Advair

Name: Advair

Precautions While Using Advair

If you will be using this medicine for a long time, it is very important that your doctor check the progress of you or your child at regular visits. This will allow your doctor to see if the medicine is working properly and to check for any unwanted effects.

Tell your doctor if you or your child are also using other medicines for your COPD. Your doctor may want you to stop using the medicine and use it only during a severe COPD attack. Follow your doctor's instructions on how you should take your medicine.

This medicine should not be used if you are having a severe COPD attack, or if symptoms of a COPD attack has already started. Your doctor may prescribe another medicine for you to use in case of an acute COPD attack. If the other medicine does not work as well, tell your doctor right away.

This medicine should only be used as an additional treatment for patients who cannot be treated with other asthma medicines (such as inhaled corticosteroids) or for asthma patients that require two medicines, including salmeterol. Ask your doctor if you have any questions.

Although this medicine decreases the number of asthma episodes, it may increase the chance of a severe asthma attack when they do occur. Be sure to read about these risks in the Medication Guide and talk to your doctor or pharmacist about any questions or concerns that you have.

You should not use this medicine if your asthma attack has already started. Your doctor will prescribe another medicine (eg, a short-acting inhaler) for you to use in case of an acute asthma attack. Make sure you understand how to use the short-acting inhaler. Talk to your doctor if you need instructions.

Talk with your doctor or get medical care right away if:

  • Your or your child's symptoms do not improve after using this medicine for 1 week or if they become worse.
  • Your short-acting inhaler does not seem to work as well as it used to and you or your child need it more often than normal (eg, you use 1 whole canister of the short-acting inhaler in 8 weeks time, or you need to use 4 or more inhalations of the short-acting inhaler for 2 or more days in a row).
  • You or your child have a big decrease in your peak flow when measured as directed by your doctor.

Do not use this medicine to treat wheezing that is getting worse. Call your doctor right away if wheezing worsens while using this medicine.

Do not use any other asthma medicine or medicine for breathing problems without talking to your doctor. This medicine should not be used with other inhalers that contain budesonide and formoterol combination (Symbicort®), formoterol (Foradil® Aerolizer®, Perforomist™), or arformoterol (Brovona™).

This medicine may cause a fungus infection of the mouth or throat (thrush). Tell your doctor right away if you have white patches in the mouth or throat; or pain when eating or swallowing.

Patients with COPD may be more likely to have pneumonia. Call your doctor if you or your child start having increased sputum (spit) production, change in sputum color, fever, chills, increased cough, or an increase in breathing problems.

Do not change your dose or stop using your medicine without first asking your doctor.

Your doctor may want you to carry a medical identification (ID) card stating that you or your child are using this medicine. The card will say that you may need additional medicine during an emergency, a severe asthma attack or other illness, or unusual stress.

Using too much of this medicine or using it for a long time may cause may increase your risk of having adrenal gland problems. Talk to your doctor if you or your child have more than one of these symptoms while you are using this medicine: darkening of the skin, diarrhea, dizziness, fainting, loss of appetite, mental depression, nausea, skin rash, unusual tiredness or weakness, or vomiting.

This medicine may cause paradoxical bronchospasm, which means your breathing or wheezing will get worse. Paradoxical bronchospasm may be life-threatening. Check with your doctor right away if you or your child are having a cough, difficulty with breathing, shortness of breath, or wheezing after using this medicine.

If you or your child develop a skin rash, hives, or any allergic reaction (including anaphylaxis) to this medicine, check with your doctor as soon as possible.

Check with your doctor right away if you or your child have chest pain, a fast heartbeat, nervousness, shaking of the hands or feet, noisy breathing, a feeling of choking, or tightness or irritation of the throat while using this medicine.

This medicine may affect blood sugar and potassium levels. If you have heart disease or are diabetic and notice a change in the results of your blood or urine sugar or potassium tests, check with your doctor.

Check with your doctor right away if blurred vision, difficulty in reading, or any other change in vision occurs during or after treatment. Your doctor may want you or your child to have your eyes checked by an ophthalmologist (eye doctor).

