Arnuity Ellipta - Uses, Side Effects, Warnings and More

Overview:

Being given a new inhaler can cause you to wonder, What is it? Will it work for me? How do I use it correctly? Let's go through it step by step.

Arnuity Ellipta (Fluticasone furoate) is an inhaled corticosteroid, a type of medication approved by the U.S. Food and Drug Administration (FDA). It's designed to suppress inflammation in your airways, the root issue with asthma. It's not used for acute symptoms but instead is a controller that maintains your symptoms in check in the long term. Imagine it like a maintenance plan for your lungs.

It's also approved for adults and children five years and older, and it's unique in that you only need to take it once a day. That ease can make it simpler to remain consistent with your asthma therapy.

Dosage and Administration:

Drug Group: Inhaled corticosteroid (ICS).

This medication is prescribed to control asthma for the long term. It does not immediately relieve asthma symptoms, but decreases airway inflammation in the long run.

Common Dosages:

1. 50 mcg: Usually prescribed for children between 5 and 11 years old.

2. 100 mcg: Typical initial dose for adolescents and adults.

3. 200 mcg: For individuals requiring more control.

How to Use It?

Arnuity Ellipta is available in a dry powder inhaler (DPI). It's made to be easy and consistent to use.

For Patients

Dealing with asthma means your airways are constantly a little swollen and tight. This can lead to:

1. A whistling sound when you breathe (wheezing).

2. A cough that keeps coming back or just won't go away.

3. Trouble catching your breath.

4. A feeling of tightness in your chest.

5. More mucus than usual.

These symptoms often get triggered by things like:

1. Allergies (like dust or pollen).

2. Getting sick with an infection.

3. Exercising.

4. Cold air.

5. Things in the air, like pollution or smoke.

6. Feeling stressed or anxious.

Mechanism of Action

Imagine Arnuity Ellipta having a strong anti-inflammatory drug named Fluticasone furoate. When you inhale it:

1. It reaches inside the cells, making your airways swell.

2. Inside the cells, it binds to some "receptors."

3. This pair enters the middle of the cell (the nucleus).

4. It acts on specific areas of the cell's instructions (DNA).

This alters the way the cell functions, resulting in:

1. Fewer production of substances that lead to swelling (such as those "IL" and "TNF" chemicals).

2. More production of substances that combat swelling.

3. Fewer inflammatory cells (such as eosinophils and mast cells) are summoned to the airways and activated.

4. Less over-response of your airways to triggers.

5. Less production of extra mucus.

6. Reducing changes in the airways that contribute to worsening asthma in the long run.

Now, in contrast to inhalers that open up your airways fast to assist you with breathing immediately, Fluticasone furoate in Arnuity Ellipta takes longer, days, or even weeks. It's as if it's soothing the underlying cause of the issue – the inflammation – to provide you with improved asthma control in the long term.

Advantages of Arnuity Ellipta

This medication does the following:

1. Decreases inflammation and avoids flare-ups.

2. Improves lung function with time.

3. Reduces symptoms at night.

4. Decreases rescue inhaler need.

5. Increases quality of life and activity levels.

6. It can stop long-term damage to the lungs if taken every day.

Note: This is not a rescue inhaler. In case of sudden symptoms, keep a quick-relief inhaler such as Albuterol with you.

Comprehensive Dosage Instructions

Adults and Adolescents (12+):

1. Begin at 100 mcg once a day.

2. It may be increased to 200 mcg if greater control is desired.

Children (5 to 11 years):

1. 50 mcg once daily is the recommended dose.

The physician will choose the optimal dose for you based on symptom severity, previous treatment, and age.

The Arnuity Ellipta dosage for your condition can be determined on the basis of:

1. Severity of asthma.

2. Prior use of other asthma medications.

3. Therapy response.

4. Age.

5. Concomitant medications.

This drug should be taken at the same time every day for the best effect, ideally in the evening. Regular Arnuity Ellipta dosing is required even during good health since withdrawal may cause the symptoms to recur. Wait for up to 1 to 2 weeks before initial improvement is seen, with peak effect usually occurring after 4-6 weeks of continuous therapy.

Detailed Administration Instructions

1. Prepare: Draw the cover downwards to hear the click.

2. Inhale: Breathe out completely away from the inhaler. Hold the mouthpiece between your lips, and take a deep breath in.

