Advair

Name: Advair

Proper Use of fluticasone and salmeterol

This section provides information on the proper use of a number of products that contain fluticasone and salmeterol. It may not be specific to Advair. Please read with care.

Inhaled fluticasone and salmeterol is used to prevent asthma attacks and to treat chronic obstructive pulmonary disease (COPD). It is not used to relieve an asthma attack that has already started. For relief of an asthma attack that has already started, you should use another medicine. If you do not have another medicine to use for an attack or if you have any questions about this, check with your doctor.

Inhaled fluticasone and salmeterol is used with a special inhaler that comes with patient directions or a Medication Guide. Read the directions carefully before using this medicine. If you do not understand the directions or you are not sure how to use the Diskus® or inhaler, ask your doctor to show you what to do. Also, ask your doctor to check regularly how you use the Diskus® or inhaler to make sure you are using it properly.

Use this medicine only as directed by your doctor. Do not use more of it and do not use it more often than your doctor ordered. Also, do not stop using this medicine without telling your doctor. To do so may increase the chance of side effects.

In order for this medicine to help prevent asthma attacks, it must be used every day in regularly spaced doses, as ordered by your doctor.

Do not stop using this medicine or other asthma medicines that your doctor has prescribed for you unless you have discussed this with your doctor.

When you use the Advair® HFA inhaler for the first time, or if you have not used it for 7 days or longer, or if the inhaler has been dropped, it may not deliver the right amount of medicine with the first puff. Therefore, before using the inhaler, prime it by spraying the medicine four times into the air away from the face, and shaking it well for 5 seconds before each spray. Avoid spraying it in your eyes.

Rinsing your mouth with water after each dose may help prevent hoarseness, throat irritation, and infection in the mouth. However, do not swallow the water after rinsing.

To use the Diskus®:

  • Open the foil pouch containing the Diskus®.
  • To open the Diskus®, push the thumb grip away from you as far as it will go. You will hear a click and feel a snap. When open, the mouthpiece will appear.
  • Slide the mouthpiece lever away from you as far as it will go until it clicks. The Diskus® is now ready to use. If you close the Diskus® or push the lever again, you will lose medicine.
  • Turn your head away from the Diskus®, and breathe out to the end of a normal breath. Do not breathe into the Diskus®.
  • Holding the Diskus® level, put the mouthpiece between your lips and teeth, and close your lips around the mouthpiece. Do not bite down on the mouthpiece. Do not block the mouthpiece with your teeth or tongue.
  • Breathe in through your mouth as deeply as you can until you have taken a full deep breath. Do not breathe through your nose.
  • Hold your breath and remove the mouthpiece from your mouth. Continue holding your breath as long as you can up to 10 seconds before breathing out slowly. This gives the medicine time to settle in your airways and lungs.
  • Turn your head away from the Diskus®, and breathe out slowly to the end of a normal breath. Do not breathe into the Diskus®.
  • If your doctor has told you to inhale more than one puff of medicine at each dose, take the second puff following exactly the same steps you used for the first puff.
  • When you are finished, close the Diskus®. Place your thumb on the thumb grip, and slide it back toward you as far as it will go. You will hear it click shut.
  • Keep the Diskus® dry. Do not wash the mouthpiece, or any other part of the Diskus®. You may use a dry cloth to wipe it clean.
  • The Diskus® has a window that shows the number of doses that are left. This tells you when you are getting low on medicine. When the Diskus® has 5 doses left, the numbers from 5 to 0 will show up in red to remind you to refill your prescription.

To use the Advair® HFA inhaler:

  • Take the inhaler out of the pouch before you use it for the first time.
  • Do not use the inhaler for this medicine with any other medicine.
  • Remove the cap and look at the mouthpiece to make sure it is clean.
  • Prime the inhaler before use by shaking the inhaler well and then releasing 4 test sprays.
  • To inhale this medicine, breathe out fully, trying to get as much air out of the lungs as possible. Put the mouthpiece fully into your mouth and close your lips around it. Do not block the mouthpiece with your teeth or tongue.
  • While pressing down firmly and fully on the purple top of the inhaler, breathe in through your mouth as deeply as you can until you have taken a full deep breath.
  • Wait for 30 seconds and repeat these steps for the next puff, starting with shaking the inhaler.
  • Gargle and rinse your mouth with water after each dose; this will help prevent hoarseness, throat irritation, and infection in the mouth. Do not swallow the water after rinsing.
  • Replace the mouthpiece cover after using the medicine.
  • The inhaler has a window that shows the number of doses remaining. This tells you when you are getting low on medicine. The doses counting down from 20 to 0 will show up in red to remind you to refill your prescription. Throw away the inhaler when the count is 000. You may not receive the right amount of medicine.