This medicine may decrease bone mineral density when used for a long time. A low bone mineral density can cause weak bones or osteoporosis. If you have any questions about this, ask your doctor.

This medicine may cause children to grow more slowly than usual. Talk to your child's doctor if you have any concerns.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Indications and Usage for Advair

Advair HFA is indicated for the treatment of asthma in patients aged 12 years and older.

LABA, such as salmeterol, one of the active ingredients in Advair HFA, increase the risk of asthma-related death. 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 (5.1)]. Therefore, when treating patients with asthma, physicians should only prescribe Advair HFA for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid, or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue Advair HFA) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use Advair HFA for patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids.

Important Limitation of Use

Advair HFA is NOT indicated for the relief of acute bronchospasm.

Adverse Reactions

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 U.S. 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 (5.1)]. 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 (5.1)].

Systemic and local corticosteroid use may result in the following:

• Candida albicans infection [see Warnings and Precautions (5.4)] • Pneumonia in patients with COPD [see Warnings and Precautions (5.5)] • Immunosuppression [see Warnings and Precautions (5.6)] • Hypercorticism and adrenal suppression [see Warnings and Precautions (5.8)] • Reduction in bone mineral density [see Warnings and Precautions (5.13)] • Growth effects [see Warnings and Precautions (5.14)] • Glaucoma and cataracts [see Warnings and Precautions (5.15)]

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, U.S. clinical trials (Trials 1 and 3) and 1 active-controlled 12-week U.S. 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-U.S. 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.

Use in specific populations

Pregnancy

Teratogenic Effects

Pregnancy Category C. There are no adequate and well-controlled trials with Advair HFA in pregnant women. Corticosteroids and beta2-agonists have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Because animal reproduction studies are not always predictive of human response, Advair HFA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women should be advised to contact their physicians if they become pregnant while taking Advair HFA.

Fluticasone Propionate and Salmeterol: In the mouse reproduction assay, fluticasone propionate at a dose approximately equivalent to the maximum recommended human daily inhalation dose (MRHDID) (on a mcg/m2 basis at a maternal subcutaneous dose of 150 mcg/kg) combined with salmeterol at a dose approximately 580 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 10 mg/kg) produced cleft palate, fetal death, increased implantation loss, and delayed ossification. These observations are characteristic of glucocorticoids. No developmental toxicity was observed at combination doses of fluticasone propionate up to approximately 1/5 the MRHDID (on a mcg/m2 basis at a maternal subcutaneous dose of 40 mcg/kg) and doses of salmeterol up to approximately 80 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 1.4 mg/kg).

In rats, combining fluticasone propionate at a dose equivalent to the MRHDID (on a mcg/m2 basis at a maternal subcutaneous dose of 100 mcg/kg) and a dose of salmeterol at approximately 1,200 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 10 mg/kg) produced decreased fetal weight, umbilical hernia, delayed ossification, and changes in the occipital bone. No such effects were seen when combining fluticasone propionate at a dose less than the MRHDID (on a mcg/m2 basis at a maternal subcutaneous dose of 30 mcg/kg) and a dose of salmeterol at approximately 120 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 1 mg/kg).

Fluticasone Propionate: Mice and rats at fluticasone propionate doses less than or equivalent to the MRHDID (on a mcg/m2 basis at maternal subcutaneous doses of 45 and 100 mcg/kg, respectively) showed fetal toxicity characteristic of potent corticosteroid compounds, including embryonic growth retardation, omphalocele, cleft palate, and retarded cranial ossification. No teratogenicity was seen in rats at doses approximately equivalent to the MRHDID (on a mcg/m2 basis at maternal inhaled doses up to 68.7 mcg/kg).

In rabbits, fetal weight reduction and cleft palate were observed at a fluticasone propionate dose less than the MRHDID (on a mcg/m2 basis at a maternal subcutaneous dose of 4 mcg/kg). However, no teratogenic effects were reported at fluticasone propionate doses up to approximately 6 times the MRHDID (on a mcg/m2 basis at maternal oral doses up to 300 mcg/kg). No fluticasone propionate was detected in the plasma in this study, consistent with the established low bioavailability following oral administration [see Clinical Pharmacology (12.3)].

