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Advair Diskus (Fluticasone Propionate / Salmeterol Xinafoate Inhalation) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Long-acting beta 2 -adrenergic agonists, such as salmeterol, may 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 (see WARNINGS). Salmeterol is a component of ADVAIR DISKUS. However, the data from this study are not adequate to determine whether concurrent use of inhaled corticosteroids, such as fluticasone propionate, the other component of ADVAIR DISKUS, or other asthma controller therapy modifies the risk of asthma-related death.

Asthma

Adult and Adolescent Patients 12 Years of Age and Older

The incidence of common adverse events in Table 4 is based upon 2 placebo-controlled, 12-week, US clinical studies (Studies 1 and 2). A total of 705 adolescent and adult patients (349 females and 356 males) previously treated with salmeterol or inhaled corticosteroids were treated twice daily with ADVAIR DISKUS (100/50- or 250/50-mcg doses), fluticasone propionate inhalation powder (100- or 250-mcg doses), salmeterol inhalation powder 50 mcg, or placebo.

Table 4. Overall Adverse Events With ≥3% Incidence in US Controlled Clinical Trials With ADVAIR DISKUS in Patients With Asthma

ADVAIR

ADVAIR

Fluticasone

Fluticasone

DISKUS

DISKUS

Propionate

Propionate

Salmeterol

Placebo

100/50

250/50

100 mcg

250 mcg

50 mcg

(N =

(N = 92)

(N = 84)

(N = 90)

(N = 84)

(N = 180)

175)

Adverse Event

%

%

%

%

%

%

Ear, nose, & throat

Upper respiratory tract

27

21

29

25

19

14

infection

Pharyngitis

13

10

7

12

8

6

Upper respiratory

7

6

7

8

8

5

inflammation

Sinusitis

4

5

6

1

3

4

Hoarseness/dysphonia

5

2

2

4

<1

<1

Oral candidiasis

1

4

2

2

0

0

Lower respiratory

Viral respiratory infections

4

4

4

10

6

3

Bronchitis

2

8

1

2

2

2

Cough

3

6

0

0

3

2

Neurology

Headaches

12

13

14

8

10

7

Gastrointestinal

Nausea & vomiting

4

6

3

4

1

1

Gastrointestinal discomfort

4

1

0

2

1

1

& pain

Diarrhea

4

2

2

2

1

1

Viral gastrointestinal

3

0

3

1

2

2

infections

Non-site specific

Candidiasis unspecified site

3

0

1

4

0

1

Musculoskeletal

Musculoskeletal pain

4

2

1

5

3

3

Average duration of exposure (days)

77.3

78.7

72.4

70.1

60.1

42.3

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 either of the groups receiving ADVAIR DISKUS and were more common than in the placebo group. In considering these data, differences in average duration of exposure should be taken into account. Rare cases of immediate and delayed hypersensitivity reactions, including rash and other rare events of angioedema and bronchospasm, have been reported.

These adverse reactions were mostly mild to moderate in severity.

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

Blood and Lymphatic

Lymphatic signs and symptoms.

Cardiovascular

Palpitations.

Drug Interaction, Overdose, and Trauma

Muscle injuries, fractures, wounds and lacerations, contusions and hematomas, burns.

Ear, Nose, and Throat

Rhinorrhea/postnasal drip; ear, nose, and throat infections; ear signs and symptoms; nasal signs and symptoms; nasal sinus disorders; rhinitis; sneezing; nasal irritation; blood in nasal mucosa.

Eye

Keratitis and conjunctivitis, viral eye infections, eye redness.

Gastrointestinal

Dental discomfort and pain, gastrointestinal signs and symptoms, gastrointestinal infections, gastroenteritis, gastrointestinal disorders, oral ulcerations, oral erythema and rashes, constipation, appendicitis, oral discomfort and pain.

Hepatobiliary Tract and Pancreas

Abnormal liver function tests.

Lower Respiratory

Lower respiratory signs and symptoms, pneumonia, lower respiratory infections.

Musculoskeletal

Arthralgia and articular rheumatism; muscle stiffness, tightness, and rigidity; bone and cartilage disorders.

Neurology

Sleep disorders, tremors, hypnagogic effects, compressed nerve syndromes.

Non-Site Specific

Allergies and allergic reactions, congestion, viral infections, pain, chest symptoms, fluid retention, bacterial infections, wheeze and hives, unusual taste.

Skin

Viral skin infections, urticaria, skin flakiness and acquired ichthyosis, disorders of sweat and sebum, sweating.

The incidence of common adverse events reported in Study 3, a 28-week, non-US clinical study of 503 patients previously treated with inhaled corticosteroids who were treated twice daily with ADVAIR DISKUS 500/50, fluticasone propionate inhalation powder 500 mcg and salmeterol inhalation powder 50 mcg used concurrently, or fluticasone propionate inhalation powder 500 mcg was similar to the incidences reported in Table 4.

Pediatric Patients

Pediatric Study

ADVAIR DISKUS 100/50 was well tolerated in clinical trials conducted in children with asthma aged 4 to 11 years. The incidence of common adverse events in Table 5 is based upon a 12-week US study in 203 patients with asthma aged 4 to 11 years (74 females and 129 males) who were receiving inhaled corticosteroids at study entry and were randomized to either ADVAIR DISKUS 100/50 or fluticasone propionate inhalation powder 100 mcg twice daily.

