Augmentin Es-600

Description

AUGMENTIN ES-600 Powder for Oral Suspension is an oral antibacterial combination that includes the semisynthetic antibiotic amoxicillin and the β-lactamase inhibitor clavulanate potassium, the potassium salt of clavulanic acid.

Amoxicillin, an analog of ampicillin derived from the penicillin nucleus 6-aminopenicillanic acid, has 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-azabicyclo3.2.0heptane-2-carboxylic acid trihydrate.

Clavulanic acid, produced by the fermentation of Streptomyces clavuligerus, is a β-lactam that is structurally related to penicillins. It effectively inactivates a variety of β-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. Its chemical structure is potassium (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo3.2.0-heptane-2-carboxylate.

Uses and Indications

AUGMENTIN ES-600 Powder for Oral Suspension is indicated for the treatment of pediatric patients with recurrent or persistent acute otitis media caused by specific pathogens. This includes infections due to Streptococcus pneumoniae (penicillin minimum inhibitory concentrations MICs ≤ 2 mcg/mL), Haemophilus influenzae (including β-lactamase–producing strains), and Moraxella catarrhalis (including β-lactamase–producing strains). The targeted patient population includes those with the following risk factors: antibiotic exposure for acute otitis media within the preceding 3 months, and either age ≤ 2 years or daycare attendance.

It is important to note that acute otitis media due to S. pneumoniae alone can be effectively treated with amoxicillin. AUGMENTIN ES-600 Powder for Oral Suspension is not indicated for the treatment of acute otitis media caused by S. pneumoniae with penicillin MIC ≥ 4 mcg/mL. Therapy may be initiated prior to obtaining results from bacteriological studies if there is a clinical suspicion that the infection may involve both S. pneumoniae (penicillin MIC ≤ 2 mcg/mL) and the aforementioned β-lactamase–producing organisms.

Dosage and Administration

Pediatric patients aged 3 months and older are recommended to receive AUGMENTIN ES-600 Powder for Oral Suspension at a dosage of 90 mg/kg/day, divided into two doses every 12 hours, for a duration of 10 days. The volume of the suspension to be administered is determined by the patient's body weight, as follows:

• For a weight of 8 kg: 3.0 mL twice daily

• For a weight of 12 kg: 4.5 mL twice daily

• For a weight of 16 kg: 6.0 mL twice daily

• For a weight of 20 kg: 7.5 mL twice daily

• For a weight of 24 kg: 9.0 mL twice daily

• For a weight of 28 kg: 10.5 mL twice daily

• For a weight of 32 kg: 12.0 mL twice daily

• For a weight of 36 kg: 13.5 mL twice daily

There is no available experience with AUGMENTIN ES-600 Powder for Oral Suspension in pediatric patients weighing 40 kg and more, nor in adults. It is important to note that adults who have difficulty swallowing should not use AUGMENTIN ES-600 Powder for Oral Suspension as a substitute for the 500-mg or 875-mg tablet formulations.

For preparation of the oral suspension, the following steps should be followed at the time of dispensing:

1. Tap the bottle until all the powder flows freely.

2. Add approximately two-thirds of the total amount of water required for reconstitution and shake vigorously to suspend the powder.

3. Add the remaining water and shake vigorously again.

The amount of water required for reconstitution varies by bottle size:

• For a 75 mL bottle: 70 mL of water

• For a 125 mL bottle: 110 mL of water

• For a 200 mL bottle: 180 mL of water

Each teaspoonful (5 mL) of the prepared suspension contains 600 mg of amoxicillin as the trihydrate and 42.9 mg of clavulanic acid as the potassium salt. It is essential to SHAKE the oral suspension well before use.

To minimize the potential for gastrointestinal intolerance, AUGMENTIN ES-600 Powder for Oral Suspension should be administered at the start of a meal, as this may enhance the absorption of clavulanate potassium.

Contraindications

AUGMENTIN ES-600 Powder for Oral Suspension is contraindicated in patients with a history of allergic reactions to any penicillin. Additionally, it should not be used in individuals with a previous history of cholestatic jaundice or hepatic dysfunction associated with AUGMENTIN.

