Patient Information
17.1 Information for Patients
Patients should be informed that amoxicillin and clavulanate potassium suspension may be taken every 8 hours or every 12 hours, depending on the dose prescribed. Each dose should be taken with a meal or snack to reduce the possibility of gastrointestinal upset.
Patients should be counseled that antibacterial drugs, including amoxicillin and clavulanate potassium suspension, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When amoxicillin and clavulanate potassium suspension is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by amoxicillin and clavulanate potassium suspension or other antibacterial drugs in the future.
Counsel patients that diarrhea is a common problem caused by antibacterials, and it usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken their last dose of the antibacterial. If diarrhea is severe or lasts more than 2 or 3 days, patients should contact their physician.
Patients should be advised to keep suspension refrigerated. Shake well before using. When dosing a child with the suspension (liquid) of amoxicillin and clavulanate potassium suspension, use a dosing spoon or medicine dropper. Be sure to rinse the spoon or dropper after each use. Bottles of suspension of amoxicillin and clavulanate potassium suspension may contain more liquid than required. Follow your doctor s instructions about the amount to use and the days of treatment your child requires. Discard any unused medicine.
Patients should be aware that amoxicillin and clavulanate potassium suspension contains a penicillin class drug product that can cause allergic reactions in some individuals.
CLINITESTis a registered trademark of Miles, Inc.
Distributed by:
West-Ward Pharmaceutical Corp.
Eatontown, NJ 07724 USAManufactured by:
HIKMAPharmaceuticals
P.O. Box 182400
Amman 11118 - JordanRevised April 2013
- No Title 1572551925
- No Title 1572554023
- Package Label-principal Display Panel - 400 Mg/57 Mg* Per 5 Ml (75 Ml Bottle Label)
- No Title 1572451163
- Description
- Clinical Pharmacology
- Warnings
- Precautions
- Overdosage
- How Supplied
- Storage
- Description Of Clinical Studies
- References
- Principal Display Panel
- Highlights Of Prescribing Information
- Indications And Usage
- Dosage And Administration
- Dosage Forms And Strengths
- Contraindications
- Warnings And Precautions
- Adverse Reactions
- Drug Interactions
- Use In Specific Populations
- 1 Indications And Usage
- 2 Dosage And Administration
- 3 Dosage Forms And Strengths
- 4 Contraindications
- 5 Warnings And Precautions
- 6 Adverse Reactions
- 7 Drug Interactions
- 8 Use In Specific Populations
- 10 Overdosage
- 11 Description
- 12 Clinical Pharmacology
- 13 Nonclinical Toxicology
- 14 Clinical Studies
- 15 References
- 16 How Supplied/storage And Handling
- Storage
- Amoxicillin And Clavulanate Potassium
- Package Label-principal Display Panel - 400 Mg/57 Mg* Per 5 Ml (100 Ml Bottle Label)
- Package Label-principal Display Panel - 400 Mg/57 Mg* Per 5 Ml (50 Ml Bottle Label)
- No Title 1572452408
- Package Label-principal Display Panel - 125 Mg/31.25 Mg Per 5 Ml (75 Ml Bottle Label)
- Package Label-principal Display Panel - 250 Mg/62.5 Mg Per 5 Ml (75 Ml Bottle Label)
- Package Label-principal Display Panel - 200 Mg/28.5 Mg* Per 5 Ml (50 Ml Bottle Label)
- 1 Indications And Usage
- 2 Dosage And Administration
- 3 Dosage Forms And Strengths
- 4 Contraindications
- 5 Warnings And Precautions
- 6 Adverse Reactions
- 7 Drug Interactions
- 8 Use In Specific Populations
- 11 Description
- 12 Clinical Pharmacology
- 13 Nonclinical Toxicology
- 14 Clinical Studies
- 15 References
- 16 How Supplied/storage And Handling
- 10 Overdosage
- Principal Display Panel
No Title 1572551925 ⮝
1111
PRESCRIBING INFORMATIONTo reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL and other antibacterial drugs, Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
No Title 1572554023 ⮝
1111
PRESCRIBING INFORMATIONTo reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL and other antibacterial drugs, Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Package Label-principal Display Panel - 400 Mg/57 Mg* Per 5 Ml (75 Ml Bottle Label) ⮝
NDC 33261-0989-01
Amoxicillin and Clavulanate
Potassium for Oral Suspension, USP
400 mg/57 mg* per 5 mL
Rx only
75 mL when reconstituted
AMOXICILLIN AND CLAVULANATE POTASSIUM
amoxicillin and clavulanate potassium powder, for suspension
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:33261-989(NDC:65862-534) Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AMOXICILLIN (UNII: 804826J2HU) (AMOXICILLIN ANHYDROUS - UNII:9EM05410Q9) AMOXICILLIN ANHYDROUS 400 mg in 5 mL CLAVULANATE POTASSIUM (UNII: Q42OMW3AT8) (CLAVULANIC ACID - UNII:23521W1S24) CLAVULANIC ACID 57 mg in 5 mL
Inactive Ingredients Ingredient Name Strength ASPARTAME (UNII: Z0H242BBR1) HYPROMELLOSE 2910 (50 MPA.S) (UNII: 1IVH67816N) ORANGE (UNII: 5EVU04N5QU) SILICON DIOXIDE (UNII: ETJ7Z6XBU4) SUCCINIC ACID (UNII: AB6MNQ6J6L) XANTHAN GUM (UNII: TTV12P4NEE)
Product Characteristics Color WHITE (White to Off-white) Score Shape Size Flavor ORANGE Imprint Code Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:33261-989-01 75 mL in 1 BOTTLE, PLASTIC
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA201090 12/20/2011
Labeler - Aidarex Pharmaceuticals LLC (801503249) Revised: 11/2013 Document Id: 603f002e-7b62-4777-be74-66e0ffffb894 34391-3 Set id: 9290fcb9-7991-44b6-9045-1ed3fdfe2b28 Version: 1 Effective Time: 20131121 Aidarex Pharmaceuticals LLC
No Title 1572451163 ⮝
1111
PRESCRIBING INFORMATIONTo reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL and other antibacterial drugs, Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Description ⮝
Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL is an oral antibacterial combination consisting of the semisynthetic antibiotic amoxicillin and the -lactamase inhibitor, clavulanate potassium (the potassium salt of clavulanic acid). Amoxicillin is an analog of ampicillin, derived from the basic penicillin nucleus, 6-aminopenicillanic acid. The amoxicillin molecular formula is C16H19N3O5S 3H2O, and the molecular weight is 419.46. Chemically, amoxicillin is (2S,5R,6R)-6-[(R)-(-)-2-Amino-2-(p-hydroxyphenyl)acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate and may be represented structurally as:
Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is a -lactam structurally related to the penicillins and possesses the ability to inactivate a wide variety of -lactamases by blocking the active sites of these enzymes. Clavulanic acid is particularly active against the clinically important plasmid-mediated -lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins. The clavulanate potassium molecular formula is C8H8KNO5, and the molecular weight is 237.25. Chemically, clavulanate potassium is potassium (Z)-(2R ,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]-heptane-2-carboxylate and may be represented structurally as:
Inactive Ingredients:
Powder for Oral Suspension- Colloidal silicon dioxide, strawberry cream flavor, xanthan gum, aspartamea, sodium carboxymethylcellulose, and silicon dioxide.
a See PRECAUTIONS Information for the Patient/Phenylketonurics.
Each 5 mL of reconstituted 600 mg/42.9 mg per 5 mL oral suspension of Amoxicillin and Clavulanate Potassium contains 0.23 mEq potassium.
Clinical Pharmacology ⮝
The pharmacokinetics of amoxicillin and clavulanate were determined in a study of 19 pediatric patients, 8 months to 11 years, given Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL at an amoxicillin dose of 45 mg/kg q12h with a snack or meal. The mean plasma amoxicillin and clavulanate pharmacokinetic parameter values are listed in the following table.
Table 1. Mean ( SD) Plasma Amoxicillin and Clavulanate Pharmacokinetic Parameter Values Following Administration of 45 mg/kg of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL Every 12 Hours to Pediatric Patients PARAMETER* AMOXICILLIN CLAVULANATE
- *
- Arithmetic mean standard deviation, except Tmax values which are medians (ranges).
Cmax (mcg/mL) 15.7 7.7 1.7 0.9 Tmax (hr) 2.0 (1.0 - 4.0) 1.1 (1.0 - 4.0) AUC0-t (mcg hr/mL) 59.8 20.0 4.0 1.9 T1/2 (hr) 1.4 0.3 1.1 0.3 CL/F (L/hr/kg) 0.9 0.4 1.1 1.1 The effect of food on the oral absorption of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL has not been studied.
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 10 mL of 250 mg/5 mL suspension of amoxicillin and clavulanate potassium.
Concurrent administration of probenecid delays amoxicillin excretion but does not delay renal excretion of clavulanic acid.
Neither component in Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL is highly protein-bound; clavulanic acid has been found to be approximately 25% bound to human serum and amoxicillin approximately 18% bound.
Oral administration of a single dose of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL at 45 mg/kg (based on the amoxicillin component) to pediatric patients, 9 months to 8 years, yielded the following pharmacokinetic data for amoxicillin in plasma and middle ear fluid (MEF).
Table 2. Amoxicillin Concentrations in Plasma and Middle Ear Fluid Following Administration of 45 mg/kg of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL to Pediatric Patients Timepoint Amoxicillin concentration in plasma (mcg/mL) Amoxicillin concentration in MEF (mcg/mL) 1 hour mean
median
range7.7
9.3
1.5 - 14.0
(n = 5)3.2
3.5
0.2 - 5.5
(n = 4)2 hour mean
median
range15.7
13.0
11.0 - 25.0
( n= 7)3.3
2.4
1.9 - 6
(n = 5)3 hour mean
median
range13.0
12.0
5.5 - 21.0
(n = 5)5.8
6.5
3.9 - 7.4
(n = 5)Dose administered immediately prior to eating.
Amoxicillin diffuses readily into most body tissues and fluids with the exception of the brain and spinal fluid. The results of experiments involving the administration of clavulanic acid to animals suggest that this compound, like amoxicillin, is well distributed in body tissues.
Microbiology:
Amoxicillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms. Amoxicillin is, however, susceptible to degradation by -lactamases, and therefore, its spectrum of activity does not include organisms which produce these enzymes. Clavulanic acid is a -lactam, structurally related to penicillin, which possesses the ability to inactivate a wide range of -lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid-mediated -lactamases frequently found responsible for transferred drug resistance.
The clavulanic acid component of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL protects amoxicillin from degradation by -lactamase enzymes and effectively extends the antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other -lactam antibiotics. Thus, Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL possesses the distinctive properties of a broad-spectrum antibiotic and a -lactamase inhibitor.
Amoxicillin/clavulanic acid has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.
Aerobic Gram-Positive Microorganisms:
Streptococcus pneumoniae (including isolates with penicillin MICs 2 mcg/mL)
Aerobic Gram-Negative Microorganisms:
Haemophilus influenzae (including -lactamase producing isolates)
Moraxella catarrhalis (including -lactamase producing isolates)
The following in vitro data are available, but their clinical significance is unknown.
At least 90% of the following microorganisms exhibit in vitro minimum inhibitory concentrations (MICs) less than or equal to the susceptible breakpoint for amoxicillin/clavulanic acid. However, the safety and efficacy of amoxicillin/clavulanic acid in treating infections due to these microorganisms have not been established in adequate and well-controlled trials.
Aerobic Gram-Positive Microorganisms:
Staphylococcus aureus (including -lactamase producing isolates)
NOTE: Staphylococci which are resistant to methicillin/oxacillin must be considered resistant to amoxicillin/clavulanic acid.
Streptococcus pyogenes
NOTE: S. pyogenes do not produce -lactamase, and therefore, are susceptible to amoxicillin alone. Adequate and well-controlled clinical trials have established the effectiveness of amoxicillin alone in treating certain clinical infections due to S. pyogenes.
Susceptibility Test Methods:
When available, the clinical microbiology laboratory should provide cumulative results of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.
Dilution Technique:
Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure.1,2 Standardized procedures are based on dilution methods (broth for S. pneumoniae and H. influenzae) or equivalent with standardized inoculum concentration and standardized concentrations of amoxicillin/clavulanate potassium powder.
