AMOXICILLIN AND CLAVULANATE POTASSIUM- amoxicillin and clavulanate potassium_powder, for suspension

Amoxicillin and clavulanate potassium is an antibacterial drug. [see Microbiology 12. 4 ] Mean amoxicillin and clavulanate potassium pharmacokinetic parameters in normal adults following administration of AUGMENTIN Tablets are shown in Table 6 and following administration of AUGMENTIN for Oral Suspension and Chewable Tablets are shown in Table 7. Table 6: Mean (+/-S. ) Amoxicillin and Clavulanate Potassium Pharmacokinetic Parameters a,b with Amoxicillin and Clavulanate Potassium Tablets Dose and Regimen of AUGMENTIN C max AUC 0-24 Amoxicillin and Clavulanate potassium Amoxicillin Clavulanate potassium Amoxicillin Clavulanate potassium 250/125 mg every 8 hours 3. 25 500/125 mg every 12 hours 6. 95 500 125 mg every 8 hours 7. 86 875/125 mg every 12 hours 11. 04 a b Table 7: Mean (+/-S. ) Amoxicillin and Clavulanate Potassium Pharmacokinetic Parameters a,b Dose of AUGMENTIN C max AUC 0-24 Amoxicillin and Clavulanate potassium Amoxicillin Clavulanate potassium Amoxicillin Clavulanate potassium 400/57 mg(5 mL of suspension) 6. 94 400/57 mg(1 chewable tablet) 6. 73 a b Oral administration of 5 mL of the 250 mg/62. 5 mg suspension of AUGMENTIN or the equivalent dose of 10 mL of the 125 mg/31. 25 mg suspension of AUGMENTIN provides average peak serum concentrations approximately 1 hour after dosing of 6. 9 mcg/mL for amoxicillin and 1. 6 mcg/mL for clavulanic acid. The areas under the serum concentration curves obtained during the first 4 hours after dosing were 12. 6 mcg*h/mL for amoxicillin and 2. 9 mcg*h/mL for clavulanic acid when 5 mL of the 250 mg/62. 5 mg suspension of AUGMENTIN or equivalent dose of 10 mL of the 125 mg/31. 25 mg suspension of AUGMENTIN were administered to normal adults. One 250 mg/62. 5 mg chewable tablet of AUGMENTIN or two 125 mg/31. 25 mg chewable tablets of AUGMENTIN are equivalent to 5 mL of the 250 mg/62. 5 mg suspension of AUGMENTIN and provide similar serum concentrations of amoxicillin and clavulanic acid. Amoxicillin serum concentrations achieved with AUGMENTIN are similar to those produced by the oral administration of equivalent doses of amoxicillin alone. Time above the minimum inhibitory concentration of 1 mcg/mL for amoxicillin has been shown to be similar after corresponding every 12 hour and every 8-hour dosing regimens of AUGMENTIN in adults and children. Absorption: Distribution: Amoxicillin diffuses readily into most body tissues and fluids with the exception of the brain and spinal fluid. Two hours after oral administration of a single 35 mg/kg dose of suspension of AUGMENTIN to fasting children, average concentrations of 3 mcg/mL of amoxicillin and 0. 5 mcg/mL of clavulanic acid were detected in middle ear effusions. Metabolism and Excretion: Approximately 50% to 70% of the amoxicillin and approximately 25% to 40% of the clavulanic acid are excreted unchanged in urine during the first 6 hours after administration of a single 250 mg/125 mg or 500 mg/125 mg tablet of AUGMENTIN. Amoxicillin is a semisynthetic antibacterial with in vitro bactericidal activity against Gram-positive and Gram-negative bacteria. Amoxicillin is, however, susceptible to degradation by beta-lactamases, and therefore, the spectrum of activity does not include organisms which produce these enzymes. Clavulanic acid is a beta-lactam, structurally related to the penicillins, which possesses the ability to inactivate some beta-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid-mediated beta- lactamases frequently responsible for transferred drug resistance. The formulation of amoxicillin and clavulanic acid in Amoxicillin and clavulanate potassium protects amoxicillin from degradation by some beta-lactamase enzymes and extends the antibacterial spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin. Amoxicillin and clavulanic acid has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections [see Indications and Usage ( 1 Gram-positive bacteria Staphylococcus aureus Gram-negative bacteria Enterobacter Escherichia coli Haemophilus influenzae Klebsiella species Moraxella catarrhalis The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for amoxicillin and clavulanic acid. However, the efficacy of amoxicillin and clavulanic acid in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials. Gram-positive bacteria Enterococcus faecalis Staphylococcus epidermidis Staphylococcus saprophyticus Streptococcus pneumoniae Streptococcus pyogenes Viridans group Streptococcus Gram-negative Bacteria Eikenella corrodens Proteus mirabilis Anaerobic Bacteria Bacteroides Bacteroides fragilis Fusobacterium species Peptostreptococcus species Susceptibility Test Methods For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.

