Airsupra

Albuterol sulfate and budesonide · Aerosol, Metered · Respiratory (inhalation)

Prescription (Rx) Corticosteroid beta2-Adrenergic Agonist 1 recall

Uses

1 INDICATIONS AND USAGE AIRSUPRA is indicated for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients with asthma 18 years of age and older. AIRSUPRA is a combination of albuterol, a beta 2 -adrenergic agonist and budesonide, a corticosteroid, indicated for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients with asthma 18 years of age and older. ( 1 )

Dosage and administration

• Recommended Dosage: AIRSUPRA 180 mcg/160 mcg (administered as 2 actuations of albuterol/budesonide 90 mcg/80 mcg) by oral inhalation as needed for asthma symptoms. ( 2.1 )
• Do not take more than 6 doses (12 inhalations) in a 24-hour period. ( 2.1 )
• Prime inhaler prior to first use. Re-prime when inhaler has not been used for more than 7 days, is dropped, or after cleaning. ( 2.2 )
• Discard when the dose counter displays 0. ( 2.3 ) 2.1 Recommended Dosage and Administration The recommended dosage of AIRSUPRA is albuterol 180 mcg and budesonide 160 mcg (administered as 2 actuations of AIRSUPRA [albuterol/budesonide 90 mcg/80 mcg]) as needed for asthma symptoms by oral inhalation. Do not take more than 6 doses (12 inhalations) in a 24-hour period [see Warnings and Precautions (5.4) ] . 2.2 Priming Before Use
• Priming AIRSUPRA is essential to ensure appropriate drug content in each actuation. Prime AIRSUPRA before using for the first time. To prime AIRSUPRA, release 4 sprays into the air away from the face, shaking well before each spray.
• AIRSUPRA must be re-primed when the inhaler has not been used for more than 7 days, is dropped, or after cleaning. To re-prime AIRSUPRA, release 2 sprays into the air away from the face, shaking well before each spray. 2.3 Dose Counter The canister has an attached dose indicator (also known as puff indicator) which indicates how many inhalations (puffs) remain. The dose indicator pointer will move after every actuation. The pointer will show the number of inhalations remaining in the canister. When nearing the end of the usable inhalations, the color behind the number in the dose indicator display window changes to yellow. AIRSUPRA should be discarded when the pointer reaches zero.

Dosage forms and strengths

Inhalation aerosol: a pressurized metered dose inhaler (a pressurized canister with an attached dose indicator, supplied with a white plastic actuator with a frosted clear plastic dust cap) that delivers a combination of albuterol 90 mcg and budesonide 80 mcg per actuation. Inhalation aerosol: Pressurized metered dose inhaler that delivers a combination of albuterol 90 mcg and budesonide 80 mcg per actuation. ( 3 )

Contraindications

4 CONTRAINDICATIONS AIRSUPRA is contraindicated in patients with a history of hypersensitivity to albuterol, budesonide, or any of the excipients [see Warnings and Precautions (5.5) , Description (11) ] . Hypersensitivity to albuterol, budesonide, or to any of the excipients. ( 4 )