The recommended dilution pattern utilizes a constant amoxicillin/clavulanate potassium ratio of 2 to 1 in all tubes with varying amounts of amoxicillin. MICs are expressed in terms of the amoxicillin concentration in the presence of clavulanic acid at a constant 2 parts amoxicillin to 1 part clavulanic acid. The MIC values should be interpreted according to criteria provided in Table 3.
Diffusion Technique:
Quantitative methods that require measurement of zone diameters also provides reproducible estimates of the susceptibility of bacteria to antimicrobials. One such standardized technique requires the use of a standardized inoculum concentration.2,3 This procedure uses paper disks impregnated with 30 mcg amoxicillin/clavulanate potassium (20 mcg amoxicillin plus 10 mcg clavulanate potassium) to test susceptibility of microorganisms to amoxicillin/clavulanate potassium. Disk diffusion zone sizes should be interpreted according to criteria provided in Table 3.
Table 3. Susceptibility Test Result Interpretive Criteria for Amoxicillin/Clavulanate Potassium Pathogen Minimum Inhibitory Concentration
(mcg/mL)Disk Diffusion
(Zone Diameter in mm)Pathogen S I R S I R Streptococcus pneumoniae
(non-meningitis isolates)2/1 4/2 8/4 Not Applicable (NA) Haemophilus influenzae 4/2 NA 8/4 20 NA 19 NOTE: Susceptibility of S. pneumoniae should be determined using a 1-mcg oxacillin disk. Isolates with oxacillin zone sizes of 20 mm are susceptible to amoxicillin/clavulanic acid. An amoxicillin/clavulanic acid MIC should be determined on isolates of S. pneumoniae with oxacillin zone sizes of 19 mm.
NOTE: -lactamase negative, ampicillin-resistant H. influenzae isolates must be considered resistant to amoxicillin/clavulanic acid.
A report of S ( Susceptible ) indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound in the blood reaches the concentration usually achievable. A report of I ( Intermediate ) indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible antimicrobials, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high doses of antimicrobial can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of R ( Resistant ) indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound in the blood reaches the concentration usually achievable; other therapy should be selected.
Standardized susceptibility test procedures require the use of quality control microorganisms to determine the performance of the test procedures.1-3 Standard amoxicillin/clavulanate potassium powder should provide the MIC ranges for the quality control organisms in Table 4. For the disk diffusion technique, the 30 mcg-amoxicillin/clavulanate potassium disk should provide the zone diameter ranges for the quality control organisms in Table 4.
Table 4. Acceptable Quality Control Ranges for Amoxicillin/Clavulanate Potassium Quality Control Organism Minimum Inhibitory
Concentration Range
(mcg/mL)Disk Diffusion
(Zone Diameter
Range in mm)
- *
- ATCC is a trademark of the American Type Culture Collection.
- When using Haemophilus Test Medium (HTM).
Escherichia coli ATCC * 35218
(H. influenzae quality control)4/2 to 16/8 17 to 22 Haemophilus influenzae ATCC 49247 2/1 to 16/8 15 to 23 Streptococcus pneumoniae ATCC 49619 0.03/0.016 to 0.12/0.06 NA
Warnings ⮝
SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH AMOXICILLIN AND CLAVULANATE POTASSIUM 600 MG/42.9 MG PER 5 ML, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, OR OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, AMOXICILLIN AND CLAVULANATE POTASSIUM 600 MG/42.9 MG PER 5 ML SHOULD BE DISCONTINUED AND THE APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including amoxicillin/clavulanate potassium, and has ranged in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of antibiotic-associated colitis.
After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against C. difficile colitis.
Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL should be used with caution in patients with evidence of hepatic dysfunction. Hepatic toxicity associated with the use of amoxicillin/clavulanate potassium is usually reversible. On rare occasions, deaths have been reported (less than 1 death reported per estimated 4 million prescriptions worldwide). These have generally been cases associated with serious underlying diseases or concomitant medications. (See CONTRAINDICATIONS and ADVERSE REACTIONS Liver.)
Precautions ⮝
General:
While amoxicillin/clavulanate possesses the characteristic low toxicity of the penicillin group of antibiotics, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic function, is advisable if therapy is for longer than the drug is approved for administration.
A high percentage of patients with mononucleosis who receive ampicillin develop an erythematous skin rash. Thus, ampicillin-class antibiotics should not be administered to patients with mononucleosis.
The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Pseudomonas or Candida), the drug should be discontinued and/or appropriate therapy instituted.
Prescribing Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Information for the Patient:
Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL should be taken every 12 hours with a meal or snack to reduce the possibility of gastrointestinal upset. If diarrhea develops and is severe or lasts more than 2 or 3 days, call your doctor.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.
Keep suspension refrigerated. Shake well before using. When dosing a child with the suspension (liquid) of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL, use a dosing spoon or medicine dropper. Be sure to rinse the spoon or dropper after each use. Bottles of suspension of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL may contain more liquid than required. Follow your doctor s instructions about the amount to use and the days of treatment your child requires. Discard any unused medicine.
Patients should be counseled that antibacterial drugs, including Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL or other antibacterial drugs in the future.
Phenylketonurics:
Each 5 mL of the 600 mg/42.9 mg per 5 mL suspension of Amoxicillin and Clavulanate Potassium contains 7 mg phenylalanine.
Drug Interactions:
Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL may result in increased and prolonged blood levels of amoxicillin. Co-administration of probenecid cannot be recommended.
Abnormal prolongation of prothrombin time (increased international normalized ratio [INR]) has been reported rarely in patients receiving amoxicillin and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.
The concurrent administration of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to patients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia present in these patients. There are no data with Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL and allopurinol administered concurrently.
In common with other broad-spectrum antibiotics, amoxicillin/clavulanate may reduce the efficacy of oral contraceptives.
Drug/Laboratory Test Interactions:
Oral administration of AMOXICILLIN AND CLAVULANATE POTASSIUM will result in high urine concentrations of amoxicillin. High urine concentrations of ampicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITEST , Benedict s Solution, or Fehling s Solution. Since this effect may also occur with amoxicillin and therefore Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as CLINISTIX ) be used.
Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been noted. This effect may also occur with amoxicillin and therefore Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Long-term studies in animals have not been performed to evaluate carcinogenic potential. The mutagenic potential of AMOXICILLIN AND CLAVULANATE POTASSIUM was investigated in vitro with an Ames test, a human lymphocyte cytogenetic assay, a yeast test, and a mouse lymphoma forward mutation assay, and in vivo with mouse micronucleus tests and a dominant lethal test. All were negative apart from the in vitro mouse lymphoma assay where weak activity was found at very high, cytotoxic concentrations. AMOXICILLIN AND CLAVULANATE POTASSIUM at oral doses of up to 1,200 mg/kg/day (5.7 times the maximum adult human dose based on body surface area) was found to have no effect on fertility and reproductive performance in rats, dosed with a 2:1 ratio formulation of amoxicillin:clavulanate.
Teratogenic Effects:
Pregnancy (Category B). Reproduction studies performed in pregnant rats and mice given AMOXICILLIN AND CLAVULANATE POTASSIUM at oral dosages up to 1,200 mg/kg/day (4.9 and 2.8 times the maximum adult human oral dose based on body surface area, respectively), revealed no evidence of harm to the fetus due to AMOXICILLIN AND CLAVULANATE POTASSIUM. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Labor and Delivery:
Oral ampicillin-class antibiotics are generally poorly absorbed during labor. Studies in guinea pigs have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions, and duration of contractions. However, it is not known whether the 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 that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary. In a single study in women with premature rupture of fetal membranes, it was reported that prophylactic treatment with AMOXICILLIN AND CLAVULANATE POTASSIUM may be associated with an increased risk of necrotizing enterocolitis in neonates.
Nursing Mothers:
Ampicillin-class antibiotics are excreted in human milk; therefore, caution should be exercised when AMOXICILLIN AND CLAVULANATE POTASSIUM is administered to a nursing woman.
Pediatric Use:
Safety and efficacy of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL in infants younger than 3 months have not been established. Safety and efficacy of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL have been demonstrated for treatment of acute otitis media in infants and children 3 months to 12 years (see Description of Clinical Studies).
The safety and effectiveness of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL have been established for the treatment of pediatric patients (3 months to 12 years) with acute bacterial sinusitis. This use is supported by evidence from adequate and well-controlled studies of AMOXICILLIN AND CLAVULANATE POTASSIUM Extended Release Tablets in adults with acute bacterial sinusitis, studies of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL in pediatric patients with acute otitis media, and by similar pharmacokinetics of amoxicillin and clavulanate in pediatric patients taking Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL (see CLINICAL PHARMACOLOGY) and adults taking AMOXICILLIN AND CLAVULANATE POTASSIUM Extended Release Tablets.
Overdosage ⮝
Following overdosage, patients have experienced primarily gastrointestinal symptoms including stomach and abdominal pain, vomiting, and diarrhea. Rash, hyperactivity, or drowsiness have also been observed in a small number of patients.
In the case of overdosage, discontinue Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL, treat symptomatically, and institute supportive measures as required. If the overdosage is very recent and there is no contraindication, an attempt at emesis or other means of removal of drug from the stomach may be performed. 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 symptoms and do not require gastric emptying.4
Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxicillin.
Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin 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 both amoxicillin and clavulanate. Both amoxicillin and clavulanate are removed from the circulation by hemodialysis.
How Supplied ⮝
Amoxicillin and Clavulanate Potassium, 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.
HOW SUPPLIED
NDC 33261-0600-01 75 mL bottle
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 Amoxicillin and Clavulanate Potassium 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 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 (4-6 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 Amoxicillin and Clavulanate Potassium 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 4-6 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
- *
- CI = confidence intervals; 95% CIs are not adjusted for multiple comparisons.
Pathogen n/N % 95% CI* All S. pneumoniae 121/123 98.4 (94.3, 99.8) S. pneumoniae with penicillin
MIC = 2 mcg/mL19/19 100 (82.4, 100.0) S. pneumoniae with penicillin
MIC = 4 mcg/mL12/14 85.7 (57.2, 98.2) H. influenzae 75/81 92.6 (84.6, 97.2) M. catarrhalis 11/11 100 (71.5, 100.0) 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.
Table 6. Clinical Assessments in the Per Protocol Population (Includes S. pneumoniae Patients With Penicillin MICs = 2 or 4 mcg/mL*) 2-4 Days Post-Therapy (Primary Endpoint)
- *
- 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.
Pathogen n/N % 95% CI All S. pneumoniae 122/137 89.1 (82.6, 93.7) S. pneumoniae with penicillin
MIC = 2 mcg/mL17/20 85.0 (62.1, 96.8) S. pneumoniae with penicillin
MIC = 4 mcg/mL11/14 78.6 (49.2, 95.3) H. influenzae 141/162 87.0 (80.9, 91.8) M. catarrhalis 22/26 84.6 (65.1, 95.6) 15-18 Days Post-Therapy (Secondary Endpoint) Pathogen n/N % 95% CI All S. pneumoniae 95/136 69.9 (61.4, 77.4) S. pneumoniae with penicillin
MIC = 2 mcg/mL11/20 55.0 (31.5, 76.9) S. pneumoniae with penicillin
MIC = 4 mcg/mL5/14 35.7 (12.8, 64.9) H. influenzae 106/156 67.9 (60.0, 75.2) M. catarrhalis 14/25 56.0 (34.9, 75.6) 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 Amoxicillin and Clavulanate Potassium 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 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 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 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 600 mg/42.9 mg per 5mL and 1 patient in the group treated with AMOXICILLIN AND CLAVULANATE POTASSIUM were withdrawn due to diarrhea.
References ⮝
- Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing 21st Informational Supplement. CSLI Document M100-S21. CLSI, 940 West Valley Rd., Suite 1400, Wayne, PA 19087, 2011.
- Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria Approved Standard 7th ed. CSLI Document M11-A7. CLSI, 940 West Valley Rd., Suite 1400, Wayne, PA 19087, 2007.
- Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard 8th ed. CLSI Document M07-A8. CLSI, 940 West Valley Rd., Suite 1400, Wayne, PA 19087, 2009.
- Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Susceptibility Test; Approved Standard 10th ed. CLSI Document M02-A10. CLSI, 940 West Valley Rd., Suite 1400, Wayne, PA 19087, 2009.
- 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.
CLINITEST is a registered trademark of Miles, Inc.
CLINISTIX is a registered trademark of Bayer Corporation.
FLAVORx is a trademark of FLAVORx. Inc.
Mfd. by:
Dr. Reddy's Laboratories Inc.,
Bridgewater, NJ 08807
Repackaged By :
Aidarex Pharmaceuticals LLC,
Corona, CA 92880
Principal Display Panel ⮝
NDC 33261-0600-01
600 mg/42.9 mg per 5 mL
AMOXICILLIN/CLAVULANATE POTASSIUM
powder for oral suspension
When reconstituted, each 5 mL contains:
AMOXICILLIN, 600 MG,
as the trihydrate
CLAVULANIC ACID, 42.9 MG,
as clavulanate potassium
75 mL (when reconstituted)
Rx only
Directions for mixing:
1. Tap bottle until all powder flows freely. ADD 70 mL OF WATER IN TWO PARTS.
2. Add approximately 2/3 of the water for reconstitution. Shake vigorously.
3. Add remaining water; shake vigorously.Dosage: Administer every 12 hours. See accompanying prescribing information.
Phenylketonurics: Contains phenylalanine 7 mg per 5 mL.
Keep tightly closed.
Shake well before using.
Must be refrigerated.
Discard after 10 days.
Use only if inner seal is intact.
Net contents: Equivalent to 9 g amoxicillin and 0.643 g clavulanic acid.
Store dry powder at room temperature.
Mfd. By: Dr. Reddy's Laboratories Inc.,
Bridgewater, NJ 08807
I1111
150035376
Repackaged By :
Aidarex Pharmaceuticals LLC,
Corona, CA 92880
AMOXICILLIN AND CLAVULANATE POTASSIUM
amoxicillin and clavulanate potassium powder, for suspension
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:33261-600(NDC:43598-203) Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AMOXICILLIN (UNII: 804826J2HU) (AMOXICILLIN ANHYDROUS - UNII:9EM05410Q9) AMOXICILLIN ANHYDROUS 600 mg in 5 mL CLAVULANATE POTASSIUM (UNII: Q42OMW3AT8) (CLAVULANIC ACID - UNII:23521W1S24) CLAVULANIC ACID 42.9 mg in 5 mL
Inactive Ingredients Ingredient Name Strength SILICON DIOXIDE (UNII: ETJ7Z6XBU4) XANTHAN GUM (UNII: TTV12P4NEE) ASPARTAME (UNII: Z0H242BBR1) CARBOXYMETHYLCELLULOSE SODIUM (UNII: K679OBS311)
Product Characteristics Color Score Shape Size Flavor STRAWBERRY Imprint Code Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:33261-600-01 75 mL in 1 BOTTLE, PLASTIC
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA050755 06/22/2001
Labeler - Aidarex Pharmaceuticals LLC (801503249) Revised: 11/2013 Document Id: 7f5fefc0-1979-45a2-966c-616ca2ccfa7f 34391-3 Set id: f5cdf1cd-bdcd-413a-b2ba-5d99050b2dc6 Version: 2 Effective Time: 20131121 Aidarex Pharmaceuticals LLC
Highlights Of Prescribing Information ⮝
These highlights do not include all the information needed to use amoxicillin and clavulanate potassium for oral suspension, USP safely and effectively. See full prescribing information for amoxicillin and clavulanate potassium for oral suspension, USP.
AMOXICILLIN and CLAVULANATE potassium for oral suspension, USP for oral use
Initial U.S. Approval: 1984
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 infections that are proven or strongly suspected to be caused by bacteria.
Indications And Usage ⮝
Amoxicillin and clavulanate potassium for oral suspension, USP 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 beta-lactamase producing strains), or M. catarrhalis (including beta-lactamase-producing strains) characterized by the following risk factors (1):
- antibacterial drug exposure for acute otitis media within the preceding 3 months, and either of the following: 1) age 2 years or younger 2) daycare attendance
Dosage And Administration ⮝
- Pediatric Patients less than 40 kg: 90 mg/kg/day divided every 12 hours, administered for 10 days. (2)
Dosage Forms And Strengths ⮝
600 mg/42.9 mg per 5 mL. (3)
Contraindications ⮝
History of a serious hypersensitivity reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin and clavulanate potassium for oral suspension or to other beta-lactams (e.g., penicillins or cephalosporins). (4.1)
History of cholestatic jaundice/hepatic dysfunction associated with amoxicillin and clavulanate potassium for oral suspension. (4.2)
Warnings And Precautions ⮝
Serious (including fatal) hypersensitivity reactions: Discontinue amoxicillin and clavulanate potassium for oral suspension if a reaction occurs. (5.1)
Hepatic dysfunction and cholestatic jaundice: Discontinue if signs/symptoms of hepatitis occur. Monitor liver function tests in patients with hepatic impairment. (5.2)
Clostridium difficile-associated diarrhea (CDAD): Evaluate patients if diarrhea occurs. (5.3)
Patients with mononucleosis who receive amoxicillin and clavulanate potassium for oral suspension develop skin rash. Avoid amoxicillin and clavulanate potassium for oral suspension use in these patients.(5.4)
Adverse Reactions ⮝
The most frequently reported adverse reactions were diaper rash (4%), diarrhea (3%), vomiting (2%), candidiasis (1%), and rash (1%). (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Northstar Rx LLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug Interactions ⮝
Co-administration with probenecid is not recommended. (7.1)
Concomitant use of amoxicillin and clavulanate potassium for oral suspension with oral anticoagulants may increase the prolongation of prothrombin time. (7.2)
Co-administration with allopurinol increases the risk of rash. (7.3)
Amoxicillin and clavulanate potassium for oral suspension may reduce efficacy of oral contraceptives. (7.4)
Use In Specific Populations ⮝
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 8/2018
1 Indications And Usage ⮝
To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin and clavulanate potassium for oral suspension, USP and other antibacterial drugs, amoxicillin and clavulanate potassium for oral suspension, USP should be used only to treat 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, USP 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 beta-lactamase producing strains), or M. catarrhalis (including beta-lactamase- producing strains) characterized by the following risk factors:
- antibacterial drug exposure for acute otitis media within the preceding 3 months, and either of the following:
-age 2 years or younger
-daycare attendance
[see CLINICAL PHARMACOLOGY, Microbiology (12.4)]
NOTE: Acute otitis media due to S. pneumoniae alone can be treated with amoxicillin. Amoxicillin and clavulanate potassium for oral suspension, USP 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 beta-lactamase-producing organisms listed above.
2 Dosage And Administration ⮝
Amoxicillin and clavulanate potassium for oral suspension does not contain the same amount of clavulanic acid (as the potassium salt) as any of the other suspensions of amoxicillin and clavulanate potassium. Amoxicillin and clavulanate potassium for oral suspension contains 42.9 mg of clavulanic acid per 5 mL, whereas the 200 mg/5 mL suspension of amoxicillin and clavulanate potassium 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/28.5 mg/5 mL and 400 mg/57 mg/5 mL suspensions of amoxicillin and clavulanate potassium should not be substituted for amoxicillin and clavulanate potassium for oral suspension 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 amoxicillin and clavulanate potassium for oral suspension is 90 mg/kg/day divided every 12 hours, administered for 10 days (see chart below). This dose provides 6.4 mg/kg/day of the clavulanic acid component.
Body Weight (kg)
Volume of Amoxicillin and Clavulanate Potassium Powder for Oral Suspension providing 90 mg/kg/day
8
3 mL twice daily
12
4.5 mL twice daily
16
6 mL twice daily
20
7.5 mL twice daily
24
9 mL twice daily
28
10.5 mL twice daily
32
12 mL twice daily
36
13.5 mL twice daily
Pediatric patients weighing 40 kg and more: Experience with amoxicillin and clavulanate potassium for oral suspension in this group is not available.
Adults: Experience with amoxicillin and clavulanate potassium for oral suspension in adults is not available and adults who have difficulty swallowing should not be given amoxicillin and clavulanate potassium for oral suspension in place of the 500 mg or 875 mg tablet of amoxicillin and clavulanate potassium.
Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals [see WARNINGS and PRECAUTIONS (5)].
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.
Amoxicillin and Clavulanate Potassium for Oral Suspension
Bottle Size
Amount of Water Required for Reconstitution
75 mL
71 mL
125 mL
112 mL
200 mL
176 mL
Each teaspoonful (5 mL) will contain 600 mg amoxicillin as the trihydrate and 42.9 mg of clavulanic acid as the potassium salt.
NOTE: SHAKE ORAL SUSPENSION WELL BEFORE USING.
Information for the Pharmacist: For patients who wish to alter the taste of amoxicillin and clavulanate potassium for oral suspension, immediately after reconstitution 1 drop of FLAVORx (apple, banana cream, bubble gum, cherry, or watermelon flavor) may be added for every 5 mL of amoxicillin and clavulanate potassium for oral suspension. The resulting suspension is stable for 10 days under refrigeration. Stability of amoxicillin and clavulanate potassium for oral suspension when mixed with other flavors distributed by FLAVORx has not been evaluated for flavors other than the five flavors listed above.
Administration: To minimize the potential for gastrointestinal intolerance, amoxicillin and clavulanate potassium for oral suspension should be taken at the start of a meal. Absorption of clavulanate potassium may be enhanced when amoxicillin and clavulanate potassium for oral suspension is administered at the start of a meal.
3 Dosage Forms And Strengths ⮝
Powder for Oral Suspension:
- 600 mg/42.9 mg per 5 mL: Strawberry-flavored powder for oral suspension (each 5 mL of reconstituted suspension contains 600 mg amoxicillin and 42.9 mg of clavulanic acid as the potassium salt).
4 Contraindications ⮝
4.1 Serious Hypersensitivity Reactions
Amoxicillin and clavulanate potassium for oral suspension are contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin, clavulanate or to other beta-lactam antibacterial drugs (e.g., penicillins and cephalosporins).
4.2 Cholestatic Jaundice/Hepatic Dysfunction
Amoxicillin and clavulanate potassium for oral suspension is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with treatment with amoxicillin/clavulanate potassium.
5 Warnings And Precautions ⮝
5.1 Serious Allergic Reactions, Including Anaphylaxis
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving amoxicillin and clavulanate potassium for oral suspension. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens.
Before initiating therapy with amoxicillin and clavulanate potassium for oral suspension, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, discontinue amoxicillin and clavulanate potassium for oral suspension and institute appropriate therapy.
5.2 Hepatic Dysfunction
Use amoxicillin and clavulanate potassium for oral suspension with caution in patients with evidence of hepatic dysfunction. Hepatic toxicity associated with the use of amoxicillin/clavulanate potassium is usually reversible. Deaths have been reported (fewer than one death reported per estimated four million prescriptions worldwide). These have generally been cases associated with serious underlying diseases or concomitant medications [see Contraindications (4.2) and Adverse Reactions (6.2)].
5.3 Clostridium difficile-Associated Diarrhea
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including amoxicillin and clavulanate potassium for oral suspension, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
5.4 Skin Rash in Patients with Mononucleosis
A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus, amoxicillin and clavulanate potassium for oral suspension should not be administered to patients with mononucleosis.
5.5 Potential for Microbial Overgrowth
The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Pseudomonas spp. or Candida spp.), the drug should be discontinued and/or appropriate therapy instituted.
5.6 Phenylketonurics
Amoxicillin and clavulanate potassium for oral suspension contains aspartame which contains phenylalanine. Each 5 mL of the 600 mg/42.9 mg per 5 mL suspension of amoxicillin and clavulanate potassium powder for oral suspension contains 7.02 mg phenylalanine.
5.7 Development of Drug-Resistant Bacteria
Prescribing amoxicillin and clavulanate potassium for oral suspension in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
6 Adverse Reactions ⮝
6.1 Clinical Trial Experience
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.