Amoxicillin and clavulanate potassium for oral suspension is indicated for the treatment of infections in adults and pediatric patients, due to susceptible isolates of the designated bacteria in the conditions listed below: Lower Respiratory Tract Infections Haemophilus influenzae Moraxella catarrhalis Acute Bacterial Otitis Media H. influenzae M. catarrhalis. Sinusitis H. catarrhalis Skin and Skin Structure Infections Staphylococcus aureus, Escherichia coli Klebsiella Urinary Tract Infections E. coli, Klebsiella Enterobacter Limitations of Use When susceptibility test results show susceptibility to amoxicillin, indicating no beta-lactamase production, Amoxicillin and clavulanate potassium for oral suspension should not be used. Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin and clavulanate potassium for oral suspension and other antibacterial drugs, Amoxicillin and clavulanate potassium for oral suspension 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. Amoxicillin and Clavulanate Potassium for Oral Suspension is a combination of amoxicillin, a penicillin-class antibacterial and clavulanate potassium, a beta-lactamase inhibitor indicated for treatment of the following infections in adults and pediatric patients: ( 1 Lower respiratory tract infections Acute bacterial otitis media Sinusitis Skin and skin structure infections Urinary tract infections Limitations of Use When susceptibility test results show susceptibility to amoxicillin, indicating no beta-lactamase production, Amoxicillin and clavulanate potassium for oral suspension should not be used. ( 1 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin and clavulanate potassium for oral suspension and other antibacterial drugs, Amoxicillin and clavulanate potassium for oral suspension should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Adults and Pediatric Patients greater than 40 kg: 500 or 875 mg every 12 hours or 250 or 500 mg every 8 hours, based on amoxicillin component. 3 Pediatric patients aged 12 weeks (3 months) and older: 25 to 45 mg/kg/day every 12 hours or 20 to 40 mg/kg/day every 8 hours, up to the adult dose. 3 Neonates and infants less than 12 weeks of age: 30 mg/kg/day divided every 12 hours, based on the amoxicillin component. Use of the 125 mg/5 mL oral suspension is recommended. 3 Amoxicillin and clavulanate potassium for oral suspension may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when Amoxicillin and clavulanate potassium for oral suspension is administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, Amoxicillin and clavulanate potassium for oral suspension should be taken at the start of a meal. See dosing regimens of Amoxicillin and clavulanate potassium for oral suspension (based on the amoxicillin component) provided in Table 1 below. Dosing Regimens of Amoxicillin and Clavulanate Potassium for Oral Suspension in Adult Patients TYPE OF INFECTION DOSING REGIMEN OF AMOXICILLIN AND CLAVULANATE POTASSIUM Severe infections and infections of the respiratory tract one 875 mg tablet Adults who have difficulty swallowing may be given the Amoxicillin and clavulanate potassium 200 mg/28. 5 mg per 5 mL suspension or the Amoxicillin and clavulanate potassium 400 mg/57 mg per 5 mL suspension may be used in place of the AUGMENTIN 875 mg/125 mg tablet. or one 500 mg tablet Adults who have difficulty swallowing may be given the Amoxicillin and clavulanate potassium 125 mg/31. 25 mg per 5 mL or Amoxicillin and clavulanate potassium 250 mg/62. 5 mg per 5 mL suspension in place of the AUGMENTIN 500 mg/125 mg tablet. Two AUGMENTIN 250 mg/125 mg tablets are NOT substitutable with one 500 mg/125 mg AUGMENTIN tablet [ see Dosage and Administration ( 2. 6 Less severe infections one 500 mg tablet , or one 250 mg tablet AUGMENTIN 250 mg/125 mg tablet is NOT substitutable with AUGMENTIN 250 mg/62. 5 mg chewable tablet [ see Dosage and Administration ( 2. 