To use the Airduo™ Respiclick®:

  • Take the inhaler out of the pouch before you use it for the first time.
  • Do not use the inhaler for this medicine with any other medicine.
  • This medicine does not require priming. Do not use it with a spacer or volume holding chamber.
  • Hold the inhaler upright and open the yellow cap all the way until it clicks. Do not open the yellow cap until you are ready to take a dose of this medicine.
  • To inhale this medicine, breathe out fully, trying to get as much air out of the lungs as possible. Put the mouthpiece fully into your mouth and close your lips around it. Do not block the mouthpiece with your teeth or tongue. Do not block the vent above the mouthpiece with your lips or fingers.
  • Breathe in through your mouth quickly and deeply as you can until you have taken a full deep breath. Hold your breath for about 10 seconds.
  • Close the yellow cap after each inhalation. Rinse your mouth with water without swallowing after each inhalation.
  • Keep the inhaler dry and clean at all times. Gently wipe the mouthpiece with a dry cloth or tissue as needed.
  • The inhaler has a window that shows the number of doses remaining. This tells you when you are getting low on medicine. The doses counting down from 20 to 0 will show up in red to remind you to refill your prescription. Throw away the inhaler when the dose counter displays 0, 30 days after opening the pouch.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For inhalation dosage form (aerosol liquid):
    • For preventing an asthma attack:
      • Adults and children 12 years of age and older—2 puffs in the morning and another 2 puffs in the evening. The doses should be at least 12 hours apart.
      • Children younger than 12 years of age—Use and dose must be determined by your child's doctor.
  • For inhalation dosage form (aerosol powder):
    • Advair® Diskus®:
      • For preventing an asthma attack:
        • Adults and children 4 years of age and older—1 inhalation 2 times per day (morning and evening). The doses should be at least 12 hours apart.
        • Children younger than 4 years of age—Use and dose must be determined by your doctor.
      • For maintenance treatment of COPD:
        • Adults—1 inhalation (250/50) 2 times per day (morning and evening). The doses should be at least 12 hours apart.
        • Children—Use and dose must be determined by your doctor.
    • Airduo™ Respiclick®:
      • For treatment of asthma:
        • Adults and children 12 years of age and older—1 inhalation 2 times per day (morning and evening). The doses should be at least 12 hours apart. Do not use it more than 2 times every 24 hours.
        • Children younger than 12 years of age—Use and dose must be determined by your child's doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss a dose of Airduo™ Respiclick®, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the canister at room temperature, away from heat and direct light. Do not freeze. Do not keep this medicine inside a car where it could be exposed to extreme heat or cold. Do not poke holes in the canister or throw it into a fire, even if the canister is empty.

Keep the medicine in the foil pouch until you are ready to use it. Store at room temperature, away from heat and direct light. Do not freeze.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Advair Dosage and Administration

Advair HFA should be administered as 2 inhalations twice daily by the orally inhaled route only. After inhalation, the patient should rinse his/her mouth with water without swallowing to help reduce the risk of oropharyngeal candidiasis.

More frequent administration or a greater number of inhalations (more than 2 inhalations twice daily) of the prescribed strength of Advair HFA is not recommended as some patients are more likely to experience adverse effects with higher doses of salmeterol. Patients using Advair HFA should not use additional LABA for any reason. [See Warnings and Precautions (5.3, 5.12).]

If asthma symptoms arise in the period between doses, an inhaled, short-acting beta2-agonist should be taken for immediate relief.

For patients aged 12 years and older, the dosage is 2 inhalations twice daily, approximately 12 hours apart.

The recommended starting dosages for Advair HFA for patients aged 12 years and older are based upon patients’ asthma severity.

The maximum recommended dosage is 2 inhalations of Advair HFA 230/21 twice daily.

Improvement in asthma control following inhaled administration of Advair HFA can occur within 30 minutes of beginning treatment, although maximum benefit may not be achieved for 1 week or longer after starting treatment. Individual patients will experience a variable time to onset and degree of symptom relief.

For patients who do not respond adequately to the starting dosage after 2 weeks of therapy, replacing the current strength of Advair HFA with a higher strength may provide additional improvement in asthma control.

If a previously effective dosage regimen fails to provide adequate improvement in asthma control, the therapeutic regimen should be reevaluated and additional therapeutic options (e.g., replacing the current strength of Advair HFA with a higher strength, adding additional inhaled corticosteroid, initiating oral corticosteroids) should be considered.

Prime Advair HFA before using for the first time by releasing 4 sprays into the air away from the face, shaking well for 5 seconds before each spray. In cases where the inhaler has not been used for more than 4 weeks or when it has been dropped, prime the inhaler again by releasing 2 sprays into the air away from the face, shaking well for 5 seconds before each spray.

Drug Interactions

Advair HFA has been used concomitantly with other drugs, including short-acting beta2-agonists, methylxanthines, and intranasal corticosteroids, commonly used in patients with asthma without adverse drug reactions [see Clinical Pharmacology (12.2)]. No formal drug interaction trials have been performed with Advair HFA.

Inhibitors of Cytochrome P450 3A4

Fluticasone propionate and salmeterol, the individual components of Advair HFA, are substrates of CYP3A4. The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with Advair HFA is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur.

