Ultibro Dry Powder Inhalation Capsule (DPI)

This is indicated for the long-term once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. It should not be used in acute episodes of bronchospasm. This is not indicated for asthma.

Each dry powder inhaler capsule contains-

• Indacaterol 110 mcg as Indacaterol Maleate INN (Micronized)
• Glycopyrronium 50 mcg as Glycopyrronium Bromide BP (Micronized)

This is an inhalation powder drug product for delivery of a combination of Glycopyrronium (an anticholinergic) and Indacaterol (a LABA) to patients by oral inhalation. The pharmacologic effects of beta2-adrenoceptor agonist drugs, including Indacaterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3, 5-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. Glycopyrronium is a long-acting muscarinic antagonist, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation.

Adults (18 years or older): For oral inhalation only. Should be used at the same time every day, not more than 1 time every 24 hours.

Maintenance treatment of COPD: 1 inhalation once daily.

Limitations of use: Not indicated for relief of acute bronchospasm or for the treatment of asthma.

Geriatric: This can be used at the recommended dose in elderly patients (65 years of age and older).

Use in Children & Adolescents: It is not indicated for use in children and adolescents. The safety and efficacy in pediatric patients (aged 17 years and younger) have not been established.

Renal impairment: It can be used at the recommended dose in patients with mild to moderate renal impairment. In patients with severe renal impairment or end-stage renal disease requiring dialysis (estimated glomerular filtration rate is below 30 mL/min/1.73 m2), it should be used only if the expected benefit outweighs the potential risk.

Hepatic impairment: It can be used at the recommended dose in patients with mild and moderate hepatic impairment. There are no data available for the use of this in patients with severe hepatic impairment, therefore caution should be observed in these patients.

No specific interaction studies were conducted for Glycopyrronium and Indacaterol combination. Information on the potential for interactions is based on the potential for each individual component. The concomitant use of Glycopyrronium and Indacaterol with β-adrenergic blockers, anticholinergics or sympathomimetic agents is not recommended. Sympathomimetic agents may potentiate the adverse events of Indacaterol. Caution is required with the concomitant use of hypokalemic treatment.

It is contraindicated in patients with hypersensitivity to Glycopyrronium or Indacaterol, or to any other component of this combination; Patients with severe hypersensitivity to milk proteins and All LABA are contraindicated in patients with asthma without use of a long-term asthma control medication.

Adverse reactions that have been associated with muscarinic antagonists include cardiovascular effects (atrial arrhythmias and tachycardia), ocular disorders (e.g., blurred vision), urinary retention, gastrointestinal disorders, dry mouth and cough. Adverse reactions that have been associated with β2-agonists include immediate hypersensitivity reactions (urticaria, rash, bronchospasm, edema and angioedema), cardiovascular effects (tachycardia, arrhythmia, palpitations, myocardial ischaemia, hypertension or. hypotension), hypokalemia, hyperglycemia, headache, nervousness, insomnia, muscle spasms, fatigue, malaise and tremor. The most common adverse drug reactions related to the drug product (reported >3% and greater than placebo) were cough and oropharyngeal pain (including throat irritation).

Pregnancy category C. There are no data from the use of this combination in pregnant women available. Therefore, this combination should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the foetus. It is not known whether Indacaterol or Glycopyrronium and their metabolites are excreted in human milk. The use of this combination by breast-feeding women should only be considered if the expected benefit to the woman is greater than any possible risk to the infant.

• LABA monotherapy increases the risk of serious asthma-related events.
• Do not initiate in acutely deteriorating COPD or asthma. Do not use to treat acute symptoms.
• Do not use in combination with additional therapy containing a LABA because of risk of overdose.
• If paradoxical bronchospasm occurs, discontinue and institute alternative therapy.
• Use with caution in patients with cardiovascular disorders because of beta-adrenergic stimulation.
• Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis.
• Worsening of narrow-angle glaucoma may occur. Use with caution in patients with narrow-angle glaucoma and instruct patients to contact a healthcare provider immediately if symptoms occur.
• Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction contact a physician immediately if symptoms occur.
• Be alert to hypokalemia and hyperglycemia.

There is no information on clinically relevant overdosing with Ultibro. An overdose could lead to exaggerated effects typical of β2-adrenergic stimulants, i.e. tachycardia, tremor, palpitations, headache, nausea, vomiting, drowsiness, ventricular arrhythmias, metabolic acidosis, hypokalemia and hyperglycaemia or could induce anticholinergic effects such as increased intraocular pressure (causing pain, vision disturbances or reddening of the eye), obstipation or difficulties in voiding. Supportive and symptomatic treatment is indicated. In serious cases, patients should be hospitalized.

Combined bronchodilators

Avoid storage in direct sunlight or heat. Store in a cool & dry place. Keep away from eyes. Keep all medicines out of reach of children.