3. Hold: Hold your breath for a second or two, then breathe slowly out.

4. Rinse: Rinse the mouth with water and spit. This prevents thrush in the mouth.

5. Close: Push the cover back upwards until it clicks.

Potential Side Effects

Common side effects of Arnuity Ellipta are:

1. Headache.

2. Nasal stuffiness.

3. Throat inflammation.

4. Mild upper respiratory infections.

5. Oral thrush.

Less common but serious:

1. Hoarseness or a change in your voice.

2. Squelched immune system.

3. Weak bones (keep an eye out).

4. Increased eye pressure (cataract or glaucoma).

5. Child's slow growth (follow up routinely).

Should any of these or your breathing degrade, refer back to your doctor.

Important Information for Your Doctor

Tell your healthcare provider about:

1. All the medicines you are taking now (prescription, over-the-counter, vitamins, and herbal supplements).

2. Any medical conditions, particularly:

• Tuberculosis or other infections (active or latent).

• Herpes simplex eye infection.

• Immune system disorders or immunosuppression.

• Osteoporosis or risk factors for bone loss.

• Liver disease.

• Cataracts, glaucoma, or elevated intraocular pressure.

• Diabetes mellitus (influences blood glucose levels).

• History of adrenal insufficiency.

3. If you are pregnant, intend to become pregnant, or are breastfeeding.

4. If you've had recent exposure to chickenpox or measles (enhanced risk of serious infection).

5. If you're currently on or have discontinued in the recent past, oral corticosteroid therapy (adrenal insufficiency upon transition).

6. All medications or other products to which you have any type of allergy, such as milk proteins.

7. If you have recently had any sort of trauma to the nose, ulceration, or any surgery.

Practical Usage Guidelines

Dietary Considerations

There is no dietary limitation when taking the drug. However, it is recommended to:

1. Swish the water around your mouth after each use. It will help you reduce the chance of developing thrush.

2. Spit out the water, and don't swallow it.

3. Use a spacer device if instructed by your doctor.

4. Ensure proper calcium and vitamin D levels if on long-term therapy because of possible effects on bone density.

Managing a Missed Dose

If you forget a dose, take it. If your next dose is nearly due (within 12 hours), however, and you remember a missed dose, simply omit it and continue with your usual dosing. Take a single dose even if you have missed the dose.

Overdose Management

In case of a suspected overdose, call a healthcare provider immediately. Acute overdose symptoms are less likely with inhaled therapy, but can involve:

1. Enhanced side effects, such as adrenal suppression.

2. Cushing's syndrome (moon face, new weight gain, hypertension).

3. Hyperglycemia (elevated blood glucose).

4. Other effects of corticosteroids.

Overdosage on a long-term basis can result in more profound systemic effects. Effects such as adrenal suppression, immunosuppression, and metabolic effects.

Proper Storage Guidelines

1. Store the inhaler at room temperature (68°F to 77°F or 20°C to 25°C).

2. Brief excursions are permitted between 59°F and 86°F (15°C and 30°C).

3. Like any other medication, Arnuity Ellipta must be stored away from moisture, heat, and direct light.

4. Do not store it in the bathroom.

5. To protect it from moisture, you can keep it in a sealed foil tray.

6. Once the tray is opened, the inhaler should be used within 6 weeks.

7. Keep track of when you first open the tray (write the "discard by" date on the inhaler label).

8. Discard the inhaler after 6 weeks, even if it still contains medication.

9. Keep out of reach of children.

10. Do not store in a refrigerator or freezer.

Special Handling Instructions

1. Do not use the inhaler with a spacer unless specifically directed by your healthcare provider.

2. Do not wash the mouthpiece or any part of the inhaler.

3. Do not attempt to take the inhaler apart.

4. Keep the cover closed when not in use to protect the medication.

5. The inhaler contains a dose counter that shows how many doses remain.

6. The counter displays the doses in intervals of 10 (counts down from 30 to 0).

7. When fewer than 10 doses remain, the left half of the counter displays red.

8. Discard the inhaler when the dose counter reads "0" (do not use the inhaler past this point).

9. The Ellipta device is breath-activated; you do not need to press any button during inhalation.

Switching From Other Asthma Medications

1. When changing from oral corticosteroids, taper gradually under medical supervision.

2. Keep taking your rescue inhaler as needed for unexpected symptoms.

3. If you are already on a different inhaled corticosteroid, you can begin Arnuity Ellipta. At the correct dose without tapering off the old medication.