6 Based on the amoxicillin component, Amoxicillin and clavulanate potassium should be dosed as follows: Neonates and Infants Aged less than 12 weeks (less than 3 months) Table 2: Dosing Regimens of Amoxicillin and clavulanate potassium in Neonates and Infants Aged Less than 12 Weeks (Less than 3 Months) PATIENT POPULATION DOSING REGIMEN Amoxicillin and clavulanate potassium 125 mg/31. 25 mg per 5 mL for oral suspension Experience with the Amoxicillin and clavulanate potassium 200 mg/28. 5 mg per 5 mL formulation in this age group is limited, and thus, use of the Amoxicillin and clavulanate potassium 125 mg/31. 25 mg per 5 mL for oral suspension is recommended. Neonates and Infants aged less than 12 weeks (less than 3 months) 30 mg/kg/day every 12 hours Patients Aged 12 weeks (3 months) and Older and Weighing Less than 40 kg: The every 12 hour regimen is recommended as it is associated with significantly less diarrhea [ see Clinical Studies ( 14. 2 Table 3: Dosing in Patients Aged 12 weeks (3 Months) and Older and Weighing Less than 40 kg INFECTION DOSING REGIMEN Every 12 hours Every 8 hours Amoxicillin and clavulanate potassium 200 mg/28. 5 mg per 5 mL or Amoxicillin and clavulanate potassium 400 mg/57 mg per 5 mL for oral suspension Each strength of Amoxicillin and clavulanate potassium for oral suspension is available as an AUGMENTIN chewable tablet for use by older children. Amoxicillin and clavulanate potassium 125 mg/31. 5 mg per 5 mL for oral suspension* Otitis media Duration of therapy studied and recommended for acute otitis media is 10 days. 45 mg/kg/day every 12 hours 40 mg/kg/day every 8 hours Less severe infections 25mg/kg/day every 12 hours 20 mg/kg/day every 8 hours a Each strength of Amoxicillin and clavulanate potassium for oral suspension is available as an AUGMENTIN chewable tablet for use by older children. b Duration of therapy studied and recommended for acute otitis media is 10 days. Patients Weighing 40 kg or More The 250 mg/125 mg tablet of AUGMENTIN should NOT Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Renal impairment patients with a glomerular filtration rate (GFR) of less than 30 mL/min should NOT receive the 875 mg dose (based on the amoxicillin component) of amoxicillin and clavulanate potassium. See dosing regimens in patients with severe renal impairment provided in Table 4. Table 4: Dosing Regimens of Amoxicillin and Clavulanate Potassium in Patients with Severe Renal Impairment Patients with Renal Impairment Dosing Regimen GFR 10 mL/min to 30 mL/min 500 mg or 250 mg every 12 hours, depending on the severity of the infection GFR less than 10 mL/min 500 mg or 250 mg every 24hours, depending on the severity of the infection Hemodialysis 500 mg or 250 mg every 24 hours, depending on severity of the infection Administer an additional dose both during and at the end of dialysis Prepare amoxicillin and clavulanate potassium for oral suspension at time of dispensing as follows: Tap bottle until all the powder flows freely. Measure a total (see Table 5 below for total amount of water for reconstitution) OF WATER. Add approximately 2/3 of the water to the powder. Replace cap and shake VIGOROUSLY. Add remaining water. Table 5: Amount of Aquatic for Mixing Amoxicillin and Clavulanate Potassium for Oral Suspension Strength Bottle Size Amount of Water for Reconstitution Contents of Each Teaspoonful (5 mL) 250 mg/5 mL 75 mL 100 mL 150 mL 65 mL 87 mL 130 mL 250 mg amoxicillin and 62. 5 mg of clavulanic acid as the potassium salt Shake oral suspension well before using. Reconstituted suspension must be stored under refrigeration and discarded after 10 days. Some color change is normal during dosing period. AUGMENTIN 250 mg/125 mg Tablet is NOT The 250 mg/125 mg tablet of AUGMENTIN and the 250 mg/62. 5 mg chewable tablet of AUGMENTIN should NOT NOT [see Dosage and Administration ( 2. 3 Two AUGMENTIN 250 mg/125 mg Tablets are NOT Two 250 mg/125 mg tablets of AUGMENTIN should NOT.