Warnings and precautions

• If symptoms continue after using AIRSUPRA, this may be a marker of destabilization of asthma and requires reevaluation of treatment. ( 5.1 )
• If paradoxical bronchospasm occurs, discontinue AIRSUPRA immediately and institute alternative therapy. ( 5.2 )
• Cardiovascular effects may occur. Use with caution in patients sensitive to sympathomimetic drugs and patients with cardiovascular disorders. ( 5.3 )
• Excessive use may be fatal. Do not exceed maximum recommended dosage. ( 5.4 )
• Hypersensitivity reactions may occur. Discontinue AIRSUPRA immediately. ( 5.5 )
• Use with caution in patients with convulsive disorders, hyperthyroidism, diabetes mellitus, and ketoacidosis. ( 5.6 )
• Hypokalemia may occur. ( 5.7 )
• Potential worsening of infections (e.g., existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex). Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients. ( 5.8 )
• Oropharyngeal candidiasis may occur. Advise patients to rinse mouth with water, if available, without swallowing after use. Monitor patients periodically. ( 5.9 )
• Hypercorticism and adrenal suppression may occur with very high dosages in susceptible individuals. If such changes occur, consider appropriate therapy. ( 5.10 )
• Monitor patients with major risk factors for decreased bone mineral content. ( 5.11 )
• Glaucoma and cataracts may occur. Consider referral to an ophthalmologist in patients who develop ocular symptoms. ( 5.12 ) 5.1 Deterioration of Asthma Asthma may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient continues to experience symptoms after using AIRSUPRA or requires more doses of AIRSUPRA than usual, this may be a marker of destabilization of asthma and requires evaluation of the patient and their treatment regimen. 5.2 Paradoxical Bronchospasm AIRSUPRA can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with AIRSUPRA, it should be discontinued immediately, and alternative therapy should be instituted. It should be recognized that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new canister. 5.3 Cardiovascular Effects AIRSUPRA, like other drugs containing beta 2 -adrenergic agonists, can produce clinically significant cardiovascular effects in some patients as measured by increases in pulse rate, blood pressure, and/or other symptoms. If such effects occur, AIRSUPRA may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the T wave, prolongation of the QTc interval, and ST-segment depression. The clinical significance of these findings is unknown. Therefore, AIRSUPRA, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. 5.4 Do Not Exceed Recommended Dosage As with other inhaled drugs containing beta-adrenergic agents, AIRSUPRA should not be used more than the maximum daily dose [see Dosage and Administration (2.1) ] , as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. 5.5 Hypersensitivity Reactions, Including Anaphylaxis Hypersensitivity reactions can occur after administration of albuterol sulfate and budesonide, components of AIRSUPRA, as demonstrated by cases of anaphylaxis, angioedema, bronchospasm, oropharyngeal edema, rash, and urticaria. Discontinue AIRSUPRA if such reactions occur [see Contraindications (4) ] . 5.6 Risk of Sympathomimetic Amines with Certain Coexisting Conditions AIRSUPRA, like all therapies containing sympathomimetic amines, should be used with caution in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus and in patients who are unusually responsive to sympathomimetic amines. Large doses of intravenous albuterol have been reported to aggravate preexisting diabetes mellitus and ketoacidosis. 5.7 Hypokalemia Beta-adrenergic agonist medicines may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects [see Warnings and Precautions (5.3) , Clinical Pharmacology (12.1) ] . The decrease in serum potassium is usually transient, not requiring supplementation. 5.8 Immunosuppression and Risk of Infections Patients who are using drugs that suppress the immune system are more susceptible to infection. Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible patients using corticosteroids. In patients who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affects the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If a patient is exposed to chicken pox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated (see the respective Prescribing Information for VZIG and IG). If chicken pox develops, treatment with antiviral agents may be considered. Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infection of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. 5.9 Oropharyngeal Candidiasis AIRSUPRA contains budesonide, an inhaled corticosteroid (ICS).

Side effects

The following clinically significant adverse reactions are described elsewhere in labeling:
• Deterioration of Asthma [see Warnings and Precautions (5.1) ]
• Paradoxical Bronchospasm [see Warnings and Precautions (5.2) ]
• Cardiovascular Effects [see Warnings and Precautions (5.3) ]
• Hypersensitivity Reactions, including Anaphylaxis [see Warnings and Precautions (5.5) ]
• Hypokalemia [see Warnings and Precautions (5.7) ]
• Immunosuppression and Risk of Infections [see Warnings and Precautions (5.8) ]
• Oropharyngeal Candidiasis [see Warnings and Precautions (5.9) ]
• Hypercorticism and Adrenal Suppression [see Warnings and Precautions (5.10) ]
• Reduction in Bone Mineral Density [see Warnings and Precautions (5.11) ]
• Glaucoma and Cataracts [see Warnings and Precautions (5.12) ]
• Effects on Growth in Pediatric Patients [see Warnings and Precautions (5.14) ] Most common adverse reactions (incidence ≥ 1%) are headache, oral candidiasis, cough, dysphonia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of AIRSUPRA is based on data from 3 trials: MANDALA, DENALI and BATURA [see Clinical Studies (14) ] . All reported safety data is based on patients who received AIRSUPRA 180 mcg/160 mcg. While patients 12 to 17 years of age were included in these trials, AIRSUPRA is not approved in this age group [see Use in Specific Populations (8.4) ] . In MANDALA, AIRSUPRA 180 mcg/160 mcg was administered as needed in patients with asthma who were receiving medium to high dose ICS or low to high dose ICS/LABA, with or without another controller medicine as maintenance therapy. A total of 1015 patients 12 to 84 years of age (mean age: 51 years) received at least one dose of AIRSUPRA and participated in the study for a mean duration of 310 days. Of these, 905 patients were exposed for at least 24 weeks and 323 patients had exposure for at least 1 year. The mean daily use was 2.6 actuations. On the majority of study days, patients used 2 or less actuations; more than 8 actuations were used on less than 2% of study days. The incidence of common adverse reactions in MANDALA is described in Table 1. Table 1 Summary of Adverse Reactions with AIRSUPRA Reported in ≥ 1% of Patients (MANDALA) Adverse Reaction AIRSUPRA 180 mcg/160 mcg N = 1015 (%) AS MDI 1 180 mcg N = 1015 (%) Headache 44 (4.3) 50 (4.9) Oral candidiasis 2 13 (1.3) 5 (0.5) Cough 10 (1.0) 11 (1.1) 1 Albuterol Metered Dose Inhaler = AS MDI 2 Oral candidiasis also includes those reactions reported under the preferred term oropharyngeal candidiasis. The safety profile of AIRSUPRA in MANDALA was similar to that observed with AS MDI, irrespective of background ICS dose. In DENALI, AIRSUPRA 180 mcg/160 mcg was administered 4 times a day for 12 weeks in patients with asthma who were previously treated with as-needed short-acting beta 2 -agonists (SABA) alone or with low-dose ICS maintenance therapy plus as-needed SABA. A total of 197 patients 13 to 81 years of age (mean age: 50 years) received at least one dose of AIRSUPRA. The adverse reactions profile was similar to MANDALA except for the following adverse reactions for AIRSUPRA with an incidence ≥ 1.0% that exceeded the incidence in MANDALA: headache (5.1%), dysphonia (2.0%), and oral/oropharyngeal candidiasis (1.5%), compared to headache (7.1%), dysphonia (0%), and oral/oropharyngeal candidiasis (0%) in the placebo arm. In BATURA, AIRSUPRA 180 mcg/160 mcg was administered as needed for 12 to 52 weeks in patients with asthma who were previously treated with as-needed SABA alone, or as-needed SABA plus background maintenance of either low-dose ICS or leukotriene receptor antagonist (LTRA). The 26% of patients on background ICS or LTRA were instructed to continue these treatments throughout the study period. A total of 1209 patients 12 to 95 years of age (mean age: 43 years) received at least one dose of AIRSUPRA and participated in the study for a mean duration of 259 days. Of them, 1109 patients were exposed for at least 12 weeks and 258 patients were exposed for at least 1 year. The mean daily use was 1.5 actuations for AIRSUPRA and 1.8 actuations for AS MDI 180 mcg. On the majority of study days, patients used 2 or less actuations of AIRSUPRA or AS MDI 180 mcg; more than 8 actuations were used on 2% of study days for patients on AIRSUPRA and 4% of study days for patients on AS MDI 180 mcg. The safety profile of AIRSUPRA in BATURA was similar to that in MANDALA. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of budesonide or albuterol. 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.

