Budesonide

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

2 DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

The recommended starting dose and highest recommended dose of budesonide inhalation suspension, 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 as 0.5 mg twice daily 1 mg total daily dose

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

Budesonide inhalation suspension is available in two strengths, each containing 2 mL: 0.25 mg/2 mL and 0.5 mg/2 mL. Budesonide inhalation suspension is supplied in sealed aluminum foil envelopes containing one plastic strip of five single-dose vials. There are 30 vials in a carton. Each single-dose vial contains 2 mL of sterile liquid suspension.

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

The use of budesonide inhalation suspension 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 budesonide inhalation suspension [see Warnings and Precautions ( 5.3 ), Description ( 11 ) , Adverse Reactions ( 6.2 ) ].

5 WARNINGS AND PRECAUTIONS

WARNINGS AND PRECAUTIONS SECTION

6 ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

Systemic and inhaled corticosteroid use may result in the following: Candida albicans Infection [see Warnings and Precautions ( 5.1 ) ] Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions ( 5.3 ) ] Immunosuppression [see Warnings and Precautions ( 5.4 ) ] Hypercorticism and Adrenal Suppression [see Warnings and Precautions ( 5.6 ) ] Reduction in Bone Mineral Density [see Warnings and Precautions ( 5.7 ) ] Growth Effects in Pediatric Patients [see Warnings and Precautions ( 5.8 ), Use in Specific Populations ( 8.4 ) ] Glaucoma, Increased Intraocular Pressure and Cataracts [see Warnings and Precautions ( 5.9 ) ] Eosinophilic Conditions and Churg-Strauss Syndrome [see Warnings and Precautions ( 5.11 ) ]

7 DRUG INTERACTIONS

DRUG INTERACTIONS SECTION

8 USE IN SPECIFIC POPULATIONS

USE IN SPECIFIC POPULATIONS SECTION

10 OVERDOSAGE

OVERDOSAGE SECTION

The potential for acute toxic effects following overdose of budesonide inhalation suspension is low. If inhaled corticosteroids are used at excessive doses for prolonged periods, systemic corticosteroid effects such as hypercorticism or growth suppression may occur [see Warnings and Precautions ( 5.6 ) ].

11 DESCRIPTION

DESCRIPTION SECTION

Budesonide, USP, the active component of budesonide inhalation suspension, 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, USP is provided as a mixture of two epimers (22R and 22S) and it has the following structural formula: Budesonide, USP is a white to off-white, tasteless, odorless 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 . Budesonide inhalation suspension is a sterile suspension for inhalation via jet nebulizer and contains the active ingredient budesonide, USP (micronized), and the inactive ingredients: citric acid monohydrate, disodium edetate, polysorbate 80, sodium chloride, tri-sodium citrate dihydrate and water for injection. Two dose strengths are available in single-dose vials: 0.25 mg and 0.5 mg per 2 mL vial. For budesonide inhalation suspension, like all other nebulized treatments, the amount delivered to the lungs will depend on patient factors, the jet nebulizer utilized, and compressor performance. Using the Pari-LC-Jet Plus ® Nebulizer/Pari Master ® compressor system, under in vitro conditions, the mean delivered dose at the mouthpiece (% nominal dose) was approximately 17% at a mean flow rate of 5.5 L/min. The mean nebulization time was 5 minutes or less. Budesonide inhalation suspension should be administered from jet nebulizers at adequate flow rates, via face masks or mouthpieces [see Dosage and Administration ( 2 ) ].

