氟替美维吸入粉雾剂(Trelegy Ellipta)的详细说明书：作用与功效,用法用量,副作用,注意事项等

Flutimavir inhalation powder spray (TrelegyEllipta) is a triple compound inhalation powder spray, which contains three drug ingredients with different mechanisms of action: inhaled glucocorticoids, long-acting anticholinergic drugs and long-acting β₂ receptor agonists.

Indications of flutimavir inhalation powder (Trelegy Ellipta)

1. Maintenance treatment of chronic obstructive pulmonary disease

It is suitable for the maintenance treatment of patients with chronic obstructive pulmonary disease.

2. Maintenance treatment of asthma

Flutimavir inhalation powder is suitable for maintenance treatment of asthma patients aged 18 years and above.

3. Limitation of use

Flutimavir inhalation powder is not suitable for relieving acute bronchospasm.

Usage and Dosage of Flutimavir Inhalation Powder Aerosol (Trelegy Ellipta)

1. Administration Method

Inhale 1 spray of Flutimavir Inhalation Powder Aerosol by mouth once a day.

After inhalation, rinse your mouth with water without swallowing to help reduce the risk of candida infection in the oropharynx.

Flutimavir inhalation powder should be used at the same time every day. Do not use more than once every 24 hours.

2. Recommended dosage for maintenance treatment of chronic obstructive pulmonary disease

The recommended dosage of flutimevir inhalation powder for maintenance treatment of chronic obstructive pulmonary disease is fluticasone furoate 100mcg, umeclidinium bromide 62.5mcg and vilanterol 25mcg (flutimevir inhalation powder 100/62.5/25mcg 1 spray), once daily by oral inhalation.

Flutimavir inhalation powder 100/62.5/25mcg is the only specification suitable for the treatment of chronic obstructive pulmonary disease.

If shortness of breath occurs between doses, an inhaled short-acting beta2-agonist (rescue drug, such as albuterol) should be used for immediate relief.

3. Recommended dosage for asthma maintenance treatment

The recommended starting dose of fluticasone furoate for asthma maintenance treatment is 100mcg of fluticasone furoate, 62.5mcg of umeclidinium bromide and 25mcg of vilanterol (flutimevir inhalation powder (Tr) elegy Ellipta) 100/62.5/25mcg 1 spray) or fluticasone furoate 200mcg, umeclidinium bromide 62.5mcg and vilanterol 25mcg (flutimavir inhalation powder spray 200/62.5/25mcg 1 spray), once daily by oral inhalation.

When selecting the starting dose strength of flutimavir inhalation powder, the patient's disease severity, their previous asthma treatment (including the dose of inhaled corticosteroids), as well as the patient's current asthma symptom control and risk of future exacerbations should be considered.

4. Dose adjustment

The maximum recommended dose is flutimavir inhalation powder spray 200/62.5/25mcg once daily.

In patients who do not respond well to flutemevir inhalation powder 100/62.5/25 mcg once daily, increasing the dose to flutimevir inhalation powder 200/62.5/25 mcg once daily may provide additional improvements in asthma control.

Patients who do not respond well to once-daily flutimavir inhalation powder 200/62.5/25mcg should be re-evaluated and considered for other treatment options and additional treatment options.

If asthma symptoms occur between doses, an inhaled short-acting beta2-agonist (rescue medication, such as albuterol) should be used for immediate relief.

No dose adjustment is usually required in elderly patients, patients with renal impairment, or patients with moderate hepatic impairment.

5. Dosage forms and specifications

Each spray contains fluticasone furoate 100mcg, umeclidinium bromide 62.5mcg and vilanterol 25mcg (100/62.5/25mcg).

Each spray contains fluticasone furoate 200mcg, umeclidinium bromide 62.5mcg and vilanterol 25mcg (200/62.5/25mcg).

6. Overdose

Flutemevir inhalation powder contains fluticasone furoate, umeclidinium bromide, and vilanterol; overdose treatment includes discontinuing flutemevir inhalation powder and initiating appropriate symptomatic and/or supportive treatment. Cardioselective beta-blockers may be considered for cautious use, with the caveat that these agents may produce bronchospasm. Cardiac monitoring is recommended in cases of overdose.