Drug interactions

No formal drug interaction studies have been performed with AIRSUPRA.
• Strong cytochrome P450 3A4 inhibitors (e.g. ritonavir): Use with caution. May cause systemic corticosteroid effects. ( 7.1 )
• Other short-acting bronchodilators: Use judiciously with other short-acting beta agonists. ( 7.2 )
• Beta blockers: May decrease effectiveness of AIRSUPRA and produce severe bronchospasm. When there are no acceptable alternatives to the use of beta-adrenergic-blocking agents, consider cardioselective beta-blockers and use with caution. ( 7.3 )
• Diuretics, or non-potassium-sparing diuretics: May potentiate hypokalemia or ECG changes. Consider monitoring potassium levels with concomitant use. ( 7.4 )
• Digoxin: May decrease serum digoxin levels. Carefully evaluate digoxin levels with concomitant use. ( 7.5 )
• Monoamine oxidase inhibitors (MAOI) and tricyclic antidepressants: Use AIRSUPRA with extreme caution with concomitant use. ( 7.6 ) 7.1 Inhibitors of Cytochrome P450 3A4 The main route of metabolism of corticosteroids, including budesonide, a component of AIRSUPRA, is via cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4). After oral administration of ketoconazole, a strong inhibitor of CYP3A4, the mean plasma concentration of orally administered budesonide increased. Concomitant administration of a CYP3A4 inhibitor may inhibit the metabolism of, and increase the systemic exposure to, budesonide. Caution should be exercised when considering the co-administration of AIRSUPRA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions (5.11) ] . 7.2 Use with Other Short-Acting Bronchodilators AIRSUPRA contains the short-acting beta-agonist, albuterol. Therefore, concomitant use of additional beta-agonists with AIRSUPRA should be used judiciously to prevent beta-agonist overdose. 7.3 Beta-Blockers Beta-adrenergic receptor blocking agents not only block the pulmonary effect of beta-agonists, such as albuterol, a component of AIRSUPRA, 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, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-adrenergic-blocking agents in these patients. In this setting, consider cardioselective beta-blockers, although they should be administered with caution. 7.4 Diuretics The ECG changes and/or hypokalemia which may result from the administration of non-potassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, 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 AIRSUPRA with non-potassium-sparing diuretics. Consider monitoring potassium levels. 7.5 Digoxin Mean decreases of 16% and 22% in serum digoxin levels were demonstrated after single-dose intravenous and oral administration of albuterol, respectively, to normal volunteers who had received digoxin for 10 days. The clinical significance of these findings for patients with obstructive airway disease who are receiving albuterol and digoxin on a chronic basis is unclear. Nevertheless, it would be prudent to carefully evaluate the serum digoxin levels in patients who are currently receiving digoxin and AIRSUPRA. 7.6 Monoamine Oxidase Inhibitors or Tricyclic Antidepressants AIRSUPRA 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 albuterol on the cardiovascular system may be potentiated.

