Trihale Dry Powder Inhalation Capsule (DPI)

This is indicated for-

• The maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).
• The maintenance treatment of asthma in patients aged 18 years and older.

Limitation of use: Not indicated for relief of acute bronchospasm.

Each dry powder inhaler capsule contains

• Vilanterol 25 mcg (as Vilanterol Trifenatate INN), Fluticasone Furoate INN 100 mcg and Umeclidinium 62.5 mcg (as Umeclidinium Bromide INN).
• Vilanterol 25 mcg (as Vilanterol Trifenatate INN), Fluticasone Furoate INN 200 mcg and Umeclidinium 62.5 mcg (as Umeclidinium Bromide INN).

This capsule is an inhalation powder drug product for delivery of a combination of futicasone furoate (an ICS), umeclidinium (an anticholinergic), and vilanterol (a LABA) to patients by oral inhalation. The pharmacologic efects of beta 2-adrenoceptor agonist drugs, including vilanterol, 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.

The precise mechanism through which futicasone furoate afects COPD and asthma symptoms is not known. Infammation is an important component in the pathogenesis of COPD and asthma. Corticosteroids have been shown to have a wide range of actions on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) involved in infammation.

Umeclidinium is a long-acting muscarinic antagonist, which is often referred to as an anticholinergic. It has similar afnity to the subtypes of muscarinic receptors M1 to M5 . In the airways, it exhibits pharmacological efects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation.

This inhalation capsule must not be swallowed. Only to be used with the device. Remove the capsule from the blister pack only immediately before using it in the inhalation device. After inhalation, rinse your mouth with water without swallowing to reduce the risk of oropharyngeal candidiasis.

Adults (18 years or older): Should be used at the same time every day, not more than once every 24 hours. If shortness of breath or other asthma symptoms arise in the period between doses, an inhaled SABA (Short Acting β-Agonist) should be taken for immediate relief.

Maintenance treatment of COPD: 1 inhalation capsule once daily.

Maintenance treatment of Asthma: 1 inhalation capsule once daily.

Strong cytochrome P450 3A4 inhibitors (e.g., ketoconazole): Use with caution. May cause systemic corticosteroid and cardiovascular effects.

Monoamine oxidase inhibitors and tricyclic antidepressants: Use with extreme caution. May potentiate the effect of vilanterol on the vascular system.

Beta-blockers: Use with caution. May block the bronchodilatory effects of beta-agonists and produce severe bronchospasm.

Diuretics: Use with caution. Electrocardiographic changes and/or hypokalemia associated with non–potassium-sparing diuretics may worsen with concomitant beta-agonists.

Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administration of Trihale with other anticholinergic-containing drugs.

• Primary treatment of status asthmaticus or acute episodes of COPD or asthma requiring intensive measures
• Severe hypersensitivity to milk proteins or any ingredients.

COPD: Most common adverse reactions (incidence ≥1%) are upper respiratory tract infection, pneumonia, bronchitis, oral candidiasis, headache, back pain, arthralgia, infuenza, sinusitis, pharyngitis, rhinitis, dysgeusia, constipation, urinary tract infection, diarrhea, gastroenteritis, oropharyngeal pain, cough, and dysphonia.

Asthma: Most common adverse reactions (incidence ≥2%) are pharyngitis/nasopharyngitis, upper respiratory tract infection/viral upper respiratory tract infection, bronchitis, respiratory tract infection/viral respiratory tract infection, sinusitis/acute sinusitis, urinary tract infection, rhinitis, infuenza, headache, and back pain.

Insufficient data on the use of this preparation in pregnant women and lactating mothers.

• 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.
• Candida albicans infection of the mouth and pharynx may occur. Monitor patients periodically. Advise the patient to rinse his/her mouth with water without swallowing after inhalation to help reduce the risk.
• Increased risk of pneumonia in patients with COPD. Monitor patients for signs and symptoms of pneumonia.
• If paradoxical bronchospasm occurs, discontinue and institute alternative therapy.
• Use with caution in patients with cardiovascular disorders because of beta-adrenergic stimulation.
• Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction.
• Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis.

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.

Elderly population: Based on available data, no adjustment of the dosage in geriatric patients is necessary, but greater sensitivity in some older individuals cannot be ruled out.

Renal impairment: It has not been studied in subjects with renal impairment.

Hepatic impairment: It has not been studied in subjects with hepatic impairment.

There are no data available from clinical trials on overdose with this inhalation capsule.

Combined bronchodilators

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