Two clinical trials evaluated the safety of a 10 day treatment course of amoxicillin and clavulanate potassium for oral suspension 90/6.4 mg/kg/day, divided every 12 hours, in pediatric patients with acute otitis media [see Clinical Studies (14)]. The first trial involved 521 pediatric patients (3 months to 50 months) and the second trial involved 450 pediatric patients (3 months to 12 years). In the intent-to-treat population of the first trial of 521 patients, the most frequently reported adverse events were vomiting (7%), fever (6%), contact dermatitis (i.e., diaper rash) (6%), upper respiratory tract infection (4%), and diarrhea (4%). 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 13% of patients. The primary objective of the second study was to compare the safety of amoxicillin and clavulanate potassium for oral suspension (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 ten days. There was no statistically significant difference between treatments in the proportion of patients with 1 or more adverse events. The most frequently reported adverse reactions for amoxicillin and clavulanate potassium for oral suspension and the comparator of amoxicillin and clavulanate potassium were coughing (12% versus 7%), vomiting (7% versus 8%), contact dermatitis (i.e., diaper rash, 6% versus 5%), fever (6% versus 4%), and upper respiratory infection (3% versus 9%), respectively. The frequencies of protocol-defined diarrhea with amoxicillin and clavulanate potassium for oral suspension (11%) and amoxicillin and clavulanate potassium (9%) were not statistically different. Two patients in the group treated with amoxicillin and clavulanate potassium for oral suspension and one patient in the group treated with amoxicillin and clavulanate potassium were withdrawn due to diarrhea.6.2 Postmarketing Experience
In addition to adverse reactions reported from clinical trials, the following have been identified during postmarketing use of amoxicillin and clavulanate potassium products, including amoxicillin and clavulanate potassium for oral suspension. 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 amoxicillin and clavulanate potassium.
Gastrointestinal: Nausea, indigestion, gastritis, stomatitis, glossitis, black hairy tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudo membranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibacterial drug treatment.
Hypersensitivity Reactions: Skin rashes, pruritus, urticaria, angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), erythema multiforme, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, hypersensitivity vasculitis, and an occasional case of exfoliative dermatitis (including toxic epidermal necrolysis) have been reported [see Warnings and Precautions (5.1)].
Liver: A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted in patients treated with ampicillin-class antibacterial drugs. Hepatic dysfunction, including hepatitis and cholestatic jaundice, increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been reported with amoxicillin and clavulanate potassium or amoxicillin and clavulanate potassium for oral suspension. It has been reported more commonly in the elderly, in males, or in patients on prolonged treatment. The histologic findings on liver biopsy have consisted of cholestatic, hepatocellular, or mixed cholestatic-hepatocellular changes. The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy has been discontinued. The hepatic dysfunction, which may be severe, is usually reversible. Deaths have been reported [see Contraindications (4.2), Warnings and Precautions (5.2)].
Renal: Interstitial nephritis, hematuria, and crystalluria have been reported [see Overdosage (10)].
Hemic and Lymphatic Systems: Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. There have been reports of increased prothrombin time in patients receiving amoxicillin and clavulanate potassium and anticoagulant therapy concomitantly.
Central Nervous System: Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, headache, insomnia, and reversible hyperactivity have been reported.
Miscellaneous: Tooth discoloration (brown, yellow, or gray staining) has been reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.
7 Drug Interactions ⮝
7.1 Probenecid
Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with amoxicillin and clavulanate potassium for oral suspension may result in increased and prolonged blood levels of amoxicillin. Co -administration of probenecid is not recommended.
7.2 Oral Anticoagulants
Abnormal prolongation of prothrombin time (increased international normalized ratio [INRI]) has been reported in patients receiving amoxicillin and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.
7.3 Allopurinol
The concurrent administration of allopurinol and amoxicillin increases substantially 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. There are no data with amoxicillin and clavulanate potassium for oral suspension and allopurinol administered concurrently.
7.4 Oral Contraceptives
Amoxicillin and clavulanate potassium for oral suspension may affect intestinal flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.
7.5 Effects on Laboratory Tests
High urine concentrations of amoxicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITEST , Benedict s Solution, or Fehling s Solution. Since this effect may also occur with amoxicillin and clavulanate potassium for oral suspension, 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.
8 Use In Specific Populations ⮝
8.1 Pregnancy
Pregnancy Category B.
There are no adequate and well-controlled studies of amoxicillin and clavulanate potassium in pregnant women. Because animal reproduction studies are not always predictive of human response, use this drug during pregnancy only if clearly needed.
Reproduction studies performed in pregnant rats and mice given amoxicillin and clavulanate potassium (2:1 ratio formulation of amoxicillin:clavulanate) at oral doses up to 1200 mg/kg/day revealed no evidence of harm to the fetus due to amoxicillin and clavulanate potassium. The amoxicillin doses in rodents (based on body surface area and assuming a 20 kg child) were approximately 2 times (rats) or equal to (mice) the recommended clinical amoxicillin and clavulanate potassium for oral suspension dose of 90/6.4 mg/kg/day. For clavulanate, these dose multiples were approximately 15 times and 7.5 times the recommended daily dose of amoxicillin and clavulanate potassium for oral suspension.8.2 Labor and Delivery
Oral ampicillin-class antibacterial drugs are generally poorly absorbed during labor. Studies in guinea pigs have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions, and duration of contractions. However, it is not known whether the 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 that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary. In a single study in women with premature rupture of fetal membranes, it was reported that prophylactic treatment with amoxicillin and clavulanate potassium may be associated with an increased risk of necrotizing enterocolitis in neonates.
8.3 Nursing Mothers
Ampicillin-class antibacterial drugs are excreted in human milk; therefore, caution should be exercised when amoxicillin and clavulanate potassium is administered to a nursing woman.
8.4 Pediatric Use
Safety and efficacy of amoxicillin and clavulanate potassium for oral suspension in infants younger than 3 months have not been established. Safety and efficacy of amoxicillin and clavulanate potassium for oral suspension have been demonstrated for treatment of acute otitis media in infants and children 3 months to 12 years [see Description of Clinical Studies (14)].
The safety and effectiveness of amoxicillin and clavulanate potassium for oral suspension have been established for the treatment of pediatric patients (3 months to 12 years) with acute bacterial sinusitis. This use is supported by evidence from adequate and well-controlled studies of amoxicillin and clavulanate potassium extended-release tablets in adults with acute bacterial sinusitis, studies of amoxicillin and clavulanate potassium for oral suspension in pediatric patients with acute otitis media, and by similar pharmacokinetics of amoxicillin and clavulanate in pediatric patients taking amoxicillin and clavulanate potassium for oral suspension [see CLINICAL PHARMACOLOGY (12)] and adults taking amoxicillin and clavulanate potassium extended-release tablets.
10 Overdosage ⮝
Following overdosage, patients have experienced primarily gastrointestinal symptoms including stomach and abdominal pain, vomiting, and diarrhea. Rash, hyperactivity, or drowsiness has also been observed in a small number of patients.
In the case of overdosage, discontinue amoxicillin and clavulanate potassium for oral suspension, treat symptomatically, and institute supportive measures as required. If the overdosage is very recent and there is no contraindication, an attempt at emesis or other means of removal of drug from the stomach may be performed. A prospective study of 51 pediatric patients at a poison control center suggested that overdosage of less than 250 mg/kg of amoxicillin is not associated with significant clinical symptoms and does not require gastric emptying4.
Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxicillin.
Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin 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 both amoxicillin and clavulanate. Both amoxicillin and clavulanate are removed from the circulation by hemodialysis.
11 Description ⮝
Amoxicillin and clavulanate potassium for oral suspension, USP is an oral antibacterial combination consisting of the semisynthetic antibacterial amoxicillin and the beta-lactamase inhibitor, clavulanate potassium (the potassium salt of clavulanic acid). Amoxicillin is an analog of ampicillin, derived from the basic penicillin nucleus, 6-aminopenicillanic acid. The amoxicillin molecular formula is C16H19N305S 3H2O, and the molecular weight is 419.46. Chemically, amoxicillin is (2S,5R,6R)-6-[(R)-(-)-2-Amino-2-(p -hydroxyphenyl)acetamido]-3,3-dimethyl-7- oxo-4-thia-1-azabicyclo [3.2.0] heptane-2-carboxylic acid trihydrate and may be represented structurally as:
Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is a beta-lactam structurally related to the penicillins and possesses the ability to inactivate a wide variety of beta-lactamases by blocking the active sites of these enzymes. Clavulanic acid is particularly active against the clinically important plasmid-mediated beta-lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins. The clavulanate potassium molecular formula is C8H8KN05 and the molecular weight is 237.25. Chemically, clavulanate potassium is potassium (Z)-(2R,5R)-3-(2-hydroxyethylidene) -7-oxo-4-oxa- 1-azabicyclo [3.2.0] - heptane-2 -carboxylate and may be represented structurally as:
Amoxicillin and clavulanate potassium for oral suspension, USP is white to off-white granular powder and becomes white to pale yellow suspension with strawberry flavor after reconstitution.
Inactive Ingredients: Aspartame*, colloidal silicon dioxide, hypromellose, silicon dioxide, strawberry cream permaseal, succinic acid, and xanthan gum [see Warnings and Precautions (5.6)].Each 5 mL of reconstituted amoxicillin and clavulanate potassium for oral suspension USP, 600 mg/42.9 mg per 5 mL contains 600 mg amoxicillin as the trihydrate and 42.9 mg clavulanic acid as the potassium salt (clavulanate potassium). The potassium content per 5 mL is 0.21 mEq.
12 Clinical Pharmacology ⮝
12.1 Mechanism of Action
Amoxicillin and clavulanate potassium for oral suspension is an antibacterial drug [see Microbiology (12.4 )].
12.3 Pharmacokinetics
The pharmacokinetics of amoxicillin and clavulanate were determined in a study of 19 pediatric patients, 8 months to 11 years, given amoxicillin and clavulanate potassium for oral suspension at an amoxicillin dose of 45 mg/kg q12h with a snack or meal. The mean plasma amoxicillin and clavulanate pharmacokinetic parameter values are listed in the following table.
Table 1. Mean ( SD) Plasma Amoxicillin and Clavulanate Pharmacokinetic Parameter Values Following Administration of 45 mg/kg of Amoxicillin and Clavulanate Potassium for Oral Suspension Every 12 Hours to Pediatric Patients
PARAMETER
AMOXICILLIN
CLAVULANATE
Cmax (mcg/mL)
15.7 7.7
1.7 0.9
Tmax (hour)
2 (1 to 4)
1.1 (1 to 4)
AUC0-T (mcg*hour/mL)
59.8 20
4 1.9
T (hour)
1.4 0.3
1.1 0.3
CL/F (L/hour/kg)
0.9 0.4
1.1 1.1
* Arithmetic mean standard deviation, except Tmax values which are medians (ranges).
The effect of food on the oral absorption of amoxicillin and clavulanate potassium for oral suspension has not been studied.
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 10 mL of 250 mg/5 mL suspension of amoxicillin and clavulanate potassium.
Concurrent administration of probenecid delays amoxicillin excretion but does not delay renal excretion of clavulanic acid.
Neither component in amoxicillin and clavulanate potassium for oral suspension is highly protein-bound; clavulanic acid has been found to be approximately 25% bound to human serum and amoxicillin approximately 18% bound.
Oral administration of a single dose of amoxicillin and clavulanate potassium for oral suspension at 45 mg/kg (based on the amoxicillin component) to pediatric patients, 9 months to 8 years, yielded the following pharmacokinetic data for amoxicillin in plasma and middle ear fluid (MEF):
Table 2. Amoxicillin Concentrations in Plasma and Middle Ear Fluid Following Administration of 45 mg/kg of Amoxicillin and Clavulanate Potassium For Oral Suspension to Pediatric Patients
Time Point
Amoxicillin concentration in plasma (mcg/mL)
Amoxicillin concentration in MEF (mcg/mL)
1 hour
mean
median
range
7.7
9.3
1.5 to 14
(n=5)
3.2
3.5
0.2 to 5.5
(n=4)
2 hour
mean
median
range
15.7
13
11 to 25
(n=7)
3.3
2.4
1.9 to 6
(n=5)
3 hour
mean
median
range
13
12
5.5 to 21
(n=5)
5.8
6.5
3.9 to 7.4
(n=5)
Dose administered immediately prior to eating.
Amoxicillin diffuses readily into most body tissues and fluids with the exception of the brain and spinal fluid. The results of experiments involving the administration of clavulanic acid to animals suggest that this compound, like amoxicillin, is well distributed in body tissues.
