warnings and cautions
5 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). Localized infections of the mouth and pharynx with Candida albicans have occurred in patients treated with ICS agents. Monitor patients periodically. When such an infection develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while treatment with AIRSUPRA continues. In some cases, therapy with AIRSUPRA may need to be interrupted. Advise the patient to rinse his/her mouth with water, if available, without swallowing following administration of AIRSUPRA to help reduce the risk of oropharyngeal candidiasis. 5.10 Hypercorticism and Adrenal Suppression Budesonide, a component of AIRSUPRA, will often help control asthma symptoms with less suppression of hypothalamic-pituitary-adrenal (HPA) function than therapeutically equivalent oral doses of prednisone. Since budesonide is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of AIRSUPRA in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded. Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing AIRSUPRA. Because of the possibility of systemic absorption of ICS, patients treated with AIRSUPRA should be observed carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response. It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients who are sensitive to these effects. If such effects occur, appropriate therapy should be initiated as needed. 5.11 Reduction in Bone Mineral Density Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing ICS. The clinical significance of small changes in BMD with regard to long-term consequences such as fracture is unknown. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, post-menopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care. 5.12 Glaucoma and Cataracts Glaucoma, increased intraocular pressure, and cataracts have been reported following the long-term administration of ICS, including budesonide, a component of AIRSUPRA. Consider referral to an ophthalmologist in patients who develop ocular symptoms. 5.13 Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors 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) because adverse effects related to increased systemic exposure to budesonide may occur [see Drug Interactions (7.1) , Clinical Pharmacology (12.3) ] . 5.14 Effects on Growth in Pediatric Patients Orally inhaled corticosteroids, including budesonide, may cause a reduction in growth velocity when administered to pediatric patients. The safety and effectiveness of AIRSUPRA have not been established in pediatric patients, and AIRSUPRA is not indicated for use in this population [see Use in Specific Populations (8.4) ] .