Asthma/COPD:

Indications for: PULMICORT RESPULES

Maintenance treatment of asthma and as prophylactic therapy.

Clinical Trials:

  • The efficacy of Pulmicort Respules was evaluated in three 12-week, double-blind, placebo-controlled, parallel group, randomized US clinical trials. Each trial included 1018 pediatric patients 6 months to 8 years of age with persistent asthma of varying disease duration and severity. Patients were randomly assigned to receive Pulmicort Respules 0.15 mg, 0.5 mg, and 1 mg or placebo administered either once or twice daily. Pulmicort Respules were delivered via a Pari-LC-Jet Plus Nebulizer connected to a Pari Master compressor. The coprimary endpoints were nighttime and daytime asthma symptom scores (0-3 scale).

  • Results from the 3 clinical trials showed that treatment with Pulmicort Respules doses of 0.25 mg once daily, 0.25 mg twice daily, and 0.5 mg twice daily achieved statistically significant decreases in nighttime and daytime symptoms scores of asthma compared with placebo. The use of Pulmicort Respules 0.5 mg or 1 mg once daily achieved statistically significant decreases in either nighttime or daytime symptom scores, but not both. All doses of Pulmicort Respules also achieved statistically significant reductions in the need for bronchodilatory therapy.

  • While maximum benefit was not achieved for 4 to 6 weeks, a numerical reduction in nighttime and daytime symptom scores were observed for Pulmicort Respules within 2 to 8 days. These reductions were maintained throughout the 12 weeks.

Patients Not Receiving Inhaled Corticosteroid Therapy

  • The efficacy of Pulmicort Respules at doses of 0.25 mg, 0.5 mg, and 1 mg once daily was evaluated in 344 pediatric patients 12 months to 8 years of age with mild to moderate persistent asthma who were not well controlled by bronchodilators alone.

  • Treatment with Pulmicort Respules showed a statistically significant decrease in nighttime asthma symptoms scores compared with placebo; similar decreases were observed for daytime asthma symptom scores.

Patients Previously Maintained on Inhaled Corticosteroids

  • The efficacy of Pulmicort Respules 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.

  • Treatment with Pulmicort Respules showed a statistically significant decrease in nighttime asthma symptoms scores compared with placebo; similar decreases were observed for daytime asthma symptom scores. 

  • Pulmicort Respules at a dose of 0.5 mg twice daily achieved statistically significant increases in FEV1 compared with placebo; and at doses of 0.25 mg and 0.5 mg twice daily, there were statistically significant increases in morning PEF compared with placebo.

Patients Receiving Once-Daily or Twice-Daily Dosing 

  • The efficacy of Pulmicort Respules at doses of 0.25 mg once daily, 0.25 mg twice daily, 0.5 mg twice daily, and 1 mg once daily, was evaluated in 469 pediatric patients 12 months to 8 years of age. The trial included approximately 70% who were not previously receiving inhaled corticosteroids.

  • Results showed that Pulmicort Respules at doses of 0.25 mg and 0.5 mg twice daily, and 1 mg once daily, achieved statistically significant decreases in nighttime asthma symptom scores compared with placebo; similar decreases were observed for daytime asthma symptom scores.

  • Compared with placebo, there were statistically significant increases in FEV1 for Pulmicort Respules at a dose of 0.5 mg twice daily, and statistically significant increases in morning PEF for Pulmicort at doses of 0.25 mg and 0.5 mg twice daily, and 1 mg once daily.

  • Evidence supports the efficacy for Pulmicort Respules to be administered on either a once-daily or twice-daily schedule. But the evidence is stronger for twice-daily dosing when all measures are considered together.

Adult Dosage:

Use Flexhaler.

Children Dosage:

Use jet nebulizer; do not mix with other drugs. 6–12months: not established (see full labeling). 12months–8yrs: Previously on bronchodilators alone: 0.5mg/day once daily or in 2 divided doses (if symptomatic and unresponsive to nonsteroidal therapy, may start at 0.25mg once daily). Previously on inhaled corticosteroids: 0.5mg/day once daily or in 2 divided doses; max 1mg/day. Previously on oral corticosteroids: 1mg/day once daily or in 2 divided doses. Rinse mouth and face (if face mask used) after use.

PULMICORT RESPULES Contraindications:

Not for primary treatment of acute attack.

PULMICORT RESPULES Warnings/Precautions:

Maintain regular regimen. Infections. If exposed to chickenpox or measles, consider antiinfective prophylactic therapy. Adrenal insufficiency may occur when transferring patients from systemic corticosteroids to inhaled corticosteroids: see full labeling. Monitor for growth suppression in children. Post-op or during stress: monitor adrenal response. Monitor for hypercorticism and HPA axis suppression (if occur discontinue gradually). Transferring from oral corticosteroids: see full labeling. Pregnancy. Nursing mothers.

See Also:

PULMICORT RESPULES Classification:

Steroid.

PULMICORT RESPULES Interactions:

Caution with CYP3A4 inhibitors (eg, ketoconazole, itraconazole, atazanavir, ritonavir, indinavir, nefazodone, nelfinavir, saquinavir, clarithromycin, telithromycin).

Adverse Reactions:

Pulmicort Flexhaler: nasopharyngitis, nasal congestion, pharyngitis, allergic rhinitis, viral upper respiratory tract infection, oral candidiasis, viral gastroenteritis, nausea, otitis media, bronchospasm (rare). Pulmicort Respules: Respiratory or other infection, GI upset, moniliasis, fatigue, cough, dysphonia, rash, epistaxis, hypersensitivity reactions (discontinue if occurs).

Metabolism:

In vitro studies with human liver homogenates have shown that budesonide is rapidly and extensively metabolized. Two major metabolites formed via cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4) catalyzed biotransformation have been isolated and identified as 16α-hydroxyprednisolone and 6β-hydroxybudesonide. The corticosteroid activity of each of these two metabolites is less than 1% of that of the parent compound. No qualitative difference between the in vitro and in vivo metabolic patterns has been detected. Negligible metabolic inactivation was observed in human lung and serum preparations. 

Drug Elimination:

Budesonide is primarily cleared by the liver. Budesonide is excreted in urine and feces in the form of metabolites. In adults, approximately 60% of an intravenous radiolabeled dose was recovered in the urine. No unchanged budesonide was detected in the urine. In asthmatic children 4-6 years of age, the terminal half-life of budesonide after nebulization is 2.3 hours, and the systemic clearance is 0.5 L/min, which is approximately 50% greater than in healthy adults after adjustment for differences in weight. 

Generic Drug Availability:

Flexhaler (NO); Respules (YES)

How Supplied:

Flexhaler (90mcg/dose)—1 (60 inh); Flexhaler (180mcg/dose)—1 (120 inh); Respules—30