AUDIENCE: Pharmacy, Pulmonology, Internal Medicine, Family Practice
ISSUE: FDA's most prominent warning, the Boxed Warning, about asthma-related death has been removed from the drug labels of medicines that contain both an ICS and LABA. A FDA review of four large clinical safety trials shows that treating asthma with long-acting beta agonists (LABAs) in combination with inhaled corticosteroids (ICS) does not result in significantly more serious asthma-related side effects than treatment with ICS alone. A description of the four trials is now also included in the Warnings and Precautions section of the drug labels. These trials showed that LABAs, when used with ICS, did not significantly increase the risk of asthma-related hospitalizations, the need to insert a breathing tube known as intubation, or asthma-related deaths, compared to ICS alone.
BACKGROUND: In 2011, FDA required the drug companies manufacturing fixed-dose combination drugs containing an ICS and LABA (GlaxoSmithKline, Merck, Astra Zeneca) to conduct several large, 26-week, randomized, double-blind, active-controlled clinical safety trials to evaluate the risk of serious asthma-related events when long-acting beta agonists (LABAs) were used in fixed-dose combination with an inhaled corticosteroid (ICS) compared to ICS alone in patients with asthma. FDA reviewed the results of four trials involving 41,297 patients. The results demonstrate that the use of ICS/LABA in fixed-dose combination does not result in a significant increase in the risk of serious asthma-related events compared to ICS alone. The results of subgroup analyses for gender, adolescents 12-18 years, and African Americans are consistent with the primary endpoint results.
The four trials also assessed efficacy of the ICS/LABA products. The primary efficacy endpoint was asthma exacerbation, defined as a deterioration of asthma requiring the use of systemic corticosteroids for at least 3 days, or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. The results showed that the ICS/LABA combination reduced asthma exacerbations compared to ICS alone, noting that the majority of these exacerbations were those that required at least 3 days of systemic corticosteroids. This efficacy information has been added to the Clinical Studies section of the ICS/LABA drug labels.
RECOMMENDATION: Health care professionals should refer to the most recently approved drug labels for recommendations on using ICS/LABA medicines (see links in Table 1 of the Drug Safety Communication, available at: http://bit.ly/2kC3Kc4,). Patients and parents/caregivers should talk to your health care professional if you have any questions or concerns. Do not stop taking your asthma medicines without first talking to your health care professional. Also read the patient information leaflet that comes with every prescription.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
In a large clinical study, more people who used an asthma medication similar to vilanterol experienced severe episodes of asthma that had to be treated in a hospital or caused death than patients who did not use the medication. Use of vilanterol inhalation may increase the risk of serious asthma problems or death in people who have asthma. Fluticasone and vilanterol inhalation has not been approved by the Food and Drug Administration (FDA) for the treatment of asthma. There is not enough information to tell whether inhaling fluticasone and vilanterol increases the risk of death in people who have chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways, which includes chronic bronchitis and emphysema).
Talk to your doctor about the risks of using this medication.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with fluticasone and vilanterol and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.
Why is this medication prescribed?
The combination of fluticasone and vilanterol is used to control wheezing, shortness of breath, coughing, and chest tightness caused by chronic obstructive pulmonary (COPD; a group of diseases that affect the lungs and airways, that includes chronic bronchitis and emphysema). Fluticasone is in a class of medications called steroids. It works by reducing swelling in the airways. Vilanterol is in a class of medications called long-acting beta-agonists (LABAs). It works by relaxing and opening air passages in the lungs, making it easier to breathe.
How should this medicine be used?
The combination of fluticasone and vilanterol comes as a powder to inhale by mouth using a special inhaler. It is usually inhaled once a day. Inhale fluticasone and vilanterol at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part that you do not understand. Do not use more or less of it or use it more often than prescribed by your doctor.
Do not use fluticasone and vilanterol inhalation during a sudden COPD attack. Your doctor will prescribe a short acting (rescue) inhaler to use during COPD attacks.
Fluticasone and vilanterol inhalation controls COPD but does not cure it. Continue to use fluticasone and vilanterol even if you feel well. Do not stop using fluticasone and vilanterol without talking to your doctor. If you stop using fluticasone and vilanterol inhalation, your symptoms may return.
Before you use fluticasone and vilanterol inhalation for the first time, ask your doctor, pharmacist, or respiratory therapist to show you how to use the inhaler. Practice using your inhaler while he or she watches.
To use the inhaler, follow these steps:
- If you will be using a new inhaler for the first time, remove it from the box and the foil wrapper. Fill in the "Tray opened" and "Discard" blanks on the inhaler label with the date that you opened the pouch and the date 6 weeks later when you must replace the inhaler.
- When you are ready to inhale your dose, slide the cover down to expose the mouthpiece until it clicks. If you open and close the inhaler without using your dose, you will waste the medication.
- The counter will count down by 1 each time you open the cover. If the counter does not count down, your inhaler will not provide the medicine. If your inhaler does not count down, call your pharmacist or doctor.