Use in specific populations

Hepatic impairment: Budesonide systemic exposure may increase in patients with severe hepatic impairment. Monitor patients with hepatic disease. ( 8.6 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to asthma medications during pregnancy. For more information, contact the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists at 1-877-311-8972 or visit http://mothertobaby.org/pregnancy-studies/ . Risk Summary Available data from published case series, epidemiological studies and reviews with budesonide use in pregnant women have not identified a drug-related risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Available data from epidemiological studies and postmarketing case reports of pregnancy outcomes following inhaled albuterol use do not consistently demonstrate a risk of major birth defects or miscarriage. The available epidemiological studies have methodologic limitations, including inconsistent comparator groups, definitions of outcomes, and assessment of disease impact. There are risks to the mother and fetus associated with asthma in pregnancy (see Clinical Considerations) . Animal reproduction studies have not been conducted with AIRSUPRA, however, animal studies are available with its individual components, albuterol and budesonide. Administration of albuterol to mice and rabbits during the period of organogenesis revealed evidence of adverse developmental outcomes (cleft palate in mice, delayed ossification in rabbits) at less than maximum recommended human daily inhalation dose (MRHDID) (see Data) . In animal reproduction studies, budesonide, administered by the subcutaneous route, caused structural abnormalities, was embryocidal, and reduced fetal weights in rats and rabbits at less than the MRHDID in adults, but these effects were not seen in rats that received inhaled doses approximately 2.5 times the MRHDID in adults (see Data) . Experience with oral corticosteroids suggests that rodents are more prone to structural abnormalities from corticosteroid exposure than humans. The background risk of major birth defects and miscarriage of the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal risk In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control. Labor or Delivery Because of the potential for beta-agonist interference with uterine contractility, use of AIRSUPRA during labor should be restricted to those patients in whom the benefits clearly outweigh the risk. AIRSUPRA has not been approved for the management of pre-term labor. Serious adverse reactions, including pulmonary edema, have been reported during or following treatment of premature labor with beta 2 -agonists, including albuterol. Data Animal Data Albuterol In a study in pregnant mice, subcutaneously administered albuterol sulfate produced cleft palate formation in 5 of 111 (4.5%) fetuses at an exposure less than the MRHDID in adults (on a mg/m 2 basis at a maternal dose of 0.25 mg/kg) and in 10 of 108 (9.3%) fetuses at approximately 9 times the MRHDID in adults (on a mg/m 2 basis at a maternal dose of 2.5 mg/kg). Cleft palate also occurred in 22 of 72 (30.5%) fetuses from females treated subcutaneously with isoproterenol, another beta 2 -agonist. In a study in pregnant rabbits, orally administered albuterol sulfate produced cranioschisis in 7 of 19 fetuses (37%) at approximately 750 times the MRHDID in adults (on a mg/m 2 basis at a maternal dose of 50 mg/kg). In a study in pregnant rabbits, an albuterol/HFA-134a formulation administered by inhalation produced enlargement of the frontal portion of the fetal fontanelles at approximately one third of the MRHDID on a mg/m 2 basis. A study in which pregnant rats were dosed with radiolabeled albuterol sulfate demonstrated that drug-related material is transferred from the maternal circulation to the fetus. Budesonide In a fertility and reproduction study, male rats were subcutaneously dosed with budesonide for 9 weeks and females for 2 weeks prior to pairing and throughout the mating period. Females were dosed up until weaning of their offspring. Budesonide caused a decrease in prenatal viability and viability in the pups at birth and during lactation, along with a decrease in maternal body-weight gain, at doses 0.2 times the MRHDID in adults (on a mcg/m 2 basis at maternal subcutaneous doses of 20 mcg/kg/day and above). No such effects were noted at a dose 0.05 times the MRHDID in adults (on a mcg/m 2 basis at a maternal subcutaneous dose of 5 mcg/kg/day). In an embryo-fetal development study in pregnant rabbits dosed during the period of organogenesis from gestation days 6-18, budesonide produced fetal loss, decreased fetal weight, and skeletal abnormalities at doses 0.5 times the MRHDID in adults (on a mcg/m 2 basis at a maternal subcutaneous dose of 25 mcg/kg/day). In an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 6-15, budesonide produced similar adverse fetal effects at doses approximately 5 times the MRHDID in adults (on a mcg/m 2 basis at a maternal subcutaneous dose of 500 mcg/kg/day).

