INDICATIONS AND USAGE
AUGMENTIN ES-600 is indicated for the treatment of pediatric patients with recurrent or persistent acute otitis media due to S. pneumoniae (penicillin MICs ≤2 mcg/mL), H. influenzae (including β-lactamase−producing strains), or M. catarrhalis (including β-lactamase−producing strains) characterized by the following risk factors:
- antibiotic exposure for acute otitis media within the preceding 3 months, and either of the following:
− age ≤2 years
− daycare attendance
[See CLINICAL PHARMACOLOGY, Microbiology.]
NOTE: Acute otitis media due to S. pneumoniae alone can be treated with amoxicillin. AUGMENTIN ES-600 is not indicated for the treatment of acute otitis media due to S. pneumoniae with penicillin MIC ≥4 mcg/mL.
Therapy may be instituted prior to obtaining the results from bacteriological studies when there is reason to believe the infection may involve both S. pneumoniae (penicillin MIC ≤2 mcg/mL) and the β-lactamase–producing organisms listed above.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of AUGMENTIN ES-600 and other antibacterial drugs, AUGMENTIN ES-600 should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
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DOSAGE AND ADMINISTRATION
AUGMENTIN ES-600 , 600 mg/5 mL, does not contain the same amount of clavulanic acid (as the potassium salt) as any of the other suspensions of AUGMENTIN. AUGMENTIN ES-600 contains 42.9 mg of clavulanic acid per 5 mL, whereas the 200 mg/5 mL suspension of AUGMENTIN contains 28.5 mg of clavulanic acid per 5 mL and the 400 mg/5 mL suspension contains 57 mg of clavulanic acid per 5 mL. Therefore, the 200 mg/5 mL and 400 mg/5 mL suspensions of AUGMENTIN should not be substituted for AUGMENTIN ES-600 , as they are not interchangeable.
Dosage
Pediatric patients 3 months and older
Based on the amoxicillin component (600 mg/5 mL), the recommended dose of AUGMENTIN ES-600 is 90 mg/kg/day divided every 12 hours, administered for 10 days (see chart below).
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Body Weight (kg)
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Volume of AUGMENTIN ES-600 providing 90 mg/kg/day
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8
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3.0 mL twice daily
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12
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4.5 mL twice daily
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16
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6.0 mL twice daily
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20
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7.5 mL twice daily
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24
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9.0 mL twice daily
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28
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10.5 mL twice daily
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32
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12.0 mL twice daily
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36
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13.5 mL twice daily
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Pediatric patients weighing 40 kg and more
Experience with AUGMENTIN ES-600 (600 mg/5 mL formulation) in this group is not available.
Adults
Experience with AUGMENTIN ES-600 (600 mg/5 mL formulation) in adults is not available and adults who have difficulty swallowing should not be given AUGMENTIN ES-600 (600 mg/5 mL) in place of the 500-mg or 875-mg tablet of AUGMENTIN.
Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals. (See WARNINGS.)
Directions for Mixing Oral Suspension
Prepare a suspension at time of dispensing as follows: Tap bottle until all the powder flows freely. Add approximately 2/3 of the total amount of water for reconstitution (see table below) and shake vigorously to suspend powder. Add remainder of the water and again shake vigorously.
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AUGMENTIN ES-600 (600 mg/5 mL Suspension)
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Bottle Size
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Amount of Water
Required for Reconstitution
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75 mL
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70 mL
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125 mL
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110 mL
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200 mL
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180 mL
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NOTE: SHAKE ORAL SUSPENSION WELL BEFORE USING.
Information for the Pharmacist
For patients who wish to alter the taste of AUGMENTIN ES-600, immediately after reconstitution 1 drop of FLAVORx™ (apple, banana cream, bubble gum, cherry, or watermelon flavor) may be added for every 5 mL of AUGMENTIN ES-600. The resulting suspension is stable for 10 days under refrigeration. Other than the 5 flavors listed above, GlaxoSmithKline has not evaluated the stability of AUGMENTIN ES-600 when mixed with other flavors distributed by FLAVORx.
Administration
To minimize the potential for gastrointestinal intolerance, AUGMENTIN ES-600 should be taken at the start of a meal. Absorption of clavulanate potassium may be enhanced when AUGMENTIN ES-600 is administered at the start of a meal.
