Advair Side Effects

Please note - some side effects for Advair may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Advair - for the Consumer

Advair HFA Inhaler

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Advair HFA Inhaler:

Dizziness; headache; mild muscle or bone pain; nausea; nervousness; throat irritation; tremor; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Advair HFA Inhaler:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); behavior changes; blurred vision or other vision changes; burning, numbness, or tingling; chest pain; choking; fast or irregular heartbeat; hoarseness; overexcitement; seizures; severe muscle weakness, cramps, or spasms; severe or persistent bone pain; severe or persistent dizziness, headache, nervousness, or tremor; signs of infection (eg, fever, chills, cough, persistent sore throat, ear pain, increased mucus production or change in mucus color); swelling or tightness in the throat; symptoms of high blood sugar (eg, confusion; increased thirst, urination, or hunger; unusual weakness or drowsiness); trouble sleeping; unusual tiredness or weakness; vaginal odor or discharge; weight gain; white patches or sores on the tongue or mouth; worsening of asthma symptoms (eg, chest tightness, coughing, increased wheezing, shortness of breath).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Advair Diskus Powder

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Advair Diskus Powder:

Diarrhea; dizziness; headache; mild muscle or bone pain; nausea; nervousness; throat irritation; tremor; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Advair Diskus Powder:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); behavior changes; blurred vision or other vision changes; burning, numbness, or tingling; chest pain; choking; fast or irregular heartbeat; overexcitement; seizures; severe muscle weakness, cramps, or spasms; severe or persistent bone pain; severe or persistent dizziness, headache, nervousness, or tremor; signs of infection (eg, fever, chills, cough, persistent sore throat, ear pain, increased mucus production, change in mucus color); swelling or tightness in the throat; symptoms of high blood sugar (eg, increased thirst, urination, or hunger; unusual weakness or drowsiness; confusion); trouble sleeping; unusual tiredness or weakness; vaginal odor or discharge; weight gain; white patches or sores on the tongue or mouth; worsening of asthma or COPD symptoms (eg, increased wheezing, coughing, chest tightness, shortness of breath).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Top

Advair Side Effects - for the Professional

Advair

LABAs, 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 study that compared the safety of salmeterol (SEREVENT Inhalation Aerosol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. 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 LABAs. Available data from controlled clinical trials suggest that LABAs increase the risk of asthma-related hospitalization in pediatric and adolescent patients.

The incidence of common adverse events in Table 4 is based upon 2 placebo-controlled, 12-week, US clinical studies (Studies 1 and 3) and 1 active-controlled, 12-week, US clinical study (Study 2). A total of 1,008 adolescent and adult patients 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.

Table 4. Overall Adverse Events With ≥3% Incidence in US Controlled Clinical Trials With Advair HFA Inhalation Aerosol in Patients With Asthma

Adverse Events	Advair HFA		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, & 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 infections	3	5	4	5	3	4
Neurology
Headaches	21	15	24	16	20	11
Dizziness	4	1	1	0	<1	0
Gastrointestinal
Nausea & vomiting	5	3	4	2	2	3
Viral gastrointestinal infections	4	2	2	0	1	2
Gastrointestinal signs & symptoms	3	2	2	1	1	1
Non-site specific
Pain	3	1	2	1	2	2
Musculoskeletal
Musculoskeletal pain	5	7	8	2	4	4
Muscle pain	4	1	1	1	3	<1
Drug interaction, overdose, & trauma
Muscle injuries	3	0	2	1	3	2
Reproduction
Menstruation symptoms	5	3	1	0	<1	<1
Psychiatry
Intoxication & hangover	3	0	0	0	0	0
Average duration of exposure (days)	81.3	78.6	79.9	74.6	71.4	56.3

Table 4 includes all events (whether considered drug-related or nondrug-related by the investigator) that occurred at a rate of 3% or greater in any of the groups receiving Advair HFA and were more common than in the placebo group. In considering these data, differences in average duration of exposure should be taken into account. These adverse reactions were mostly mild to moderate in severity.

Other adverse events that occurred in the groups receiving Advair HFA in these studies with an incidence of 1% to 3% and that occurred at a greater incidence than with placebo were:

Cardiovascular: Tachycardia, arrhythmias, myocardial infarction.

Drug Interaction, Overdose, and Trauma: Postoperative complications, wounds and lacerations, soft tissue injuries, poisoning and toxicity, pressure-induced disorder.

Ear, Nose, and Throat: Ear, nose, and throat infection; ear signs and symptoms; rhinorrhea/postnasal drip; epistaxis; nasal congestion/blockage; laryngitis; unspecified oropharyngeal plaques; dryness of nose.