Pregnancy

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to asthma medications during pregnancy. For more information, contact the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists at 1-877-311-8972 or visit http://mothertobaby.org/pregnancy-studies/ . Risk Summary Available data from published case series, epidemiological studies and reviews with budesonide use in pregnant women have not identified a drug-related risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Available data from epidemiological studies and postmarketing case reports of pregnancy outcomes following inhaled albuterol use do not consistently demonstrate a risk of major birth defects or miscarriage. The available epidemiological studies have methodologic limitations, including inconsistent comparator groups, definitions of outcomes, and assessment of disease impact. There are risks to the mother and fetus associated with asthma in pregnancy (see Clinical Considerations) . Animal reproduction studies have not been conducted with AIRSUPRA, however, animal studies are available with its individual components, albuterol and budesonide. Administration of albuterol to mice and rabbits during the period of organogenesis revealed evidence of adverse developmental outcomes (cleft palate in mice, delayed ossification in rabbits) at less than maximum recommended human daily inhalation dose (MRHDID) (see Data) . In animal reproduction studies, budesonide, administered by the subcutaneous route, caused structural abnormalities, was embryocidal, and reduced fetal weights in rats and rabbits at less than the MRHDID in adults, but these effects were not seen in rats that received inhaled doses approximately 2.5 times the MRHDID in adults (see Data) . Experience with oral corticosteroids suggests that rodents are more prone to structural abnormalities from corticosteroid exposure than humans. The background risk of major birth defects and miscarriage of the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal risk In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control. Labor or Delivery Because of the potential for beta-agonist interference with uterine contractility, use of AIRSUPRA during labor should be restricted to those patients in whom the benefits clearly outweigh the risk. AIRSUPRA has not been approved for the management of pre-term labor. Serious adverse reactions, including pulmonary edema, have been reported during or following treatment of premature labor with beta 2 -agonists, including albuterol. Data Animal Data Albuterol In a study in pregnant mice, subcutaneously administered albuterol sulfate produced cleft palate formation in 5 of 111 (4.5%) fetuses at an exposure less than the MRHDID in adults (on a mg/m 2 basis at a maternal dose of 0.25 mg/kg) and in 10 of 108 (9.3%) fetuses at approximately 9 times the MRHDID in adults (on a mg/m 2 basis at a maternal dose of 2.5 mg/kg). Cleft palate also occurred in 22 of 72 (30.5%) fetuses from females treated subcutaneously with isoproterenol, another beta 2 -agonist. In a study in pregnant rabbits, orally administered albuterol sulfate produced cranioschisis in 7 of 19 fetuses (37%) at approximately 750 times the MRHDID in adults (on a mg/m 2 basis at a maternal dose of 50 mg/kg). In a study in pregnant rabbits, an albuterol/HFA-134a formulation administered by inhalation produced enlargement of the frontal portion of the fetal fontanelles at approximately one third of the MRHDID on a mg/m 2 basis. A study in which pregnant rats were dosed with radiolabeled albuterol sulfate demonstrated that drug-related material is transferred from the maternal circulation to the fetus. Budesonide In a fertility and reproduction study, male rats were subcutaneously dosed with budesonide for 9 weeks and females for 2 weeks prior to pairing and throughout the mating period. Females were dosed up until weaning of their offspring. Budesonide caused a decrease in prenatal viability and viability in the pups at birth and during lactation, along with a decrease in maternal body-weight gain, at doses 0.2 times the MRHDID in adults (on a mcg/m 2 basis at maternal subcutaneous doses of 20 mcg/kg/day and above). No such effects were noted at a dose 0.05 times the MRHDID in adults (on a mcg/m 2 basis at a maternal subcutaneous dose of 5 mcg/kg/day). In an embryo-fetal development study in pregnant rabbits dosed during the period of organogenesis from gestation days 6-18, budesonide produced fetal loss, decreased fetal weight, and skeletal abnormalities at doses 0.5 times the MRHDID in adults (on a mcg/m 2 basis at a maternal subcutaneous dose of 25 mcg/kg/day). In an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 6-15, budesonide produced similar adverse fetal effects at doses approximately 5 times the MRHDID in adults (on a mcg/m 2 basis at a maternal subcutaneous dose of 500 mcg/kg/day). In another embryo-fetal development study in pregnant rats, no structural abnormalities or embryocidal effects were seen at doses approximately 2.5 times the MRHDID in adults (on a mcg/m 2 basis at maternal inhalation doses up to 250 mcg/kg/day).