The following are discussed in more detail in other sections of the labeling: Anaphylactic reactions [see Warnings and Precautions ( 5. 1 Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5. 2 Hepatic Dysfunction [see Warnings and Precautions ( 5. 3 Clostridioides difficile [see Warnings and Precautions ( 5. 4 The most frequently reported adverse effects were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%),vomiting (1%) and vaginitis (1%) (6. 1 To report SUSPECTED ADVERSE REACTIONS, contact Devatis Inc. at 1-833-534-4406 or druginfo@devatis. com or FDA at 1-800-FDA-1088 or www. gov/medwatch or www. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In pediatric patients (aged 2 months to 12 years), 1 US/Canadian clinical trial was conducted which compared 45/6. 4 mg/kg/day (divided every 12 hours) of AUGMENTIN for 10 days versus 40/10 mg/kg/day (divided every 8 hours) of AUGMENTIN for 10 days in the treatment of acute otitis media. A total of 575 patients were enrolled, and only the suspension formulations were used in this trial. Overall, the adverse reactions seen were comparable to that noted above; however, there were differences in the rates of diarrhea, skin rashes/urticaria, and diaper area rashes [See Clinical Studies (14. 2) ] In addition to adverse reactions reported from clinical trials, the following have been identified during postmarketing use of AUGMENTIN. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to AUGMENTIN. Gastrointestinal: [see Warnings and Precautions ( 5. 5 Immune: [see Warnings and Precautions ( 5. 1 Skin and Appendages: Liver: [see Contraindications ( 4. 4 Renal: [see Overdosage ( 10 Hemic and Lymphatic Systems: [see Drug Interactions ( 7. 2 Central Nervous System: Miscellaneous:.

History of a serious hypersensitivity reaction (e. , anaphylaxis or Stevens-Johnson syndrome) to Amoxicillin and Clavulanate Potassium for Oral Suspension or to other beta-lactams (e. , penicillins or cephalosporins). 1 History of cholestatic jaundice/hepatic dysfunction associated with Amoxicillin and Clavulanate Potassium for Oral Suspension ( 4. 2 Amoxicillin and Clavulanate Potassium for Oral Suspension is contraindicated in patients with a history of serious hypersensitivity reactions (e. , anaphylaxis or Stevens-Johnson syndrome) to amoxicillin, clavulanate or to other beta-lactam antibacterial drugs (e. , penicillins and cephalosporins). Amoxicillin and Clavulanate Potassium for Oral Suspension is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with Amoxicillin and Clavulanate Potassium for Oral Suspension.

Pediatric Use: Modify dose in patients 12 weeks or younger. 4) Renal impairment; Dosage adjustment is recommended for severe renal impairment (GFRless than 30mL/min). 6 Teratogenic Effects Oral ampicillin-class antibacterials are poorly absorbed during labor. It is not known whether use of amoxicillin and clavulanate potassium in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood of the necessity for an obstetrical intervention. Amoxicillin has been shown to be excreted in human milk. Amoxicillin and clavulanate potassium use by nursing mothers may lead to sensitization of infants. Caution should be exercised when amoxicillin and clavulanate potassium is administered to a nursing woman. The safety and effectiveness of AUGMENTIN for Oral Suspension and Chewable Tablets have been established in pediatric patients. Use of AUGMENTIN in pediatric patients is supported by evidence from studies of AUGMENTIN Tablets in adults with additional data from a study of AUGMENTIN for Oral Suspension in pediatric patients aged 2 months to 12 years with acute otitis media [see Clinical Studies (14. 2 Because of incompletely developed renal function in neonates and young infants, the elimination of amoxicillin may be delayed; clavulanate elimination is unaltered in this age group. Dosing of Amoxicillin and clavulanate potassium should be modified in pediatric patients aged less than 12 weeks (less than 3 months) [see Dosage and Administration (2. 3 ] Of the 3,119 patients in an analysis of clinical studies of AUGMENTIN, 32% were greater than or equal to 65 years old, and 14% were greater than or equal to 75 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Amoxicillin is primarily eliminated by the kidney and dosage adjustment is usually required in patients with severe renal impairment (GFR less than 30 mL/min). See Patients with Renal Impairment [see Dosage and Administration ( 2.

