Fluticasone Furoate, Umeclidinium, and Vilanterol are the active components found in Trelegy Ellipta, a strong inhaled corticosteroid, anticholinergic antimuscarinic, and extended-acting beta-agonist. It is suggested for use in people with chronic obstructive pulmonary disease as maintenance therapy

Trelegy Ellipta Uses:

• As a long-term, a once-daily maintenance drug for individuals with chronic obstructive pulmonary disease (COPD), including chronic bronchitis or emphysema, Trelegy Ellipta is recommended.
• In patients with a record of relapses, it is also employed in management to lessen those of COPD.
• Limitations of Use
  • The purpose of Trelegy Ellipta is NOT to relieve severe bronchospasm.

Update: Trelegy Ellipta Inhaler got FDA Approval for the Management of COPD and Asthma

The FDA approved the use of Trelegy Ellipta for the maintenance therapy of adult patients with asthma. It is a once-daily administered, triple combination inhaler containing a potent inhalational corticosteroid, an anticholinergic, and a long-acting beta-agonist.

It must not be used as a recovery drug for acute severe asthma and should not replace short-acting beta-agonists or oral/ parenteral corticosteroids in severe cases.

Trelegy Ellipta Dose in Adults:

Trelegy Ellipta should be administered as 1 inhalation once a day by the orally inhaled route only.

• It ought to be used always at the same time.
• Use this no more frequently than once per 24 hours.
• Geriatric individuals, patients that have renal dysfunction, and patients that have moderate hepatic dysfunction don't need their doses to be adjusted.
• The patient should cleanse his or her mouth thoroughly with water after inhaling to reduce the chance of developing oropharyngeal candidiasis.

Trelegy Ellipta Dose in Children:

In children, it is not instructed because the safety and effectiveness in pediatric patients have not yet been examined. 

Pregnancy Risk Category: N

• The safety of the drug in pregnant females has not been established.
• A study on animal reproduction found that fluticasone furoate or vilanterol inhaled alone or together with pregnant rats during organogenesis did not cause any anomalies in the structure of the fetus.
• The highest dosages of fluticasone furoate and vilanterol in this investigation ranged from 9 to 40 times the 100 mcg and 25 mcg, respectively, of the maximum daily recommended inhalation dosages for grownups.
• Umeclidinium was administered subcutaneously or by inhalation to pregnant rats, rabbits, and humans at exposure levels that were roughly 50 and 200 times higher than those experienced by humans at MRHDID.
• It is unknown if there is a risk of miscarriage or major birth defects in the residents. The chance of miscarriage and significant anomalies during birth in pregnancies that are clinically diagnosed in the United States is between 2% and 4%, and 15% to 20% respectively.
• Beta-agonists can interfere with uterine contractions in labor so it is important to use them with caution.

Use during Lactation

• Its effects on the production and excretion of breast milk have not been examined. Umeclidinium has been found in analysis to be present in rat milk.
• Think about the edges breastfeeding has on a child's growth and health as well as the mother's clinical necessity for TRELEGY-ELLIPTA.
• It is influential to consider any probable negative effects that umeclidinium, fluticasone furoate, or the underlying maternal disease may have on breastfeeding children.

Trelegy Ellipta Dose in Kidney disease:

Patients with kidney diseases have not yet been studied in relation to it.

Vianterol/Fluticasone Furoate:

• Participants with significant renal dysfunction (CrCl 30 mL/min) did not experience any appreciable increases in their vulnerability to fluticasone furoate or vilanterol compared to healthy subjects.
• Therefore, no medication change is needed.

Umeclidinium:

• There were no notable alterations in Cmax or AUC seen in Ckd 4 or 5 patients (CrCl 30 mL/min), and there were no differences in protein binding between individuals with severe renal impairment and their healthy controls.
  Therefore, dosage adjustments are not necessary for patients with renal insufficiency.

Trelegy Ellipta Dose in Liver disease:

It hasn't been studied in people with impaired liver function. Below is information on each part of the system. 

Fluticasone Furoate/Vilanterol:

• Compared to subjects without hepatic impairment, Fluticasone furoate exposure in the body was up to three times higher in participants having a hepatic impairment. 
• Hepatic dysfunction has no effect on the systemic exposure to vilanterol. Watch out for corticosteroid-related adverse effects in patients.

Umeclidinium:

• There haven't been any studies done on people who have severe hepatic impairment.

• Patients with mild to moderate hepatic impairment (Child-Pugh score of 7-9) showed no appreciable changes in Cmax or AUC, and there was no difference in protein binding between these patients and their healthy controls.

Side Effects of Trelegy Ellipta:

See individual agents

Contraindications to Trelegy Ellipta:

• Patients should not use it if they have:
  • Responses of extreme responsiveness to milk proteins
  • Those who are hypersensitive to umeclidinium or fluticasone furoate.

