Arnuity Ellipta

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• weakness, tired feeling, nausea, vomiting, feeling like you might pass out;
• wheezing, choking, or other breathing problems after using this medicine;
• blurred vision, tunnel vision, eye pain, or seeing halos around lights;
• worsening of your asthma symptoms; or
• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

• cold symptoms such as stuffy nose, sneezing, sore throat, sinus pain;
• low fever, cough, wheezing, chest tightness;
• hoarseness or deepened voice;
• white patches or sores inside your mouth or on your lips;
• headache; or
• nausea, vomiting, upset stomach.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

No human overdosage data have been reported for ARNUITY ELLIPTA. The potential for acute toxic corticosteroid effects following overdosage with ARNUITY ELLIPTA is low. Because of low systemic bioavailability (13.9%) and an absence of acute drug-related systemic findings in clinical trials, overdosage of fluticasone furoate is unlikely to require any treatment other than observation. If used at excessive doses for prolonged periods, systemic effects such as hypercorticism may occur [see WARNINGS AND PRECAUTIONS].

Single- and repeat-dose trials of fluticasone furoate at doses of 50 to 4,000 mcg have been studied in human subjects. Decreases in mean serum cortisol were observed at dosages of 500 mcg or higher given once daily for 14 days.

Use Arnuity Ellipta exactly as prescribed.

• Arnuity Ellipta comes in an inhaler form and is typically used once a day. For best results, use at the same time each day. It may take up to 2 weeks for Arnuity Ellipta to reach its full effectiveness.
• Seek medical attention immediately if your asthma symptoms get worse with time.
• Arnuity Ellipta is not meant to relieve acute asthma attacks and extra doses should not be used for that purpose.

Do not use Arnuity Ellipta unless your healthcare provider has taught you how to use the inhaler and you understand how to use it correctly. Always follow your physician's instructions on use exactly. 

Important Notes

• Each time you fully open the cover of the inhaler (you will hear a clicking sound), a dose is ready to be inhaled. This is shown by a decrease in the number on the 30-dose counter.
• If you open and close the cover without inhaling the medicine, you will lose the dose. The lost dose will be held in the inhaler, but it will no longer be available to be inhaled. It is not possible to accidentally take a double dose or an extra dose in 1 inhalation.
• Do not open the cover of the inhaler until you are ready to use it. To avoid wasting doses after the inhaler is ready, do not close the cover until after you have inhaled the medicine.
• Write the “Tray opened” and “Discard” dates on the inhaler label. The “Discard” date is 6 weeks from the date you open the tray.
• Check the counter. Before the inhaler is used for the first time, the counter should show the number 30 (14 if you have a sample or institutional pack). This is the number of doses in the inhaler. Each time you open the cover, you prepare 1 dose of medicine. The counter counts down by 1 each time you open the cover.
• When you have less than 10 doses remaining in your inhaler, the left half of the counter shows red as a reminder to get a refill. 
• After you have inhaled the last dose, the counter will show “0” and will be empty.

Administration:

1. Slide the cover down to expose the mouthpiece. You should hear a “click.” The counter will count down by 1 number. You do not need to shake this type of inhaler. Your inhaler is now ready to use. If the counter does not count down as you hear the click, the inhaler will not deliver the medicine. Call your healthcare provider or pharmacist if this happens.
2. While holding the inhaler away from your mouth, breathe out (exhale) fully. Do not breathe out into the mouthpiece.
3. Put the mouthpiece between your lips, and close your lips firmly around it. Your lips should fit over the curved shape of the mouthpiece. Take 1 long, steady, deep breath in through your mouth. Do not breathe in through your nose. Do not block the air vent with your fingers. Remove the inhaler from your mouth and hold your breath for about 3 to 4 seconds (or as long as comfortable for you). 
4. Breathe out slowly and gently. You may not taste or feel the medicine, even when you are using the inhaler correctly. Do not take another dose from the inhaler even if you do not feel or taste the medicine.
5. Close the inhaler. You can clean the mouthpiece if needed, using a dry tissue, before you close the cover. Routine cleaning is not required. Slide the cover up and over the mouthpiece as far as it will go.
6. Rinse your mouth. Rinse your mouth with water after you have used the inhaler and spit the water out. Do not swallow the water.

If you miss a dose of Arnuity Ellipta, take it as soon as you remember. Do not take more than one inhalation each day. Take your next dose at your usual time. Do not take two doses at one time.    

Do not stop using Arnuity Ellipta unless told to do so by your healthcare provider because your symptoms might get worse. Your healthcare provider will change your medicines as needed.