Fluticasone propionate crossed the placenta following subcutaneous administration to mice and rats and oral administration to rabbits.

Experience with oral corticosteroids since their introduction in pharmacologic, as opposed to physiologic, doses suggests that rodents are more prone to teratogenic effects from corticosteroids than humans. In addition, because there is a natural increase in corticosteroid production during pregnancy, most women will require a lower exogenous corticosteroid dose and many will not need corticosteroid treatment during pregnancy.

Salmeterol: No teratogenic effects occurred in rats at salmeterol doses approximately 230 times the MRHDID (on a mg/m2 basis at maternal oral doses up to 2 mg/kg). In pregnant Dutch rabbits administered salmeterol doses approximately 25 times the MRHDID (on an AUC basis at maternal oral doses of 1 mg/kg and higher), salmeterol exhibited fetal toxic effects characteristically resulting from beta-adrenoceptor stimulation. These included precocious eyelid openings, cleft palate, sternebral fusion, limb and paw flexures, and delayed ossification of the frontal cranial bones. No such effects occurred at a salmeterol dose approximately 10 times the MRHDID (on an AUC basis at a maternal oral dose of 0.6 mg/kg).

New Zealand White rabbits were less sensitive since only delayed ossification of the frontal cranial bones was seen at a salmeterol dose approximately 2,300 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 10 mg/kg). Salmeterol xinafoate crossed the placenta following oral administration to mice and rats.

Nonteratogenic Effects

Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should be carefully monitored.

Labor and Delivery

There are no well-controlled human trials that have investigated effects of Advair HFA on preterm labor or labor at term. Because of the potential for beta-agonist interference with uterine contractility, use of Advair HFA during labor should be restricted to those patients in whom the benefits clearly outweigh the risks.

Nursing Mothers

Plasma levels of salmeterol, a component of Advair HFA, after inhaled therapeutic doses are very low. In rats, salmeterol xinafoate is excreted in the milk. There are no data from controlled trials on the use of salmeterol by nursing mothers. It is not known whether fluticasone propionate, a component of Advair HFA, is excreted in human breast milk. However, other corticosteroids have been detected in human milk. Subcutaneous administration to lactating rats of tritiated fluticasone propionate resulted in measurable radioactivity in milk.

Since there are no data from controlled trials on the use of Advair HFA by nursing mothers, caution should be exercised when Advair HFA is administered to a nursing woman.

Pediatric Use

Thirty-eight (38) subjects aged 12 to 17 years were treated with Advair HFA in U.S. pivotal clinical trials. Subjects in this age-group demonstrated efficacy results similar to those observed in subjects aged 18 years and older. There were no obvious differences in the type or frequency of adverse events reported in this age-group compared with subjects aged 18 years and older.

In a 12-week trial, the safety of Advair HFA 45/21 given as 2 inhalations twice daily was compared with that of fluticasone propionate 44 mcg HFA (FLOVENT® HFA) 2 inhalations twice daily in 350 subjects aged 4 to 11 years with persistent asthma currently being treated with inhaled corticosteroids. No new safety concerns were observed in children aged 4 to 11 years treated for 12 weeks with Advair HFA 45/21 compared with adults and adolescents aged 12 years and older. Common adverse reactions (greater than or equal to 3%) seen in children aged 4 to 11 years treated with Advair HFA 45/21 but not reported in the adult and adolescent clinical trials of Advair HFA include: pyrexia, cough, pharyngolaryngeal pain, rhinitis, and sinusitis [see Adverse Reactions (6.1)].This trial was not designed to assess the effect of salmeterol, a component of Advair HFA, on asthma hospitalizations and death in subjects aged 4 to 11 years.