Table 5. Overall Adverse Events With ≥3% Incidence With ADVAIR DISKUS 100/50 in Patients 4 to 11 Years of Age With Asthma

ADVAIR DISKUS

Fluticasone Propionate

100/50

100 mcg

(N = 101)

(N = 102)

Adverse Event

%

%

Ear, nose, & throat

Upper respiratory tract infection

10

17

Throat irritation

8

7

Ear, nose, & throat infections

4

<1

Epistaxis

4

<1

Pharyngitis/throat infection

3

2

Ear signs & symptoms

3

<1

Sinusitis

3

0

Neurology

Headache

20

20

Gastrointestinal

Gastrointestinal discomfort &

7

5

pain

Nausea & vomiting

5

3

Candidiasis mouth/throat

4

<1

Non-site specific

Fever

5

13

Chest symptoms

3

<1

Average duration of exposure (days)

74.8

78.8

Table 5 includes all events (whether considered drug-related or nondrug-related by the investigator) that occurred at a rate of 3% or greater in the group receiving ADVAIR DISKUS 100/50.

Chronic Obstructive Pulmonary Disease Associated With Chronic Bronchitis

The incidence of common adverse events in Table 6 is based upon 1 placebo-controlled, 24-week, US clinical trial in patients with COPD associated with chronic bronchitis. A total of 723 adult patients (266 females and 457 males) were treated twice daily with ADVAIR DISKUS 250/50, fluticasone propionate inhalation powder 250 mcg, salmeterol inhalation powder 50 mcg, or placebo.

Table 6. Overall Adverse Events With ≥3% Incidence With ADVAIR DISKUS 250/50 in Patients With Chronic Obstructive Pulmonary Disease Associated With Chronic Bronchitis

ADVAIR

Fluticasone

DISKUS

Propionate

Salmeterol

250/50

250 mcg

50 mcg

Placebo

(N = 178)

(N = 183)

(N = 177)

(N = 185)

Adverse Event

%

%

%

%

Ear, nose, & throat

Candidiasis mouth/throat

10

6

3

1

Throat irritation

8

5

4

7

Hoarseness/dysphonia

5

3

<1

0

Sinusitis

3

8

5

3

Lower respiratory

Viral respiratory infections

6

4

3

3

Neurology

Headaches

16

11

10

12

Dizziness

4

<1

3

2

Non-site specific

Fever

4

3

0

3

Malaise & fatigue

3

2

2

3

Musculoskeletal

Musculoskeletal pain

9

8

12

9

Muscle cramps & spasms

3

3

1

1

Average duration of exposure (days)

141.3

138.5

136.1

131.6

Table 6 includes all events (whether considered drug-related or nondrug-related by the investigator) that occurred at a rate of 3% or greater in the group receiving ADVAIR DISKUS 250/50 and were more common than in the placebo group.

These adverse reactions were mostly mild to moderate in severity.

Other adverse events that occurred in the groups receiving ADVAIR DISKUS 250/50 with an incidence of 1% to 3% and that occurred at a greater incidence than with placebo were:

Cardiovascular

Syncope.

Drug Interaction, Overdose, and Trauma

Postoperative complications.

Ear, Nose, and Throat

Ear, nose, and throat infections; ear signs and symptoms; laryngitis; nasal congestion/blockage; nasal sinus disorders; pharyngitis/throat infection.

Endocrine and Metabolic

Hypothyroidism.

Eye

Dry eyes, eye infections.

Gastrointestinal

Constipation, gastrointestinal signs and symptoms, oral lesions.

Hepatobiliary Tract and Pancreas

Abnormal liver function tests.

Lower Respiratory

Breathing disorders, lower respiratory signs and symptoms.

Non-Site Specific

Bacterial infections, candidiasis unspecified site, edema and swelling, nonspecific conditions, viral infections.

Psychiatry

Situational disorders.

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 DISKUS, fluticasone propionate, and/or salmeterol or a combination of these factors.

In extensive US and worldwide postmarketing experience with salmeterol, a component of ADVAIR DISKUS, 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 (see WARNINGS), 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), ventricular tachycardia.

Ear, Nose, and Throat

Aphonia, earache, facial and oropharyngeal edema, paranasal sinus pain, throat soreness.

Endocrine and Metabolic

Cushing syndrome, Cushingoid features, growth velocity reduction in children/adolescents, hypercorticism, hyperglycemia, weight gain, osteoporosis.

Eye

Cataracts, glaucoma.

Gastrointestinal

Abdominal pain, dyspepsia, xerostomia.

Musculoskeletal

Back pain, cramps, muscle spasm, myositis.

Neurology

Paresthesia, restlessness.

Non-Site Specific

Immediate and delayed hypersensitivity reaction (including very rare anaphylactic reaction), pallor. Very rare anaphylactic reaction in patients with severe milk protein allergy.

Psychiatry

Agitation, aggression, depression.

Respiratory

Chest congestion; chest tightness; dyspnea; immediate bronchospasm; influenza; paradoxical bronchospasm; tracheitis; wheezing; reports of upper respiratory symptoms of laryngeal spasm, irritation, or swelling such as stridor or choking.

Skin

Contact dermatitis, contusions, ecchymoses, photodermatitis.

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 DISKUS, 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 DISKUS 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 (see PRECAUTIONS: General: Eosinophilic Conditions).

Drug label data at the top of this Page last updated: 2006-11-21

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