12.4 Microbiology
Mechanism of Action
Amoxicillin binds to penicillin-binding proteins within the bacterial cell wall and inhibits bacterial cell wall synthesis. Clavulanic acid is a beta-lactam, structurally related to penicillin, that may inactivate certain beta-lactamase enzymes.
Mechanism of Resistance
Resistance to penicillins may be mediated by destruction of the beta-lactam ring by a beta-lactamase, altered affinity of penicillin for target, or decreased penetration of the antimicrobial drug to reach the target site. Amoxicillin alone is susceptible to degradation by beta-lactamases, and therefore its spectrum of activity does not include bacteria that produce these enzymes.
Amoxicillin/clavulanic acid has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section (1).
Gram-positive bacteria:
Streptococcus pneumoniae (including isolates with penicillin MICs 2 mcg/mL)
Gram-negative bacteria:
Haemophilus influenzae (including beta-lactamase-producing isolates)
Moraxella catarrhalis (including beta-lactamase-producing isolates)
The following in vitro data are available, but their clinical significance is unknown. At least 90% of the following microorganisms exhibit in vitro minimum inhibitory concentrations (MICs) less than or equal to the susceptible breakpoint for amoxicillin/clavulanic acid. However, the safety and efficacy of amoxicillin/clavulanic acid in treating infections due to these microorganisms have not been established in adequate and well-controlled trials.
Gram-positive bacteria:
Staphylococcus aureus (including beta-lactamase-producing isolates)
Streptococcus pyogenes
Susceptibility Test Methods: When available, the clinical microbiology laboratory should provide cumulative results of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.
Dilution Technique: Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standard test method1, 2 (broth for S. pneumoniae and H. influenzae). The recommended dilution pattern utilizes a constant amoxicillin/clavulanate potassium ratio of 2 to 1 in all tubes with varying amounts of amoxicillin. MICs are expressed in terms of the amoxicillin concentration in the presence of clavulanic acid at a constant 2 parts amoxicillin to 1 part clavulanic acid. The MIC values should be interpreted according to criteria provided in Table 3.
Diffusion Technique: Quantitative methods that require measurement of zone diameters also provides reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method2, 3. This procedure uses paper disks impregnated with 30 mcg amoxicillin/clavulanate potassium (20 mcg amoxicillin plus 10 mcg clavulanate potassium) to test susceptibility of microorganisms to amoxicillin/clavulanate potassium. Disk diffusion zone sizes should be interpreted according to criteria provided in Table 3.
Table 3. Susceptibility Test Result Interpretive Criteria for Amoxicillin/Clavulanate Potassium
Pathogen
Minimum Inhibitory
Concentration (mcg/mL)
Disk Diffusion
(Zone Diameter in mm)
Pathogen
S
I
R
S
I
R
Streptococcus pneumoniae
(non-meningitis isolates)
< 2/1
4/2
> 8.4
Not Applicable (NA)
Haemophilus influenzae
< 4/2
NA
> 8/4
>20
NA
<19
S=Susceptible, I=Intermediate, R=Resistant
NOTE: Susceptibility of S. pneumoniae should be determined using a 1mcg oxacillin disk.
NOTE: For nonmeningitis isolates, a penicillin MIC of 0.06 mcg/mL (or oxacillin zone 20 mm) can predict susceptibility to amoxicillin/clavulanic acid2.
NOTE: Beta-lactamase-negative, ampicillin-resistant (BLNAR) H. influenzae isolates should be considered resistant to amoxicillin/clavulanic acid despite apparent in vitro susceptibility of some BLNAR isolates to these agents.
A report of Susceptible (S) indicates that the antimicrobial drug is likely to inhibit growth of the microorganism if the antimicrobial drug reaches the concentration usually achievable at the site of infection. A report of Intermediate (I) indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible antimicrobials, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high doses of antimicrobial can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of Resistant (R) indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the infection site; other therapy should be selected.
Quality Control: Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test.1-3 Standard amoxicillin/clavulanate potassium powder should provide the following range of MIC noted in Table 4. For the disk diffusion technique using the 30 mcg amoxicillin/clavulanate potassium disk, the criteria in Table 4 should be achieved.
Table 4. Acceptable Quality Control Ranges for Amoxicillin/Clavulanate Potassium
Quality Control Organism
Minimum Inhibitory
Concentration
(mcg/mL)
Disk Diffusion
(Zone Diameter in mm)
Enterococcus faecalis
ATCC a 29212
0.25/0.12 to 1/0.5
NA
Escherichia coli
ATCC 25922
2/1 to 8/4
18 to 24
Escherichia coli
ATCC 35218b,c
4/2 to 16/8
17 to 22
Haemophilus influenzae
ATCC 49247
2/1 to 16/8
15 to 23
Staphylococcus aureus
ATCC 25923
NA
28 to 36
Staphylococcus aureus
ATCC 29213
0.12/0.06 to 0.5/0.25
NA
Staphylococcus pneumoniae
ATCC 49619
0.03/0.015 to 0.12/0.06
NA
aATCC = American Type Culture Collection
b. QC strain recommended when testing beta-lactam/beta-lactamase inhibitors2.
c. This strain may lose its plasmid and develop susceptibility to beta-lactam antimicrobial agents after repeated transfers onto culture media. Minimize by removing new culture from storage at least monthly or whenever the strain begins to show decreased MICs to ampicillin, piperacillin, or ticarcillin2.
13 Nonclinical Toxicology ⮝
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate carcinogenic potential. Amoxicillin and clavulanate potassium (4:1 ratio formulation of amoxicillin:clavulanate) was non-mutagenic in the Ames bacterial mutation assay, and the yeast gene conversion assay. Amoxicillin and clavulanate potassium was weakly positive in the mouse lymphoma assay, but the trend toward increased mutation frequencies in this assay occurred at concentrations that were also associated with decreased cell survival. Amoxicillin and clavulanate potassium 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.
Amoxicillin and clavulanate potassium (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 (assuming a 20 kg child), this dose of amoxicillin is approximately 2 times the recommended clinical amoxicillin and clavulanate potassium for oral suspension dose of 90/6.4 mg/kg/day. For clavulanate, the dose multiple is approximately 15 times higher than the recommended clinical daily dose, also based on body surface area.
14 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 (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 antibacterial therapy for acute otitis media in the previous 3 months, history of recurrent episodes of acute otitis media, 2 years or younger, or daycare attendance. Prior to receiving amoxicillin and clavulanate potassium for oral suspension, 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 to18 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; 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:
Table 5. Bacteriologic Eradication Rates in the Per Protocol Population
Pathogen
Bacteriologic Eradication on Therapy
n/N
%
95% CI*
All S. pneumoniae
121/123
98
(94.3, 99.8)
S. pneumoniae with penicillin
MIC = 2 mcg/mL
19/19
100
(82.4, 100)
S. pneumoniae with penicillin
MIC = 4 mcg/mL
12/14
86
(57.2, 98.2)
H. influenzae
75/81
93
(84.6, 97.2)
M. catarrhalis
11/11
100
(71.5, 100)
* CI = confidence intervals; 95% CIs are not adjusted for multiple comparisons.
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.
Table 6. Clinical Assessments in the Per Protocol Population (Includes S. pneumoniae Patients With Penicillin MICs = 2 mcg/mL or 4 mcg/mL*)
Pathogen
2 to 4 Days Post-Therapy (Primary Endpoint)
Clinical Response
95% CI
n/N
%
All S. pneumoniae
122/137
89
(82.6, 93.7)
S. pneumoniae with penicillin
MIC = 2 mcg/mL
17/20
85
(62.1, 96.8)
S. pneumoniae with penicillin
MIC = 4 mcg/mL
11/14
79
(49.2, 95.3)
H. influenzae
141/162
87
(80.9, 91.8)
M. catarrhalis
22/26
85
(65.1, 95.6)
Pathogen
15 to 18 Days Post-Therapy
(Secondary Endpoint)
Clinical Response
95% CI
n/N
%
All S. pneumoniae
95/136
70
(61.4, 77.4)
S. pneumoniae with penicillin
MIC = 2 mcg/mL
11/20
55
(31.5, 76.9)
S. pneumoniae with penicillin
MIC = 4 mcg/mL
5/14
36
(12.8, 64.9)
H. influenzae
106/156
68
(60, 75.2)
M. catarrhalis
14/25
56
(34.9, 75.6)
*S.pneumoniae strains with penicillin MICs of 2 mcg/mL or 4 mcg/mL are considered resistant to penicillin.
CI = confidence intervals; 95% CIs are not adjusted for multiple comparisons.
Clinical assessments at 15 to 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 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 (42%), respectively.
15 References ⮝
1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard -Ninth Edition. CLSI document M07-A9, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.
2. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fourth Informational Supplement, CLSI document M100-S24, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2014.
3. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard Eleventh Edition. CLSI document M02-A11, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.
4. 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.
16 How Supplied/storage And Handling ⮝
Product: 50090-1857
NDC: 50090-1857-0 125 mL in a BOTTLE
⮝
Distributed by:
Aurobindo Pharma USA, Inc.
279 Princeton-Hightstown Road
East Windsor, NJ 08520
Manufactured by:
Aurobindo Pharma Limited
Hyderabad-500 038, India
Revised: 08/2018
Storage ⮝
Dispense in original container. Store dry powder at 20 to 25 C (68 to 77 F). [See USP Controlled Room Temperature.] Store reconstituted suspension under refrigeration. Discard unused suspension after 10 days. Keep out of the reach of children.
