Augmentin Es-600

Description

AUGMENTIN ES-600 is an oral antibacterial combination that includes the semisynthetic antibacterial amoxicillin and the beta-lactamase inhibitor clavulanate potassium, which is the potassium salt of clavulanic acid. Amoxicillin, an analog of ampicillin, is derived from the basic penicillin nucleus, 6-aminopenicillanic acid, with a molecular formula of C16H19N3O5S•3H2O and a molecular weight of 419.46 g/mol. Its chemical structure is defined as (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.

Clavulanic acid, produced by the fermentation of Streptomyces clavuligerus, is a beta-lactam that is structurally related to penicillins. It effectively inactivates a wide variety of beta-lactamases by blocking their active sites, particularly those that are plasmid-mediated and responsible for drug resistance to penicillins and cephalosporins. The molecular formula for clavulanate potassium is C8H8KNO5, with a molecular weight of 237.25 g/mol, and its chemical structure is potassium (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo3.2.0-heptane-2-carboxylate.

Upon reconstitution, each 5 mL of AUGMENTIN ES-600 oral suspension contains 600 mg of amoxicillin as the trihydrate and 42.9 mg of clavulanic acid, equivalent to 51.1 mg of clavulanate potassium. Additionally, each 5 mL of the suspension provides approximately 9 mg of potassium and 4 mg of sodium. Inactive ingredients include aspartame, colloidal silicon dioxide, silicon dioxide, sodium carboxymethylcellulose, strawberry cream flavor, and xanthan gum.

Uses and Indications

AUGMENTIN ES-600 is indicated for the treatment of pediatric patients aged 3 months to 12 years who weigh less than or equal to 40 kg and present with recurrent or persistent acute otitis media. This condition may be due to the following pathogens: Streptococcus pneumoniae (with penicillin minimum inhibitory concentrations MICs less than or equal to 2 mcg/mL), Haemophilus influenzae (including beta-lactamase-producing strains), and Moraxella catarrhalis (including beta-lactamase-producing strains).

Patients characterized by specific risk factors are particularly suitable for treatment with AUGMENTIN ES-600. These risk factors include antibacterial exposure for acute otitis media within the preceding 3 months, as well as either being 2 years of age or younger or attending day care.

To mitigate the development of drug-resistant bacteria and preserve the efficacy of AUGMENTIN ES-600 and other antibacterial agents, it is essential that this medication is utilized solely for the treatment or prevention of infections that are either proven or strongly suspected to be of bacterial origin.

Dosage and Administration

Pediatric patients aged 3 months to 12 years who weigh less than or equal to 40 kg should receive a dosage of 90 mg/kg/day. This dosage should be divided and administered every 12 hours for a total duration of 10 days.

Healthcare professionals are advised to calculate the total daily dose based on the patient's weight and ensure that the medication is administered at consistent intervals to maintain effective therapeutic levels.

Contraindications

Use of AUGMENTIN ES-600 is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis or Stevens-Johnson syndrome, to AUGMENTIN ES-600 or any other beta-lactam antibiotics, such as penicillins or cephalosporins. Additionally, it is contraindicated in individuals with a history of cholestatic jaundice or hepatic dysfunction associated with AUGMENTIN ES-600.

Warnings and Precautions

Serious hypersensitivity reactions, including those that may be fatal, have been associated with the use of AUGMENTIN ES-600. In the event of such a reaction, it is imperative to discontinue the medication immediately and initiate appropriate therapeutic measures.

Severe cutaneous adverse reactions (SCAR) have also been reported. Patients should be monitored closely for any signs of rash, and AUGMENTIN ES-600 should be discontinued if the rash progresses.

Drug-induced enterocolitis syndrome (DIES) has been documented in patients receiving amoxicillin, a component of AUGMENTIN ES-600. Should symptoms of DIES arise, the medication must be discontinued, and suitable therapy should be initiated.

Patients with hepatic dysfunction or those exhibiting signs of cholestatic jaundice should be closely monitored. If any signs or symptoms of hepatitis occur, AUGMENTIN ES-600 should be discontinued, and liver function tests should be performed in patients with pre-existing hepatic impairment.

Clostridioides difficile-associated diarrhea (CDAD) can manifest in a spectrum from mild diarrhea to severe, potentially fatal colitis. It is essential to evaluate patients for CDAD if diarrhea develops during treatment with AUGMENTIN ES-600.

The use of AUGMENTIN ES-600 is contraindicated in patients with mononucleosis, as these individuals are at risk of developing a skin rash upon administration of the medication.

Additionally, high urine concentrations of amoxicillin may lead to false-positive results when testing for glucose in urine using CLINITEST®, Benedict's Solution, or Fehling's Solution. Therefore, it is recommended to utilize glucose tests that are based on enzymatic glucose oxidase reactions for accurate results.

Side Effects

Patients receiving AUGMENTIN ES-600 may experience a range of adverse reactions, which can be categorized into common and serious reactions.

Common adverse reactions reported include coughing, vomiting, contact dermatitis (such as diaper rash), fever, upper respiratory tract infections, and diarrhea. These reactions are generally mild and may not require discontinuation of therapy.

Serious adverse reactions, however, necessitate immediate attention. Patients may experience serious hypersensitivity reactions, which can be fatal; in such cases, AUGMENTIN ES-600 should be discontinued, and appropriate therapy should be initiated. Severe cutaneous adverse reactions (SCAR) have also been observed, and patients should be monitored closely, with discontinuation of the medication if any rash progresses. Drug-induced enterocolitis syndrome (DIES) is another serious reaction that requires discontinuation of AUGMENTIN ES-600 and appropriate therapeutic measures.

Hepatic dysfunction and cholestatic jaundice have been reported, necessitating discontinuation of the drug if signs or symptoms of hepatitis occur. Liver function tests should be monitored in patients with pre-existing hepatic impairment. Additionally, Clostridioides difficile-associated diarrhea (CDAD), which can range from mild diarrhea to fatal colitis, has been noted; patients should be evaluated if diarrhea occurs.

It is important to note that patients with mononucleosis who receive AUGMENTIN ES-600 may develop a skin rash, and the use of this medication should be avoided in such individuals. A history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to AUGMENTIN ES-600 or other beta-lactams (including penicillins or cephalosporins) is also a significant consideration.

In the context of overdosage, patients have primarily experienced gastrointestinal symptoms, including stomach and abdominal pain, vomiting, and diarrhea. Some patients have reported rash, hyperactivity, or drowsiness. Rarely, interstitial nephritis resulting in oliguric renal failure has been documented following amoxicillin overdosage. Furthermore, crystalluria, which in some cases has led to renal failure, has been reported in both adult and pediatric patients after amoxicillin overdosage.

Drug Interactions

Co-administration of AUGMENTIN ES-600 with probenecid is not recommended due to potential interactions that may affect the pharmacokinetics of the drug.

When AUGMENTIN ES-600 is used concurrently with oral anticoagulants, there is an increased risk of prolonged prothrombin time. It is advisable to monitor prothrombin time closely in patients receiving both medications to ensure appropriate anticoagulation levels.

The concomitant use of AUGMENTIN ES-600 and allopurinol has been associated with an increased risk of rash. Patients should be monitored for dermatological reactions when these drugs are used together.

Additionally, AUGMENTIN ES-600 may reduce the efficacy of oral contraceptives. Patients using oral contraceptives should be advised to consider alternative or additional contraceptive methods during treatment with AUGMENTIN ES-600 to prevent unintended pregnancy.

Packaging & NDC

The table below lists all NDC Code configurations of Augmentin Es-600 (amoxicillin and clavulanate potassium), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of AUGMENTIN ES-600 have been established in pediatric patients aged 3 months to 12 years, weighing less than or equal to 40 kg, for the treatment of acute otitis media and acute bacterial sinusitis. However, the safety and effectiveness of AUGMENTIN ES-600 have not been established in pediatric patients younger than 3 months of age or in those aged 3 months to 12 years who weigh more than 40 kg. Caution is advised when considering treatment in these populations.

Geriatric Use

The safety and effectiveness of AUGMENTIN ES-600 have not been established in elderly patients, specifically those aged 65 and older. Caution is advised when prescribing this medication to geriatric patients, particularly in the presence of hepatic dysfunction. In this population, there is an increased incidence of hepatic dysfunction, which may manifest as elevations in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase.

For elderly patients with hepatic impairment, it is essential to administer AUGMENTIN ES-600 with caution and to monitor hepatic function at regular intervals. While hepatic dysfunction in these patients is often reversible, it can be severe and has been associated with fatalities, particularly among elderly individuals or those undergoing prolonged treatment. Therefore, careful consideration and monitoring are critical when treating geriatric patients with this medication.

Pregnancy

Available data from published epidemiologic studies and pharmacovigilance case reports over several decades of use with amoxicillin and clavulanate during pregnancy have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal outcomes. However, a study involving women with preterm prelabor rupture of membranes (PPROM) indicated that prophylactic treatment with amoxicillin and clavulanate may be associated with an increased risk of necrotizing enterocolitis in neonates.

Reproduction studies conducted in pregnant rodents, which received doses up to approximately 2 times the amount of amoxicillin and 15 times the amount of clavulanate in the Maximum Human Recommended Dose (MHRD) of AUGMENTIN ES-600, revealed no evidence of harm to the fetus. Similarly, studies in pregnant rats and mice given amoxicillin and clavulanate at oral doses up to 1200 mg/kg/day showed no evidence of fetal harm.

The background risk of major birth defects and miscarriage for the indicated populations remains unknown. It is important to note that all pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

In light of these findings, healthcare professionals should weigh the potential benefits and risks when considering the use of amoxicillin and clavulanate in pregnant patients, particularly those with PPROM, and monitor for any adverse neonatal outcomes.

Lactation

There is no specific information available regarding the use of this medication in nursing mothers or its effects on lactation. Additionally, no data are provided concerning the excretion of this medication in breast milk or its potential effects on breastfed infants. Healthcare professionals should consider the lack of information when advising lactating mothers about the use of this medication.

Renal Impairment

Patients with renal impairment have no specific information regarding dosage adjustments, special monitoring, or safety considerations provided in the text. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing to patients with reduced kidney function. Regular monitoring of renal function may be warranted in these patients, although specific guidelines are not outlined.

Hepatic Impairment

Patients with hepatic impairment should be closely monitored for liver function tests. In the event that signs or symptoms of hepatitis occur, it is recommended to discontinue treatment. Careful assessment of liver function is essential to ensure patient safety and to guide therapeutic decisions.

Overdosage

In cases of overdosage, patients have predominantly exhibited gastrointestinal symptoms, which include stomach and abdominal pain, vomiting, and diarrhea. Additionally, a small subset of patients has reported symptoms such as rash, hyperactivity, or drowsiness.

Upon suspicion of overdosage, it is imperative to discontinue AUGMENTIN ES-600 immediately. Symptomatic treatment should be initiated, and supportive measures should be implemented as necessary. If the overdosage has occurred recently and there are no contraindications, healthcare professionals may consider inducing emesis or employing other methods to remove the drug from the stomach. A prospective study involving 51 pediatric patients at a poison control center indicated that overdosages of amoxicillin below 250 mg/kg are generally not associated with significant clinical symptoms and do not necessitate gastric emptying.

There have been reports of interstitial nephritis leading to oliguric renal failure in a limited number of patients following amoxicillin overdosage. Furthermore, crystalluria, which in some instances has resulted in renal failure, has been documented in both adult and pediatric patients after amoxicillin overdosage. To mitigate the risk of crystalluria, it is essential to maintain adequate fluid intake and diuresis.

Renal impairment observed in these cases appears to be reversible upon cessation of the drug. It is important to note that patients with impaired renal function may experience elevated blood levels of amoxicillin and clavulanate due to decreased renal clearance. Both amoxicillin and clavulanate can be effectively removed from circulation through hemodialysis.

Nonclinical Toxicology

Long-term studies in animals have not been conducted to assess the carcinogenic potential of the combination of amoxicillin and clavulanate. In mutagenicity testing, the formulation of amoxicillin and clavulanate at a 4:1 ratio was found to be non-mutagenic in both the Ames bacterial mutation assay and the yeast gene conversion assay. However, it exhibited weakly positive results in the mouse lymphoma assay; this observation was noted at concentrations that also resulted in decreased cell survival, suggesting that the increased mutation frequencies may not be indicative of a true mutagenic effect.

Further testing revealed that amoxicillin and clavulanate was negative in the mouse micronucleus test and in the dominant lethal assay in mice, indicating a lack of genotoxicity in these models. Clavulanate potassium, when tested alone in the Ames bacterial mutation assay and the mouse micronucleus test, also yielded negative results in both assays.

In terms of reproductive toxicity, the formulation of amoxicillin and clavulanate at a 2:1 ratio, administered at oral doses of up to 1,200 mg/kg/day, demonstrated no adverse effects on fertility and reproductive performance in rats.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions reported voluntarily or through surveillance programs. These include severe allergic reactions, such as anaphylaxis, and severe cutaneous adverse reactions (SCAR), which encompass Stevens-Johnson syndrome and toxic epidermal necrolysis.

Additionally, hepatic dysfunction has been reported, including cases of cholestatic jaundice and hepatitis. Renal dysfunction, specifically interstitial nephritis, has also been noted. Hematologic reactions, including thrombocytopenia, leukopenia, and hemolytic anemia, have been documented.

Furthermore, cases of Clostridium difficile-associated diarrhea and other gastrointestinal disorders, such as colitis, have been observed. There have also been reports of superinfection with non-susceptible organisms.

Patient Counseling

Patients should be informed to take AUGMENTIN ES-600 every 12 hours with a meal or snack to minimize the risk of gastrointestinal upset. They should be advised to contact their doctor if they experience severe diarrhea that lasts more than 2 or 3 days.

It is important to counsel patients that AUGMENTIN ES-600 contains a penicillin class drug, which may cause allergic reactions in some individuals. Patients should be made aware of the signs and symptoms of serious skin reactions. They should be instructed to discontinue AUGMENTIN ES-600 immediately and report any signs or symptoms of skin rash, mucosal lesions, or other indications of hypersensitivity without delay.

Patients should also be informed that diarrhea is a common side effect associated with antibacterial drugs, typically resolving upon discontinuation of the medication. However, they should be cautioned that watery and bloody stools, with or without stomach cramps and fever, can occur even up to 2 months after the last dose of the antibacterial drug. If such symptoms arise, patients should seek medical attention promptly.

Counsel patients that antibacterial drugs, including AUGMENTIN ES-600, are indicated solely for the treatment of bacterial infections and are ineffective against viral infections, such as the common cold. When prescribed AUGMENTIN ES-600 for a bacterial infection, patients should be reminded that it is common to feel better early in the treatment. However, it is crucial to take the medication exactly as directed, as skipping doses or failing to complete the full course may reduce the effectiveness of the treatment and increase the risk of bacterial resistance to AUGMENTIN ES-600 and other antibacterial drugs in the future.

For patients receiving the suspension form of AUGMENTIN ES-600, it should be kept refrigerated and shaken well before use. When dosing a child, a dosing spoon or medicine dropper should be utilized, and it is essential to rinse the spoon or dropper after each use. Patients should follow their doctor's instructions regarding the appropriate amount and duration of treatment for their child, and any unused medicine should be discarded.

Additionally, patients with phenylketonuria should be counseled that each 5 mL of the suspension contains 7 mg of phenylalanine.

Storage and Handling

The dry powder for oral suspension is supplied in its original container to ensure stability and integrity. It should be stored at or below 25°C (77°F) to maintain its efficacy. Once reconstituted, the suspension must be stored under refrigeration. Any unused portion of the reconstituted suspension should be discarded after 10 days to ensure patient safety and product effectiveness.

Additional Clinical Information

High urine concentrations of amoxicillin may lead to false-positive results for glucose when using CLINITEST®, Benedict's Solution, or Fehling's Solution. Clinicians are advised to utilize glucose tests that rely on enzymatic glucose oxidase reactions for accurate results. Additionally, administration of amoxicillin in pregnant women has been associated with a temporary reduction in plasma levels of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Augmentin Es-600 as submitted by USAntibiotics, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)