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 patients who used an asthma medication similar to formoterol experienced severe episodes of asthma that had to be treated in a hospital or caused death than patients who did not use the medication. If you have asthma, use of formoterol may increase the chance that you will experience serious or fatal asthma problems.
Formoterol nebulizer solution (Performist) is used to treat chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema). It should not be prescribed to treat asthma. If you have COPD and asthma, formoterol nebulizer solution should not be prescribed to treat your COPD unless you are taking another medication to control your asthma.
Your doctor will only prescribe formoterol inhalation powder (Foradil) to treat asthma that is so severe that two medications are needed to control it. You should never use formoterol alone to treat asthma; you must always use it along with another asthma controller medication. Children and teenagers who need to be treated for asthma with formoterol will probably be treated with a product that combines formoterol and another medication in a single inhaler to make it easier for them to use both medications as prescribed.
Because of the risks of using formoterol inhalation powder to treat asthma, you should only use this medication as long as it is needed to bring your asthma symptoms under control. Once your asthma is controlled, your doctor will probably tell you to stop using formoterol inhalation powder but continue using the other asthma medication.
Do not use formoterol inhalation powder or nebulizer solution if you have asthma that is quickly getting worse. Tell your doctor if you have had many severe asthma attacks or if you have ever been hospitalized because of asthma symptoms. If you have any of the following signs of worsening asthma, call your doctor immediately:
- your short-acting inhaler (inhaled medication such as albuterol [Proventil, Ventolin] that is used to treat sudden attacks of asthma symptoms) does not work as well as it did in the past
- you need to use more puffs than usual of your short-acting inhaler or use it more often
- you need to use four or more puffs per day of your short-acting inhaler for 2 or more days in a row
- you use more than one canister (200 inhalations) of your short-acting inhaler during an 8-week period
- your peak-flow meter (home device used to test breathing) shows your breathing is worsening
- you need to go to the emergency room for asthma treatment
- your symptoms do not improve after you use formoterol inhalation powder regularly for 1 week or your symptoms get worse at any time during your treatment
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 formoterol 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?
Formoterol inhalation powder (Foradil) and nebulizer solution (Perforomist) are used to treat wheezing, shortness of breath, and breathing difficulties caused by chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema) in adults. Formoterol inhalation powder is also used with another medication to treat asthma and to prevent breathing difficulties during exercise in adults and children 5 years of age and older. Formoterol 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?
Formoterol inhalation comes as a powder-filled capsule to inhale by mouth using a special inhaler and as a solution (liquid) to inhale by mouth using a nebulizer(machine that turns medication into a mist that can be inhaled). If you are using the inhalation powder to treat asthma or COPD or the nebulizer solution to treat COPD, you will probably inhale it twice a day in the morning and the evening. Inhale your next dose of formoterol inhalation powder or nebulizer solution 12 hours after you inhaled your last dose and try to inhale it at about the same times every day. If you are using formoterol inhalation powder to prevent breathing difficulties during exercise, you will probably inhale it at least 15 minutes before exercise, but not more often than once in 12 hours. If you are using formoterol inhalation powder twice a day on a regular basis, do not use an additional dose before exercising. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use formoterol exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor.
Do not swallow formoterol capsules or nebulizer solution.
If you have asthma, talk to your doctor about how you should take your other oral or inhaled medications for asthma during your treatment with formoterol inhalation. If you were taking a corticosteroid (a type of medication used to prevent airway swelling in patients with asthma), your doctor will probably tell you to continue taking it just as you did before you began using formoterol inhalation. If you were using a short-acting beta agonist inhaler such as albuterol (Proventil, Ventolin) on a regular basis, your doctor will probably tell you to stop using it regularly, but to continue to use it to treat sudden attacks of asthma symptoms. Follow these directions carefully. Do not change the way you use any of your medications without talking to your doctor.
Formoterol inhalation helps to prevent asthma or COPD attacks but will not stop an attack that has already started. Do not use formoterol during an attack of asthma or COPD. Your doctor will prescribe a short-acting inhaler to use during attacks.
Formoterol inhalation should not be used to treat COPD that is quickly getting worse. Call your doctor or get emergency medical help if your breathing problems worsen, if you have to use your short-acting inhaler to treat attacks of COPD more often, or if your short-acting inhaler does not relieve your symptoms.