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

14 CLINICAL STUDIES

CLINICAL STUDIES SECTION

Three double-blind, placebo-controlled, parallel group, randomized U.S. clinical trials of 12 weeks duration each were conducted in 1018 pediatric patients, 6 months to 8 years of age, 657 males and 361 females (798 Caucasians, 140 Blacks, 56 Hispanics, 3 Asians, 21 Others) with persistent asthma of varying disease duration (2 to 107 months) and severity. Doses of 0.25 mg and 0.5 mg administered twice daily were compared to placebo to provide information about appropriate dosing to cover a range of asthma severity. A Pari-LC-Jet Plus Nebulizer (with a face mask or mouthpiece) connected to a Pari Master compressor was used to deliver budesonide inhalation suspension to patients in the 3 U.S. controlled clinical trials. The co-primary endpoints were nighttime and daytime asthma symptom scores (0 to 3 scale). Improvements were addressed in terms of the primary efficacy variables of changes from baseline to the double-blind treatment period in nighttime and daytime asthma symptom scores (scale 0 to 3) as recorded in the patient diaries. Baseline was defined as the mean of the last seven days prior to randomization. The double-blind treatment period was defined as the mean over 12 week treatment period. Each of the five doses discussed below were studied in one or two, but not all three of the U.S. studies. Results of the 3 controlled clinical trials for recommended dosages of budesonide inhalation suspension (0.25 mg to 0.5 mg once or twice daily up to a total daily dose of 1 mg) in patients, 12 months to 8 years of age, are presented below. Statistically significant decreases in nighttime and daytime symptom scores of asthma were observed at budesonide inhalation suspension doses of 0.25 mg once daily (one study), 0.25 mg twice daily, and 0.5 mg twice daily compared to placebo. Use of budesonide inhalation suspension resulted in statistically significant decreases in either nighttime or daytime symptom scores, but not both, at doses of 0.5 mg once daily (one study). Symptom reduction in response to budesonide inhalation suspension occurred across gender and age. Statistically significant reductions in the need for bronchodilator therapy were also observed at all the doses of budesonide inhalation suspension studied. Improvements in lung function were associated with budesonide inhalation suspension in the subgroup of patients capable of performing lung function testing. Statistically significant increases were seen in FEV 1 [budesonide inhalation suspension 0.5 mg twice daily] and morning PEF [budesonide inhalation suspension 0.25 mg twice daily; 0.5 mg twice daily] compared to placebo. A numerical reduction in nighttime and daytime symptom scores (0 to 3 scale) of asthma was observed within 2 to 8 days, although maximum benefit was not achieved for 4 to 6 weeks after starting treatment. The reduction in nighttime and daytime asthma symptom scores was maintained throughout the 12 weeks of the double-blind trials. Patients Not Receiving Inhaled Corticosteroid Therapy The efficacy of budesonide inhalation suspension at doses of 0.25 mg and 0.5 mg once daily was evaluated in pediatric patients, 12 months to 8 years of age, with mild to moderate persistent asthma (mean baseline nighttime asthma symptom scores of the treatment groups ranged from 1.07 to 1.34) who were not well controlled by bronchodilators alone. The changes from baseline to Weeks 0 to 12 in nighttime asthma symptom scores are shown in Figure 1. Nighttime asthma symptom scores showed statistically significant decreases in the patients treated with budesonide inhalation suspension compared to placebo. Similar decreases were also observed for daytime asthma symptom scores. Changes from baseline to the double-blind phase for the budesonide treatment groups compared to placebo were made using analysis of variance techniques. The model included terms for the respective changes from baseline as the dependent variable and terms for treatment, center and treatment by center interaction as exploratory variables (see Figures 1 to 3). Figure 1: A 12 Week Trial in Pediatric Patients Not on Inhaled Corticosteroid Therapy Prior to Study Entry. Nighttime Asthma Change From Baseline Patients Previously Maintained on Inhaled Corticosteroids The efficacy of budesonide inhalation suspension at doses of 0.25 mg and 0.5 mg twice daily was evaluated in 133 pediatric asthma patients, 4 to 8 years of age, previously maintained on inhaled corticosteroids (mean FEV 1 79.5% predicted; mean baseline nighttime asthma symptom scores of the treatment groups ranged from 1.04 to 1.18; mean baseline dose of beclomethasone dipropionate of 265 mcg/day, ranging between 42 to 1008 mcg/day; mean baseline dose of triamcinolone acetonide of 572 mcg/day, ranging between 200 to 1200 mcg/day). The changes from baseline to Weeks 0 to 12 in nighttime asthma symptom scores are shown in Figure 2. Nighttime asthma symptom scores showed statistically significant decrease in patients treated with budesonide inhalation suspension compared to placebo. Similar decreases were also observed for daytime asthma symptom scores. Statistically significant increases in FEV 1 compared to placebo were observed with budesonide inhalation suspension at a dose of 0.5 mg twice daily and in morning PEF for both doses (0.25 mg and 0.5 mg twice daily). Figure 2: A 12 Week Trial in Pediatric Patients Previously Maintained on Inhaled Corticosteroid Therapy Prior to Study Entry. Nighttime Asthma Change From Baseline Patients Receiving Once-Daily or Twice-Daily Dosing The efficacy of budesonide inhalation suspension at doses of 0.25 mg once daily, 0.25 mg twice daily and 0.5 mg twice daily was evaluated in pediatric patients 12 months to 8 years of age (mean baseline nighttime asthma symptom scores of the treatment groups ranged from 1.13 to 1.31). Approximately 70% were not previously receiving inhaled corticosteroids. The changes from baseline to Weeks 0 to 12 in nighttime asthma symptom scores are shown in Figure 3. Budesonide inhalation suspension at doses of 0.25 mg and 0.5 mg twice daily demonstrated statistically significant decreases in nighttime asthma symptom scores compared to placebo. Similar decreases were also observed for daytime asthma symptom scores. Budesonide inhalation suspension at a dose of 0.5 mg twice daily resulted in statistically significant increases compared to placebo in FEV 1 , and at doses of 0.25 mg and 0.5 mg twice daily statistically significant increases in morning PEF. The evidence supports the efficacy of the same nominal dose of budesonide inhalation suspension administered on either a once-daily or twice-daily schedule. However, when all measures are considered together, the evidence is stronger for twice-daily dosing [ see Dosage and Administration ( 2 ) ]. Figure 3: A 12 Week Trial in Pediatric Patients Either Maintained on Bronchodilators Alone or Inhaled Corticosteroid Therapy Prior to Study Entry. Nighttime Asthma Change From Baseline