Ritonavir

Fluticasone Propionate: A drug interaction trial with fluticasone propionate aqueous nasal spray in healthy subjects has shown that ritonavir (a strong CYP3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations [see Clinical Pharmacology (12.3)]. During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression.

Ketoconazole

Fluticasone Propionate: Coadministration of orally inhaled fluticasone propionate (1,000 mcg) and ketoconazole (200 mg once daily) resulted in a 1.9-fold increase in plasma fluticasone propionate exposure and a 45% decrease in plasma cortisol area under the curve (AUC), but had no effect on urinary excretion of cortisol.

Salmeterol: In a drug interaction trial in 20 healthy subjects, coadministration of inhaled salmeterol (50 mcg twice daily) and oral ketoconazole (400 mg once daily) for 7 days resulted in greater systemic exposure to salmeterol (AUC increased 16-fold and Cmax increased 1.4-fold). Three (3) subjects were withdrawn due to beta2-agonist side effects (2 with prolonged QTc and 1 with palpitations and sinus tachycardia). Although there was no statistical effect on the mean QTc, coadministration of salmeterol and ketoconazole was associated with more frequent increases in QTc duration compared with salmeterol and placebo administration.

Monoamine Oxidase Inhibitors and Tricyclic Antidepressants

Advair HFA should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, because the action of salmeterol, a component of Advair HFA, on the vascular system may be potentiated by these agents.

Beta-adrenergic Receptor Blocking Agents

Beta-blockers not only block the pulmonary effect of beta-agonists, such as salmeterol, a component of Advair HFA, but may also produce severe bronchospasm in patients with asthma. Therefore, patients with asthma should not normally be treated with beta-blockers. However, under certain circumstances, there may be no acceptable alternatives to the use of beta-adrenergic blocking agents for these patients; cardioselective beta-blockers could be considered, although they should be administered with caution.

Non–Potassium-Sparing Diuretics

The ECG changes and/or hypokalemia that may result from the administration of non–potassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, such as salmeterol, a component of Advair HFA, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the coadministration of Advair HFA with non–potassium-sparing diuretics.

Before taking this medicine

You should not use Advair if you are allergic to fluticasone or salmeterol (Serevent), or:

  • if you have a severe allergy to milk proteins; or

  • if you are having an asthma attack or severe COPD symptoms.

To make sure this medicine is safe for you, tell your doctor if you have:

  • a food or drug allergy;

  • heart disease or high blood pressure;

  • epilepsy or other seizure disorder;

  • any type of infection;

  • a weak immune system;

  • diabetes;

  • glaucoma;

  • tuberculosis;

  • osteoporosis;

  • a thyroid disorder; or

  • liver disease.

Long-term use of steroids may lead to bone loss (osteoporosis), especially if you smoke, if you do not exercise, if you do not get enough vitamin D or calcium in your diet, or if you have a family history of osteoporosis.

It is not known whether Advair is harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using Advair.

It is not known whether this medicine passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Fluticasone can affect growth in children. Talk with your doctor if you think your child is not growing at a normal rate while using this medication.

Advair is not approved for use by anyone younger than 4 years old.

Advair side effects

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

Call your doctor at once if you have:

  • wheezing, choking, or other breathing problems after using this medicine;

  • chest pain, fast or uneven heart beats, restless feeling, tremors;

  • severe headache, pounding in your neck or ears, nosebleed;

  • fever, chills, swollen glands, mouth sores, skin sores, flu symptoms, cough with yellow or green mucus;

  • blurred vision, tunnel vision, eye pain, or seeing halos around lights;

  • high blood sugar - increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin;

  • low potassium - confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling; or

  • signs of a hormonal disorder - worsening tiredness or muscle weakness, feeling light-headed, anxiety, feeling irritable, nausea, vomiting, loss of appetite, diarrhea, weight loss, weight gain, slow wound healing.

Common Advair side effects may include:

  • headache, muscle pain, bone pain, back pain;

  • nausea, vomiting;

  • throat irritation, white patches in the mouth or throat;

  • cold symptoms such as stuffy nose, sneezing, sore throat; or

  • ongoing cough, hoarseness or deepened voice.

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.

Fluticasone / salmeterol Breastfeeding Warnings

UK: A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. US: Caution is recommended. AU: The manufacturer makes no recommendation regarding use during lactation. Excreted into human milk: Unknown (fluticasone-salmeterol) Excreted into animal milk: Yes (fluticasone-salmeterol) Comments: The effects in the nursing infant are unknown.

Salmeterol: Plasma levels of salmeterol, after inhaled therapeutic doses, are very low. In rats, salmeterol xinafoate is excreted in the milk. Fluticasone: Subcutaneous administration to lactating rats of tritiated fluticasone propionate resulted in measurable radioactivity in the milk. There are no controlled data on the use of this drug by nursing mothers.

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