The pictures are from public channels (such as the official website of the FDA, the official website of the original drug manufacturer, etc.) and are for reference only.

Contraindications of flutimavir inhalation powder (Trelegy Ellipta)

1. Main treatment for status asthmaticus or other acute exacerbations of chronic obstructive pulmonary disease or asthma that require intensive measures.

2. Those who are severely allergic to milk protein or have proven hypersensitivity to fluticasone furoate, umeclidinium bromide, vilanterol or any excipients.

Precautions for flutimavir inhalation powder (Trelegy Ellipta)

1. Serious asthma-related events – hospitalization, intubation, death

Long-acting β2-adrenergic agonists used as monotherapy (without ICS) in asthma are associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that LABA use as monotherapy increases the risk of asthma-related hospitalization in children and adolescents. These findings are considered a class effect of LABA monotherapy.

Data from large clinical trials have not shown a significantly increased risk of severe asthma-related events (hospitalization, intubation, death) when LABAs are used in combination with fixed-dose ICS compared with ICS alone (see Serious asthma-related events with inhaled corticosteroids/long-acting beta2-adrenergic agonists).

2. Disease exacerbations and acute exacerbations

Flutimavir inhalation powder should not be initiated during a rapidly exacerbating or potentially life-threatening exacerbation of chronic obstructive pulmonary disease or asthma. Flutimavir inhalation powder has not been studied in subjects with acute exacerbations of COPD or asthma.

Flutimavir Inhalation Powder should not be used for acute symptom relief, i.e. as rescue therapy for the treatment of acute bronchospasm attacks. Flutimavir inhalation powder has not been studied for the relief of acute symptoms and additional doses should not be used for this purpose. Acute symptoms should be treated with inhaled short-acting beta2-agonists.

When initiating flutimavir inhalation powder therapy, patients who are regularly (e.g., four times daily) taking oral or inhaled short-acting beta2-agonists should be instructed to discontinue regular use of these medications and to use them only for relief of acute respiratory symptoms. When prescribing flutimavir inhalation powder, health care providers should also prescribe an inhaled short-acting beta2-agonist and instruct patients on its use.

3. Avoid overuse of flutimavir inhalation powder and avoid combination with other long-acting beta2-agonists

Flutimevir inhalation powder should not be used more frequently than recommended, at higher than recommended doses, or in combination with other LABA-containing therapies, as overdose may result. Clinically significant cardiovascular effects and death have been reported associated with overdose of inhaled sympathomimetics.

Patients taking flutimevir inhalation powder should not use another LABA-containing therapy (e.g., salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason.

4. Oropharyngeal candidiasis

Flutimavir inhalation powder contains the ICS fluticasone furoate, and local infection of the oropharynx with Candida albicans has occurred in subjects treated with oral inhalation drug products containing fluticasone furoate.

When such an infection occurs, appropriate topical or systemic (i.e., oral) antifungal treatment should be used while continuing treatment with flutimavir inhalation powder. In some cases, it may be necessary to interrupt flutimavir inhalation powder therapy. Patients are advised to rinse their mouth with water (without swallowing) after inhaling flutimavir inhalation powder to help reduce the risk of oropharyngeal candidiasis.

5. Pneumonia

Lower respiratory tract infections, including pneumonia, have been reported after inhaled corticosteroids.

Physicians should be alert to the possibility of pneumonia in patients with COPD because the clinical features of pneumonia and exacerbations often overlap.

6. Immunosuppression and risk of infection

People who use drugs that suppress the immune system are more susceptible to infection than healthy individuals. Chickenpox and measles may have a more severe or even fatal course in susceptible children or adults taking corticosteroids. Special care should be taken to avoid exposure to such children or adults who have not had these illnesses or are not appropriately immunized. How the dose, route, and duration of corticosteroid administration affect the risk of developing disseminated infection is unclear.

The safety and effectiveness of flutimevir inhalation powder in pediatric patients have not been established, and flutimevir inhalation powder is not suitable for this population.