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

Product: 50090-1467 NDC: 50090-1467-0 2 mL in a VIAL / 30 in a CARTON

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

SPL PATIENT PACKAGE INSERT SECTION

SPL PATIENT PACKAGE INSERT SECTION

Patient Information and Instructions for Use BUDESONIDE (bew DEH so nide) INHALATION SUSPENSION 2 mL vials containing 0.25 mg or 0.5 mg For inhalation only. Do not swallow. Only use budesonide inhalation suspension with a jet nebulizer machine that is connected to an air compressor. Do not use with an ultrasonic nebulizer. Read the Patient Information that comes with budesonide inhalation suspension before your child starts using it and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your child’s medical condition or treatment. If you have any questions about budesonide inhalation suspension, ask your healthcare provider or pharmacist. What is budesonide inhalation suspension? Budesonide inhalation suspension is an inhaled corticosteroid medicine. Budesonide inhalation suspension is a long-term maintenance medicine used to control and prevent asthma symptoms in children ages 12 months to 8 years. Inhaled corticosteroids help to decrease inflammation in the lungs. Inflammation in the lungs can lead to asthma symptoms. Budesonide inhalation suspension helps reduce swelling and inflammation in the lungs, and helps keep the airways open to reduce asthma symptoms. Budesonide inhalation suspension does not treat the sudden symptoms (wheezing, cough, shortness of breath, and chest pain or tightness) of an asthma attack. Always have a short-acting beta 2 -agonist medicine (rescue inhaler) with you to treat sudden symptoms. If your child does not have an inhaled, short-acting bronchodilator, ask your healthcare provider to have one prescribed for your child. It is not known if budesonide inhalation suspension is safe or effective in children younger than 12 months or older than 8 years. Who should not use budesonide inhalation suspension? Do not use budesonide inhalation suspension: to treat sudden symptoms of asthma if your child is allergic to budesonide or any of the ingredients in budesonide inhalation suspension. See the end of this leaflet for a complete list of ingredients in budesonide inhalation suspension. What should I tell my healthcare provider before using budesonide inhalation suspension? Before your child uses budesonide inhalation suspension, tell your healthcare provider if your child: has an allergy. See the section “Who should not use budesonide inhalation suspension?" There is a complete list of ingredients in budesonide inhalation suspension at the end of this leaflet. has or recently had chicken pox or measles, or has recently been near anyone with chicken pox or measles. has or had tuberculosis of the respiratory tract. has certain kinds of infections that have not been treated, including: fungal infections bacterial infections viral infections parasitic infections herpes simplex infection of the eye (ocular herpes simplex) Budesonide inhalation suspension may not be right for children who have had any of these types of infections. has decreased bone mineral density (bone strength). Your child is at risk for decreased bone mineral density if he or she: is inactive for a long period of time has a family history of osteoporosis does not eat well (poor nutrition) takes bone thinning medicines (such as anticonvulsant medicines or corticosteroids) for a long time. has an eye problem such as increased pressure in the eye, glaucoma or cataracts. has liver problems. is planning to have surgery. has any other medical conditions. is pregnant or plans to become pregnant. It is not known if budesonide inhalation suspension will harm your unborn baby. is breast-feeding or plans to breast-feed. Budesonide can pass into breast milk. You and your healthcare provider should decide if you will use budesonide inhalation suspension or breast-feed. Tell your healthcare provider about all the medicine your child takes, including prescription and non-prescription