Endocrine and Metabolic: Weight gain.

Eye: Allergic eye disorders, eye edema and swelling.

Gastrointestinal: Gastrointestinal discomfort and pain, dental discomfort and pain, candidiasis mouth/throat, hyposalivation, gastrointestinal infections, disorders of hard tissue of teeth, hemorrhoids, gastrointestinal gaseous symptoms, abdominal discomfort and pain, constipation, oral abnormalities.

Musculoskeletal: Arthralgia and articular rheumatism, muscle cramps and spasms, musculoskeletal inflammation, bone and skeletal pain.

Neurology: Sleep disorders, migraines.

Non-Site Specific: Allergies and allergic reactions, viral infections, bacterial infections, candidiasis unspecified site, congestion, inflammation.

Reproduction: Bacterial reproductive infections.

Respiratory: Lower respiratory signs and symptoms, lower respiratory infections, lower respiratory hemorrhage.

Skin: Eczema, dermatitis and dermatosis.

Urology: Urinary infections.

Rare cases of immediate and delayed hypersensitivity reactions, including rash and other rare events of angioedema and bronchospasm, have been reported.

The incidence of common adverse events reported in Study 4, a 12-week, non-US clinical study of 509 patients 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 4.

Observed During Clinical Practice

In addition to adverse events reported from clinical trials, the following events have been identified during worldwide use of any formulation of Advair, fluticasone propionate, and/or salmeterol regardless of indication. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. 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.

In extensive US and worldwide postmarketing experience with salmeterol, a component of Advair HFA, serious exacerbations of asthma, including some that have been fatal, have been reported. In most cases, these have occurred in patients with severe asthma and/or in some patients in whom asthma has been acutely deteriorating, but they have also occurred in a few patients with less severe asthma. It was not possible from these reports to determine whether salmeterol contributed to these events.

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 and irritation, tonsillitis.

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

Eye: Cataracts, glaucoma.

Gastrointestinal: Dyspepsia, xerostomia.

Hepatobiliary Tract and Pancreas: Abnormal liver function tests.

Musculoskeletal: Back pain, myositis.

Neurology: Paresthesia, restlessness.

Non-Site Specific: Fever, immediate and delayed hypersensitivity reaction, 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; stridor; choking.

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

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

Eosinophilic Conditions: In rare cases, patients on inhaled fluticasone propionate, a component of Advair HFA, may present with systemic eosinophilic conditions, with some patients presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction and/or withdrawal of oral corticosteroid therapy following the introduction of fluticasone propionate. Cases of serious eosinophilic conditions have also been reported with other inhaled corticosteroids in this clinical setting. While Advair HFA should not be used for transferring patients from systemic corticosteroid therapy, physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal relationship between fluticasone propionate and these underlying conditions has not been established.

Top

Side Effects by Body System - for Healthcare Professionals

Endocrine

Endocrine side effects of fluticasone have rarely included symptoms of hypothalamic-pituitary-adrenal (HPA) axis suppression. These effects were more likely when higher potency corticosteroids were used in large doses. The use of a large-volume spacer has helped minimize HPA suppression when fluticasone was inhaled orally.

Due to extensive first-pass metabolism of fluticasone to an inactive carboxylic acid, significant systemic effects are not expected from any amount of the drug that may be ingested via inhalation of normally recommended dosages.

Gastrointestinal

Gastrointestinal side effects of fluticasone have included nausea, vomiting, and diarrhea. Oropharyngeal candidiasis and candida-like lesions have also been reported. Gastrointestinal intolerance to salmeterol has occurred resulting in nausea and diarrhea.

Hypersensitivity

Cases of serious eosinophilic conditions also have been reported with other inhaled corticosteroids in this clinical setting.

Hypersensitivity side effects of fluticasone have included rare cases of immediate and delayed reactions including rash, angioedema and bronchospasm. Hypersensitivity side effects have also included postmarketing reports of a systemic eosinophilic condition. Clinical features of this condition have included a vasculitis consistent with Churg-Strauss syndrome, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy. These events have usually been associated with a reduction and/or discontinuation of oral corticosteroid therapy following introduction of fluticasone. Hypersensitivity reactions to salmeterol have presented as rash or urticaria.

Immunologic

Immunologic side effects of fluticasone may have included infections resulting from immune suppression associated with inhaled corticosteroids. No conclusive evidence is available to support an increase in tuberculosis or viral infections in patients receiving inhaled fluticasone.