The pharmacokinetics and pharmacodynamic effect on serum cortisol of 21 days of treatment with Advair HFA 45/21 (2 inhalations twice daily with or without a spacer) or Advair DISKUS 100/50 (1 inhalation twice daily) was evaluated in a trial of 31 children aged 4 to 11 years with mild asthma. Systemic exposure to salmeterol xinafoate was similar for Advair HFA, Advair HFA delivered with a spacer, and Advair DISKUS while the systemic exposure to fluticasone propionate was lower with Advair HFA compared with that of Advair HFA delivered with a spacer or Advair DISKUS. There were reductions in serum cortisol from baseline in all treatment groups (14%, 22%, and 13% for Advair HFA, Advair HFA delivered with a spacer, and Advair DISKUS, respectively) [see Clinical Pharmacology (12.2, 12.3)].

The safety and effectiveness of Advair HFA in children younger than 12 years have not been established.

Effects on Growth

Inhaled corticosteroids, including fluticasone propionate, a component of Advair HFA, may cause a reduction in growth velocity in children and adolescents [see Warnings and Precautions (5.14)]. The growth of pediatric patients receiving orally inhaled corticosteroids, including Advair HFA, should be monitored.

A 52-week placebo-controlled trial to assess the potential growth effects of fluticasone propionate inhalation powder (FLOVENT® ROTADISK®) at 50 and 100 mcg twice daily was conducted in the U.S. in 325 prepubescent children (244 males and 81 females) aged 4 to 11 years. The mean growth velocities at 52 weeks observed in the intent-to-treat population were 6.32 cm/year in the placebo group (n = 76), 6.07 cm/year in the 50-mcg group (n = 98), and 5.66 cm/year in the 100-mcg group (n = 89). An imbalance in the proportion of children entering puberty between groups and a higher dropout rate in the placebo group due to poorly controlled asthma may be confounding factors in interpreting these data. A separate subset analysis of children who remained prepubertal during the trial revealed growth rates at 52 weeks of 6.10 cm/year in the placebo group (n = 57), 5.91 cm/year in the 50-mcg group (n = 74), and 5.67 cm/year in the 100-mcg group (n = 79). In children aged 8.5 years, the mean age of children in this trial, the range for expected growth velocity is: boys – 3rd percentile = 3.8 cm/year, 50th percentile = 5.4 cm/year, and 97th percentile = 7.0 cm/year; girls – 3rd percentile = 4.2 cm/year, 50th percentile = 5.7 cm/year, and 97th percentile = 7.3 cm/year. The clinical relevance of these growth data is not certain.

If a child or adolescent on any corticosteroid appears to have growth suppression, the possibility that he/she is particularly sensitive to this effect of corticosteroids should be considered. The potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained. To minimize the systemic effects of orally inhaled corticosteroids, including Advair HFA, each patient should be titrated to the lowest strength that effectively controls his/her asthma [see Dosage and Administration (2.1)].

Geriatric Use

Clinical trials of Advair HFA did not include sufficient numbers of subjects aged 65 years and older to determine whether older subjects respond differently than younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. In addition, as with other products containing beta2-agonists, special caution should be observed when using Advair HFA in geriatric patients who have concomitant cardiovascular disease that could be adversely affected by beta2-agonists.

Hepatic Impairment

Formal pharmacokinetic studies using Advair HFA have not been conducted in patients with hepatic impairment. However, since both fluticasone propionate and salmeterol are predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of fluticasone propionate and salmeterol in plasma. Therefore, patients with hepatic disease should be closely monitored.

Renal Impairment

Formal pharmacokinetic studies using Advair HFA have not been conducted in patients with renal impairment.

Overdosage

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 (5.7)]. 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.

How Supplied/Storage and Handling

Advair HFA 45/21 Inhalation Aerosol is supplied in 12-g pressurized aluminum canisters containing 120 metered actuations in boxes of 1 (NDC 0173-0715-20) and 8-g pressurized aluminum canisters containing 60 metered actuations in institutional pack boxes of 1 (NDC 0173-0715-22).