ICS should be used with caution (if necessary) in patients with active or quiescent respiratory tuberculosis infection, systemic fungal, bacterial, viral or parasitic infection, or ocular herpes simplex.

7. Patients switching from systemic corticosteroid therapy

Special caution is needed in patients switching from systemically active corticosteroids to ICS, as there have been cases of death due to adrenal insufficiency during and after switching from systemic corticosteroids to less systemically available ICS. Recovery of hypothalamic-pituitary-adrenal axis function after discontinuation of systemic corticosteroids requires several months.

Patients who are switched from systemic corticosteroid therapy to flutimavir inhalation powder may develop allergic symptoms previously suppressed by systemic corticosteroid therapy, such as rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic disease.

8. Hypercortisolism and adrenal suppression

Because sensitive patients may have significant systemic absorption of ICS, patients treated with flutimavir inhalation powder should be carefully observed for any evidence of systemic corticosteroid effects. Special attention should be paid to observing patients postoperatively or during periods of stress for evidence of adrenal insufficiency.

Systemic corticosteroid effects such as hypercortisolism and adrenal suppression (including adrenal crisis) may occur in a small subset of patients who are susceptible to such effects. If such effects occur, the dose of flutimavir inhalation powder should be slowly reduced in accordance with accepted procedures for reducing systemic corticosteroids, and alternative treatments should be considered to control symptoms of COPD or asthma.

9. Paradoxical bronchospasm

Like other inhaled therapies, flutimavir inhalation powder spray may produce paradoxical bronchospasm, which may be life-threatening. If paradoxical bronchospasm occurs after use of flutemevir inhalation powder, treatment should be immediate with an inhaled short-acting bronchodilator; flutemevir inhalation powder should be discontinued immediately, and alternative treatment should be initiated.

10. Hypersensitivity reaction

Hypersensitivity reactions, such as allergic reactions, angioedema, rash and urticaria, may occur after using flutimavir inhalation powder. If such a reaction occurs, flutimavir inhalation powder should be discontinued. Anaphylaxis has been reported in patients with severe milk protein allergy after inhalation of other lactose-containing powdered medicines; therefore, flutimavir inhalation powder should not be used in patients with severe milk protein allergy.

11. Cardiovascular effects

Like other β2-agonists, flutimavir inhalation powder may produce clinically significant cardiovascular effects in some patients, manifested as increases in pulse rate, systolic or diastolic blood pressure, and cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles. If such effects occur, flutimavir inhalation powder may need to be discontinued.

In addition, beta-agonists have been reported to cause ECG changes, such as T wave flattening, QTc interval prolongation, and ST segment depression, although the clinical significance of these findings is unknown, and deaths have been reported associated with overdose of inhaled sympathomimetics.

12. Reduced bone mineral density

Patients with major risk factors for reduced bone mineral density, such as family history of osteoporosis, postmenopausal status, smoking, advanced age, malnutrition, or long-term use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids), should be monitored and treated according to established standards of care.

Because patients with chronic obstructive pulmonary disease often have multiple risk factors for reduced BMD, it is recommended that BMD be assessed before initiating treatment with flutimavir inhalation powder and periodically thereafter. If a significant reduction in BMD is observed and flutimevir inhalation powder is still considered medically important for the treatment of COPD in this patient, therapy to treat or prevent osteoporosis should be strongly considered.

13. Glaucoma and cataract, exacerbation of narrow-angle glaucoma

Flutimavir inhalation powder should be used with caution in patients with narrow-angle glaucoma. Prescribers and patients should also remain alert to the signs and symptoms of acute narrow-angle glaucoma. Instruct patients to consult their healthcare provider immediately if any of these signs or symptoms occur. Consider referral to an ophthalmologist for patients who develop ocular symptoms or who have been using flutimavir inhalation powder for a long period of time.

14. Worsening of urinary retention

Flutimavir inhalation powder, like all therapies containing anticholinergic ingredients, should be used with caution in patients with urinary retention. Prescribers and patients should remain alert to signs and symptoms of urinary retention (e.g., dysuria, painful urination), particularly in patients with prostatic hyperplasia or bladder neck obstruction. Instruct patients to consult their healthcare provider immediately if any of these signs or symptoms occur.