4. Take up to 1 to 2 weeks to complete switching between inhaled corticosteroids.

For Healthcare Professionals

Pharmacodynamics

Fluticasone furoate is an inhaled trifluorinated synthetic corticosteroid with strong anti-inflammatory properties. It is highly selective and has a high affinity for the glucocorticoid receptor, with a relative receptor affinity of 29.9 and 1.7 compared to Dexamethasone and Fluticasone propionate, respectively. Its increased receptor binding helps in its sustained local activity in the lung and has a 24-hour effect with once-daily administration.

The drug has strong anti-inflammatory activity via various mechanisms, such as downregulating pro-inflammatory transcription factors like NF-κB and AP-1. In vitro experiments have established that Fluticasone furoate is more retained in human lung tissue than other inhaled corticosteroids, which could be one reason for its long duration of action.

Chemical Information

Fluticasone furoate (FF) is chemically defined as (6α,11β,16α,17α)-6,9-difluoro-17-{[(fluoromethyl)thio]carbonyl}-11-hydroxy-16-methyl-3-oxoandrosta-1,4-dien-17-yl 2-furancarboxylate.

1. Molecular Formula: C27H29F3O6S.

2. Molecular Weight: 538.6 g/mol.

It is a white solid with a partition coefficient (logP) value of 4.17 at pH 7.0, which is indicative of high lipophilicity. The drug is practically insoluble in water but is sufficiently soluble in the watery lining of the respiratory tract to reach therapeutic levels in the lungs.

Molecular and Cellular Mechanism of Action

Fluticasone furoate has multiple mechanisms of anti-inflammatory action at the molecular and cellular levels:

1. Genomic Mechanisms:

• Fluticasone furoate acts by binding to special receptors within airway cells called glucocorticoid receptors (GR), reducing inflammation.

• Activation of GRs and translocation to the nucleus.

• Then, it binds to glucocorticoid response elements (GREs) in the promoter region of target genes.

• Transactivation of genes encoding anti-inflammatory molecules (for example, annexin-1, IL-10, IκB-α).

• Transrepression of genes encoding pro-inflammatory molecules by interaction with transcription factors NF-κB and AP-1.

• In total, it decreases the production of inflammatory cytokines and chemokines and supports the regulation of airway inflammation in asthma.

2. Non-genomic Mechanisms:

• Direct inhibition of phospholipase A2.

• Arachidonic acid release reduction.

• Leukotriene, prostaglandin, and platelet-activating factor production reduction.

3. Cellular Effects:

• Inhibition of recruitment of inflammatory cells (neutrophils, eosinophils, macrophages).

• Reduction in inflammatory cell activation and viability.

• Reduction in the release of inflammatory mediators from mast cells.

• Inhibition of T-lymphocyte activation and cytokine synthesis.

• Reduction in cytokine production by epithelial cells.

• Reduction in the secretion of mucus from goblet cells.

• Prevention of airway remodeling via action on fibroblasts and smooth muscle cells.

4. Airway Effects

• Decreased microvascular permeability and plasma exudation.

• Decreased airway edema.

• Decreased airway hyperresponsiveness.

• Prevention of structural airway changes (remodeling).

Pharmacokinetics

Absorption

Following inhalation, Fluticasone furoate is minimally absorbed systemically. The absolute bioavailability is approximately 14 %, for the most part, due to absorption of the inhaled portion reaching the lungs. The remaining inhaled dose is swallowed and is subject to first-pass metabolism, and oral bioavailability is negligible (<1 %).

Systemic absorption is mostly by inhalation from the lungs, with maximum plasma concentration typically attained 0.5-1 hour after inhalation. After taking the medication every day for about 6 days, it reaches a steady level in the body, building up gradually with an accumulation factor of 1.8.

Distribution

Plasma protein binding is approximately 99 %, primarily to albumin and α1-acid glycoprotein. The apparent volume of distribution following intravenous administration is 661 L, indicating extensive tissue distribution.

Metabolism

The body mainly breaks down the drug using an enzyme called CYP3A4, turning it into forms that have much less steroid activity (>2,100-fold less active than the parent compound). The major metabolic pathway is the hydrolysis of the S-fluoromethyl carbothioate group to form the 17β-carboxylic acid metabolite.

