Budesonide

PULMICORT RESPULES ® is an inhaled corticosteroid indicated for: • Maintenance treatment of asthma and as prophylactic therapy in children 12 months to 8 years of age. Limitations of Use: Not indicated for the relief of acute bronchospasm

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 these findings is unknown. The activity of PULMICORT RESPULES is due to the parent drug, budesonide. 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 recommended starting dose and highest recommended dose of PULMICORT RESPULES, based on prior asthma therapy, are listed in the following table. Previous Therapy Recommended Starting Dose Highest Recommended Dose Bronchodilators alone 0.5 mg total daily dose administered either once daily or twice daily in divided doses 0.5 mg total daily dose Inhaled Corticosteroids 0.5 mg total daily dose administered either once daily or twice daily in divided doses 1 mg total daily dose Oral Corticosteroids 1 mg total daily dose administered either as 0.5 mg twice daily or 1 mg once daily 1 mg total daily dose Recommended dosing based on previous therapy.

The use of PULMICORT RESPULES is contraindicated in the following conditions: • Primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required. • Hypersensitivity to budesonide or any of the ingredients of PULMICORT RESPULES. • Primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required. • Hypersensitivity to any of the ingredients in PULMICORT RESPULES

• Localized Infections: Candida albicans infection of the mouth and throat may occur. Monitor patients periodically for signs of adverse effects on the oral cavity. Advise patients to rinse the mouth following inhalation. • Deterioration of Disease and Acute Asthma Episodes: Do not use for the relief of acute bronchospasm. • Hypersensitivity Reactions: Anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm have been reported with use of PULMICORT RESPULES. Discontinue PULMICORT RESPULES if such reactions occur. • Immunosuppression: Potential worsening of infections (e.g., existing tuberculosis, fungal, bacterial, viral, or parasitic infection, 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.

Systemic and inhaled corticosteroid use may result in the following: • Candida albicans Infection • Hypersensitivity Reactions Including Anaphylaxis • Immunosuppression • Hypercorticism and Adrenal Suppression • Reduction in Bone Mineral Density • Growth Effects in Pediatric Patients • Glaucoma, Increased Intraocular Pressure and Cataracts • Eosinophilic Conditions and Churg-Strauss Syndrome Most common adverse reactions (incidence > 3%) are respiratory infection, rhinitis, coughing, otitis media, viral infection, moniliasis, gastroenteritis, vomiting, diarrhea, abdominal pain, ear infection, epistaxis, conjunctivitis, rash

Strong Cytochrome P450 3A4 Inhibitors (e.g., ritonavir): Use with caution. May cause increased systemic corticosteroid effects Inhibitors of Cytochrome P450 3A4 The main route of metabolism of corticosteroids, including budesonide, 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 coadministration of PULMICORT RESPULES with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin).

PULMICORT RESPULES is available in three strengths, each containing 2 mL: NDC 0186–1988–04 0.25 mg/2 mL NDC 0186–1989–04 0.5 mg/2 mL NDC 0186–1990–04 1 mg/2 mL PULMICORT RESPULES should be stored upright at controlled room temperature 20-25°C (68-77°F), and protected from light. Do not freeze.