Cautions and safeguards

• Responses of extreme hypersensitivity to milk proteins
  Events Serious Asthma-Related: Intubations, hospitalizations, and fatalities

  • It is not known if the drug works in treating asthma.
  • If long-acting beta-2 adrenergic agonists (LABA) are used alone to treat asthma without using an inhaled corticosteroid, there is an increased risk of dying from asthma.
  • According to the study, LABA without ICS in asthmatic patients increases the risk of severe exacerbations or hospitalizations.
  • However, large-scale trials that included LABA and ICS have shown no difference in their effectiveness.
  • Clinical trials with COPD subjects have not shown an increase in death rates due to LABA.

• Acute episodes and deterioration of disease:

  • It is not recommended for use in cases of severe illness or those with a terminal illness. The more traditional approach is preferred.
  • It has not been tested in patients with COPD that are rapidly deteriorating. 
  • It must not be utilized as rescue medication to treat sudden bouts of bronchospasm with an acute onset.
  • Acute manifestations should be cured with fast-acting beta2-agonists administered by inhalation.
  • Patients who have been prescribed conventional treatments should be asked to discontinue their current medications.
  • COPD can get progressively worse over a few hours or slowly over several weeks. If symptoms worsen as seen by repeated use of brief beta 2 agonists but unless the symptoms are not managed, consider treatment failure.
  • It is now necessary to reassess the patient and begin the COPD therapy regimen.
  • Avoid taking more than the recommended maximum dose.

• Using TRELEGY ELLIPTA excessively or in conjunction with certain long-acting beta2-agonists

  • It is not used more frequently, at greater doses, or in combination with medications that include LABA. An overdose may be fatal.
  • Excessive use of inhaled sympathomimetic medications has been associated with clinically significant CVS deaths and CVS effects.
  • Patients taking the drug should not take any other LABA-containing medicine (e.g. salmeterol or formoterol fumarates, arformoterol tartrates, indacaterol) while they are on it.

• Regional consequences of inhaled corticosteroids

  • One type of ICS is fluticasone furoate. Oral inhalation of fluticasone furoate by subjects resulted in localized Candida albicans infections of the mouth and throat.
  • It is important to treat any infection that develops with antifungal treatment, whether it be local or systemic. Sometimes, however, therapy might need to be stopped.
  • The chances of oropharyngeal candidiasis are lessened if a patient is advised to rinse their mouth thoroughly

• Pneumonia:

  • Physicians should keep an eye out for pneumonia clinical signs in COPD patients.
  • ICS has been used to treat patients with COPD or asthma even if they have a lower respiratory tract infection (including pneumonia)

• Immunosuppression:

  • People who take drugs to suppress their immune system are more likely to get infected than those who do not use them.
  • For example, measles and chickenpox can be fatal in children who are susceptible or those who use corticosteroids.
  • These children and adults should not be exposed to any patient with measles or chickenpox if they have not been properly immunized or have not yet had the disease.
  • There are greater chances of spreading the disease if the dosage and administration are not correct. It is not known what role the underlying condition and previous corticosteroid therapy played in increasing the risk.
  • Patients who have had chickenpox are strongly advised to get vaccinated against varicella-zoster (VZIG) as a preventative measure.
  • In case a patient has been infected with measles, intramuscular aggregated immunoglobulin (IG) prophylaxis is advised. Antiviral medications can be used to treat chickenpox patients.
  • Patients with active or latent tuberculosis should not be given ICS.

• Patients being transferred from systemic corticosteroid therapy:

  • Patients who have received systemically active corticosteroids as ICS are in need of special care. Asthma patients have died after being transferred from systemic to systemically available corticosteroids.
  • It takes a certain time period after when the systemic steroids are withdrawn for the Hypothalamus-pituitary axis to recover. It can lead to Addison's crisis if it is not properly withdrawn.
  • The most vulnerable patients may be those who have formerly been kept on 20 milligrams or greater of prednisone (or its equivalent), especially if their systemic corticosteroids have been virtually entirely discontinued.
  • Patients may experience symptoms such as adrenal insufficiency during this period of HPA suppression if they are exposed to trauma, surgery, infection (especially gastroenteritis), and other conditions that can cause severe electrolyte loss.
  • Trelegy Ellipta can be used to control COPD symptoms. However, it provides less than the normal physiological levels of glucocorticoid systemically in recommended doses. It does not provide the mineralocorticoid activity required to manage these emergencies.
  • When under stress or experiencing severe COPD exacerbations, patients who were first prescribed systemic corticosteroids shouldn't stop taking them. They should be told to start taking oral corticosteroids again right away at large doses—or even higher than before.
  • Patients should be informed that they can carry a warning note to indicate that they might need supplementary systemic steroids during stressful periods or severe COPD exacerbations.
  • Systemic steroids should gradually be reduced after the patient has been treated.
  • Prednisone dose rate can be reduced by weekly prednisone dose reductions of 2.5 mg during therapy.
  • Monitoring lung capacity (forced exhalation volumes in 1 second [FEV1]), beta-agonist administration, and COPD signs are crucial while stopping oral corticosteroids.
  • Signs like weariness, fatigue, sickness, puking, hypotension, and lassitude should also be assessed in patients.
  • The remission of allergy disorders like rhinitis and conjunctivitis that were previously treated with central corticosteroid therapy may be possible for patients who are switched from systemic to Trelegy Ellipta medication.
    Even when their respiratory function has been maintained or improved, some patients can still experience the side effects of systemically active corticosteroid discontinuation, such as joint or muscle discomfort, lassitude, and depression.