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HOW SUPPLIED
AUGMENTIN ES-600, 600 mg/5 mL, for Oral Suspension
Each 5 mL of reconstituted strawberry cream-flavored suspension contains 600 mg amoxicillin and 42.9 mg clavulanic acid as the potassium salt.
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NDC 0029-6094-40 75 mL bottle
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NDC 0029-6094-46 …….125 mL bottle
NDC 0029-6094-25 200 mL bottle
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STORAGE
Store reconstituted suspension under refrigeration. Discard unused suspension after 10 days. Store dry powder for oral suspension at or below 25°C (77°F). Dispense in original container.
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 AUGMENTIN ES-600 (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 AUGMENTIN ES-600, 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 (4-6 days after starting therapy), as well as 2-4 days post-treatment and 15-18 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 AUGMENTN ES-600 (amoxicillin/clavulanate potassium); 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 4-6 visit) in the per protocol population is summarized in the following table:
Table 5. Bacteriologic Eradication Rates in the Per Protocol Population |
Bacteriologic Eradication on Therapy
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Pathogen
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n/N
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%
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95% CI *
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All S. pneumoniae
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121/123
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98.4
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(94.3, 99.8)
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S. pneumoniae with penicillin MIC = 2 mcg/mL
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19/19
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100
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(82.4, 100.0)
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S. pneumoniae with penicillin
MIC = 4 mcg/mL
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12/14
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85.7
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(57.2, 98.2)
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H. influenzae
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75/81
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92.6
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(84.6, 97.2)
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M. catarrhalis
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11/11
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100
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(71.5, 100.0)
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*CI = confidence intervals; 95% CIs are not adjusted for multiple comparisons.
Clinical assessments were made in the per protocol population 2-4 days post-therapy and 15-18 days post-therapy. Patients who responded to therapy 2-4 days post-therapy were followed for 15-18 days post-therapy to assess them for acute otitis media. Nonresponders at 2-4 days post-therapy were considered failures at the latter timepoint.
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2-4 Days Post-Therapy (Primary Endpoint)
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Pathogen
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n/N
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%
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95% CI †
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All S. pneumoniae
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122/137
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89.1
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(82.6, 93.7)
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S. pneumoniae with penicillin MIC = 2 mcg/mL
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17/20
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85.0
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(62.1, 96.8)
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S. pneumoniae with penicillin MIC = 4 mcg/mL
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11/14
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78.6
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(49.2, 95.3)
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H. influenzae
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141/162
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87.0
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(80.9, 91.8)
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M. catarrhalis
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22/26
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84.6
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(65.1, 95.6)
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15-18 Days Post-Therapy ‡ (Secondary Endpoint)
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N/N
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%
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95% CI †
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All S. pneumoniae
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95/136
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69.9
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(61.4, 77.4)
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S. pneumoniae with penicillin MIC = 2 mcg/mL
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11/20
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55.0
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(31.5, 76.9)
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S. pneumoniae with penicillin MIC = 4 mcg/mL
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5/14
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35.7
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(12.8, 64.9)
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H. influenzae
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106/156
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67.9
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(60.0, 75.2)
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M. catarrhalis
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14/25
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56.0
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(34.9, 75.6)
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* S. pneumoniae strains with penicillin MICs of 2 or 4 mcg/mL are considered resistant to penicillin.
†CI = confidence intervals; 95% CIs are not adjusted for multiple comparisons.
‡ Clinical assessments at 15-18 days post-therapy may have been confounded by viral infections and new episodes of acute otitis media with time elapsed post-treatment.
In the intent-to-treat analysis, overall clinical outcomes at 2-4 days and 15-18 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 AUGMENTIN ES-600 (90/6.4 mg/kg/day, divided every 12 hours) to AUGMENTIN (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 AUGMENTIN ES-600 to AUGMENTIN. 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 AUGMENTIN ES-600 and the comparator of AUGMENTIN 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 AUGMENTIN ES-600 (11.1%) and AUGMENTIN (9.4%) were similar (95% confidence interval on difference:−4.2% to 7.7%). Only 2 patients in the group treated with AUGMENTIN ES-600 and 1 patient in the group treated with AUGMENTIN were withdrawn due to diarrhea.
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