- Hold the inhaler away from your mouth and breathe out as far as you comfortably can. Do not breathe out into the mouthpiece.
- Put the mouthpiece between your lips, and close your lips firmly around it. Take a long, steady, deep breath in through your mouth. Do not breathe in through your nose. Be careful 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 you comfortably can. Breathe out slowly.
- You may or may not taste or feel the medicine released by the inhaler. Even if you do not, do not inhale another dose. If you are not sure you are getting your dose of fluticasone and vilanterol, call your doctor or pharmacist.
- You may clean the mouthpiece with a dry tissue, if needed. Slide the cover up over the mouthpiece as far as it will go to close the inhaler.
- Rinse your mouth with water, but do not swallow.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before using fluticasone and vilanterol,
- tell your doctor and pharmacist if you are allergic to fluticasone (Flonase, Flovent), vilanterol, any other medications, milk protein, or any of the ingredients in fluticasone and vilanterol inhalation. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- tell your doctor if you use another LABA such as formoterol (Foradil, in Symbicort) or salmeterol (in Advair, Serevent). These medications should not be used with fluticasone and vilanterol inhalation. Your doctor will tell you which medication you should use and which medication you should stop using.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Be sure to mention any of the following: antifungals such as itraconazole (Sporanox), ketoconazole (Nizoral), and voriconazole (Vfend); beta-blockers such as atenolol (Tenormin), labetalol (Normodyne), metoprolol (Lopressor, Toprol XL), nadolol (Corgard), and propranolol (Inderal); clarithromycin (Biaxin); conivaptan (Vaprisol); diuretics ('water pills'); HIV protease inhibitors such as indinavir (Crixivan), lopinavir (in Kaletra), nelfinavir (Viracept), ritonavir (Norvir), and saquinavir (Invirase); other medications for COPD; metronidazole (Flagyl); nefazodone (Serzone); telithromycin (Ketek); and troleandomycin (TAO) Also tell your doctor and pharmacist if you are taking the following medications or have stopped taking them during the past 2 weeks: antidepressants such as amitriptyline (Elavil), amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Adapin, Sinequan), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); and monoamine oxidase (MAO) inhibitors, including isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl), and tranylcypromine (Parnate). Many other medications may also interact with fluticasone and vilanterol, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor if you or anyone in your family has or has ever had osteoporosis (a condition in which the bones become weak and fragile), and if you have or have ever had high blood pressure, irregular heartbeat, seizures, hyperthyroidism (condition in which there is too much thyroid hormone in the body), diabetes, tuberculosis (TB), glaucoma (an eye disease), cataracts (clouding of the lens of the eyes), any condition that affects your immune system, or heart or liver disease. Also tell your doctor if you have a herpes eye infection, pneumonia, or any other type of infection.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using fluticasone and vilanterol, call your doctor.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are using fluticasone and vilanterol.
- tell your doctor if you have never had chickenpox or measles and have not been vaccinated against these infections. Stay away from people who are sick, especially people who have chickenpox or measles. If you are exposed to these infections or if you develop symptoms of these infections, call your doctor immediately. You may need to get a vaccine (shot) to protect you from these infections.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do if I forget a dose?
Inhale the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not use more than one dose in a day and do not inhale a double dose to make up for a missed one.
What side effects can this medication cause?
Fluticasone and vilanterol may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- shaking of a part of your body that you cannot control
- joint pain
- runny nose, sore throat
Some side effects can be serious. If you experience any of the following side effects, call your doctor immediately or get emergency medical treatment:
- swelling of the face, throat, tongue
- pounding fast, or irregular heartbeat
- chest pain
- coughing, wheezing, or chest tightness that begins after you inhale fluticasone and vilanterol.
- blurred vision
- white patches in the mouth or throat
- fever, chills, or other signs of infection
- cough, difficulty breathing, or change in the color of sputum (the mucus you may cough up)
Fluticasone and vilanterol may increase the risk that you will develop glaucoma, cataracts, or osteoporosis. You will probably need to have regular eye exams and bone tests during your treatment with fluticasone and vilanterol.
Fluticasone and vilanterol may cause other side effects. Call your doctor if you have any unusual problems while using this medication.
What should I know about storage and disposal of this medication?
Keep this medication in the foil tray it came in, tightly closed, and out of reach of children. Store it at room temperature and away from sunlight, excess heat and moisture (not in the bathroom). Dispose of the inhaler 6 weeks after you remove it from the foil overwrap or after every blister has been used (when the dose indicator reads 0), whichever comes first.
Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.
It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org
In case of emergency/overdose
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Symptoms of overdose may include the following:
- chest pain
- shortness of breath
- fast, pounding, or irregular heartbeat
- shaking of a part of your body that you cannot control
- muscle cramps or weakness
- dry mouth
- excessive tiredness
- difficulty falling asleep or staying asleep
What other information should I know?
Keep all appointments with your doctor.
Do not let anyone else use your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
Brand names of combination products
- Breo Ellipta® (containing Fluticasone, Vilanterol)