Advair HFA 115/21 Inhalation Aerosol is supplied in 12-g pressurized aluminum canisters containing 120 metered actuations in boxes of 1 (NDC 0173-0716-20) and 8-g pressurized aluminum canisters containing 60 metered actuations in institutional pack boxes of 1 (NDC 0173-0716-22).

Advair HFA 230/21 Inhalation Aerosol is supplied in 12-g pressurized aluminum canisters containing 120 metered actuations in boxes of 1 (NDC 0173-0717-20) and 8-g pressurized aluminum canisters containing 60 metered actuations in institutional pack boxes of 1 (NDC 0173-0717-22).

Each canister is fitted with a counter and supplied with a purple actuator with a light purple strapcap. Each inhaler is sealed in a plastic-coated, moisture-protective foil pouch with a desiccant that should be discarded when the pouch is opened. Each inhaler is packaged with a Medication Guide leaflet.

The purple actuator supplied with Advair HFA should not be used with any other product canisters, and actuators from other products should not be used with an Advair HFA canister.

The correct amount of medication in each actuation cannot be assured after the counter reads 000, even though the canister is not completely empty and will continue to operate. The inhaler should be discarded when the counter reads 000.

Keep out of reach of children. Avoid spraying in eyes.

Contents under Pressure: Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw canister into fire or incinerator.

Store at room temperature between 68°F and 77°F (20°C and 25°C); excursions permitted from 59°F to 86°F (15°C to 30°C) [See USP Controlled Room Temperature]. Store the inhaler with the mouthpiece down. For best results, the inhaler should be at room temperature before use. SHAKE WELL FOR 5 SECONDS BEFORE EACH SPRAY.

What is Advair inhalation?

Advair contains a combination of fluticasone and salmeterol. Fluticasone is a steroid that prevents the release of substances in the body that cause inflammation. Salmeterol is a bronchodilator. It works by relaxing muscles in the airways to improve breathing.

Advair is used to prevent asthma attacks attacks. It is also used to prevent flare-ups or worsening of chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis and/or emphysema.

In people with COPD, Advair is for long-term treatment. In people with asthma, this medicine is for short-term treatment until symptoms are well controlled with with other medicines.

Advair is for use in adults and children who are at least 4 years old. Advair HFA is for use in adults and children who are at least 12 years old.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Overdose symptoms may include dizziness, vomiting, weakness, chest pain, tremors, feeling nervous, fast or pounding heartbeats, or seizure.

What other drugs will affect Advair?

Many drugs can interact with this medicine. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any you start or stop using, especially:

  • an antidepressant, heart or blood pressure medicine, a diuretic or "water pill";

  • antifungal medicine such as ketoconazole; or

  • ritonavir (Norvir) or lopinavir/ritonavir (Kaletra).

This list is not complete and many other drugs can interact with fluticasone and salmeterol. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

For Healthcare Professionals

Applies to fluticasone / salmeterol: inhalation aerosol, inhalation powder

General

The most common events that occurred more frequently were nasopharyngitis, upper respiratory tract infection, nasal congestion, back pain, sinusitis, dizziness, nausea, pneumonia, candidiasis, and dysphonia.[Ref]

Nervous system

Very common (10% or more): Headache (up to 21%)
Common (1% to 10%): Migraine
Uncommon (0.1% to 1%): Tremor
Postmarketing reports: Paraesthesia, restlessness, compressed nerve syndrome, aphonia[Ref]

Respiratory

The incidence of pneumonia was higher in adult subjects with COPD older than 65 years compared with younger subjects with COPD (18% versus 14%).[Ref]