Formoterol inhalation may help control your symptoms but will not cure your condition. Do not stop using formoterol without talking to your doctor. If you suddenly stop using formoterol, your symptoms may worsen.
Before you use formoterol inhalation for the first time, read the written instructions that come with the inhaler or nebulizer. Ask your doctor, pharmacist, or respiratory therapist to show you how to use it. Practice using the inhaler or nebulizer while he or she watches.
To use the inhaler, follow these steps:
- Before you use a new inhaler for the first time, find the sticker on the box that says ''Use by'' and has been marked with a date by your pharmacist. Remove this sticker from the box and attach it to the cover of your inhaler to remind you to stop using the inhaler by this date. If the sticker on your box is blank, fill in the expiration date that is stamped on the box or the date that is 4 months after you purchased the inhaler, whichever comes sooner.
- Open the foil pouch containing a blister card of formoterol and set it aside. Do not remove a capsule until you are ready to inhale your dose.
- Pull off the inhaler cover and twist the mouthpiece open in the direction shown by the arrow on the mouthpiece. Push the buttons on each side to be sure you can see four pins in the capsule well of the inhaler.
- Separate one blister from the blister card by tearing along the dotted lines. Remove the capsule from the blister by peeling back the paper backing and pushing the capsule through the foil.
- Place the capsule in the chamber. Do not place it directly into the mouthpiece. Twist to close.
- Hold the inhaler upright and press in both side buttons at the same time. Do not press the buttons more than once. You will hear a click as the capsule is punctured. Release the buttons. If the buttons do not pop out, pull the wings of the buttons to release them.
- Exhale (breathe out) as completely as possible but not into the mouthpiece.
- Turn the inhaler on its side so that the blue buttons are on the left and right (not the top and bottom) of the inhaler. Hold the inhaler so that it is level.
- Tilt your head back slightly, place the mouthpiece in your mouth, and close your lips. Breathe in quickly and deeply. As the medicine is released from the capsule, you'll get a sweet taste and hear a whirring noise. (If you don't, the capsule may be stuck. Tap on the side of the inhaler to loosen the capsule and repeat steps 7 to 9. Do not press the side buttons again.)
- Remove the inhaler from your mouth and hold your breath for as long as you comfortably can. Then exhale.
- Open the inhaler to see if there is any powder left in the capsule. If there is, repeat steps 7 to 10.
- Once the capsule is empty, remove it and dispose of it. Do not leave it in the chamber. Close the mouthpiece and replace the cover.
The inhaler is made to pierce the capsule so that the powder can be released. However, it is possible that the capsule may break into small pieces inside the inhaler. If this happens, a screen in the inhaler should stop the pieces of capsule from reaching your mouth as you inhale the medication. Very tiny pieces of the capsule may reach your mouth or throat, but this will not hurt you. The capsule is less likely to break if you are careful to store the capsules properly, to keep the capsules in the foil package until you are ready to use them, and to press the buttons on the inhaler only once.
Keep formoterol capsules dry. Avoid exposing the capsules to moisture, and handle them with dry hands.
Do not use the dry powder inhaler with a spacer. Do not exhale into the device. Keep the inhaler dry; do not wash it. Do not take the inhaler apart. Always use the new inhaler that comes with a refill of your medication. Do not use the inhaler to inhale any other type of capsules.
To inhale the solution using a nebulizer, follow these steps:
- Remove one vial of formoterol inhalation solution from the foil pouch.
- Look at the liquid in the vial. It should be clear and colorless. Do not use the vial if the liquid is cloudy or discolored.
- Twist off the top of the vial and squeeze all of the liquid into the nebulizer reservoir. Do not mix other medications with formoterol in the reservoir.
- Connect the nebulizer reservoir to the mouthpiece or face mask.
- Connect the nebulizer to the compressor.
- Place the mouthpiece in your mouth or put on the face mask. Sit in an upright, comfortable position and turn on the compressor.
- Breathe in calmly, deeply, and evenly for about 9 minutes until mist stops forming in the nebulizer chamber.