Pediatric use

8.4 Pediatric Use The safety and effectiveness of AIRSUPRA have not been established in pediatric patients. A limited number of pediatric patients were enrolled in the efficacy trials MANDALA (4 to 17 years of age) and BATURA (12 to 17 years of age) to evaluate AIRSUPRA to reduce the risk of severe asthma exacerbations. The primary efficacy endpoint was time to first severe asthma exacerbation. MANDALA enrolled patients with asthma who were receiving medium to high dose ICS or low to high dose ICS/LABA, with or without another controller medicine as maintenance therapy. In MANDALA, there were 9 patients with severe exacerbation events in 34 patients 12 to 17 years of age treated with AIRSUPRA 180 mcg/160 mcg and 7 patients with severe exacerbation events in 34 patients treated with albuterol (AS MDI) [HR 1.44 (0.54, 3.87)]. There were 11 patients with severe exacerbation events in 41 patients 4 to 11 years of age treated with albuterol/budesonide (AS-BD MDI) 180 mcg/80 mcg and 10 in the 42 patients 4 to 11 years of age treated with AS MDI [HR: 1.09 (0.46, 2.56)]. BATURA enrolled patients with asthma who were previously treated with as-needed SABA alone, or as-needed SABA plus background maintenance of either low-dose ICS or LTRA. In the BATURA trial, 1 patient had a severe exacerbation event in 29 patients treated with AIRSUPRA 180 mcg/160 mcg and 1 patient with severe exacerbation events in 39 patients treated with AS MDI. These data are inadequate to make a determination regarding the safety or effectiveness of AIRSUPRA or AS-BD 180 mcg/80 mcg in pediatric patients 4 to 17 years of age [see Clinical Studies (14) ] . Controlled clinical studies have shown that ICS agents, including budesonide, one of the components of AIRSUPRA, may cause a reduction in growth velocity in pediatric patients. The effects of long-term treatment of pediatric patients with ICS on final adult height are not known [see Warnings and Precautions (5.14) ].

Geriatric use

8.5 Geriatric Use There were 921 patients 65 years of age and older in the clinical studies for asthma [see Clinical Studies (14) ] . Of the total number of AIRSUPRA-treated patients in these studies, 311 (13%) were 65 years of age and older, while 52 (2%) were 75 years of age and older. In general, no differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. As with other products containing beta 2 -agonists, special caution should be observed when using AIRSUPRA in geriatric patients who have concomitant cardiovascular disease that could be adversely affected by this class of drug. All beta 2 -adrenergic agonists, including albuterol, are known to be substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function. Because geriatric patients are more likely to have decreased renal function, care should be taken when dosing, and it may be useful to monitor renal function.

Overdosage

10 OVERDOSAGE AIRSUPRA contains both albuterol and budesonide; therefore, the risks associated with overdosage for the individual components described below apply to AIRSUPRA. Albuterol The expected symptoms with overdosage are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the symptoms of beta-adrenergic stimulation (e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats/minute, arrhythmias, nervousness, headache, tremor, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, insomnia, hyperglycemia, and metabolic acidosis). Hypokalemia may also occur. As with all sympathomimetic medications, cardiac arrest and even death may be associated with abuse of AIRSUPRA. Treatment consists of discontinuation of AIRSUPRA together with appropriate symptomatic therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of AIRSUPRA. Budesonide If used at excessive doses for prolonged periods, systemic corticosteroid effects such as hypercorticism may occur [see Warnings and Precautions (5.10) ] .

Description

(albuterol and budesonide) Inhalation Aerosol is a pressurized metered dose inhaler containing a combination of micronized albuterol sulfate, a relatively selective, short-acting beta 2 -adrenergic agonist and micronized budesonide, a corticosteroid, for oral inhalation. Albuterol sulfate is the official generic name in the United States. The World Health Organization recommended name for the drug is salbutamol sulfate. Albuterol sulfate has the following chemical name: USP racemic α 1 [( tert- Butylamino)methyl]-4-hydroxy- m -xylene-α,α'-diol sulfate (2:1) (salt). The empirical formula is (C 13 H 21 NO 3 ) 2
• H 2 SO 4 , and the molecular weight is 576.7. Its structural formula is: Albuterol sulfate is a white to off-white powder that is freely soluble in water, slightly soluble in alcohol and in ether, and practically insoluble in chloroform. It has a LogP of 0.44 at physiological pH. Albuterol has one chiral center and exists as a 1:1 racemic mixture. Budesonide is a corticosteroid designated chemically as (RS)-11β, 16α, 17,21-Tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with butyraldehyde. Budesonide is provided as a mixture of two epimers (22R and 22S). The empirical formula of budesonide is C 25 H 34 O 6 and its molecular weight is 430.5. Its structural formula is: Budesonide is a white to off-white powder that is practically insoluble in water and in heptane, sparingly soluble in ethanol, and freely soluble in chloroform. Its partition coefficient between octanol and water at pH 7.4 is 1.6 x 10 3 . AIRSUPRA is formulated as a hydrofluoroalkane (HFA-134a) propelled pressurized metered dose inhaler containing 120 inhalations. The canister has an attached dose indicator and is supplied with a white plastic actuator with a frosted clear plastic dust cap tethered to it. After priming, each actuation of AIRSUPRA 90 mcg/80 mcg meters 99 mcg of albuterol and 88 mcg of budesonide from the valve which delivers 90 mcg of albuterol (equivalent to 108 mcg of albuterol sulfate) and 80 mcg of budesonide from the actuator. The actual amount of drug delivered to the lung may depend on patient factors, such as the coordination between actuation of the device and inhalation through the delivery system. AIRSUPRA also contains porous particles that form a co-suspension with the drug crystals. The porous particles are comprised of the phospholipid 1,2-distearoyl- sn -glycero-3-phosphocholine (DSPC) and calcium chloride. Porous particles and HFA-134a are excipients in the formulation. Albuterol structural formula Budesonide structural formula