Arnuity Ellipta does not relieve sudden symptoms. Always have a rescue inhaler with you to treat sudden symptoms. If you do not have a rescue inhaler, call your healthcare provider to have one prescribed for you.

Call your healthcare provider or get medical care right away if:

• your breathing problems get worse
• you need to use your rescue inhaler more often than usual
• your rescue inhaler does not work as well to relieve your symptoms
• you need to use 4 or more inhalations of your rescue inhaler in 24 hours for 2 or more days in a row
• you use 1 whole canister of your rescue inhaler in 8 weeks
• your peak flow meter results decrease. Your healthcare provider will tell you the numbers that are right for you

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your age

The recommended dose range of Arnuity Ellipta for to control and prevent asthma symptoms in adults and children aged 12 years and older is one inhalation (containing 100 - 200 mcg) once every 24 hours.

Fluticasone is a steroid. It prevents the release of substances in the body that cause inflammation.

Fluticasone inhalation is used to prevent asthma attacks. Fluticasone inhalation will not treat an asthma attack that has already begun. Flovent HFA and Flovent Diskus are sometimes used together with an oral (taken by mouth) steroid medicine.

Flovent brands of fluticasone inhalation are for use in adults and children who are at least 4 years old. The Arnuity Ellipta brand is for adults and children who are at least 12 years old.

Fluticasone may also be used for purposes not listed in this medication guide.

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Fluticasone inhalation is not a rescue medicine. It will not work fast enough to treat an asthma attack. Use only a fast acting inhalation medicine for an asthma attack.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Your dose needs may change if you have surgery, are ill, are under stress, or have recently had an asthma attack. Do not change your medication dose or schedule without your doctor's advice.

Flovent is a liquid form of fluticasone that is used with an inhaler device. This device creates a spray that you inhale through your mouth and into your lungs. Your doctor or pharmacist can show you how to use an inhaler.

Flovent Diskus or Arnuity Ellipta is a powder form of fluticasone that comes with a special inhaler device preloaded with blister packs containing measured doses of fluticasone. The device opens and loads a blister of fluticasone each time you use the inhaler. The disk device is not to be used with a spacer. Follow the patient instructions provided with your medicine.

Do not allow a young child to use fluticasone inhalation without help from an adult.

To reduce the chance of developing a yeast infection in your mouth, rinse with water after using fluticasone inhalation products. Do not swallow. Pay special attention to your dental hygiene. This medicine can cause cavities or tooth discoloration.

If you switched to fluticasone from an oral (taken by mouth) steroid, you should not stop using the steroid suddenly. Follow your doctor's instructions about tapering your steroid dose. You may need to restart the oral steroid medicine if you are under stress or have an asthma attack or other medical emergency. Wear a medical alert tag or carry an ID card stating that you may need an oral steroid in an emergency.

Seek medical attention if you think any of your asthma medications are not working as well as usual. An increased need for medication could be an early sign of a serious asthma attack.

Your doctor will need to check your progress while you are using fluticasone inhalation. Your vision may also need to be checked at regular intervals.

Call your doctor if your symptoms do not improve after 2 weeks of treatment, or if symptoms get worse while using fluticasone inhalation. If you use a peak flow meter at home, call your doctor if your numbers are lower than normal.

You should not stop using fluticasone inhalation suddenly. Stopping suddenly may make your condition worse.

Store at room temperature away from moisture, heat, and light.

Store Flovent Diskus or Arnuity Ellipta in the unopened foil pouch or tray until ready to use. Throw away any unused medicine 6 weeks after opening the foil, or when the inhalations counter shows "0."

Store the Flovent HFA canister with the mouthpiece down. Keep the canister away from open flame or high heat, such as in a car on a hot day. The canister may explode if it gets too hot. Do not puncture or burn an empty inhaler canister.

Avoid being near people who are sick or have infections. Call your doctor for preventive treatment if you are exposed to chicken pox or measles. These conditions can be serious or even fatal in people who are using steroid medicine.