- Dispose of the empty vial and its top safely, so that they are out of the reach of children.
Clean your nebulizer regularly. Follow the manufacturer's directions carefully and ask your doctor or pharmacist if you have any questions about cleaning your nebulizer.
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 formoterol inhalation,
- tell your doctor and pharmacist if you are allergic to formoterol, any other medications, or any of the ingredients in formoterol inhalation powder or nebulizer solution. If you will be using the inhalation powder, also tell your doctor if you are allergic to milk proteins. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- tell your doctor if you use another LABA such as arformoterol (Brovana), fluticasone and salmeterol combination (Advair) or salmeterol (Serevent). These medications should not be used with formoterol. Your doctor will tell you which medication you should use and which medication you should stop using.
- tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: certain antibiotics including azithromycin (Zithromax), clarithromycin (Biaxin), erythromycin (E.E.S, E-Mycin, Erythrocin), and telithromycin (Ketek); aminophylline (Truphylline); amiodarone (Cordarone, Pacerone); antidepressants such as amitriptyline, amoxapine, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); beta blockers such as atenolol (Tenormin), labetalol metoprolol (Lopressor, Toprol XL), nadolol (Corgard), propranolol (Inderal), and sotalol (Betapace, Sorine); cisapride (Propulsid) (not available in the United States); clonidine (Catapres); diet pills; disopyramide (Norpace); diuretics ('water pills'); dofetilide (Tikosyn); dyphylline (Lufyllin); guanabenz; medications for colds; monoamine oxidase (MAO) inhibitors, including isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate); midodrine (Orvaten); moxifloxacin (Avelox); oral steroids such as dexamethasone (Decadron, Dexone), methylprednisolone (Medrol), and prednisone (Deltasone); pimozide (Orap); procainamide (Procanbid, Pronestyl); quinidine (in Nuedexta); sparfloxacin (Zagam); theophylline (Theo-Chron, Theolair); and thioridazine (Mellaril). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor if you have or have ever had an irregular heartbeat; high blood pressure; seizures; diabetes; an aneurysm (swelling of an artery that may burst and cause serious health problems or sudden death); pheochromocytoma (a tumor that may cause changes in blood pressure); or heart, liver, or thyroid disease.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are using formoterol inhalation.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using formoterol, call your doctor.
What special dietary instructions should I follow?
Talk to your doctor about drinking beverages that contain caffeine while using this medicine.
What should I do if I forget a dose?
Skip the missed dose and continue your regular dosing schedule. Do not use a double dose to make up for a missed one.
What side effects can this medication cause?
Formoterol may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- uncontrollable shaking of a part of the body
- dry mouth
- muscle cramps
- back pain
- stomach pain
- extreme tiredness
- difficulty falling asleep or staying asleep
- stuffed or runny nose
- sore throat
Some side effects can be serious. If you experience any of the following symptoms, stop using formoterol inhalation and call your doctor immediately or get emergency medical treatment:
- coughing, wheezing, or chest tightness that begins soon after you inhale formoterol
- swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
- difficulty swallowing or breathing
- fast, pounding, or irregular heartbeat
- chest pain
- muscle tightening or weakness
Formoterol may cause other side effects. Call your doctor if you have any unusual problems while using this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
What should I know about storage and disposal of this medication?
Keep formoterol capsules sealed in their blister cards and keep vials of nebulizer solution sealed in their foil pouches until you are ready to use them. Store the capsules at room temperature and away from excess heat and moisture (not in the bathroom). Keep the nebulizer solution in the refrigerator or store it at room temperature and away from excess heat and moisture for up to 3 months. Keep this medication out of reach of children. If you are using the inhalation powder, dispose of your old inhaler each time you refill your prescription.
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 the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.
Symptoms of overdose may include the following:
- chest pain
- fast, pounding, or irregular heartbeat
- uncontrollable shaking of a part of the body
- muscle cramps
- dry mouth
- excessive tiredness
- difficulty falling asleep or staying asleep
- trouble breathing
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.
- Bevespi Aerosphere® (as a combination product containing Glycopyrrolate, Formoterol)
Brand names of combination products
- Dulera® (containing Formoterol, Mometasone)
- Symbicort® (containing Budesonide, Formoterol)