Información de la droga para AMOXICILLIN AND CLAVULANATE POTASSIUM FOR ORAL SUSPENSION USP8675 (TEVA PHARMACEUTICALS USA): DESCRIPTION OF CLINICAL STUDIES

Two clinical studies were conducted in pediatric patients with acute otitis media.

A non-comparative, open-label study assessed the bacteriologic and clinical efficacy of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL (90/6.4 mg/kg/day, divided every 12 hours) for 10 days in 521 pediatric patients (3 to 50 months) with acute otitis media. The primary objective was to assess bacteriological response in children with acute otitis media due to S. pneumoniae with amoxicillin/clavulanic acid MICs of 4 mcg/mL. The study sought the enrollment of patients with the following risk factors: failure of antibiotic therapy for acute otitis media in the previous 3 months, history of recurrent episodes of acute otitis media, ≤ 2 years, or daycare attendance. Prior to receiving amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL, all patients had tympanocentesis to obtain middle ear fluid for bacteriological evaluation. Patients from whom S. pneumoniae (alone or in combination with other bacteria) was isolated had a second tympanocentesis 4 to 6 days after the start of therapy. Clinical assessments were planned for all patients during treatment (4 to 6 days after starting therapy), as well as 2 to 4 days post-treatment and 15 to 18 days post-treatment. Bacteriological success was defined as the absence of the pretreatment pathogen from the on-therapy tympanocentesis specimen. Clinical success was defined as improvement or resolution of signs and symptoms. Clinical failure was defined as lack of improvement or worsening of signs and/or symptoms at any time following at least 72 hours of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL; patients who received an additional systemic antibacterial drug for otitis media after 3 days of therapy were considered clinical failures. Bacteriological eradication on therapy (day 4 to 6 visit) in the per protocol population is summarized in the following table:

Clinical assessments were made in the per protocol population 2 to 4 days post-therapy and 15 to 18 days post-therapy. Patients who responded to therapy 2 to 4 days post-therapy were followed for 15 to 18 days post-therapy to assess them for acute otitis media. Nonresponders at 2 to 4 days post-therapy were considered failures at the latter timepoint.

In the intent-to-treat analysis, overall clinical outcomes at 2 to 4 days and 15 to 18 days post-treatment in patients with S. pneumoniae with penicillin MIC = 2 mcg/mL and 4 mcg/mL were 29/41 (71%) and 17/41 (41.5%), respectively.

In the intent-to-treat population of 521 patients, the most frequently reported adverse events were vomiting (6.9%), fever (6.1%), contact dermatitis (i.e., diaper rash) (6.1%), upper respiratory tract infection (4.0%), and diarrhea (3.8%). Protocol-defined diarrhea (i.e., 3 or more watery stools in one day or 2 watery stools per day for 2 consecutive days as recorded on diary cards) occurred in 12.9% of patients.

A double-blind, randomized, clinical study compared amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL (90/6.4 mg/kg/day, divided every 12 hours) to amoxicillin and clavulanate potassium (45/6.4 mg/kg/day, divided every 12 hours) for 10 days in 450 pediatric patients (3 months to 12 years) with acute otitis media. The primary objective of the study was to compare the safety of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL to amoxicillin and clavulanate potassium. There was no statistically significant difference between treatments in the proportion of patients with 1 or more adverse events. The most frequently reported adverse events for amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL and the comparator of amoxicillin and clavulanate potassium were coughing (11.9% versus 6.8%), vomiting (6.5% versus 7.7%), contact dermatitis (i.e., diaper rash, 6.0% versus 4.8%), fever (5.5% versus 3.9%), and upper respiratory infection (3.0% versus 9.2%), respectively. The frequencies of protocol-defined diarrhea with amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL (11.1%) and amoxicillin and clavulanate potassium (9.4%) were similar (95% confidence interval on difference: -4.2% to 7.7%). Only 2 patients in the group treated with amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL and 1 patient in the group treated with amoxicillin and clavulanate potassium were withdrawn due to diarrhea.