• Adrenal Reduction and Hypercortisolism:

  • Fluticasone furoate, when inhaled, travels through the bloodstream and is systemically active.
    Fluticasone furoate at therapeutic doses has no effect on the HPA axis.
  • HPA dysfunction may occur if you exceed the recommended dosage, or if you take the drug concurrently with a strong cytochrome P450 3A4 inhibitor (CYP3A4).
  • Patients who are sensitive to ICS need to be monitored closely for indications of corticosteroid effects.
  • Patients should be observed closely after surgery or when they are under stress to ensure that there is no evidence of an inadequate adrenal response.
  • Systemic corticosteroid adverse impacts, like adrenal reduction and hypercortisolism, might occur in a minority of patients.
  • These effects should be treated according to the guidelines.

• Interactions Between Drugs and Potent Cytochrome P450 3A4 Inhibitors

  • It is critical to exercise caution when taking ketoconazole with other strong CYP3A4 inhibitors such as clarithromycin.
  • Trelegy Ellipta, like other inhaled medications, can cause paradoxical spasms of the airways that could prove fatal.
  • The treatment of paradoxical bronchospasm should begin immediately after the drug is administered. This should be done with a quick-acting bronchodilator inhaled. The treatment must be stopped right away. When looking for alternative therapy, the guidelines are followed.

• Hypersensitivity reactions, including Anaphylaxis

  • After the drug is administered, hypersensitivity reactions like anaphylaxis and angioedema, skin rash, and urticaria can occur.
  • If you experience any reactions, stop taking the medication. Research has shown that patients suffering from severe milk protein allergies can experience anaphylactic reactions if they inhale powders composing lactose. Patients with intense lactose intolerance should avoid the medication.

• Cardiovascular outcomes:

  • Similar to different beta2-agonists Vilanterol can induce a dramatic cardiovascular effect in certain patients. This is measured by an increase in pulse rate, diastolic and systolic blood pressure, and cardiac arrhythmias such as extra-systoles and SVT.
  • These outcomes indicate that treatment should be stopped.
  • Excessive use of inhaled sympathomimetic medications has been linked to fatalities.
  • Patients with heart disease, such as hypertension, coronary insufficiency, or cardiac arrhythmias, should not take Trelegy Ellipta.
  • Beta-agonists have also been connected to electrocardiographic changes such T wave flattening, QTc interval lengthening, and ST-segment depression symptoms. These observations, however, have not been shown to be clinically meaningful.

• Reduced bone mineral density

  • Long-term ICS use has been linked to systemic side effects such as a reduction in bone mineral density (BMD).
  • Its clinical significance in assessing fracture risk is not known.
  • Patients at elevated danger for bone loss, e.g., those who have been immobilized for a prolonged period, are postmenopausal, have a family history of osteoporosis, and are prone to developing bone problems like poor nutrition or anticonvulsant use. These patients should be monitored and treated according to established guidelines.
  • Patients with COPD are often at risk of having a reduced BMD due to multiple factors. It is important that patients be assessed before starting treatment. This assessment is repeated frequently.
  • Consider using medicine to prevent or treat osteoporosis if there are significant reductions in BMD.

• Cataracts and Narrow-Angle Glaucoma Exacerbation:

  • Glaucoma, or enhanced pressure inside the eye, has been observed in COPD patients following long-term ICS administration and anticholinergic inhalation.
  • Patients suffering from narrow-angle glaucoma should proceed with extreme caution.
  • Patients and physicians should be aware of the signs and symptoms of acute thin-angle glaucoma, which include vision issues, eye disturbance, discomfort, blurred vision, and colored images.
  • Counsel patients to seek prompt medical attention if any of these signs appear.
  • When ocular problems arise, it is a good idea to consult an urgent ophthalmologist immediately.