• If you have an allergy to fluticasone or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you take any drugs (prescription or OTC, natural products, vitamins) that must not be taken with Arnuity Ellipta, like certain drugs that are used for HIV, infections, or depression. There are many drugs that must not be taken with this medicine. Your doctor or pharmacist can tell you if you are taking a drug that must not be taken with Arnuity Ellipta.
• If you have a milk allergy.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Arnuity Ellipta with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Store at room temperature. Do not freeze.
• Store in foil until ready for use. Be sure you know how long this brand of Arnuity Ellipta is good for after opening the foil. Throw away the inhaler after this amount of time or when the indicator reads zero, whichever comes first.
• Protect from heat.
• Protect from light.
• Protect from cold.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Arnuity Ellipta or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Arnuity Ellipta. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Systemic and local corticosteroid use may result in the following:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of Arnuity Ellipta was evaluated in 10 double-blind, parallel-group, controlled trials (7 with placebo) of 8 to 76 weeks’ duration, which enrolled 6,219 subjects with asthma. Doses of fluticasone furoate studied ranged from 25 to 800 mcg.

Arnuity Ellipta 100 mcg was studied in 1,663 subjects, and Arnuity Ellipta 200 mcg was studied in 608 subjects. Subject ages ranged from 12 to 84 years, 65% were female, and 75% were Caucasian.

In these trials, the proportion of subjects who discontinued study treatment early due to adverse reactions was 2% for subjects treated with both Arnuity Ellipta 100 mcg and Arnuity Ellipta 200 mcg and less than or equal to 1% for placebo-treated subjects. Serious adverse events, whether considered drug-related or not by the investigators, that occurred in more than 1 subject and in a greater percentage of subjects treated with Arnuity Ellipta than placebo included hypertension, abscess, breast cancer, traumatic limb amputation, subarachnoid hemorrhage, and intervertebral disc protrusion; all events occurred at rates less than or equal to 1%.

The incidence of adverse reactions associated with Arnuity Ellipta 100 mcg is shown in Table 1 and is based on one 24-week trial (Trial 1) in adolescent and adult subjects with asthma.

Table 1. Adverse Reactions with Arnuity Ellipta 100 mcg with Greater than or Equal to 3% Incidence and More Common than Placebo (Trial 1, Intent-to-Treat Population)

The incidence of adverse reactions associated with Arnuity Ellipta 200 mcg is shown in Table 2 and is based on one 24-week trial (Trial 3) in adolescent and adult subjects with asthma. This trial did not have a placebo arm.

Table 2. Adverse Reactions with Arnuity Ellipta 200 mcg with Greater than or Equal to 3% Incidence (Trial 3, Safety Population)

Adverse reactions observed in the other trials were consistent with those described in Tables 1 and 2.

Long-Term Safety: Long-term safety data are based on 2 trials in adolescent and adult subjects with asthma. In one 52-week trial, subjects received fluticasone furoate 100 mcg (n = 201) or fluticasone furoate 200 mcg (n = 202) in combination with a LABA. Subjects had a mean age of 39 years (adolescents made up 16% of the population), 63% were female, and 67% were Caucasian. In addition to the events shown in Table 1 and Table 2, adverse events occurring in greater than or equal to 3% of the subjects treated with fluticasone furoate 100 mcg or fluticasone furoate 200 mcg, in combination with a LABA, included pyrexia, extrasystoles, upper abdominal pain, respiratory tract infection, diarrhea, and allergic rhinitis.

In a second 24- to 76-week trial, subjects received fluticasone furoate 100 mcg (n = 1,010). Subjects participating in this trial had a history of one or more asthma exacerbations that required treatment with oral/systemic corticosteroids or emergency department visit or in-patient hospitalization for the treatment of asthma within the previous 12 months. Subjects had a mean age of 42 years (adolescents made up 14% of the population), 67% were female, and 73% were Caucasian. In addition to the events shown in Table 1 and Table 2, adverse events occurring in greater than or equal to 3% of subjects treated with fluticasone furoate 100 mcg for up to 76 weeks included allergic rhinitis, nasal congestion, and arthralgia.

Pregnancy

Teratogenic Effects: Pregnancy Category C. There are no adequate and well-controlled trials with Arnuity Ellipta in pregnant women. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Because animal reproduction studies are not always predictive of human response, Arnuity Ellipta should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women should be advised to contact their physicians if they become pregnant while taking Arnuity Ellipta.

There were no teratogenic effects in rats and rabbits at approximately 4 times and equal to, respectively, the maximum recommended human daily inhalation dose (MRHDID) in adults (on a mcg/m2 basis at maternal inhaled doses up to 91 and 8 mcg/kg/day in rats and rabbits, respectively). There were no effects on perinatal and postnatal development in rats at approximately equal to the MRHDID in adults (on a mcg/m2 basis at maternal doses up to 27 mcg/kg/day).

Nonteratogenic Effects: Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should be carefully monitored.

Labor and Delivery

There are no adequate and well-controlled human trials that have investigated the effects of Arnuity Ellipta during labor and delivery.

