Onriva Trio

• Chronic Obstructive Pulmonary Disease (COPD):
  Maintenance treatment of airflow obstruction in adult patients with moderate to very severe COPD who require a combination of long-acting bronchodilators and inhaled corticosteroids to improve lung function and reduce exacerbations.
• Asthma:
  Add-on maintenance treatment for adult patients with moderate to severe asthma inadequately controlled with inhaled corticosteroids and long-acting beta2-agonists.
• Not Indicated For:
  Acute bronchospasm or acute exacerbations; not suitable for immediate relief of symptoms.

• Adults:
• One inhalation once daily containing indacaterol 110 mcg, glycopyrronium 50 mcg, and mometasone furoate 160 mcg via a dry powder inhaler.
• Elderly:
• No dose adjustment needed.
• Pediatrics:
• Safety and efficacy not established; use not recommended for patients under 18 years.
• Renal and Hepatic Impairment:
• No dose adjustments required for mild to moderate impairment. Use with caution in severe renal impairment due to limited data.
• Route of Administration:
• Inhalation using the specified inhaler device.
• Duration:
• Continuous maintenance therapy; use as prescribed.

This combination contains three active agents with complementary effects. Indacaterol is a long-acting beta2-adrenergic receptor agonist that induces bronchodilation by relaxing airway smooth muscle through selective stimulation of beta2 receptors. Glycopyrronium, a long-acting muscarinic antagonist, blocks M3 receptors on airway smooth muscle, preventing acetylcholine-induced bronchoconstriction. Mometasone furoate is a potent inhaled corticosteroid that reduces airway inflammation by inhibiting multiple inflammatory cells and cytokines, thereby decreasing airway hyperresponsiveness and mucus production. Together, these actions improve airflow, relieve symptoms, and reduce exacerbations in obstructive airway diseases.

• Absorption:
  Rapid absorption of indacaterol and glycopyrronium occurs locally in the lungs after inhalation, with minimal systemic exposure. Mometasone furoate is also absorbed through pulmonary tissue, with some systemic uptake.
• Distribution:
  Moderate plasma protein binding; limited systemic distribution.
• Metabolism:
• Indacaterol undergoes metabolism primarily via direct glucuronidation and CYP3A4-mediated oxidation.
• Glycopyrronium is minimally metabolized, predominantly excreted unchanged by the kidneys.
• Mometasone furoate undergoes extensive hepatic metabolism via CYP3A4 to inactive metabolites.
• Elimination:
• Indacaterol half-life: approximately 40 to 56 hours.
• Glycopyrronium half-life: approximately 13 to 57 hours.
• Mometasone furoate half-life: approximately 5 hours; metabolites are excreted in urine and feces.
• Onset of Action: Bronchodilation occurs within 5 minutes; anti-inflammatory effects develop over days to weeks.
• Duration: Therapeutic effects last at least 24 hours, supporting once-daily dosing.

• Pregnancy:
  There are no adequate, well-controlled studies in pregnant women. Animal studies have not demonstrated teratogenicity at therapeutic doses. Use only if potential benefits justify potential risks.
• Lactation:
  It is unknown whether indacaterol, glycopyrronium, or mometasone furoate are excreted in human milk. Exercise caution when administering to breastfeeding women.

• Primary therapeutic class: Combination bronchodilator and corticosteroid therapy
• Subclass: LABA (Long-Acting Beta2-Agonist) + LAMA (Long-Acting Muscarinic Antagonist) + ICS (Inhaled Corticosteroid) fixed-dose combination

• Known hypersensitivity to indacaterol, glycopyrronium, mometasone furoate, or any formulation excipients.
• Acute episodes of bronchospasm or exacerbation of COPD or asthma requiring immediate treatment.
• Severe hypersensitivity to lactose or milk proteins if present in the inhaler.

• Not intended for relief of acute bronchospasm; ensure availability of a rescue inhaler.
• Use with caution in patients with cardiovascular diseases such as arrhythmias, ischemic heart disease, or hypertension.
• Monitor for paradoxical bronchospasm; discontinue if it occurs.
• Prolonged corticosteroid use may cause systemic effects, including adrenal suppression, osteoporosis, and growth retardation in children.
• Increased risk of pneumonia has been observed in COPD patients treated with inhaled corticosteroids; monitor patients closely.
• Use cautiously in patients with narrow-angle glaucoma or urinary retention due to anticholinergic effects.
• Observe for allergic reactions such as rash or angioedema.
• No black box warnings.

• Common:
• Nasopharyngitis
• Upper respiratory tract infections
• Headache
• Cough
• Oral candidiasis (thrush)
• Dry mouth
• Less common:
• Dysphonia (voice changes)
• Tremor
• Palpitations
• Dizziness
• Urinary retention
• Glaucoma exacerbation
• Serious (rare):
• Paradoxical bronchospasm
• Hypersensitivity reactions (rash, angioedema)
• Pneumonia in COPD patients

• Beta-blockers may reduce bronchodilator efficacy and increase risk of bronchospasm.
• CYP3A4 inhibitors (e.g., ketoconazole) can increase systemic levels of mometasone and indacaterol; monitor for corticosteroid or beta2-agonist toxicity.
• Additive anticholinergic effects may occur with concomitant use of other muscarinic antagonists.
• Use caution with monoamine oxidase inhibitors or tricyclic antidepressants due to potential cardiovascular effects.
• No known significant interactions with food or alcohol.

• GOLD (Global Initiative for Chronic Obstructive Lung Disease) and GINA (Global Initiative for Asthma) guidelines recommend triple therapy with LABA + LAMA + ICS for patients with COPD or asthma inadequately controlled on dual therapy.
• Newer inhaler devices improve drug delivery and patient adherence.
• Ongoing safety monitoring supports the use of this combination in reducing exacerbations and improving lung function.
• Increased vigilance for pneumonia risk in COPD patients treated with inhaled corticosteroids.

• Store at controlled room temperature: 20°C to 25°C (68°F to 77°F).
• Protect from heat, moisture, and direct sunlight.
• Do not freeze.
• Keep the inhaler dry and in its original packaging until use.