• Worsening Urinary Retention

  • Urinary consistency, including difficulties involved in attempting to pass urine or dysuria in subjects who have bladder neck obstruction or prostatic hyperplasia, should be noted by patients and physicians.
  • Trelegy Ellipta, like all medicines, has anticholinergic effects and should not be used in clients who have persistent urinary problems.
  • If you notice any of these symptoms, please advise your clients to see a doctor right away.

• Coexisting Disorders

  • Trelegy Ellipta, like all sympathomimetic amine medications, must be used caution by patients with spasmodic disorder or thyrotoxicosis, as well as those who are not usually able to respond to them.
  • Beta 2 receptor agonists like albuterol when given IV in diabetics have shown to exacerbate the condition of DKA in many patients.

• Hypokalemia and hyperglycemia

  • Medicines that block beta-adrenergic receptors can result in intracellular potassium switching from ECF, hypokalemia, and interlinked hyperglycemia.
  • A reduction in the serum level of potassium is typically temporary and does not necessitate medicines.
    Beta-agonist drugs may cause temporary hyperglycemia in a few patients.

Monitoring parameters:

• Lung function examinations (FEV-1, FEV-1:FVC, Residual Volume)
• Arterial blood gases for carbon dioxide retention and hypoxemia
• Chest radiographs and CBC if an infection is suspected or no improvement is observed.

How to use Trelegy Ellipta Inhaler?

It should only be taken orally once a day in the form of one dose. The patient should wash their mouth with water after inhaling without ingesting to minimize the danger of oropharyngeal candidiasis. It's used always at the same time.

Use it no more than once every 24 hours. Geriatric patients, patients with renal dysfunction, and patients with reasonable hepatic impairment do not necessitate a dosage modification.

Mechanism of action of Trelegy Ellipta:

Umeclidinium and fluticasone furoate are both ingredients in Trelegy Ellipta. The following mechanisms of action control the TRELEGY. ELLIPTA. These medications fall into 3 types of different categories of medicine (an anticholinergic and a LABA and an ICS). The impact on clinical and physiological parameters is varied for each.

Fluticasone Furoate:

• There is a manufactured trifluorinated corticosteroid called fluticasone furoate that has anti-inflammatory properties.
  Fluticasone furoate was found to bind to human glucocorticoid hormone receptors with a 29.9-fold higher affinity in vitro than dexamethasone. Fluticasone propionate's binding affinity is around 1.7 times lower than this one.
• These findings are not clinically relevant. It is unknown how fluticasone furoate causes COPD symptoms. The pathogenesis and progression of COPD are influenced by inflammation.
• In vitro and in vivo studies showed that fluticasone furoate had specific effects on glucocorticoid responses, inhibited pro-inflammatory transcription factors like NFkB, as well as inhibited antigen-induced lung eosinophilia. This may be due to the anti-inflammatory properties of corticosteroids.

Umeclidinium

• It is similar to subtypes M1 through M5 of the muscarinic receptive receptors. It has bronchodilatory effects by inhibiting the M3 receptor that are found in the smooth muscles.
• The challenging and convertible character of antagonism was proven using isolated organ preparations, receptors of both human and animal origin, and isolated organs.
• The phrase "anonymous" anticholinergic is frequently used to describe umeclidinium, a long-acting antimuscarinic drug.
• Preclinical in-vitro and in vivo investigations showed that stopping the effects of methacholine and acetylcholine on inducing bronchoconstriction varied on dose and lasted for more than 24 hours.
• These findings are not clinically relevant. Inhaling umeclidinium can cause bronchodilation, but this is a location-specific occurrence.

Vilanterol:

• Beta2-receptors, which predominate in bronchial smooth muscle cells, and β1 receptors, which prevail in the heart, are the two most common adrenergic receptors. However, beta2 receptors, which account for 10% to 50% of all beta-adrenergic receptors, are present in the human heart. Therefore, beta2 agonists may have an impact on the heart's muscles.
• LABA Vilanterol is one. Vilanterol has been demonstrated to be functionally selective in vitro tests. comparable to salmeterol It's barely clinically relevant.
• The provocation of adenyl cyclase in the cells, the enzyme that catalyzes the metamorphosis of cyclic-3',5'-adenosine monophosphate from adenosine triphosphate (ATP), is at least somewhat accountable for the pharmacologic actions of medications that act as beta2-adrenergic agonists, such as vilanterol (cyclic AMP).
• The bronchial smooth muscles relax when cyclic AMP levels rise, and mast cells, in particular, are prevented from releasing mediators of acute hypersensitivity.

International Brand Names of Fluticasone Furoate, Umeclidinium, and Vilanterol:

• Trelegy Ellipta

Brand Names in Pakistan:

No Brand Names are available in Pakistan.