Nursing Mothers

It is not known whether fluticasone furoate is excreted in human breast milk. However, other corticosteroids have been detected in human milk. Since there are no data from controlled trials on the use of Arnuity Ellipta by nursing mothers, caution should be exercised when it is administered to a nursing woman.

Pediatric Use

The safety and efficacy in pediatric patients younger than 12 years have not been established.

Effects on Growth: Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to children and adolescents. A reduction of growth velocity in children and adolescents may occur as a result of poorly controlled asthma or from use of corticosteroids, including inhaled corticosteroids. The effects of long-term treatment of children and adolescents with inhaled corticosteroids, including fluticasone furoate, on final adult height are not known.

Controlled clinical trials have shown that inhaled corticosteroids may cause a reduction in growth in children. In these trials, the mean reduction in growth velocity was approximately 1 cm/year (range: 0.3 to 1.8 cm/year) and appears to be related to dose and duration of exposure. This effect has been observed in the absence of laboratory evidence of HPA axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in children than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with orally inhaled corticosteroids, including the impact on final adult height, are unknown. The potential for “catch-up” growth following discontinuation of treatment with orally inhaled corticosteroids has not been adequately studied. The growth of children and adolescents receiving orally inhaled corticosteroids, including Arnuity Ellipta, should be monitored routinely (e.g., via stadiometry). The potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained and the risks associated with alternative therapies. To minimize the systemic effects of orally inhaled corticosteroids, including Arnuity Ellipta, each patient should be titrated to the lowest dose that effectively controls his/her symptoms.

A randomized, double-blind, parallel-group, multicenter, 1-year, placebo-controlled trial evaluated the effect of once-daily treatment with 110 mcg of fluticasone furoate in the nasal spray formulation on growth velocity assessed by stadiometry. The systemic exposure of fluticasone furoate in this trial is lower than that of Arnuity Ellipta. The subjects were 474 prepubescent children (girls aged 5 to 7.5 years and boys aged 5 to 8.5 years). Mean growth velocity over the 52-week treatment period was lower in the subjects receiving fluticasone furoate nasal spray (5.19 cm/year) compared with placebo (5.46 cm/year). The mean reduction in growth velocity was 0.27 cm/year (95% CI: 0.06, 0.48) [see Warnings and Precautions (5.10)].

Geriatric Use

For the 4 confirmatory trials, 71 subjects were aged 65 and older (56 of which were treated with Arnuity Ellipta) and 5 were aged 75 and older (1 of which was treated with Arnuity Ellipta) [see Clinical Studies (14.2)]. Based on available data, no adjustment of the dosage of Arnuity Ellipta in geriatric patients is necessary, but greater sensitivity in some older individuals cannot be ruled out. Clinical trials of Arnuity Ellipta did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Hepatic Impairment

Fluticasone furoate systemic exposure increased by up to 3-fold in subjects with hepatic impairment compared with healthy subjects. Use Arnuity Ellipta with caution in patients with moderate or severe hepatic impairment. Monitor patients for corticosteroid-related side effects [see Clinical Pharmacology (12.3)].

Renal Impairment

There were no significant increases in fluticasone furoate exposure in subjects with severe renal impairment (CrCl less than 30 mL/min) compared with healthy subjects. No dosage adjustment is required in patients with renal impairment [see Clinical Pharmacology (12.3)].

Carcinogenesis, Mutagenesis, Impairment of Fertility

Fluticasone furoate produced no treatment-related increases in the incidence of tumors in 2-year inhalation studies in rats and mice at inhaled doses up to 9 and 19 mcg/kg/day, respectively (less than the MRHDID in adults on a mcg/m2 basis).

Fluticasone furoate did not induce gene mutation in bacteria or chromosomal damage in a mammalian cell mutation test in mouse lymphoma L5178Y cells in vitro. There was also no evidence of genotoxicity in the in vivo micronucleus test in rats.

No evidence of impairment of fertility was observed in male and female rats at inhaled fluticasone furoate doses up to 29 and 91 mcg/kg/day, respectively (approximately equal to and 4 times, respectively, the MRHDID in adults on a mcg/m2 basis).

• Store at room temperature between 68°F and 77°F (20°C and 25°C). Keep in a dry place away from heat and sunlight.
• Store in the unopened foil tray and only open when ready for use.
• Safely throw away in the trash 6 weeks after you open the foil tray or when the counter reads “0”, whichever comes first. Write the date you open the tray on the label on the inhaler.
• Keep all medicines out of the reach of children.