Advair HFA

Name: Advair HFA

Side effects

LABA, such as salmeterol, one of the active ingredients in ADVAIR HFA, increase the risk of asthma-related death. Data from a large placebo-controlled US trial that compared the safety of salmeterol or placebo added to usual asthma therapy showed an increase in asthma-related deaths in subjects receiving salmeterol [see WARNINGS AND PRECAUTIONS]. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients [see WARNINGS AND PRECAUTIONS].

Systemic and local corticosteroid use may result in the following:

  • Candida albicans infection [see WARNINGS AND PRECAUTIONS]
  • Pneumonia in patients with COPD [see WARNINGS AND PRECAUTIONS]
  • Immunosuppression [see WARNINGS AND PRECAUTIONS]
  • Hypercorticism and adrenal suppression [see WARNINGS AND PRECAUTIONS]
  • Reduction in bone mineral density [see WARNINGS AND PRECAUTIONS]
  • Growth effects [see WARNINGS AND PRECAUTIONS]
  • Glaucoma and cataracts [see WARNINGS AND PRECAUTIONS]

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.

Adult and Adolescent Subjects Aged 12 Years and Older

The incidence of adverse reactions associated with ADVAIR HFA in Table 2 is based upon two 12-week, placebo-controlled, US clinical trials (Trials 1 and 3) and 1 active-controlled 12-week US clinical trial (Trial 2). A total of 1,008 adult and adolescent subjects with asthma (556 females and 452 males) previously treated with albuterol alone, salmeterol, or inhaled corticosteroids were treated twice daily with 2 inhalations of ADVAIR HFA 45/21 or ADVAIR HFA 115/21, fluticasone propionate CFC inhalation aerosol (44-or 110-mcg doses), salmeterol CFC inhalation aerosol 21 mcg, or placebo HFA inhalation aerosol. The average duration of exposure was 71 to 81 days in the active treatment groups compared with 51 days in the placebo group.

Table 2: Adverse Reactions with ADVAIR HFA with ≥ 3% Incidence in Adult and Adolescent Subjects with Asthma

Adverse Event ADVAIR HFA Inhalation Aerosol Fluticasone Propionate CFC Inhalation Aerosol Salmeterol CFC Inhalation Aerosol Placebo HFA Inhalation Aerosol
45/21
(n = 187) %
115/21
(n = 94) %
44 mcg
(n = 186) %
110 mcg
(n = 91) %
21 mcg
(n = 274) %
(n = 176) %
Ear, nose, and throat
  Upper respiratory tract infection 16 24 13 15 17 13
  Throat irritation 9 7 12 13 9 7
  Upper respiratory inflammation 4 4 3 7 5 3
  Hoarseness/dysphonia 3 1 2 0 1 0
Lower respiratory
  Viral respiratory infection 3 5 4 5 3 4
Neurology
  Headache 21 15 24 16 20 11
  Dizziness 4 1 1 0 < 1 0
Gastrointestinal
  Nausea and vomiting 5 3 4 2 2 3
  Viral gastrointestinal infection 4 2 2 0 1 2
  Gastrointestinal signs and symptoms 3 2 2 1 1 1
Musculoskeletal
  Musculoskeletal pain 5 7 8 2 4 4
  Muscle pain 4 1 1 1 3 < 1

The incidence of common adverse reactions reported in Trial 4, a 12-week non-US clinical trial in 509 subjects previously treated with inhaled corticosteroids who were treated twice daily with 2 inhalations of ADVAIR HFA 230/21, fluticasone propionate CFC inhalation aerosol 220 mcg, or 1 inhalation of ADVAIR DISKUS 500/50 was similar to the incidences reported in Table 2.

