Indigo

Approved Indications

• Chronic Obstructive Pulmonary Disease (COPD):
• Long-term, once-daily maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD, including chronic bronchitis and/or emphysema.
• Indicated to improve lung function, reduce breathlessness, and enhance quality of life in patients who require both a long-acting β₂-agonist (LABA) and a long-acting muscarinic antagonist (LAMA).
• Helps reduce the risk of exacerbations in patients with a history of frequent flare-ups.

Not Indicated For:

• Relief of acute bronchospasm.
• Use in asthma (safety and efficacy not established unless approved for combination use with inhaled corticosteroids in specific jurisdictions).

Route: Inhalation only, using the device provided (e.g., Breezhaler®, Ultibro®).

Adults (COPD):

• Typical dose: Indacaterol 110 mcg + Glycopyrronium 50 mcg (delivered dose: 85 mcg + 43 mcg) once daily at the same time each day.
• Use the lowest effective dose for symptom control.

Pediatric Use:

• Not established; not recommended in children and adolescents under 18 years.

Elderly:

• No dose adjustment required; monitor for cardiovascular and anticholinergic side effects.

Renal Impairment:

• Mild to moderate: No dose adjustment required.
• Severe renal impairment: Use with caution; monitor for increased anticholinergic effects.

Hepatic Impairment:

• Mild to moderate: No dose adjustment.
• Severe impairment: Use with caution; limited data available.

Administration Notes:

• Capsules must be used only in the supplied inhaler; do not swallow.
• If a dose is missed, take as soon as remembered on the same day; do not double the dose.

• Indacaterol: An ultra-long-acting β₂-adrenergic receptor agonist (LABA) that activates β₂-receptors on airway smooth muscle. This increases cAMP production via adenylate cyclase stimulation, causing smooth muscle relaxation and sustained bronchodilation.
• Glycopyrronium: A long-acting muscarinic antagonist (LAMA) that competitively inhibits acetylcholine at M₃ receptors in bronchial smooth muscle, preventing contraction and reducing mucus secretion.
• Combination Effect: Dual bronchodilation via complementary pathways — β₂ activation and muscarinic blockade — providing greater improvement in airflow and symptom relief than either drug alone.

Indacaterol:

• Absorption: Rapid bronchodilation within minutes; peak effect in ~30 minutes.
• Bioavailability: Low systemic levels; primary action in the lungs.
• Metabolism: Glucuronidation (UGT1A1, UGT2B7, UGT2B17) and CYP3A4-mediated oxidation.
• Half-life: ~40–52 hours.
• Elimination: Mostly via feces; minor renal excretion.

Glycopyrronium:

• Absorption: Peak plasma levels in 5 minutes post-inhalation.
• Bioavailability: Low systemic exposure.
• Metabolism: Limited hepatic metabolism; mainly unchanged in urine and feces.
• Half-life: ~33–57 hours.
• Elimination: Renal and fecal routes.

• Pregnancy: Limited human data; animal studies show potential risk at high doses. Use only if potential benefit outweighs potential fetal risk.
• Lactation: Unknown if excreted in human milk. Both drugs have the potential to cause effects in nursing infants (e.g., β₂-mediated tachycardia, anticholinergic effects). Caution advised.

• Combination: Long-acting β₂-adrenergic agonist (LABA) + Long-acting muscarinic antagonist (LAMA).
• Role: Dual bronchodilator for COPD maintenance.

• Hypersensitivity to indacaterol, glycopyrronium, or formulation components.
• Use in asthma without an inhaled corticosteroid where required by labeling.
• Acute bronchospasm treatment.
• Severe hypersensitivity reactions to inhaled anticholinergics or β₂-agonists.

• Not for acute relief: Keep a short-acting bronchodilator available.
• Cardiovascular risk: Use cautiously in patients with ischemic heart disease, arrhythmias, hypertension.
• Paradoxical bronchospasm: Discontinue immediately if this occurs.
• Anticholinergic caution: Avoid in patients with narrow-angle glaucoma, urinary retention, or severe prostatic hyperplasia.
• Hypokalemia risk: Monitor if patient is on potassium-lowering medications.
• QT prolongation risk: Use with caution when combined with QT-prolonging drugs.
• Severe renal impairment: Monitor closely for glycopyrronium accumulation.

Common:

• Cough
• Nasopharyngitis
• Sore throat
• Headache
• Muscle spasms
• Diarrhea

Uncommon/Rare:

• Tachycardia, palpitations
• Rash, urticaria
• Paradoxical bronchospasm
• Hypokalemia
• Urinary retention
• Worsening of narrow-angle glaucoma symptoms

Timing & Severity:

• Most effects are mild and occur early in treatment; systemic side effects are dose-related.

• β-blockers: May reduce LABA efficacy; avoid nonselective agents.
• Other anticholinergics: Risk of additive side effects; avoid duplication.
• Potassium-lowering drugs: Increased hypokalemia risk (e.g., diuretics, corticosteroids).
• CYP3A4 inhibitors/inducers: May alter indacaterol levels.
• QT-prolonging agents: Possible additive cardiac effects.
• MAO inhibitors/tricyclic antidepressants: May enhance cardiovascular responses.

• GOLD COPD Guidelines: LABA+LAMA combinations recommended as first-line for patients with persistent symptoms or high exacerbation risk.
• Availability in fixed-dose once-daily inhalers improves adherence and lung function outcomes.
• No recent global safety alerts; monitoring remains standard for LABA and LAMA class warnings.

• Store at 20°C to 30°C.
• Protect from moisture and light.
• Keep capsules in original blister until use; do not swallow.
• Do not freeze.
• Keep out of reach of children.