Amoxicillin And Clavulanate Potassium ⮝
AMOXICILLIN AND CLAVULANATE POTASSIUM
amoxicillin and clavulanate potassium powder, for suspension
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:50090-1857(NDC:16714-294) Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AMOXICILLIN (UNII: 804826J2HU) (AMOXICILLIN ANHYDROUS - UNII:9EM05410Q9) AMOXICILLIN ANHYDROUS 600 mg in 5 mL CLAVULANATE POTASSIUM (UNII: Q42OMW3AT8) (CLAVULANIC ACID - UNII:23521W1S24) CLAVULANIC ACID 42.9 mg in 5 mL
Inactive Ingredients Ingredient Name Strength ASPARTAME (UNII: Z0H242BBR1) HYPROMELLOSE 2910 (50 MPA.S) (UNII: 1IVH67816N) SILICON DIOXIDE (UNII: ETJ7Z6XBU4) SUCCINIC ACID (UNII: AB6MNQ6J6L) XANTHAN GUM (UNII: TTV12P4NEE) STRAWBERRY (UNII: 4J2TY8Y81V)
Product Characteristics Color WHITE (White to Off-white) Score Shape Size Flavor STRAWBERRY Imprint Code Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:50090-1857-0 125 mL in 1 BOTTLE; Type 0: Not a Combination Product 06/03/2015
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA201091 12/20/2011
Labeler - A-S Medication Solutions (830016429)
Establishment Name Address ID/FEI Business Operations A-S Medication Solutions 830016429 RELABEL(50090-1857) Revised: 8/2018 Document Id: 3e589bc8-3fc6-42be-abf6-b01d8ccd24a5 34391-3 Set id: ccb8bfb1-1303-4c2d-9106-78684e6b859f Version: 9 Effective Time: 20180822 A-S Medication Solutions
Package Label-principal Display Panel - 400 Mg/57 Mg* Per 5 Ml (100 Ml Bottle Label) ⮝
NDC 33261-0464-01
Amoxicillin and Clavulanate
Potassium for Oral Suspension, USP
400 mg/57 mg* per 5 mL
Rx only
100 mL when reconstituted
AMOXICILLIN AND CLAVULANATE POTASSIUM
amoxicillin and clavulanate potassium powder, for suspension
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:33261-464(NDC:65862-534) Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AMOXICILLIN (UNII: 804826J2HU) (AMOXICILLIN ANHYDROUS - UNII:9EM05410Q9) AMOXICILLIN ANHYDROUS 400 mg in 5 mL CLAVULANATE POTASSIUM (UNII: Q42OMW3AT8) (CLAVULANIC ACID - UNII:23521W1S24) CLAVULANIC ACID 57 mg in 5 mL
Inactive Ingredients Ingredient Name Strength ASPARTAME (UNII: Z0H242BBR1) HYPROMELLOSE 2910 (50 MPA.S) (UNII: 1IVH67816N) ORANGE (UNII: 5EVU04N5QU) SILICON DIOXIDE (UNII: ETJ7Z6XBU4) SUCCINIC ACID (UNII: AB6MNQ6J6L) XANTHAN GUM (UNII: TTV12P4NEE)
Product Characteristics Color WHITE (White to Off-white) Score Shape Size Flavor ORANGE Imprint Code Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:33261-464-01 100 mL in 1 BOTTLE, PLASTIC
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA201090 12/20/2011
Labeler - Aidarex Pharmaceuticals LLC (801503249) Revised: 11/2013 Document Id: 7ba622bc-fa2c-4ed8-a06d-c545253f39f5 34391-3 Set id: e1013b38-446b-4faf-973d-272d90ff309a Version: 1 Effective Time: 20131121 Aidarex Pharmaceuticals LLC
Package Label-principal Display Panel - 400 Mg/57 Mg* Per 5 Ml (50 Ml Bottle Label) ⮝
NDC 65862-534-50
Rx only
Amoxicillin and
Clavulanate Potassium
for Oral Suspension, USP
400 mg/57 mg* per 5 mL
50 mL when reconstituted
AUROBINDO
AMOXICILLIN AND CLAVULANATE POTASSIUM
amoxicillin and clavulanate potassium powder, for suspension
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:65862-533 Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AMOXICILLIN (UNII: 804826J2HU) (AMOXICILLIN ANHYDROUS - UNII:9EM05410Q9) AMOXICILLIN ANHYDROUS 200 mg in 5 mL CLAVULANATE POTASSIUM (UNII: Q42OMW3AT8) (CLAVULANIC ACID - UNII:23521W1S24) CLAVULANIC ACID 28.5 mg in 5 mL
Inactive Ingredients Ingredient Name Strength ASPARTAME (UNII: Z0H242BBR1) HYPROMELLOSE 2910 (50 MPA.S) (UNII: 1IVH67816N) ORANGE (UNII: 5EVU04N5QU) SILICON DIOXIDE (UNII: ETJ7Z6XBU4) SUCCINIC ACID (UNII: AB6MNQ6J6L) XANTHAN GUM (UNII: TTV12P4NEE)
Product Characteristics Color WHITE (White to Off-white) Score Shape Size Flavor ORANGE Imprint Code Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:65862-533-50 50 mL in 1 BOTTLE; Type 0: Not a Combination Product 12/20/2011 2 NDC:65862-533-75 75 mL in 1 BOTTLE; Type 0: Not a Combination Product 12/20/2011 3 NDC:65862-533-01 100 mL in 1 BOTTLE; Type 0: Not a Combination Product 12/20/2011
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA201090 12/20/2011
AMOXICILLIN AND CLAVULANATE POTASSIUM
amoxicillin and clavulanate potassium powder, for suspension
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:65862-534 Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AMOXICILLIN (UNII: 804826J2HU) (AMOXICILLIN ANHYDROUS - UNII:9EM05410Q9) AMOXICILLIN ANHYDROUS 400 mg in 5 mL CLAVULANATE POTASSIUM (UNII: Q42OMW3AT8) (CLAVULANIC ACID - UNII:23521W1S24) CLAVULANIC ACID 57 mg in 5 mL
Inactive Ingredients Ingredient Name Strength ASPARTAME (UNII: Z0H242BBR1) HYPROMELLOSE 2910 (50 MPA.S) (UNII: 1IVH67816N) ORANGE (UNII: 5EVU04N5QU) SILICON DIOXIDE (UNII: ETJ7Z6XBU4) SUCCINIC ACID (UNII: AB6MNQ6J6L) XANTHAN GUM (UNII: TTV12P4NEE)
Product Characteristics Color WHITE (White to Off-white) Score Shape Size Flavor ORANGE Imprint Code Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:65862-534-50 50 mL in 1 BOTTLE; Type 0: Not a Combination Product 12/20/2011 2 NDC:65862-534-75 75 mL in 1 BOTTLE; Type 0: Not a Combination Product 12/20/2011 3 NDC:65862-534-01 100 mL in 1 BOTTLE; Type 0: Not a Combination Product 12/20/2011
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA201090 12/20/2011
Labeler - Aurobindo Pharma Limited (650082092)
Establishment Name Address ID/FEI Business Operations Aurobindo Pharma Limited 918917683 ANALYSIS(65862-533, 65862-534) , MANUFACTURE(65862-533, 65862-534) Revised: 10/2019 Document Id: 722571d0-08c3-4c0d-a345-369fdb8f934c 34391-3 Set id: ab1dbe70-696f-4ff9-a0c7-7406bff590ae Version: 7 Effective Time: 20191029 Aurobindo Pharma Limited
No Title 1572452408 ⮝
1111
PRESCRIBING INFORMATIONTo reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL and other antibacterial drugs, Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Package Label-principal Display Panel - 125 Mg/31.25 Mg Per 5 Ml (75 Ml Bottle Label) ⮝
NDC 59651-025-75
Rx Only
Amoxicillin and
Clavulanate Potassium
for Oral Suspension, USP
125 mg/31.25 mg*
per 5 mL
75 mL when
reconstituted
AUROBINDO
Package Label-principal Display Panel - 250 Mg/62.5 Mg Per 5 Ml (75 Ml Bottle Label) ⮝
NDC 59651-026-75
Rx only
Amoxicillin and
Clavulanate Potassium
for Oral Suspension, USP
250 mg/62.5 mg*
per 5 mL
75 mL when
reconstituted
AUROBINDO
AMOXICILLIN AND CLAVULANATE POTASSIUM
amoxicillin and clavulanate potassium powder, for suspension
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:59651-025 Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AMOXICILLIN (UNII: 804826J2HU) (AMOXICILLIN ANHYDROUS - UNII:9EM05410Q9) AMOXICILLIN ANHYDROUS 125 mg in 5 mL CLAVULANATE POTASSIUM (UNII: Q42OMW3AT8) (CLAVULANIC ACID - UNII:23521W1S24) CLAVULANIC ACID 31.25 mg in 5 mL
Inactive Ingredients Ingredient Name Strength ASPARTAME (UNII: Z0H242BBR1) SILICON DIOXIDE (UNII: ETJ7Z6XBU4) HYPROMELLOSE 2910 (50 MPA.S) (UNII: 1IVH67816N) ORANGE (UNII: 5EVU04N5QU) SUCCINIC ACID (UNII: AB6MNQ6J6L) XANTHAN GUM (UNII: TTV12P4NEE) CORN SYRUP (UNII: 9G5L16BK6N) ACACIA (UNII: 5C5403N26O)
Product Characteristics Color WHITE (White to Off-white) Score Shape Size Flavor ORANGE Imprint Code Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:59651-025-75 75 mL in 1 BOTTLE; Type 0: Not a Combination Product 04/19/2019 2 NDC:59651-025-01 100 mL in 1 BOTTLE; Type 0: Not a Combination Product 04/19/2019 3 NDC:59651-025-55 150 mL in 1 BOTTLE; Type 0: Not a Combination Product 04/19/2019
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA209371 04/19/2019
AMOXICILLIN AND CLAVULANATE POTASSIUM
amoxicillin and clavulanate potassium powder, for suspension
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:59651-026 Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AMOXICILLIN (UNII: 804826J2HU) (AMOXICILLIN ANHYDROUS - UNII:9EM05410Q9) AMOXICILLIN ANHYDROUS 250 mg in 5 mL CLAVULANATE POTASSIUM (UNII: Q42OMW3AT8) (CLAVULANIC ACID - UNII:23521W1S24) CLAVULANIC ACID 62.5 mg in 5 mL
Inactive Ingredients Ingredient Name Strength ASPARTAME (UNII: Z0H242BBR1) SILICON DIOXIDE (UNII: ETJ7Z6XBU4) HYPROMELLOSE 2910 (50 MPA.S) (UNII: 1IVH67816N) ORANGE (UNII: 5EVU04N5QU) SUCCINIC ACID (UNII: AB6MNQ6J6L) XANTHAN GUM (UNII: TTV12P4NEE) CORN SYRUP (UNII: 9G5L16BK6N) ACACIA (UNII: 5C5403N26O)
Product Characteristics Color WHITE (White to Off-white) Score Shape Size Flavor ORANGE Imprint Code Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:59651-026-75 75 mL in 1 BOTTLE; Type 0: Not a Combination Product 04/19/2019 2 NDC:59651-026-01 100 mL in 1 BOTTLE; Type 0: Not a Combination Product 04/19/2019 3 NDC:59651-026-55 150 mL in 1 BOTTLE; Type 0: Not a Combination Product 04/19/2019
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA209371 04/19/2019
Labeler - Aurobindo Pharma Limited (650082092)
Establishment Name Address ID/FEI Business Operations Aurobindo Pharma Limited 918917683 ANALYSIS(59651-025, 59651-026) , MANUFACTURE(59651-025, 59651-026) Revised: 9/2019 Document Id: 268ffaeb-7559-4a68-a699-432a2ef3a0fd 34391-3 Set id: 3ae0c95f-7ffa-4317-9fea-4d07b86bee72 Version: 2 Effective Time: 20190913 Aurobindo Pharma Limited
Package Label-principal Display Panel - 200 Mg/28.5 Mg* Per 5 Ml (50 Ml Bottle Label) ⮝
NDC 65862-533-50
Rx only
Amoxicillin and
Clavulanate Potassium for
Oral Suspension, USP
200 mg/28.5 mg* per 5 mL
50 mL when reconstituted
AUROBINDO
1 Indications And Usage ⮝
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin and Clavulanate Potassium Powder for Oral Suspension, USP (amoxicillin/clavulanate potassium) and other antibacterial drugs, Amoxicillin and Clavulanate Potassium Powder for Oral Suspension, USP should be used only to treat 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 Powder for Oral Suspension, USP is a combination penicillin-class antibacterial and beta-lactamase inhibitor indicated in the treatment of infections due to susceptible isolates of the designated bacteria in the conditions listed below*:
1.1 Lower Respiratory Tract Infections
- caused by beta-lactamase-producing isolates of Haemophilus influenzae and Moraxella catarrhalis.
1.2 Acute Bacterial Otitis Media
- caused by beta-lactamase-producing isolates of H. influenzae and M. catarrhalis.
1.3 Sinusitis
- caused by beta-lactamase-producing isolates of H. influenzae and M. catarrhalis.
1.4 Skin and Skin Structure Infections
- caused by beta-lactamase-producing isolates of Staphylococcus aureus, Escherichia coli, and Klebsiella species.
1.5 Urinary Tract Infections
- caused by beta-lactamase-producing isolates of E. coli, Klebsiella species, and Enterobacter species.
1.6 Limitations of Use
- When susceptibility test results show susceptibility to amoxicillin, indicating no beta-lactamase production, Amoxicillin and Clavulanate Potassium Powder for Oral Suspension, USP should not be used.
2 Dosage And Administration ⮝
Amoxicillin and clavulanate potassium suspension may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when amoxicillin and clavulanate potassium suspension is administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, amoxicillin and clavulanate potassium suspension should be taken at the start of a meal.
2.1 Adults
The usual adult dose is one 500-mg tablet of amoxicillin and clavulanate potassium every 12 hours or one 250-mg tablet of amoxicillin and clavulanate potassium every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be one 875-mg tablet of amoxicillin and clavulanate potassium every 12 hours or one 500-mg tablet of amoxicillin and clavulanate potassium every 8 hours. Adults who have difficulty swallowing may be given the 125 mg/5 mL or 250 mg/5 mL suspension in place of the 500-mg tablet. The 200 mg/5 mL suspension or the 400 mg/5 mL suspension may be used in place of the 875-mg tablet.
Two 250-mg tablets of amoxicillin and clavulanate potassium should not be substituted for one 500-mg tablet of amoxicillin and clavulanate potassium. Since both the 250-mg and 500-mg tablets of amoxicillin and clavulanate potassium contain the same amount of clavulanic acid (125 mg, as the potassium salt), two 250-mg tablets are not equivalent to one 500-mg tablet of amoxicillin and clavulanate potassium.