Additional Adverse Reactions

Other adverse reactions not previously listed, whether considered drug-related or not by the investigators, that occurred in the groups receiving ADVAIR HFA with an incidence of 1% to 3% and that occurred at a greater incidence than with placebo include the following: tachycardia, arrhythmias, myocardial infarction, postoperative complications, wounds and lacerations, soft tissue injuries, ear signs and symptoms, rhinorrhea/postnasal drip, epistaxis, nasal congestion/blockage, laryngitis, unspecified oropharyngeal plaques, dryness of nose, weight gain, allergic eye disorders, eye edema and swelling, gastrointestinal discomfort and pain, dental discomfort and pain, candidiasis mouth/throat, hyposalivation, gastrointestinal infections, disorders of hard tissue of teeth, abdominal discomfort and pain, oral abnormalities, arthralgia and articular rheumatism, muscle cramps and spasms, musculoskeletal inflammation, bone and skeletal pain, muscle injuries, sleep disorders, migraines, allergies and allergic reactions, viral infections, bacterial infections, candidiasis unspecified site, congestion, inflammation, bacterial reproductive infections, lower respiratory signs and symptoms, lower respiratory infections, lower respiratory hemorrhage, eczema, dermatitis and dermatosis, urinary infections.

Laboratory Test Abnormalities

In Trial 3, there were more reports of hyperglycemia among adults and adolescents receiving ADVAIR HFA, but this was not seen in Trials 1 and 2.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of any formulation of ADVAIR, fluticasone propionate, and/or salmeterol regardless of indication. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to ADVAIR, fluticasone propionate, and/or salmeterol or a combination of these factors.

Cardiovascular: Arrhythmias (including atrial fibrillation, extrasystoles, supraventricular tachycardia), hypertension, ventricular tachycardia.

Ear, Nose, and Throat: Aphonia, earache, facial and oropharyngeal edema, paranasal sinus pain, rhinitis, throat soreness, tonsillitis.

Endocrine and Metabolic: Cushing's syndrome, Cushingoid features, growth velocity reduction in children/adolescents, hypercorticism, osteoporosis.

Eye: Cataracts, glaucoma.

Gastrointestinal: Dyspepsia, xerostomia.

Hepatobiliary Tract and Pancreas: Abnormal liver function tests.

Immune System: Immediate and delayed hypersensitivity reactions, including rash and rare events of angioedema, bronchospasm, and anaphylaxis.

Infections and Infestations: Esophageal candidiasis.

Musculoskeletal: Back pain, myositis.

Neurology: Paresthesia, restlessness.

Non-Site Specific: Fever, pallor.

Psychiatry: Agitation, aggression, anxiety, depression. Behavioral changes, including hyperactivity and irritability, have been reported very rarely and primarily in children.

Respiratory: Asthma; asthma exacerbation; chest congestion; chest tightness; cough; dyspnea; immediate bronchospasm; influenza; paradoxical bronchospasm; tracheitis; wheezing; pneumonia; reports of upper respiratory symptoms of laryngeal spasm, irritation, or swelling such as stridor or choking.

Skin: Contact dermatitis, contusions, ecchymoses, photodermatitis, pruritus.

Urogenital: Dysmenorrhea, irregular menstrual cycle, pelvic inflammatory disease, vaginal candidiasis, vaginitis, vulvovaginitis.

Overdose

No human overdosage data has been reported for ADVAIR HFA.

ADVAIR HFA contains both fluticasone propionate and salmeterol; therefore, the risks associated with overdosage for the individual components described below apply to ADVAIR HFA. Treatment of overdosage consists of discontinuation of ADVAIR HFA together with institution of appropriate symptomatic and/or supportive therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. Cardiac monitoring is recommended in cases of overdosage.

Fluticasone Propionate

Chronic overdosage of fluticasone propionate may result in signs/symptoms of hypercorticism [see WARNINGS AND PRECAUTIONS]. Inhalation by healthy volunteers of a single dose of 4,000 mcg of fluticasone propionate inhalation powder or single doses of 1,760 or 3,520 mcg of fluticasone propionate CFC inhalation aerosol was well tolerated. Fluticasone propionate given by inhalation aerosol at dosages of 1,320 mcg twice daily for 7 to 15 days to healthy human volunteers was also well tolerated. Repeat oral doses up to 80 mg daily for 10 days in healthy volunteers and repeat oral doses up to 20 mg daily for 42 days in subjects were well tolerated. Adverse reactions were of mild or moderate severity, and incidences were similar in active and placebo treatment groups.