Co‑administration with probenecid is not recommended. 1) Concomitant use of Amoxicillin and Clavulanate Potassium for Oral Suspension and oral anticoagulants may increase the prolongation of prothrombin time. 2 Coadministration with allopurinol increases the risk of rash. 3) Amoxicillin and Clavulanate Potassium for Oral Suspension may reduce efficacy of oral contraceptives. 4) Probenecid decreases the renal tubular secretion of amoxicillin but does not delay renal excretion of clavulanic acid. Concurrent use with Amoxicillin and clavulanate potassium may result in increased and prolonged blood concentrations of amoxicillin. Co-administration of probenecid is not recommended. Abnormal prolongation of prothrombin time (increased international normalized ratio [INR]) has been reported in patients receiving amoxicillin and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently with Amoxicillin and clavulanate potassium. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation. The concurrent administration of allopurinol and amoxicillin increases the incidence of rashes in patients receiving both drugs as compared to patients receiving amoxicillin alone. It is not known whether this potentiation of amoxicillin rashes is due to allopurinol or the hyperuricemia present in these patients. Amoxicillin and clavulanate potassium may affect intestinal flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives. High urine concentrations of amoxicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITESTregistered, Benedict’s Solution, or Fehling’s Solution. Since this effect may also occur with Amoxicillin and clavulanate potassium, it is recommended that glucose tests based on enzymatic glucose oxidase reactions be used. Following administration of amoxicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been noted.

OVERDOSAGE
In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures as required. A prospective study of 51 pediatric patients at a poison-control center suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms1. Interstitial nephritis resulting in oliguric renal failure has been reported in patients after overdosage with amoxicillin and clavulanate potassium. Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin and clavulanate potassium overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin and clavulanate potassium crystalluria. Renal impairment appears to be reversible with cessation of drug administration. High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance of amoxicillin and clavulanate potassium. Amoxicillin and clavulanate potassium may be removed from circulation by hemodialysis [see Dosage and Administration ( 2.4 )].
NONCLINICAL TOXICOLOGY
Long-term studies in animals have not been performed to evaluate carcinogenic potential. AUGMENTIN (4:1 ratio formulation of amoxicillin:clavulanate) was non-mutagenic in the Ames bacterial mutation assay, and the yeast gene conversion assay. AUGMENTIN was weakly positive in the mouse lymphoma assay, but the trend toward increased mutation frequencies in this assay occurred at doses that were also associated with decreased cell survival. AUGMENTIN was negative in the mouse micronucleus test, and in the dominant lethal assay in mice. Potassium clavulanate alone was tested in the Ames bacterial mutation assay and in the mouse micronucleus test and was negative in each of these assays. AUGMENTIN (2:1 ratio formulation of amoxicillin:clavulanate) at oral doses of up to 1,200 mg/kg/day was found to have no effect on fertility and reproductive performance in rats. Based on body surface area, this dose of amoxicillin is approximately 4 times the maximum recommended adult human oral dose (875 mg every 12 hours). For clavulanate, the dose multiple is approximately 9 times higher than the maximum recommended adult human oral dose (125 mg every 8 hours), also based on body surface area.