Mechanism of action

12.1 Mechanism of Action AIRSUPRA contains both albuterol and budesonide; therefore, the mechanisms of action described below for the individual components apply to AIRSUPRA. These drugs represent two classes of medications (a short-acting selective beta 2 -adrenergic agonist and a synthetic corticosteroid) that have different effects on clinical, physiological, and inflammatory indices of asthma. Albuterol In vitro studies and in vivo pharmacologic studies have demonstrated that albuterol has a preferential effect on beta 2 -adrenergic receptors compared with isoproterenol. Although beta 2 -adrenoceptors are the predominant adrenergic receptors in bronchial smooth muscle and beta 1 -adrenoceptors are the predominant receptors in the heart, there are also beta 2 -adrenoceptors in the human heart comprising 10% to 50% of the total beta-adrenoceptors. The precise function of these receptors has not been established, but their presence raises the possibility that even selective beta 2 -agonists may have cardiac effects. Activation of beta 2 -adrenergic receptors on airway smooth muscle leads to the activation of adenyl cyclase and to an increase in the intracellular concentration of cyclic-3′,5′-adenosine monophosphate (cyclic AMP). This increase of cyclic AMP leads to the activation of protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation. Albuterol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles. Albuterol acts as a functional antagonist to relax the airway irrespective of the spasmogen involved, thus protecting against all bronchoconstrictor challenges. Increased cyclic AMP concentrations are also associated with the inhibition of release of mediators from mast cells in the airway. Albuterol has been shown in most controlled clinical trials to have more effect on the respiratory tract, in the form of bronchial smooth muscle relaxation, than isoproterenol at comparable doses while producing fewer cardiovascular effects. Controlled clinical studies and other clinical experience have shown that inhaled albuterol, like other beta-adrenergic agonist drugs, can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or electrocardiographic changes [see Warnings and Precautions (5.3) ] . Budesonide Budesonide is an anti-inflammatory corticosteroid that exhibits potent glucocorticoid activity and weak mineralocorticoid activity. In standard in vitro and animal models, budesonide has approximately a 200-fold higher affinity for the glucocorticoid receptor and a 1000-fold higher topical anti-inflammatory potency than cortisol (rat croton oil ear edema assay). As a measure of systemic activity, budesonide is 40 times more potent than cortisol when administered subcutaneously and 25 times more potent when administered orally in the rat thymus involution assay. The clinical significance of this is unknown. In glucocorticoid receptor affinity studies, the 22R form was two times as active as the 22S epimer. In vitro studies indicated that the two forms of budesonide do not interconvert. The precise mechanism of corticosteroid actions on inflammation in asthma is not known. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have a wide range of inhibitory activities against multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic and non-allergic-mediated inflammation. These anti-inflammatory actions of corticosteroids may contribute to their efficacy in asthma. Studies in asthmatic patients have shown a favorable ratio between topical anti-inflammatory activity and both genomic and non-genomic systemic corticosteroid effects over a wide range of doses of inhaled budesonide. This is explained by a combination of a relatively high local anti-inflammatory effect, extensive first pass hepatic degradation of orally absorbed drug (85-95%), and the low potency of formed metabolites (see below).

How supplied

Inhalation Aerosol is supplied as a pressurized aluminum canister with an attached dose indicator and a white plastic actuator, with a frosted clear plastic dust cap tethered to it. Each canister is packaged in a foil overwrap pouch with a desiccant sachet and placed into a carton. Each carton contains one canister and a Patient Information leaflet. Each 120-inhalation canister has a net fill weight of 10.7 grams. AIRSUPRA is available in the following package size as presented in Table 4: Table 4 Package Information for AIRSUPRA Package Size Strength albuterol/budesonide Number of Inhalations per Canister NDC AIRSUPRA 90 mcg/80 mcg 120 0310-9080-12 The AIRSUPRA canister should only be used with the AIRSUPRA actuator, and the AIRSUPRA actuator should not be used with any other inhalation drug product. Counter The correct amount of medication in each inhalation cannot be ensured after the labeled number of inhalations from the canister have been used, when the dose indicator pointer reaches zero, even though the canister may not feel completely empty. AIRSUPRA should be discarded when the dose indicator pointer reaches zero, or 12 months after removal of the foil pouch, whichever comes first. Never immerse the canister in water to determine the amount remaining in the canister (“float test”). Storage Store at controlled room temperature 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [ see USP ] . Keep in a dry place away from heat and sunlight. For best results, the canister should be at room temperature before use. Shake well before using. Keep out of reach of children. Contents under pressure. Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 49°C (120°F) may cause bursting. Never throw canister into fire or incinerator. Avoid spraying in eyes.

