Trihale25 mcg+100 mcg+62.5 mcg

Trihale is a fixed-dose combination inhaler containing a long-acting beta2-agonist (LABA), an inhaled corticosteroid (ICS), and a long-acting muscarinic antagonist (LAMA), indicated for the following FDA-approved uses:

Established / FDA-approved indications

• Chronic Obstructive Pulmonary Disease (COPD): long-term, once-daily maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema, and to reduce exacerbations in patients with a history of exacerbations despite appropriate maintenance therapy.
• Asthma: maintenance treatment of asthma in patients aged 18 years and older whose disease is not adequately controlled on an inhaled corticosteroid combined with a long-acting beta2-agonist, or whose disease severity warrants initiation of triple maintenance therapy.

Not indicated for

• Relief of acute bronchospasm or as a rescue inhaler.
• Primary treatment of status asthmaticus or acute, life-threatening episodes of COPD or asthma requiring intensive measures.
• Use in asthma or COPD patients under 18 years of age (safety and efficacy not established).

Trihale must always be used together with a separate short-acting bronchodilator ("reliever") for sudden symptoms, as it is not a rescue medicine.

Each single actuation of Vilanterol Trifenatate + Fluticasone Furoate + Umeclidinium Bromide dry powder for oral inhalation delivers a fixed combination of three active ingredients:

• Vilanterol Trifenatate (as vilanterol) 25 mcg – a long-acting beta2-adrenergic agonist (LABA).
• Fluticasone Furoate 100 mcg or 200 mcg (strength-dependent) – an inhaled corticosteroid (ICS).
• Umeclidinium Bromide (as umeclidinium) 62.5 mcg – a long-acting muscarinic antagonist (LAMA).

The powder is carried on a lactose monohydrate base (which may contain trace milk proteins) and is delivered from a multi-dose dry powder inhaler device.

Trihale is a once-daily, triple fixed-dose combination inhaler that brings together three complementary mechanisms of action for obstructive airway disease: a long-acting bronchodilator that relaxes airway smooth muscle via beta2-receptor stimulation, a second long-acting bronchodilator that blocks muscarinic receptors, and an inhaled corticosteroid that reduces airway inflammation.

It is supplied as a dry powder inhaler and is intended strictly for long-term maintenance therapy, not for immediate relief of breathlessness. Trihale is administered as a single inhalation once daily at the same time each day.

Trihale belongs to the pharmacological group of combined long-acting bronchodilators with inhaled corticosteroid preparations, specifically a triple therapy combining a long-acting beta2-agonist (LABA), an inhaled corticosteroid (ICS), and a long-acting muscarinic antagonist (LAMA) in a single device, used for obstructive airway disease.

Vilanterol Trifenatate + Fluticasone Furoate + Umeclidinium Bromide combines three distinct and complementary mechanisms of action:

• Vilanterol Trifenatate (LABA): selectively stimulates beta2-adrenergic receptors on airway smooth muscle, activating adenylate cyclase and increasing intracellular cyclic AMP, which produces sustained bronchodilation over 24 hours.
• Fluticasone Furoate (ICS): a synthetic trifluorinated glucocorticoid with high affinity for the glucocorticoid receptor; it suppresses multiple inflammatory cell types (eosinophils, macrophages, lymphocytes) and mediators involved in airway inflammation, reducing airway hyperresponsiveness and exacerbation frequency.
• Umeclidinium Bromide (LAMA): a competitive, reversible antagonist at muscarinic acetylcholine receptors (predominantly M3) on airway smooth muscle, blocking acetylcholine-mediated bronchoconstriction and producing additional sustained bronchodilation.

Together, these three components act on distinct receptor pathways to improve lung function and reduce exacerbation risk beyond what any single component achieves alone. Systemic exposure to fluticasone furoate and vilanterol is metabolized mainly via the CYP3A4 pathway.

Trihale is taken by oral inhalation using the device provided. Instructions:

• Slide open the cover of the inhaler until it clicks, exposing the mouthpiece.
• Breathe out fully away from the device (never into the mouthpiece).
• Place the mouthpiece between the lips and take one long, steady, deep breath in through the mouth; do not inhale through the nose.
• Hold the breath for about 3–4 seconds, then breathe out slowly away from the inhaler.
• Close the cover after use.
• Rinse the mouth with water and spit out (do not swallow) after each use to reduce the risk of oral thrush.