medicines, vitamins, and herbal supplements. Using budesonide inhalation suspension with certain other medicines may affect each other causing side effects. Especially tell your healthcare provider if your child takes: corticosteroids anti-seizure medicine (anticonvulsants) medicines that suppress the immune system (immunosuppressant) ketoconazole (Nizoral) certain medicines that can affect how your liver breaks down medicine Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure. Know the medicines your child takes. Keep a list of them and show it to your healthcare provider and pharmacist when your child gets a new medicine. How should I use budesonide inhalation suspension? Use budesonide inhalation suspension exactly as prescribed by your healthcare provider. Your child must use budesonide inhalation suspension regularly for it to work. Budesonide inhalation suspension comes in two strengths. Your healthcare provider has prescribed the strength that is best for your child. Do not stop using budesonide inhalation suspension, and do not change your child’s dose of budesonide inhalation suspension without talking to your healthcare provider. Budesonide inhalation suspension is for inhaled use only. Use budesonide inhalation suspension with a jet nebulizer connected to an air compressor set up with a mouthpiece or face mask. Do not use an ultrasonic nebulizer to give budesonide inhalation suspension. Do not mix budesonide inhalation suspension with other nebulizer medicines. If your child uses another medicine by inhalation to treat asthma, talk with your healthcare provider for instructions on when to use the other medicine. If your child misses a dose, just give the next regularly scheduled dose when it is due. Do not use budesonide inhalation suspension more often than has been prescribed. Improvement in the control of asthma symptoms with budesonide inhalation suspension can occur within 2 to 8 days. It may take up to 4 to 6 weeks before maximum improvement is seen. Make sure your child always has a short-acting beta 2 -agonist medicine with him or her. Your child should use the short-acting beta 2 -agonist medicine for breathing problems between doses of budesonide inhalation suspension or if a sudden asthma attack happens. Call your healthcare provider right away if: the short-acting rescue medicine does not work as well for relieving asthma symptoms. your child needs to use the short-acting rescue medicines more often than usual. your child’s breathing problems worsen with budesonide inhalation suspension Rinse your child’s mouth with water and have him or her spit the water out after each budesonide inhalation suspension treatment. Do not swallow the water. This will lessen the chance of getting a fungal infection (thrush) in the mouth. If your child has used long-term corticosteroids and the dose is now being lowered or stopped, a warning card should be carried stating that your child may need corticosteroids during times of stress or during an asthma attack that does not get better with bronchodilator medicines. Your healthcare provider may check your child’s blood, breathing and do eye exams while using budesonide inhalation suspension. Read the Patient Information and Instructions for Use at the end of this leaflet for detailed instructions about how to use budesonide inhalation suspension. What are the possible side effects of budesonide inhalation suspension? Budesonide inhalation suspension may cause serious side effects including: Thrush ( candida ), a fungal infection in your mouth and throat. Tell your healthcare provider if your child has any redness or white colored patches in the mouth or throat. Worsening of asthma or sudden asthma attacks. Allergic reactions. Tell your healthcare provider or get medical help right away if your child has: skin rash, redness or swelling severe itching swelling of the face, mouth and tongue trouble breathing or swallowing chest pain anxiety (feeling of doom) Immune system effects and a higher chance of infe...

Budesonide

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL