AMOXICILLIN AND CLAVULANATE POTASSIUM- amoxicillin and clavulanate potassium powder, for suspension
Proficient Rx LP
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HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use Amoxicillin and Clavulanate Potassium Powder for Oral Suspension, USP safely and effectively. See full prescribing information for Amoxicillin and Clavulanate Potassium Powder for Oral Suspension, USP.
Amoxicillin and Clavulanate Potassium Powder for Oral Suspension, USP Initial U.S. Approval: 1984 Rx Only To reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin and Clavulanate Potassium 200 and 400 and other antibacterial drugs, Amoxicillin and Clavulanate Potassium 200 and 400 should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. (11.3) INDICATIONS AND USAGEAmoxicillin and Clavulanate Potassium Powder for Oral Suspension, USP is a combination penicillin-class antibacterial and beta-lactamase inhibitor indicated for treatment of the following: Lower respiratory tract infections (1.1) Acute bacterial otitis media (1.2) Sinusitis (1.3) Skin and skin structure infections (1.4) Urinary tract infections (1.5) DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHSFormulation and amoxicillin/clavulanate content is: Powder for Oral Suspension: 200 mg/28.5 mg per 5 mL, 400 mg/57 mg per 5 mL (3) CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS
ADVERSE REACTIONSThe most frequently reported adverse effects were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%) and vaginitis (1%) (6.1) To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceutical Corp. at 1-877-233-2001, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. DRUG INTERACTIONS
USE IN SPECIFIC POPULATIONSSee 17 for PATIENT COUNSELING INFORMATION. Revised: 12/2018 |
- caused by beta-lactamase-producing isolates of Haemophilus influenzae and Moraxella catarrhalis.
- caused by beta-lactamase-producing isolates of H. influenzae and M. catarrhalis.
- caused by beta-lactamase-producing isolates of Staphylococcus aureus, Escherichia coli, and Klebsiella species.
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.
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.
Based on the amoxicillin component, amoxicillin and clavulanate potassium suspension should be dosed as follows:
|
DOSING 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.
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).
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.
Strength |
Bottle Size |
Amount of Water for Reconstitution |
Contents of Each Teaspoonful (5 mL) |
200 mg/5 mL |
50 mL |
48 mL |
200 mg amoxicillin and 28.5 mg of clavulanic acid as the potassium salt |
400 mg/5 mL |
50 mL |
45 mL |
400 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.
The following are discussed in more detail in other sections of the labeling:
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.
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:
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.
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.
500-mg tablet of amoxicillin and clavulanate potassium.
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
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
Dilution techniques:
Diffusion techniques:
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:
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 |
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.
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) |
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.
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.
NDC 63187-826-00 .................. 100 mL bottle
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.
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.
CLINITEST® is a registered trademark of Miles, Inc.
Distributed by:
West-Ward Pharmaceutical Corp.
Eatontown, NJ 07724 USA
Manufactured by:
HIKMA Pharmaceuticals
P.O. Box 182400
Amman 11118 – Jordan
Relabeled by:
Proficient Rx LP
Thousand Oaks, CA 91320
Revised April 2013
AMOXICILLIN AND CLAVULANATE POTASSIUM
amoxicillin and clavulanate potassium powder, for suspension |
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Labeler - Proficient Rx LP (079196022) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
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Proficient Rx LP | 079196022 | RELABEL(63187-826) |