Use Trihale at the same time every day for consistent maintenance control.

The following clinically significant interactions should be considered with Trihale:

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir, clarithromycin): may substantially increase systemic exposure to the fluticasone furoate and vilanterol components, raising the risk of systemic corticosteroid effects (Cushingoid features, adrenal suppression) and cardiovascular effects. Use with caution and monitor closely; avoid combination when possible.
• Beta-blockers (especially non-selective): may antagonize the bronchodilator effect of the vilanterol component and can cause severe bronchospasm in COPD/asthma patients. Avoid non-selective beta-blockers; if a beta-blocker is required, a cardioselective agent should be used with caution.
• Other LABA-, LAMA-, or ICS-containing medicines: concomitant use of additional medicines from the same drug classes should be avoided because of the risk of overlapping and additive adverse effects; do not combine with other LABA/LAMA/ICS products.
• Other anticholinergic (antimuscarinic) medicines: may produce additive anticholinergic effects (e.g., dry mouth, constipation, urinary retention); avoid concomitant use where possible.
• Monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (or within 2 weeks of stopping them), and QT-interval–prolonging drugs: may potentiate the cardiovascular effects (tachycardia, arrhythmia) of the vilanterol component; use with extreme caution.
• Non-potassium-sparing diuretics (loop and thiazide diuretics): may worsen ECG changes and hypokalemia caused by the beta-agonist component; use cautiously with monitoring of serum potassium.

Reported adverse effects of Trihale include:

Common

• Nasopharyngitis / upper respiratory tract infection
• Headache
• Oral or oropharyngeal candidiasis (oral thrush)
• Cough, dysphonia (hoarseness)
• Back pain, arthralgia
• Pharyngitis, sinusitis, bronchitis, influenza
• Diarrhea, constipation
• Urinary tract infection

Less common but notable

• Pneumonia — a well-recognized risk with inhaled corticosteroid use in COPD patients; report new or worsening fever, chills, increased sputum/cough, or worsening breathlessness promptly.
• Cardiovascular effects from the LABA component — palpitations, tachycardia, and rarely arrhythmias or ECG changes.
• Anticholinergic effects from the LAMA component — dry mouth, urinary retention, blurred vision.
• Hyperglycemia, hypokalemia (usually transient).

Rare / postmarketing

• Hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria.
• Blurred vision, eye pain, glaucoma, raised intraocular pressure.
• Tremor, anxiety, muscle spasms.

Pregnancy

There are insufficient human data to establish a drug-associated risk with Trihale in pregnancy. Trihale should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus, and only under close physician supervision. Poorly controlled asthma or COPD during pregnancy carries its own risks to mother and fetus, so treatment should not be stopped abruptly without medical advice.

Lactation

There is no information on the presence of Trihale components in human breast milk or their effects on a breastfed infant. A decision to use Trihale during breastfeeding should weigh the developmental and health benefits of breastfeeding against the mother's clinical need for the medicine and any potential adverse effects on the infant. Use only if clearly needed and after consulting a physician.

The following precautions apply to Trihale:

• Not a rescue inhaler: Trihale must not be used to treat acute symptoms; a separate short-acting bronchodilator must always be available for sudden breathlessness. Increasing need for a rescue inhaler signals worsening disease control and requires medical review.
• Cardiovascular disease: use with caution in patients with coronary insufficiency, arrhythmias, or hypertension, as the LABA component can increase heart rate, blood pressure, and rarely cause arrhythmias or ECG changes.
• Pneumonia risk: the inhaled corticosteroid component is associated with an increased risk of pneumonia in COPD patients; monitor for signs of lower respiratory infection.
• Immunosuppression and infection: use with caution in patients with active or dormant tuberculosis, or untreated fungal, bacterial, viral, or parasitic infections; chickenpox and measles can be more severe in patients on inhaled corticosteroids.
• Transferring from oral corticosteroids: patients switching from systemic to inhaled corticosteroid therapy require careful, gradual tapering under medical supervision, as adrenal insufficiency and even death have been reported during withdrawal.
• Narrow-angle glaucoma: use with caution due to the anticholinergic (LAMA) component; seek immediate medical attention for eye pain, blurred vision, or visual halos.
• Urinary retention/prostatic hyperplasia/bladder-neck obstruction: use with caution due to the anticholinergic component; seek prompt medical attention for difficulty or pain on urination.
• Bone mineral density: long-term inhaled corticosteroid use may reduce bone density; use with caution in patients with risk factors for osteoporosis.
• Growth effects: not evaluated/approved in patients under 18 years; inhaled corticosteroids may reduce growth velocity in children and adolescents.
• Other coexisting conditions: use with caution in convulsive disorders, thyrotoxicosis, and diabetes mellitus (beta-agonists may worsen glycemic control).
• Paradoxical bronchospasm: if wheezing worsens immediately after use, discontinue Trihale, treat with a rescue bronchodilator, and seek medical advice.
• Dual therapy avoidance: do not use with other LABA-, LAMA-, or ICS-containing medicines.