Elimination

Following intravenous administration, the elimination phase half-life averages 15.1 hours. After oral administration, the drug is excreted primarily in feces (~101% of the dose), with a small amount eliminated in urine (~1-2% of the dose). The apparent plasma elimination half-life following inhaled administration is approximately 24 hours in most subjects.

Total plasma clearance of Fluticasone furoate following intravenous administration is 65.4 L/hour.

Toxicity Profile

Acute toxicity is low, with large doses needed to cause marked acute effects in animal tests. LD50 in rats was >2,000 mg/kg by oral administration and >2,000 mg/kg by dermal administration.

Chronic toxicity is typical of glucocorticoid activity, such as:

1. Adrenal suppression by inhibition of the hypothalamic-pituitary-adrenal (HPA) axis.

2. Immunosuppression.

3. Metabolic effects (hyperglycemia, change in fat distribution).

4. Bone metabolism changes.

In 13-week rat inhalation toxicity studies, Fluticasone furoate induced reduced body weight gain, reductions in thymus weight, and adrenal weight changes at the top doses tested.

No carcinogenic activity was seen in 104-week rat inhalation studies with inhaled Fluticasone furoate up to 10 mcg/kg/day (about 0.3 times the MRHD on an AUC basis) or in 26-week oral gavage transgenic mouse studies up to 29.5 mcg/kg/day.

Fluticasone furoate was not mutagenic in bacterial mutagenicity tests or in the mouse lymphoma assay and was not genotoxic in the rat micronucleus test.

Drug Interactions

Potent CYP3A4 Inhibitors

Concomitant administration with Ketoconazole, Ritonavir, or other potent CYP3A4 inhibitors can enhance plasma levels of Fluticasone furoate, leading to systemic effects of corticosteroids. A drug interaction study with a single dose of Ketoconazole 400 mg resulted in an increase in AUC(0-∞) of Fluticasone furoate by 1.33 fold with no change in Fluticasone furoate Cmax.

Caution is warranted when given with potent CYP3A4 inhibitors such as:

Other possible interactions are:

1. Other Corticosteroid-Containing Medications:

• Enhanced risk of systemic effects.

• Monitor for symptoms of adrenal suppression or Cushing's syndrome.

2. Beta-Blockers:

• Possible reduction of the effectiveness of each drug.

• Risk of bronchospasm in susceptible patients.

3. Diuretics:

• Increased risk of hypokalemia, particularly with thiazide or loop diuretics.

• Monitor potassium in the association.

4. QTc-Prolonging Drugs:

• Though Fluticasone furoate by itself does not prolong QTc, caution is advised when used with other medications that prolong QTc.

5. Non-potassium-Sparing Diuretics:

• The risk of hypokalemia is enhanced with thiazide and loop diuretics.

• Follow serum potassium.

Detailed Clinical Studies

Adult and Adolescent Studies

In several clinical trials, Fluticasone furoate was found to improve lung function notably more than placebo:

Study 1: Double-blind, 24-week, randomized, placebo-controlled trial involving 609 patients aged ≥12 years.

1. Single daily Fluticasone furoate 100 mcg improved through FEV₁ by 146 mL over placebo (95% CI: 36, 257 mL; P=0.009).

2. Once-daily Fluticasone furoate 200 mcg showed 136 mL trough FEV₁ improvement over placebo (95% CI: 26, 247 mL; P=0.015).

3. Both doses showed statistically significant differences in secondary outcomes such as:

• Weighted mean FEV₁ (0-24 hours).

• Percentage of rescue-free days.

• Percentage of symptom-free days.

• Evening and morning PEF (Peak Expiratory Flow).

• Withdrawals due to loss of efficacy.

Study 2: 12-week, randomized, double-blind trial comparing once-daily and twice-daily dosing regimens.

1. Once-daily Fluticasone furoate 200 mcg provided similar efficacy to Fluticasone propionate 500 mcg twice daily.

2. Mean change from baseline in trough FEV₁ was comparable between treatments (FF 200 mcg: 315 mL; FP 500 mcg BID: 351 mL; difference: -36 mL [95% CI: -165, 93]).

Study 3: 24-week, randomized, double-blind, parallel-group study evaluating dose-response.