CLINICAL STUDIES
In one of these pivotal trials, patients with either pyelonephritis (n equals 361) or a complicated urinary tract infection (i. , patients with abnormalities of the urinary tract that predispose to relapse of bacteriuria following eradication, n equals 268) were randomized (1:1) to receive either 875 mg/125 mg tablets of AUGMENTIN every 12 hours (n equals 308) or 500 mg/125 mg tablets of AUGMENTIN every 8 hours (n equals 321). The number of bacteriologically evaluable patients was comparable between the two dosing regimens. AUGMENTIN produced comparable bacteriological success rates in patients assessed 2 to 4 days immediately following end of therapy. The bacteriologic efficacy rates were comparable at one of the follow-up visits (5 to 9 days post-therapy) and at a late post-therapy visit (in the majority of cases, this was 2 to 4 weeks post-therapy), as seen in Table 8. Table 8: Bacteriologic efficacy rates for AUGMENTIN Time Post Therapy 875 mg every 12 hours % (n) 500 mg every 8 hours % (n) 2 to 4 days 81% (58) 80% (54) 5 to 9 days 58% (41) 52% (52) 2 to 4 weeks 52% (101) 55% (104) As noted, before, though there was no significant difference in the percentage of adverse events in each group, there was a statistically significant difference in rates of severe diarrhea or withdrawals with diarrhea between the regimens. One US/Canadian clinical trial was conducted which compared 45/6. 4 mg/kg/day (divided every 12 hours) of AUGMENTIN for 10 days versus 40/10 mg/kg/day (divided every 8 hours) of AUGMENTIN for 10 days in the treatment of acute otitis media. Only the suspension formulations were used in this trial. A total of 575 pediatric patients (aged 2 months to 12 years) were enrolled, with an even distribution among the 2 treatment groups and a comparable number of patients were evaluable (i. , greater than or equal to 84%) per treatment group. Otitis media-specific criteria were required for eligibility and a strong correlation was found at the end of therapy and follow-up between these criteria and physician assessment of clinical response. The clinical efficacy rates at the end of therapy visit (defined as 2 to 4 days after the completion of therapy) and at the follow-up visit (defined as 22 to 28 days post-completion of therapy) were comparable for the 2 treatment groups, with the following cure rates obtained for the evaluable patients: At end of therapy, 87% (n equals 265) and 82% (n equals 260) for 45 mg/kg/day every 12 hours and 40 mg/kg/day every 8 hours, respectively. At follow-up, 67% (n equals 249) and 69% (n equals 243) for 45 mg/kg/day every 12 hours and 40 mg/kg/day every 8 hours, respectively. Diarrhea was defined as either: (a) 3 or more watery or 4 or more loose/watery stools in 1 day; OR (b) 2 watery stools per day or 3 loose/watery stools per day for 2 consecutive days. The incidence of diarrhea was significantly lower in patients who received the every 12 hours regimen compared to patients who received the every 8 hours regimen (14% and 34%, respectively). In addition, the number of patients with either severe diarrhea or who were withdrawn with diarrhea was significantly lower in the every 12 hours treatment group (3% and 8% for the every 12 hours/10 day and every 8 hours/10 day, respectively). In the every 12 hours treatment group, 3 patients (1%) were withdrawn with an allergic reaction, while 1 patient in the every 8 hours group was withdrawn for this reason. The number of patients with a candidal infection of the diaper area was 4% and 6% for the every 12 hours and every 8 hours groups, respectively. It is not known if the finding of a statistically significant reduction in diarrhea with the oral suspensions dosed every 12 hours, versus suspensions dosed every 8 hours of AUGMENTIN, can be extrapolated to the chewable tablets of AUGMENTIN. The presence of mannitol in the chewable tablets of AUGMENTIN may contribute to a different diarrhea profile.
REFERENCES
1. Swanson-Biearman B, Dean BS, Lopez G, Krenzelok EP. The effects of penicillin and cephalosporin ingestions in children less than six years of age.Vet Hum Toxicol. 1988; 30: 66‑67.

Devatis, Inc.

AMOXICILLIN AND CLAVULANATE POTASSIUM- amoxicillin and clavulanate potassium_powder, for suspension Product manual source documgent