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Deterioration of Asthma Inform patients to seek medical attention immediately if treatment with AIRSUPRA becomes less effective for symptomatic relief, and/or symptoms become worse [see Warnings and Precautions (5.1) ] . Paradoxical Bronchospasm Instruct patients to discontinue AIRSUPRA and contact their healthcare provider right away if they develop paradoxical bronchospasm [see Warnings and Precautions (5.2) ] . Do Not Exceed Recommended Dosage Instruct patients concerning the recommended dosage of AIRSUPRA and not to exceed 6 doses (12 inhalations) in a 24-hour period [see Dosage and Administration (2.1) , Warnings and Precautions (5.4) ] . Hypersensitivity Reactions, Including Anaphylaxis Advise patients to contact their healthcare provider and discontinue AIRSUPRA if hypersensitivity reactions (e.g., anaphylaxis, rash, urticaria, angioedema, and bronchospasm) occur with AIRSUPRA use [see Warnings and Precautions (5.5) ] . Priming and Cleaning Inhaler Instruct patients to prime the inhaler before using for the first time, when the inhaler has not been used for more than 7 days, is dropped, or after cleaning and to shake well before each spray. To ensure proper dosing and to prevent actuator mouthpiece blockage, instruct patients how to clean the actuator [see Dosage and Administration (2.1) and Instructions for Use ] . Use with Other Short-Acting Bronchodilators Advise patients concerning the appropriate use of other short-acting bronchodilators while using AIRSUPRA [see Drug Interactions (7.2) ] . Immunosuppression and Risk of Infections Warn patients who are on immunosuppressant doses of corticosteroids to avoid exposure to chickenpox or measles and, if exposed, to consult their physician without delay. Patients should be informed of potential worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infections, or ocular herpes simplex [see Warnings and Precautions (5.8) ] . Oropharyngeal Candidiasis Patients should be advised that localized infections with Candida albicans occurred in the mouth and pharynx in some patients. Advise patients to rinse the mouth with water, if available, without swallowing after AIRSUPRA inhalation to help reduce the risk of thrush [see Warnings and Precautions (5.9) ] . Hypercorticism and Adrenal Suppression Advise patients that AIRSUPRA may cause systemic corticosteroid effects of hypercorticism and adrenal suppression [see Warnings and Precautions (5.10) ] . Reduction in Bone Mineral Density Advise patients who are at an increased risk for decreased BMD that the use of AIRSUPRA may pose an additional risk [see Warnings and Precautions (5.11) ] . Glaucoma and Cataracts Inform patients that long-term use of AIRSUPRA may increase the risk of increased intraocular pressure, glaucoma, and cataracts; consider regular eye examinations [see Warnings and Precautions (5.12) ] . Pregnancy Advise pregnant women that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to asthma medications during pregnancy and to contact the MotherToBaby Pregnancy Studies at 1-877-311-8972 or visit http://mothertobaby.org/pregnancy-studies/ . Manufactured for: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850 Manufactured by: AstraZeneca Dunkerque Production (AZDP), Dunkerque, France AIRSUPRA is a registered trademark of the AstraZeneca group of companies. ©AstraZeneca 2025

Label text from the FDA structured product label by AstraZeneca Pharmaceuticals LP (revised Sep 18, 2025). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Airsupra NDC products (1)

NDCStrength & formLabelerType
0310-9080Albuterol Sulfate 90 ug/1; Budesonide 80 ug/1
Aerosol, Metered		AstraZeneca Pharmaceuticals LPNDA

Airsupra recalls

Frequently asked questions

What is Airsupra used for?

1 INDICATIONS AND USAGE AIRSUPRA is indicated for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients with asthma 18 years of age and older. AIRSUPRA is a combination of albuterol, a beta 2 -adrenergic agonist and budesonide, a corticosteroid, indicated for the as-needed treatment or prevention of bronchoconstriction and to reduce the…

What are the side effects of Airsupra?

The following clinically significant adverse reactions are described elsewhere in labeling: • Deterioration of Asthma [see Warnings and Precautions (5.1) ] • Paradoxical Bronchospasm [see Warnings and Precautions (5.2) ] • Cardiovascular Effects [see Warnings and Precautions (5.3) ] • Hypersensitivity Reactions, including Anaphylaxis [see Warnings and Precautions (5.5) ] • Hypokalemia [see… See the full label for the complete list.

Who makes Airsupra?

Airsupra is listed by 1 labeler in the FDA NDC directory, including AstraZeneca Pharmaceuticals LP.

Has Airsupra been recalled?

The FDA enforcement database lists 1 recall for Airsupra, most recently D-0444-2025 (class ii): Defective delivery system