15. Hypokalemia and Hyperglycemia

Beta-adrenergic agonist therapy may produce significant hypokalemia in some patients, possibly through intracellular transfer, which has the potential to produce adverse cardiovascular effects. Decreases in serum potassium are usually temporary and do not require supplementation. Beta-agonist therapy may produce transient hyperglycemia in some patients.

Adverse reactions of flutimavir inhalation powder (Trelegy Ellipta)

1. Heart organ: palpitations.

2. Eyes: blurred vision, eye pain, glaucoma and increased intraocular pressure.

3. Immune system: Hypersensitivity reactions, including allergic reactions, angioedema, rashes and urticaria.

4. Metabolism and nutrition: hyperglycemia.

5. Musculoskeletal and connective tissue: muscle spasm.

6. Nervous system: tremor.

7. Mental illness: anxiety.

8. Kidneys and urinary system: difficulty urinating, urinary retention.

Flutimavir inhalation powder (Trelegy Ellipta) drug interactions

1. Cytochrome P4503A4 inhibitors

Fluticasone furoate and vilanterol are CYP3A4 substrates. Administration of strong CYP3A4 inhibitors will increase the systemic exposure of fluticasone furoate and vilanterol. Use caution when considering coadministration of flutimavir inhalation powder with ketoconazole and other known strong CYP3A4 inhibitors.

2. Monoamine oxidase inhibitors, tricyclic antidepressants, and drugs that prolong the QTc interval

Vilanterol, like other beta2-agonists, should be administered with extreme caution to patients receiving monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval, or within 2 weeks of discontinuing such drugs, because the effects of adrenergic agonists on the cardiovascular system may be potentiated by these drugs. Drugs known to prolong the QTc interval increase the risk of ventricular arrhythmias.

3. Non-potassium-sparing diuretics

Electrolyte changes and/or hypokalemia that may be caused by the administration of non-potassium-sparing diuretics (such as loop diuretics or thiazide diuretics) may be acutely aggravated by beta-agonists, especially when the recommended dose of beta-agonists is exceeded. Although the clinical significance of these effects is unknown, caution is recommended when beta-agonists are coadministered with non-potassium sparing diuretics.

4. Anticholinergic drugs

There is potential interaction with anticholinergic drugs used simultaneously. Therefore, avoid coadministration of flutimavir inhalation powder with other drugs containing anticholinergic ingredients, as this may lead to an increase in anticholinergic adverse reactions.

Usage of Flutimavir Inhalation Powder Aerosol (Trelegy Ellipta) in Special Populations

1. Pregnancy

There are insufficient data on the use of Flutimavir Inhalation Powder Aerosol (Trelegy Ellipta) or its individual components (fluticasone furoate, umeclidinium bromide, and vilanterol) in pregnant women to inform drug-related risks.

2. Lactation period

There is no information on the presence of flutimavir inhalation powder in human milk, or on the effects on breastfed children or on milk production. The developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for fluticasone furoate, umeclidinium, or vilanterol or the underlying maternal condition in the breastfed child.

3. Pediatric use

The safety and effectiveness of flutemevir inhalation powder have not been established in pediatric patients (17 years old and under), and flutemevir inhalation powder is not suitable for pediatric patients.

4. Medication for the elderly

Based on existing data, elderly patients do not need to adjust the dose of flutimavir inhalation powder, but it cannot be ruled out that some elderly individuals are more sensitive.

5. Hepatic Impairment

Flutimevir inhalation powder has not been studied in subjects with hepatic impairment.

6. Renal impairment

Flutimavir inhalation powder spray (Trelegy Ellipta) has not been studied in subjects with renal impairment.

Mechanism of action of Flutimavir inhalation powder spray (Trelegy Ellipta)

Flutimavir inhalation powder spray contains fluticasone furoate, umeclidinium bromide and vilanterol. These drugs represent 3 different classes of drugs (an ICS, an anticholinergic drug and a LABA), each of which has different effects on clinical and physiological indicators.