The 250-mg tablet of amoxicillin and clavulanate potassium and the 250-mg chewable tablet should not be substituted for each other, as they are not interchangeable. The 250-mg tablet of amoxicillin and clavulanate potassium and the 250-mg chewable tablet do not contain the same amount of clavulanic acid (as the potassium salt). The 250-mg tablet of amoxicillin and clavulanate potassium contains 125 mg of clavulanic acid, whereas the 250-mg chewable tablet contains 62.5 mg of clavulanic acid.
2.2 Pediatric Patients
Based on the amoxicillin component, amoxicillin and clavulanate potassium suspension should be dosed as follows:
Neonates and Infants Aged <12 weeks (<3 months): The recommended dose of amoxicillin and clavulanate potassium suspension 30 mg/kg/day divided every 12 hours, based on the amoxicillin component. Experience with the 200 mg/5 mL formulation in this age group is limited, and thus, use of the 125 mg/5 mL oral suspension is recommended.
Patients Aged 12 weeks (3 months) and Older: See dosing regimens provided in Table 1. The every 12 hours regimen is recommended as it is associated with significantly less diarrhea [see Clinical Studies (14.2)]. However, the every 12 hours suspension (200 mg/5 mL and 400 mg/5 mL) and chewable tablets (200 mg and 400 mg) contain aspartame and should not be used by phenylketonurics. [see Warnings and Precautions (5.6)]
Table 1: Dosing in Patients Aged 12 weeks (3 months) and Older
INFECTIONDOSING REGIMEN Every 12 hours Every 8 hours 200 mg/5 mL or 400 mg/5 mL oral suspensiona 125 mg/5 mL or 250 mg/5 mL oral suspensiona Otitis mediab, sinusitis, lower respiratory tract infections, and more severe infections 45 mg/kg/day every 12 hours 40 mg/kg/day every 8 hours Less severe infections 25 mg/kg/day every 12 hours 20 mg/kg/day every 8 hours a Each strength of suspension of amoxicillin and clavulanate potassium is available as a 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: Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations.
The 250-mg tablet of amoxicillin and clavulanate potassium should not be used until the child weighs at least 40 kg, due to the different amoxicillin to clavulanic acid ratios in the 250-mg tablet of amoxicillin and clavulanate potassium (250/125) versus the 250-mg chewable tablet of amoxicillin and clavulanate potassium (250/62.5).
2.3 Patients with Renal Impairment
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 of <30 mL/min should not receive the 875-mg dose. Patients with a glomerular filtration rate of 10 to 30 mL/min should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a glomerular filtration rate less than 10 mL/min should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection.
Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.
2.4 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 2 below) and shake vigorously to suspend powder. Add remainder of the water and again shake vigorously.
Table 2: Amount of Water for Mixing Oral Suspension Strength Bottle Size Amount of Water for Reconstitution Contents of Each Teaspoonful (5 mL) 200 mg/5 mL 50 mL
75 mL
100 mL48 mL
71 mL
95 mL200 mg amoxicillin and 28.5 mg of clavulanic acid as the potassium salt 400 mg/5 mL 50 mL
75 mL
100 mL45 mL
68 mL
90 mL400 mg amoxicillin and 57.0 mg of clavulanic acid as the potassium salt Note: Shake oral suspension well before using. Reconstituted suspension must be stored under refrigeration and discarded after 10 days.
3 Dosage Forms And Strengths ⮝
- 200 mg/28.5 mg per 5 mL: The dry powder is white to off white with fruity flavor. Each 5 mL of reconstituted creamy suspension contains 200 mg amoxicillin and 28.5 mg clavulanic acid as the potassium salt.
- 400 mg/57 mg per 5 mL: The dry powder is white to off white with fruity flavor. Each 5 ml of reconstituted creamy suspension contains 400 mg amoxicillin and 57 mg clavulanic acid as the potassium salt.
4 Contraindications ⮝
4.1 Serious Hypersensitivity Reactions
Amoxicillin and clavulanate potassium suspension is contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin, clavulanate or to other beta-lactam antibacterial drugs (e.g., penicillins and cephalosporins).
4.2 Cholestatic Jaundice/Hepatic Dysfunction
Amoxicillin and clavulanate potassium suspension is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with amoxicillin and clavulanate potassium suspension.
5 Warnings And Precautions ⮝
5.1 Hypersensitivity Reactions
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials, including amoxicillin and clavulanate potassium suspension. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Before initiating therapy with amoxicillin and clavulanate potassium suspension, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, amoxicillin and clavulanate potassium suspension should be discontinued and appropriate therapy instituted.
5.2 Hepatic Dysfunction
Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of amoxicillin and clavulanate potassium suspension. Hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment.
5.3 Clostridium difficile Associated Diarrhea (CDAD)
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including amoxicillin and clavulanate potassium suspension, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
5.4 Skin Rash in Patients with Mononucleosis
A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus, amoxicillin and clavulanate potassium suspension should not be administered to patients with mononucleosis.
5.5 Potential for Microbial Overgrowth
The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. If superinfection occurs, amoxicillin/clavulanate potassium suspension should be discontinued and appropriate therapy instituted.
5.6 Phenylketonurics
Amoxicillin and clavulanate potassium for oral suspension contains aspartame which contains phenylalanine. Each 5 mL of either the 200 mg/5 mL or 400 mg/5 mL suspension contains 7 mg phenylalanine.
5.7 Development of Drug-Resistant Bacteria
Prescribing amoxicillin and clavulanate potassium suspension in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient, and increases the risk of the development of drug-resistant bacteria.
6 Adverse Reactions ⮝
The following are discussed in more detail in other sections of the labeling:
- Anaphylactic reactions [see Warnings and Precautions (5.1)]
- Hepatic Dysfunction [see Warnings and Precautions (5.2)]
- CDAD [see Warnings and Precautions (5.3)]
6.1 Clinical Trials Experience
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.
The most frequently reported adverse reactions were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%) and vaginitis (1%). Less than 3% of patients discontinued therapy because of drug-related adverse reactions. The overall incidence of adverse reactions, and in particular diarrhea, increased with the higher recommended dose. Other less frequently reported adverse reactions (<1%) include: Abdominal discomfort, flatulence, and headache.
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 amoxicillin and clavulanate potassium for 10 days versus 40/10 mg/kg/day (divided every 8 hours) of amoxicillin and clavulanate potassium 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)]
6.2 Postmarketing Experience
In addition to adverse reactions reported from clinical trials, the following have been identified during postmarketing use of amoxicillin and clavulanate potassium. 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 amoxicillin and clavulanate potassium.
Gastrointestinal: Indigestion, gastritis, stomatitis, glossitis, black hairy tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment. [see Warnings and Precautions (5.3)]
Hypersensitivity Reactions: Pruritus, angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), erythema multiforme, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, hypersensitivity vasculitis, and cases of exfoliative dermatitis (including toxic epidermal necrolysis) have been reported. [see Warnings and Precautions (5.1)]
Liver: Hepatic dysfunction, including hepatitis and cholestatic jaundice, increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been reported with amoxicillin and clavulanate potassium. It has been reported more commonly in the elderly, in males, or in patients on prolonged treatment. The histologic findings on liver biopsy have consisted of predominantly cholestatic, hepatocellular, or mixed cholestatic-hepatocellular changes. The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy has been discontinued. The hepatic dysfunction, which may be severe, is usually reversible. Deaths have been reported. [see Contraindications (4.2), Warnings and Precautions (5.2)]
Renal: Interstitial nephritis, hematuria, and crystalluria have been reported. [see Overdosage (10)]
Hemic and Lymphatic Systems: Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Thrombocytosis was noted in less than 1% of the patients treated with amoxicillin and clavulanate potassium. There have been reports of increased prothrombin time in patients receiving amoxicillin and clavulanate potassium and anticoagulant therapy concomitantly. [see Drug Interactions (7.2)]
Central Nervous System: Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity have been reported.
Miscellaneous: Tooth discoloration (brown, yellow, or gray staining) has been reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.
7 Drug Interactions ⮝
7.1 Probenecid
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. Coadministration of probenecid is not recommended.
7.2 Oral Anticoagulants
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.
7.3 Allopurinol
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.
7.4 Oral Contraceptives
Amoxicillin and clavulanate potassium may affect intestinal flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.
7.5 Effects on Laboratory Tests
High urine concentrations of amoxicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITEST , 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.
8 Use In Specific Populations ⮝
8.1 Pregnancy
Teratogenic Effects: Pregnancy Category B. Reproduction studies performed in pregnant rats and mice given amoxicillin and clavulanate potassium (2:1 ratio formulation of amoxicillin:clavulanate) at oral doses up to 1200 mg/kg/day revealed no evidence of harm to the fetus due to amoxicillin and clavulanate potassium. The amoxicillin doses in rats and mice (based on body surface area) were approximately 4 and 2 times the maximum recommended adult human oral dose (875 mg every 12 hours). For clavulanate, these dose multiples were approximately 9 and 4 times the maximum recommended adult human oral dose (125 mg every 8 hours). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
8.2 Labor and Delivery
Oral ampicillin-class antibiotics are poorly absorbed during labor. It is not known whether use of amoxicillin/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.
8.3 Nursing Mothers
Amoxicillin has been shown to be excreted in human milk. Amoxicillin/clavulanate potassium use by nursing mothers may lead to sensitization of infants. Caution should be exercised when amoxicillin/clavulanate potassium is administered to a nursing woman.
8.4 Pediatric Use
The safety and effectiveness of amoxicillin and clavulanate potassium for oral suspension has been established in pediatric patients. Use of amoxicillin and clavulanate potassium in pediatric patients is supported by evidence from studies of amoxicillin and clavulanate potassium tablets in adults with additional data from a study of amoxicillin and clavulanate potassium powder 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 <12 weeks (<3 months). [see Dosage and Administration (2.2)]
8.5 Geriatric Use
Of the 3,119 patients in an analysis of clinical studies of amoxicillin and clavulanate potassium, 32% were 65 years old, and 14% were 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.
8.6 Dosing in Renal Impairment
Amoxicillin is primarily eliminated by the kidney and dosage adjustment is usually required in patients with severe renal impairment (GFR <30 mL/min). See Patients with Renal Impairment (2.3) for specific recommendations in patients with renal impairment.
11 Description ⮝
Amoxicillin and Clavulanate Potassium Powder for Oral Suspension, USP is an oral antibacterial combination consisting of amoxicillin and the beta-lactamase inhibitor, clavulanate potassium (the potassium salt of clavulanic acid).
Amoxicillin is an analog of ampicillin, derived from the basic penicillin nucleus, 6-aminopenicillanic acid. The amoxicillin molecular formula is C16H19N3O5S 3H2O, and the molecular weight is 419.46. Chemically, amoxicillin is (2S,5R,6R)-6-[(R)-(-)-2-Amino-2-(p-hydroxyphenyl)acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate and may be represented structurally as:
Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is a beta-lactam structurally related to the penicillins and possesses the ability to inactivate some beta-lactamases by blocking the active sites of these enzymes. The clavulanate potassium molecular formula is C8H8KNO5, and the molecular weight is 237.25. Chemically, clavulanate potassium is potassium (Z)(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]-heptane-2-carboxylate and may be represented structurally as:
Inactive Ingredients:
Aspartame, colloidal silicon dioxide, HPMC 2910/ hypromellose 5 cP, silicon dioxide, succinic acid, xanthan gum, golden syrup flavor, orange flavor.
See PRECAUTIONS - Information for the Patient.
Each 5 mL of reconstituted amoxicillin and clavulanate potassium 400 mg/57 mg per 5 mL suspension contains 0.268 mEq of potassium.
Each 5 mL of reconstituted amoxicillin and clavulanate potassium 200 mg/28.5 mg per 5 mL suspension contains 0.143 mEq of potassium
12 Clinical Pharmacology ⮝
12.1 Mechanism of Action
Amoxicillin and clavulanate potassium for oral suspension is an antibacterial drug. [see Microbiology 12.4]
12.3 Pharmacokinetics
Mean amoxicillin and clavulanate potassium pharmacokinetic parameters in normal adults following administration of amoxicillin and clavulanate potassium tablets are shown in Table 3 and following administration of amoxicillin and clavulanate potassium powder for oral suspension and chewable tablets are shown in Table 4.
