating or potentially life-threatening episodes of COPD; also do not use for the relief of acute symptoms (ie, as rescue therapy) for treating acute episodes of bronchospasm
Do not use more often than recommended, at higher doses than recommended, or in conjunction with other medications containing LABAs, as an overdose may result
Can produce paradoxical bronchospasm that may be life-threatening Immediate hypersensitivity reactions have been reported after administration of indacaterol or glycopyrrolate
LABAs can produce clinically significant cardiovascular effects, including increases in pulse rate or systolic or diastolic blood pressure
Caution with convulsive disorders, thyrotoxicosis, patients who are unusually responsive to sympathomimetic amines, narrow-angle glaucoma (may worsen), or urinary retention (eg, prostatic hyperplasia, bladder-neck obstruction); instruct patients to contact their physician immediately with worsening disease symptoms
Doses of the related beta2-agonist albuterol, when administered IV, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis
LABAs may produce significant hypokalemia, which has the potential to produce adverse cardiovascular effect; in patients with severe COPD, hypokalemia may be potentiated by hypoxia and concomitant treatment, which may increase the susceptibility for cardiac arrhythmias
Pregnancy
Pregnancy
There are no adequate and well-controlled studies in humans with Utibron Neohaler or its individual components
Animal studies have not shown teratogenicity
Lactation
Unknown if distributed in human breast milk
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
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 Utibron Neohaler (indacaterol, inhaled/glycopyrrolate, inhaled)
Mechanism of action
Glycopyrronium: Long-acting muscarinic antagonist (LAMA); often referred to as an anticholinergic; produces bronchodilation by inhibiting acetylcholine’s effect on muscarinic receptors in the airway smooth muscle
Indacaterol: Long-acting beta2-agonist (LABA); stimulates intracellular adenyl cyclase, causing conversion of ATP to cyclic AMP; increased cyclic AMP levels cause relaxation of bronchial smooth muscle
Absorption
Absolute bioavailability: 43-45% (indacaterol)
Peak plasma time: 5 minutes (glycopyrrolate); 15 minutes (indacaterol)
Distribution
Protein bound: 38-41% (glycopyrrolate); ~95% (indacaterol)
Vd: 83-376 L (glycopyrrolate); 2361-2557 L (indacaterol)
Metabolism
IndacateroL
- Metabolized by UGT1A to the phenolic O-glucuronide
- Also undergoes hydroxylation (predominantly by CYP3A4)
Glycopyrrolate
- Hydroxylation of results in a variety of mono-and bishydroxylated metabolites and direct hydrolysis results in the formation of a carboxylic acid derivative (M9)
- M9 is hydrolyzed by multiple CYP isoenzymes
Elimination
Half-life: 40-56 hr (indacaterol oral); 33-53 hr (glycopyrrolate inhaled)
Renal clearance: 0.46-1.2 L/hr (indacaterol)
Systemic clearance: 18.8-23.3 L/hr (indacaterol)
Excretion
- Indacaterol: 54% (unchanged) and 23% (metabolites) in feces
- Glycopyrrolate: 60-70% urine; 30-40% nonrenal (mostly by metabolism; also biliary)
Pharmacogenomics
IndacateroL
- The pharmacokinetics of indacaterol were prospectively investigated in subjects 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
Administration
Instructions
For oral inhalation only
Do not swallow the capsules, as the intended effects on the lungs will not be obtained
Capsules should only be used with the Neohaler device
Should be administered at the same time of the day, (1 capsule in the morning and 1 capsule in the evening), every day
More frequent administration or a greater number of inhalations (>1 capsule BID) is not recommended
Storage
Store in a dry place at controlled room temperature (77°F [25°C]); excursions permitted to 59-86°F (15-30°C)
Store capsules in the blister package that they are packaged in, and only remove immediately before use with the Neohaler device