1. Fluticasone furoate

Fluticasone furoate is a synthetic trifluorinated corticosteroid with anti-inflammatory activity. In vitro studies have shown that the binding affinity of fluticasone furoate to human glucocorticoid receptors is approximately 29.9 times that of dexamethasone and 1.7 times that of fluticasone propionate.

The exact mechanism by which fluticasone furoate affects symptoms of chronic obstructive pulmonary disease and asthma is unclear. The specific effects of fluticasone furoate demonstrated in in vitro and in vivo models include activation of glucocorticoid response elements, inhibition of pro-inflammatory transcription factors such as NFkB, and inhibition of antigen-induced pulmonary eosinophilia in sensitized rats. These anti-inflammatory effects of corticosteroids may contribute to their efficacy.

2. Umeclidinium bromide

Umeclidinium bromide is a long-acting muscarinic antagonist, often called an anticholinergic drug, with similar affinity for the M1 to M5 muscarinic receptor subtypes.

In the airways, it exhibits pharmacological effects by inhibiting M3 receptors on smooth muscle, causing bronchiectasis. Competitiveness and reversibility of antagonism were demonstrated in receptors and isolated organ preparations of human and animal origin.

In preclinical in vitro and in vivo studies, prevention of methacholine and acetylcholine-induced bronchoconstriction was dose-dependent and persisted over 24 hours. The clinical relevance of these findings is unknown. Bronchodilation after inhaled umeclidinium bromide is primarily a site-specific effect.

3. Vilanterol

Vilanterol is a LABA. In vitro tests show that the functional selectivity of vilanterol is similar to that of salmeterol.

The pharmacological effects of beta2-adrenergic agonist drugs, including vilanterol, are attributable, at least in part, to stimulation of intracellular adenylyl cyclase, which catalyzes the conversion of adenosine triphosphate to cyclic adenosine monophosphate. Increased cyclic adenosine monophosphate levels cause bronchial smooth muscle relaxation and inhibit the release of immediate hypersensitivity mediators from cells, especially mast cells.

Flutimavir Inhalation Powder Aerosol (Trelegy Ellipta) Pharmacokinetics

Fluticasone furoate (200 to 800mcg), umeclidinium bromide (62.5 to 500mcg) and vilanterol (25 to 100mcg) exhibit linear pharmacokinetics. The pharmacokinetics of fluticasone furoate, umeclidinium bromide, and vilanterol from fluticasone furoate inhalation powder (Trelegy Ellipta) are comparable to those when administered as fluticasone furoate/vilanterol or umeclidinium bromide/vilanterol.

Based on a pooled pharmacokinetic data set from 3 studies in subjects with COPD, systemic drug levels (steady-state Cmax and AUC(0 -24)) is within the range observed after administration of fluticasone furoate/vilanterol plus umeclidinol via 2 inhalers, fluticasone furoate/vilanterol and umeclidinium/vilanterol as a double combination, and fluticasone furoate, umeclidinium and vilanterol as monotherapy.

Based on a population pharmacokinetic analysis from asthmatic subjects, after administration of fluticasone furoate, umeclidinium bromide inhalation powder spray (100/62.5/25 or 200/62.5/25mcg) and vilanterol systemic drug levels (steady-state Cmax and AUC(0-24)) were within the range observed after administration of fluticasone furoate/vilanterol as a dual combination compared to fluticasone furoate 100 and 200 mcg, respectively.

The systemic exposure of umeclidinium bromide 62.5 mcg after administration of flutimevir inhalation powder (100/62.5/25 or 200/62.5/25 mcg) was within the range observed after administration of umeclidinium bromide 62.5 mcg as monotherapy.

Storage of Flutimavir Inhalation Powder Aerosol (Trelegy Ellipta)

Store at room temperature between 68°F and 77°F (20°C and 25°C), with an allowed excursion between 59°F and 86°F (15°C and 30°C). Store in a dry place away from direct heat or sunlight. Please keep out of reach of children.

Flutimavir inhalation powder should be stored in an unopened moisture-proof aluminum foil tray and removed from the tray only before initial use. Discard flutimavir inhalation powder after 6 weeks from opening the foil tray or when the counter reads "0", whichever comes first. Inhalers are not reusable. Do not attempt to disassemble the inhaler.