In 1993, the American Academy of Allergy and Immunology (AAAI) requested that the FDA review its decision regarding the labeled risks of the use of inhaled corticosteroids during severe viral infections. The AAAI's request was based on the lack of data linking inhaled corticosteroids to increases in complications of viral infections.

Local

Local side effects associated with inhaled fluticasone have included dysphonia, sore throat, bronchitis, chest congestion, nasal congestion, nasal discharge, and eye irritation.

Asthma treatment with high doses of inhaled fluticasone powder apparently led to a serious case of laryngeal aspergillosis in a 75-year-old-man. The patient had been using fluticasone 1 mg twice daily via Diskhaler for about 3 years. The patient experienced progressive hoarseness which led to complete aphonia. Aspergillosis fumigatus was cultured from the vocal cords. Amphotericin B lozenges were used to treat the infection. After 14 weeks the patient's voice was still gruff but intelligible. It is recommended that tests for fungal infection be performed in patients on fluticasone therapy who become hoarse, particularly if taking high doses.

Musculoskeletal

Musculoskeletal side effects of fluticasone have included joint pain and muscle soreness. Long-term use of inhaled corticosteroids has been associated with a reduction in bone density. This effect may have been dose related and has been reported with high dosages of orally inhaled beclomethasone and budesonide (>=800 mcg/day for >=1 year). Reduced levels of total body calcium have also been demonstrated in patients receiving lower dosages. The musculoskeletal effects of salmeterol are mediated by beta-2 receptors and have been manifested as tremors, especially at higher doses. Tolerance can lead to the tremorogenic effects. Severe muscle cramping is rarely reported.

Nervous system

One patient has reported episodes of vertigo lasting 36 hours each following inhalation of salmeterol. These episodes occurred several months apart during separate attempts to reinstitute therapy.

Nervous system side effects of fluticasone have included headache, dizziness, giddiness, fatigue, and insomnia. The nervous system has been adversely affected by salmeterol resulting in headache, restlessness, anxiety, nervousness, irritability, and insomnia.

Ocular

Ocular side effects of fluticasone have included occasional reports of posterior capsular cataracts. In addition, one epidemiologic study suggested that prolonged use of high-dose inhaled corticosteroids (>= 1500 mcg of fluticasone) may have been associated with increased risk of ocular hypertension and open-angle glaucoma.

Cardiovascular

Changes in heart rate of approximately 8 to 16 beats per minute may be produced by 0.2 mg of salmeterol given by MDI. At an inhaled dose of 0.4 mg, two subjects have experienced nonspecific T-wave changes, and one subject experienced QT prolongation. Higher doses of salmeterol should be used with caution in patients with cardiac disease, arrhythmias, or hypertension. All of these effects are dose-related and lower doses may be tolerated.

Cardiovascular side effects of salmeterol have included palpitations and peripheral vasodilation, commonly resulting in reflex tachycardia. Blood pressure has been increased and decreased. Higher doses have rarely aggravated angina, myocardial ischemia, or caused atrial or ventricular arrhythmias.

General

Salmeterol has been generally well-tolerated and adverse effects seen were consistent with its pharmacological action. In general, the severity of these adverse effects were dependent on dose. Tolerance to the adverse effects of salmeterol has occurred.

Metabolic

Following a 400-mcg dose of salmeterol via MDI, a decrease in plasma potassium concentrations of 0.45 mEq/L has been reported. Salmeterol may stimulate sodium-potassium ATPase resulting in an intracellular shift of potassium.

Metabolic side effects associated with salmeterol have included hypokalemia, and less commonly hyperglycemia.

Respiratory

Respiratory side effects of salmeterol have occasionally included cough and paradoxical bronchospasm. Additional side effects reported have included upper respiratory tract infections, viral respiratory infections, bronchitis, and pneumonia.

Less commonly respiratory side effects have included chest congestion, chest tightness, dyspnea, immediate bronchospasm, influenza, tracheitis, wheezing, and reports of upper respiratory symptoms of laryngeal spasm, irritation, or swelling such as stridor or choking. Lower respiratory tract infections, including pneumonia, have been reported following the inhaled administration of corticosteroids. There was a higher incidence of pneumonia among patients receiving fluticasone-salmeterol (7%) than among those receiving salmeterol (4%) in a clinical study.

Other

Other side effects have concerned the development of tachyphylaxis to the bronchodilating and bronchoprotective effects of beta-agonists. Although conflicting data exist, the development of complete tolerance has not been reported.

Psychiatric

Psychiatric side effects have included post marketing reports of agitation, aggression, depression. Behavioral changes, including hyperactivity and irritability, have been reported very rarely and primarily in children.

Top

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.