Overdose with Trihale may cause exaggerated effects of its individual components: excessive beta-adrenergic stimulation (tachycardia up to very high rates, palpitations, tremor, headache, nervousness, hypertension or hypotension, arrhythmias, seizures, hypokalemia, hyperglycemia, and rarely cardiac arrest), anticholinergic effects (dry mouth, blurred vision, urinary retention), and, with prolonged excessive corticosteroid exposure, features of hypercorticism.

There is no specific antidote. If an overdose of Trihale is suspected, seek immediate medical attention or contact a poison control center. Treatment is supportive and symptomatic, with cardiac monitoring; a cardioselective beta-blocker may be considered by a physician with caution, since beta-blockade can provoke bronchospasm. Do not attempt home treatment for a suspected overdose.

Store the inhaler at room temperature, below 25°C (77°F), away from direct heat and moisture. Keep the inhaler inside its sealed foil tray until ready for first use, and discard 6 weeks after opening the tray or when the dose counter reads "0", whichever comes first. Do not wash or immerse any part of the inhaler in water. Keep out of the reach and sight of children.

• Pediatric: safety and efficacy of Trihale have not been established in patients under 18 years of age; it is not indicated in this population.
• Geriatric: no dosage adjustment is required based on age alone; clinical studies showed no overall differences in safety or effectiveness between elderly and younger patients.
• Renal impairment: no dosage adjustment is required, including in severe renal impairment.
• Hepatic impairment: no dosage adjustment needed in mild-to-moderate impairment; use with caution in moderate-to-severe hepatic impairment, as systemic corticosteroid exposure may increase — monitor for corticosteroid-related side effects.
• Pregnancy and lactation: see Pregnancy and Lactation section above.

Trihale is intended for long-term, continuous, once-daily maintenance treatment of COPD or asthma; it is not intended for short-term or as-needed (PRN) use. Treatment should be continued regularly as prescribed, even when symptoms improve, and reassessed periodically by the physician. Do not stop Trihale abruptly without medical advice, as this may worsen underlying airway disease.

Vilanterol Trifenatate + Fluticasone Furoate + Umeclidinium Bromide is a fixed-dose triple combination of three distinct drug classes used for inhaled maintenance therapy of obstructive airway disease:

• Long-acting beta2-adrenergic agonist (LABA) — vilanterol trifenatate
• Inhaled corticosteroid (ICS) — fluticasone furoate
• Long-acting muscarinic antagonist (LAMA) — umeclidinium bromide

Vilanterol Trifenatate + Fluticasone Furoate + Umeclidinium Bromide works through three complementary and simultaneous mechanisms:

• Vilanterol Trifenatate stimulates beta2-adrenergic receptors in airway smooth muscle, raising intracellular cyclic AMP and producing sustained relaxation and bronchodilation over 24 hours.
• Fluticasone Furoate binds the glucocorticoid receptor and suppresses the transcription of pro-inflammatory genes, reducing airway inflammation, mucosal edema, and mucus hypersecretion.
• Umeclidinium Bromide blocks muscarinic (M3) acetylcholine receptors on airway smooth muscle, preventing acetylcholine-induced bronchoconstriction and providing additional, sustained bronchodilation.

The combined effect is greater improvement in airflow (FEV1) and reduction in exacerbation frequency than achieved with any single component or dual combination alone.

Trihale is not indicated for use in children or adolescents under 18 years of age. Safety and effectiveness have not been established in this age group, and it is not approved for pediatric asthma or COPD (COPD itself is rare in this age group).

Inhaled corticosteroids, including the fluticasone furoate component, may reduce growth velocity in children and adolescents when used long-term; this effect is dose- and duration-dependent, and the impact on final adult height is not fully established. If a pediatric patient is inadvertently exposed, growth should be monitored and a pediatrician consulted.