1. Statistically significant improvements in trough FEV₁ compared with placebo for all doses of FF (50, 100, and 200 mcg).

2. The dose-ordering response was observed across all doses for trough FEV₁.

3. The 100 mcg and 200 mcg doses of FF showed a clear reduction in the risk of serious asthma flare-ups compared to a placebo.

Pediatric Studies

Study 4: 12-week, randomized, double-blind, placebo-controlled study in 593 children aged 5-11 years.

1. FF 50 mcg once daily demonstrated significant improvement in trough FEV₁ compared to placebo (difference: 111 mL [95% CI: 51, 172]; P<0.001).

2. The safety profile in children is the same as that observed in adults and teens.

3. Growth velocity was not significantly different between the FF 50 mcg and placebo groups over the 12-week treatment period.

Long-Term Safety Study: 52-week, randomized, double-blind study of FF 50 mcg vs. FF 100 mcg in pediatric patients.

1. No clinically significant differences in safety parameters between doses. The mean change in growth velocity was -0.4 cm/year in the FF 50 mcg group compared with baseline.

Use in Specific Populations

Pregnancy

Pregnancy category C (under the former FDA classification system).

There is not much data from clinical studies or real-world use yet. This medication should only be used during pregnancy if the potential benefits outweigh the possible risks to the baby.

In Animal Studies

1. When the drug was given at higher doses than what people would normally get, some effects were seen in the developing babies, like lower birth weights, changes in development, and a few malformations.

2. These effects occurred primarily at maternally toxic doses.

3. Studies suggest that no teratogenic effects were seen in rats after inhalation doses up to four times the MRHD (on a mcg/m² basis).

There are no well-controlled studies in pregnant women. Monitor infants born to mothers who received corticosteroids during pregnancy for hypoadrenalism.

Breastfeeding

It is not known whether Fluticasone furoate is excreted in human milk. Other inhaled steroids have been found in breast milk, so it's important to weigh the benefits of breastfeeding against the mother's need to use Arnuity Ellipta.

When deciding whether to continue breastfeeding while using this medication, it’s important to consider the following:

1. The risk of exposure to the infant (likely to be minimal with inhaled administration).

2. The benefits of therapy to the mother.

3. The benefits of breastfeeding to the infant.

Pediatric Use

This medication has been proven to be safe and effective for children aged 5 and older.

1. The efficacy in patients 5-11 years was evaluated in a 12-week clinical trial comparing FF 50 mcg, FF 100 mcg, and placebo in 593 pediatric patients.

2. FF 50 mcg significantly improved lung function versus placebo.

3. The efficacy of FF 100 mcg was not significantly different from FF 50 mcg.

Not approved for use in children younger than 5 years. The safety and effectiveness of this medication haven’t been confirmed for children younger than 5.

Effects of Arnuity Ellipta on the growth of children:

1. Oral inhaled corticosteroids can cause a decrease in growth rate when given to children.

2. Growth should be regularly monitored in children who are on FF.

3. The long-term consequences of this decline in growth rate related to orally inhaled corticosteroids, including the effect on ultimate adult height, are not known.

Geriatric Use

Clinical studies included 130 subjects aged 65 and older and 36 subjects aged 75 and older. There were no significant differences between older and younger patients in how well the drug worked or how safe it was. However, greater sensitivity in some older individuals cannot be ruled out.

Hepatic Impairment

If a person has a liver impairment, the body might metabolize Fluticasone furoate differently, maybe resulting in higher blood levels and an increased risk of side effects.

1. Moderate hepatic impairment (Child-Pugh Class B): Increased AUC(0-∞) by up to 3-fold

2. No data available for severe hepatic impairment

Individuals with severe to moderate liver disease should be watched closely for possible side effects of the corticosteroid.

Renal Impairment

People with kidney problems don’t need to change their dose of this medication. People with kidney problems (including those with low kidney function) didn’t show higher levels of the medication in their system compared to healthy individuals.

Key Takeaway From iCliniq

Arnuity Ellipta can make managing asthma simpler with just one dose a day, helping reduce inflammation and improve breathing over time. While it’s easy to use, it’s important to follow the right steps and be aware of any side effects. At iCliniq, we’re here for you! If you have questions or want more advice on using Arnuity Ellipta, feel free to reach out to us. We’re always happy to help!