Table 3: Mean ( S.D.) Amoxicillin and Clavulanate Potassium Pharmacokinetic Parametersa,bwith Amoxicillin and Clavulanate Potassium Tablets Dose and Regimen Cmax (mcg/mL) AUC0-24 (mcg*h/mL) Amoxicillin/Clavulanate potassium Amoxicillin Clavulanate potassium Amoxicillin Clavulanate potassium 250/125 mg every 8 hours 3.3 1.12 1.5 0.70 26.7 4.56 12.6 3.25 500/125 mg every 12 hours 6.5 1.41 1.8 0.61 33.4 6.76 8.6 1.95 500 125 mg every 8 hours 7.2 2.26 2.4 0.83 53.4 8.87 15.7 3.86 875/125 mg every 12 hours 11.6 2.78 2.2 0.99 53.5 12.31 10.2 3.04 a Mean ( standard deviation) values of 14 normal adults (N=15 for clavulanate potassium in the low-dose regimens). Peak concentrations occurred approximately 1.5 hours after the dose.
b Amoxicillin/clavulanate potassium administered at the start of a light meal.
Table 4: Mean ( S.D.) Amoxicillin and Clavulanate Potassium Pharmacokinetic Parametersa,bwith Amoxicillin and Clavulanate Potassium Powder for Oral Suspension and Chewable Tablets Dose Cmax (mcg/mL) AUC0-24 (mcg*h/mL) Amoxicillin/Clavulanate potassium Amoxicillin Clavulanate potassium Amoxicillin Clavulanate potassium 400/57 mg (5 mL of suspension) 6.94 1.24 1.10 0.42 17.29 2.28 2.34 0.94 400/57 mg (1 chewable tablet) 6.67 1.37 1.03 0.33 17.24 2.64 2.17 0.73 a Mean ( standard deviation) values of 28 normal adults. Peak concentrations occurred approximately 1 hour after the dose.
b Amoxicillin/clavulanate potassium administered at the start of a light meal.Oral administration of 5 mL of 250 mg/62.5 mg per 5 mL suspension of amoxicillin and clavulanate potassium or the equivalent dose of 10 mL of 125 mg/31.25 mg per 5 mL suspension of amoxicillin and clavulanate potassium 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 250 mg/62.5 mg per 5 mL suspension of amoxicillin and clavulanate potassium or equivalent dose of 10 mL of 125 mg/31.25 mg per 5 mL suspension of amoxicillin and clavulanate potassium were administered to normal adults. One 250 mg/62.5 mg chewable tablet of amoxicillin and clavulanate potassium or two 125 mg/31.25 mg chewable tablets of amoxicillin and clavulanate potassium are equivalent to 5 mL of 250 mg/ 62.5 mg per 5 mL suspension of amoxicillin and clavulanate potassium and provide similar serum concentrations of amoxicillin and clavulanic acid.
Amoxicillin serum concentrations achieved with amoxicillin and clavulanate potassium suspension 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 amoxicillin and clavulanate potassium suspension in adults and children.
Absorption: Dosing in the fasted or fed state has minimal effect on the pharmacokinetics of amoxicillin. While amoxicillin and clavulanate potassium suspension can be given without regard to meals, absorption of clavulanate potassium when taken with food is greater relative to the fasted state. In one study, the relative bioavailability of clavulanate was reduced when amoxicillin and clavulanate potassium suspension was dosed at 30 and 150 minutes after the start of a high-fat breakfast.
Distribution: Neither component in amoxicillin and clavulanate potassium suspension is highly protein-bound; clavulanic acid is approximately 25% bound to human serum and amoxicillin approximately 18% bound.
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 amoxicillin and clavulanate potassium 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: The half-life of amoxicillin after the oral administration of amoxicillin and clavulanate potassium suspension is 1.3 hours and that of clavulanic acid is 1 hour.
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 or
500-mg tablet of amoxicillin and clavulanate potassium.
12.4 Microbiology
Amoxicillin is a semisynthetic antibiotic 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 for oral suspension protects amoxicillin from degradation by some beta-lactamase enzymes and extends the antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin.
Amoxicillin/clavulanic acid has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.
Gram-positive bacteria
Staphylococcus aureus
Gram-negative bacteria
Enterobacter species
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/clavulanic acid. However, the efficacy of amoxicillin/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 species including Bacteroides fragilis
Fusobacterium species
Peptostreptococcus species
Susceptibility Test Methods
When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug product for treatment.
Dilution techniques:
Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method2, 3 (broth and/or agar). The MIC values should be interpreted according to criteria provided in Table 5.
Diffusion techniques:
Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method3,4. This procedure uses paper disks impregnated with 30 mcg amoxicillin/clavulanic acid (20 mcg amoxicillin plus 10 mcg clavulanic acid) to test the susceptibility of bacteria to amoxicillin/clavulanic acid. The disc diffusion interpretive criteria are provided in Table 5.
Table 5: Susceptibility Test Interpretive Criteria for Amoxicillin Clavulanic Acid Minimum Inhibitory Concentrations (mcg/mL) Disk Diffusion (zone diameters in mm) Pathogen S I R S I R Enterobacteriaceae 8/4 16/8 32/16 18 14-17 13 Haemophilus influenzae and Staphylococcus aureus 4/2 -- 8/4 20 -- 19 Quality Control:
Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test2,3,4. Standard amoxicillin/clavulanic acid powder should provide the following range of MIC values noted in Table 6 for the diffusion technique using the 30 mcg amoxicillin/clavulanic acid (20 mcg amoxicillin plus 10 mcg clavulanic acid) disk, the criteria in Table 6 should be achieved.
Table 6: Acceptable Quality Control Ranges for Amoxicillin/Clavulanic Acid QC Strain Minimum Inhibitory Concentration (mcg/mL) Disk Diffusion (zone diameter in mm) Escherichia coli ATCC 25922 2/1 to 8/4 18 to 24 Escherichia coli ATCC 35218 4/2 to 16/8 17 to 22 Haemophilus influenzae ATCC 49247 2/1 to 16/8 15 to 23 Staphylococcus aureus ATCC 29213 0.12/0.06 to 0.5/0.25 - Staphylococcus aureus ATCC 29523 - 28 to 36
13 Nonclinical Toxicology ⮝
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate carcinogenic potential.
Amoxicillin and clavulanate potassium (4:1 ratio formulation of amoxicillin:clavulanate) was non-mutagenic in the Ames bacterial mutation assay, and the yeast gene conversion assay. Amoxicillin and clavulanate potassium 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.
Amoxicillin and clavulanate potassium suspension 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.
Amoxicillin and clavulanate potassium suspension (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.
14 Clinical Studies ⮝
14.1 Lower Respiratory Tract and Complicated Urinary Tract Infections
Data from 2 pivotal trials in 1,191 patients treated for either lower respiratory tract infections or complicated urinary tract infections compared a regimen of 875-mg tablets of amoxicillin and clavulanate potassium every 12 hours to 500-mg tablets of amoxicillin and clavulanate potassium dosed every 8 hours (584 and 607 patients, respectively). Comparable efficacy was demonstrated between the every 12 hours and every 8 hours dosing regimens. There was no significant difference in the percentage of adverse events in each group. The most frequently reported adverse event was diarrhea; incidence rates were similar for the 875-mg every 12 hours and 500-mg every 8 hours dosing regimens (15% and 14%, respectively); however, there was a statistically significant difference (p < 0.05) in rates of severe diarrhea or withdrawals with diarrhea between the regimens: 1% for 875-mg every 12 hours regimen versus 2% for the 500-mg every 8 hours regimen.
In one of these pivotal trials, patients with either pyelonephritis (n = 361) or a complicated urinary tract infection (i.e., patients with abnormalities of the urinary tract that predispose to relapse of bacteriuria following eradication, n = 268) were randomized (1:1) to receive either 875-mg tablets of amoxicillin and clavulanate potassium every 12 hours (n=308) or 500-mg tablets of amoxicillin and clavulanate potassium every 8 hours (n=321).
The number of bacteriologically evaluable patients was comparable between the two dosing regimens. Amoxicillin and clavulanate potassium 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 7.
Table 7: Bacteriologic efficacy rates for Amoxicillin and Clavulanate Potassium 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.
14.2 Acute Bacterial Otitis Media and Diarrhea in Pediatric Patients
One US/Canadian clinical trial was conducted which compared 45/6.4 mg/kg/day (divided every 12 hours) of amoxicillin and clavulanate potassium for 10 days versus 40/10 mg/kg/day (divided every 8 hours) of amoxicillin and clavulanate potassium 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.e., 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 2-4 days after the completion of therapy) and at the follow-up visit (defined as 22-28 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 = 265) and 82% (n = 260) for 45 mg/kg/day every 12 hours and 40 mg/kg/day every 8 hours, respectively. At follow-up, 67% (n = 249) and 69% (n = 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, can be extrapolated to the chewable tablets. The presence of mannitol in the chewable tablets may contribute to a different diarrhea profile. The every 12 hour oral suspensions (200 mg/5 mL and 400 mg/5 mL) are sweetened with aspartame.
15 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.
2. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard 8th ed. CLSI Document M7-A9. CLSI, 940 West Valley Road, Suite 1400, Wayne, PA, 19087, 2012.
3. Clinical and Laboratory Standards Institute (CLSI). Performance Standard for Antimicrobial Disk Susceptibility Tests; Approved Standard 11th ed. CLSI Document M2-A11. CLSI, 940 West Valley Road, Suite 1400, Wayne, PA, 19087, 2012.
4. CLSI. Performance Standards for Antimicrobial Susceptibility Testing: 22nd Informational Supplement. CLSI document M100-S22. CLSI, Wayne, PA, 2012.
16 How Supplied/storage And Handling ⮝
Amoxicillin and Clavulanate Potassium for Oral Suspension USP, 400 mg/57 mg per 5 mL: The dry powder is white to off white with fruity flavor. Each 5 ml of reconstituted creamy suspension contains 400 mg amoxicillin and 57 mg clavulanic acid as the potassium salt.
100 MILLILITER in a BOTTLE (53217-286-01)
Dispense in original container.
Store dry powder at 20 to 25 C (68 to 77 F) [See USP Controlled Room Temperature].
Store reconstituted suspension under refrigeration. Discard unused suspension after 10 days. Keep out of the reach of children.
Repackaged by
Aidarex Pharmaceuticals, LLC
Corona, CA 92880
10 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/clavulanate potassium.
Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin/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/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/clavulanate potassium. Amoxicillin/clavulanate potassium may be removed from circulation by hemodialysis. [see Dosage and Administration (2.3)]
Principal Display Panel ⮝
SPL Image
AMOXICILLIN AND CLAVULANATE POTASSIUM
amoxicillin and clavulanate potassium powder, for suspension
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:53217-286(NDC:0143-9982) Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AMOXICILLIN (UNII: 804826J2HU) (AMOXICILLIN ANHYDROUS - UNII:9EM05410Q9) AMOXICILLIN ANHYDROUS 400 mg in 5 mL CLAVULANIC ACID (UNII: 23521W1S24) (CLAVULANIC ACID - UNII:23521W1S24) CLAVULANIC ACID 57 mg in 5 mL
Inactive Ingredients Ingredient Name Strength ASPARTAME (UNII: Z0H242BBR1) SILICON DIOXIDE (UNII: ETJ7Z6XBU4) HYPROMELLOSE 2910 (5 MPA.S) (UNII: R75537T0T4) SUCCINIC ACID (UNII: AB6MNQ6J6L) XANTHAN GUM (UNII: TTV12P4NEE)
Product Characteristics Color Score Shape Size Flavor FRUIT (Fruity Flavor) Imprint Code Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:53217-286-01 100 mL in 1 BOTTLE; Type 0: Not a Combination Product 12/01/2007
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA065191 12/01/2007
Labeler - Aidarex Pharmaceuticals LLC (801503249) Revised: 4/2017 Document Id: 2829df2c-64eb-486b-bf41-ca3358b14241 34391-3 Set id: 80f535ea-085f-4e53-bdae-cd7c10df426c Version: 1 Effective Time: 20170426 Aidarex Pharmaceuticals LLC
Preventative Healthcare Newsletter
Subscribe - $200 Give Away - by 1/1/25 - Receive exciting health news that can extend your lifespan and improve quality of life. Win $100 on Pharmacy HQ.