Very common (10% or more): Upper respiratory tract infections (up to 27%), pharyngitis (up to 13%), nasopharyngitis
Common (1% to 10%): Pneumonia, bronchitis, throat irritation, hoarseness, dysphonia, sinusitis, upper respiratory inflammation, viral respiratory infections, cough, rhinorrhea/postnasal drip, epistaxis, nasal congestion/blockage, laryngitis, unspecified oropharyngeal plaques, dryness of nose, lower respiratory signs and symptoms, lower respiratory infections, lower respiratory hemorrhage, congestion
Uncommon (0.1% to 1%): Dyspnea
Rare (less than 0.1%): Oropharyngeal angioedema, bronchospasm, paradoxical bronchospasm
Frequency not reported: Nose, and throat infections, laryngitis, nasal sinus disorders, nasal sinus disorders
Postmarketing reports: Paranasal sinus pain, rhinitis, throat soreness, tonsillitis, asthma, asthma exacerbation, chest congestion, chest tightness, tracheitis, wheezing, report of upper respiratory symptoms of laryngeal spasm, irritation, or swelling such as stridor or chocking[Ref]

Cardiovascular

Common (1% to 10%): Palpitations, tachycardia, arrhythmias, myocardial infarction, postoperative complications
Uncommon (0.1% to 1%): Atrial fibrillation, angina pectoris
Rare (less than 0.1%): Cardiac arrhythmias (including supraventricular tachycardia and extrasystoles)
Frequency not reported: Hematomas
Postmarketing reports: Ventricular tachycardia, pallor[Ref]

Dermatologic

Common (1% to 10%): Contusions, wounds, eczema, dermatitis, dermatosis
Frequency not reported: Skin flakiness and acquired ichthyosis, disorders of sweat and sebum
Postmarketing reports: Ecchymoses, photodermatitis[Ref]

Gastrointestinal

Common (1% to 10%): Oral and throat candidiasis, nausea and vomiting, gastrointestinal discomfort and pain, dental discomfort and pain, hyposalivation, gastrointestinal infections, disorders of hard tissue of teeth, abdominal discomfort and pain, oral abnormalities, gastrointestinal discomfort and pain, viral gastrointestinal infections, diarrhea
Rare (less than 0.1%): Esophageal candidiasis
Frequency not reported: Oral lesions
Postmarketing reports: Oral ulcerations, dyspepsia, xerostomia[Ref]

Immunologic

Common (1% to 10%): Allergies and allergic reactions[Ref]

Metabolic

Common (1% to 10%): Hypokalemia, weight gain
Uncommon (0.1% to 1%): Hyperglycemia
Frequency not reported: Fluid retention[Ref]

Musculoskeletal

Common (1% to 10%): Muscle cramps, traumatic fractures, arthralgia, myalgia, arthralgia, articular rheumatism, muscle spasms, musculoskeletal inflammation, bone and skeletal pain, muscle injuries, soft tissue injuries
Postmarketing reports: Muscle stiffness, tightness and rigidity, bone and cartilage disorders, myositis, osteoporosis, fractures[Ref]

Ocular

Common (1% to 10%): Allergic eye disorders, eye edema and swelling
Uncommon (0.1% to 1%): Cataract
Rare (less than 0.1%): Glaucoma
Frequency not reported: Dry eyes, eye infections, keratitis, conjunctivitis[Ref]

Other

Common (1% to 10%): Candidiasis unspecified site, ear signs and symptoms, viral infections, bacterial infections, inflammation, bacterial reproductive infections
Rare (less than 0.1%): Angioedema, facial angioedema
Frequency not reported: Syncope, edema and swelling, dysmenorrhea, pain, unusual taste, lacerations
Postmarketing reports: Ear ache, fever[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Cutaneous hypersensitivity reactions
Rare (less than 0.1%): Anaphylactic reactions including anaphylactic shock[Ref]

Psychiatric

Uncommon (0.1% to 1%): Anxiety, sleep disorders
Rare (less than 0.1%): Behavioral changes, including psychomotor hyperactivity and irritability (predominately in children)
Frequency not reported: Depression, aggression (predominantly in children)
Postmarketing reports: Agitation[Ref]

Endocrine

Rare (less than 0.1%): Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease bone mineral density
Frequency not reported: Hypothyroidism
Postmarketing reports: Hypercorticism[Ref]

Hepatic

Frequency not reported: Abnormal liver function tests[Ref]

Some side effects of Advair Diskus may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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