Salmeterol

The expected signs and symptoms with overdosage of salmeterol are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the signs and symptoms of beta-adrenergic stimulation (e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, insomnia, hyperglycemia, hypokalemia, metabolic acidosis). Overdosage with salmeterol can lead to clinically significant prolongation of the QTc interval, which can produce ventricular arrhythmias.

As with all inhaled sympathomimetic medicines, cardiac arrest and even death may be associated with an overdose of salmeterol.

Advair HFA Interactions

 

Tell your doctor about all the medications you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.  Especially tell your doctor if you take:

  • medications that block action of a protein in the body (CYP3A4) such as some macrolide antibiotics (clarithromycin, telithromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan (Vaprisol), delavirdine (Rescriptor), and nefazodone (Serzone)
  • monoamine oxidase inhibitors such as tranylcypromine (Parnate), phenelzine (Nardil), selegiline (Eldepryl, Zelapar), isocarboxazid (Marplan), and rasagiline (Azilect)
  • tricyclic antidepressants such as trimipramine (Surmontil), amitriptyline (Elavil), nortriptyline (Pamelor, Aventyl), protriptyline (Vivactil), and clomipramine (Anafranil)
  • beta blockers such as metoprolol (Toprol XL, Lopressor), carvedilol (Coreg), bisoprolol (Zebeta), betaxolol (Kerlone), nebivolol (Bystolic), propranolol (Inderal)
  • non-potassium-sparing diuretics such as bumetanide (Bumex), chlorothiazide (Diuril), chlorthalidone (Thalitone), ethacrynic acid (Edecrin), furosemide (Lasix), hydrochlorothiazide (Microzide, HCTZ), metolazone (Zaroxolyn), torsemide (Demadex)

This is not a complete list of Advair HFA drug interactions.  Ask your doctor or pharmacist for more information.

 

Advair HFA and Lactation

 

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Advair HFA crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication.  Your doctor and you will decide if the benefits outweigh the risk of using Advair HFA.

 

What happens if I miss a dose?

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Advair HFA (fluticasone and salmeterol) side effects

Get emergency medical help if you have signs of an allergic reaction: 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 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.

Liver Dose Adjustments

Use with caution.

Dose Adjustments

-Titrate to the lowest dose that maintains symptoms control.
-Once control of asthma is achieved and maintained, assess the patient regularly and step down therapy (e.g., discontinue this drug) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid.
-If asthma remains poorly controlled the total daily dose of the inhaled corticosteroid can be increased by administering a higher strength of this combination product.
-No adjustment is needed in geriatric patients.

Other Comments

Administration advice:
-Rinse mouth with water without swallowing after each inhalation to reduce the risk of oropharyngeal candidiasis.
-Increasing the recommended dose can increase the risk of adverse effects with higher doses of salmeterol.
-This drug should not be used with other products containing LABA.
-Prime the inhalation aerosol 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. If 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.

General:
-Limitation of Use: This drug is not indicated for the relief of acute bronchospasm.
-This drug should not be used to relieve of acute symptoms; the use of short acting inhaled bronchodilator is recommended for these situations.
-Only the inhalation powder fluticasone 250 mcg-salmeterol 50 mcg is indicated for the treatment of COPD.

Monitoring:
-Ocular: Changes in vision, intraocular pressure, glaucoma, cataracts
-Pediatric: Growth
-Respiratory: Lung function tests, bronchospasm, signs and symptoms of pneumonia

Patient advice:
-This drug is not indicated relieve acute asthma symptoms or exacerbations of COPD and extra doses should not be used for that purpose.
-Patients should seek medical attention immediately if they experience decreasing effectiveness of inhaled, short-acting beta2-agonists; need for more inhalations than usual dose of inhaled, short-acting beta2-agonists; significant decrease in lung function.
-Therapy with this drug should not be discontinued without medical advice as symptoms may recur after discontinuation.
-Patients should consider regular eye exam.

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