The use of ampicillin-class antibiotics, including AUGMENTIN, is also contraindicated in patients with mononucleosis. Furthermore, prescribing this medication in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is not recommended, as it does not provide benefit and may increase the risk of developing drug-resistant bacteria.

Warnings and Precautions

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients undergoing penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or sensitivity to multiple allergens. Notably, there have been instances of individuals with a history of penicillin hypersensitivity experiencing severe reactions when treated with cephalosporins. Prior to initiating therapy with Augmentin ES-600 Powder for Oral Suspension, a thorough inquiry regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens is essential. Should an allergic reaction occur, Augmentin ES-600 Powder for Oral Suspension must be discontinued immediately, and appropriate therapy should be instituted.

In the event of serious anaphylactic reactions, immediate emergency treatment with epinephrine is required. Additional measures may include the administration of oxygen, intravenous steroids, and airway management, including intubation, as clinically indicated.

Pseudomembranous colitis has been associated with nearly all antibacterial agents, including amoxicillin/clavulanate potassium, and can range in severity from mild to life-threatening. Therefore, this diagnosis should be considered in patients who present with diarrhea following the administration of antibacterial agents.

Caution is advised when using Augmentin ES-600 Powder for Oral Suspension in patients with evidence of hepatic dysfunction. Hepatic toxicity linked to amoxicillin/clavulanate potassium is typically reversible; however, rare cases of fatalities have been reported (less than one death per estimated four million prescriptions worldwide), generally in patients with serious underlying conditions or those receiving concomitant medications.

While amoxicillin/clavulanate is characterized by the low toxicity typical of the penicillin group of antibiotics, periodic assessment of organ system functions—including renal, hepatic, and hematopoietic function—is recommended if therapy extends beyond the approved duration.

It is important to note that a significant percentage of patients with mononucleosis who receive ampicillin develop an erythematous skin rash. Consequently, ampicillin-class antibiotics should not be administered to patients diagnosed with mononucleosis.

Healthcare professionals should remain vigilant for the possibility of superinfections with mycotic or bacterial pathogens during therapy. If superinfections occur, typically involving Pseudomonas or Candida, the drug should be discontinued, and appropriate therapy should be initiated.

Prescribing Augmentin ES-600 Powder for Oral Suspension in the absence of a proven or strongly suspected bacterial infection, or a prophylactic indication, is unlikely to benefit the patient and may increase the risk of developing drug-resistant bacteria.

For patients undergoing therapy for longer than the approved duration, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic function, is advisable to ensure safety and efficacy.

Side Effects

Patients may experience a range of adverse reactions associated with the use of this medication. Common adverse reactions observed in clinical trials include contact dermatitis (diaper rash) in 3.5% of participants, diarrhea in 2.9%, and vomiting in 2.2%. Additionally, moniliasis was reported in 1.4% of subjects, while rash occurred in 1.1%. Notably, diarrhea and vomiting led to withdrawal in 2.5% and 1.4% of patients, respectively.

Gastrointestinal adverse reactions may include diarrhea, nausea, vomiting, indigestion, gastritis, stomatitis, glossitis, black “hairy” tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic or pseudomembranous colitis, which can occur during or after antibiotic treatment.

Hypersensitivity reactions have been documented, including skin rashes, pruritus, urticaria, angioedema, and serum sickness-like reactions characterized by urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever. Rarely, erythema multiforme, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, and exfoliative dermatitis (including toxic epidermal necrolysis) have been reported. Serious and occasionally fatal hypersensitivity reactions, such as anaphylaxis, may also occur.

Liver-related adverse reactions include a moderate rise in AST (SGOT) and/or ALT (SGPT), hepatic dysfunction indicated by increases in serum transaminases, serum bilirubin, and/or alkaline phosphatase, and severe hepatic dysfunction, which is usually reversible. There have been rare reports of deaths associated with serious underlying diseases or concomitant medications.

Renal adverse reactions are rare and may include interstitial nephritis, hematuria, and crystalluria.

Hemic and lymphatic system reactions can manifest as anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, agranulocytosis, slight thrombocytosis (less than 1%), and increased prothrombin time in patients receiving anticoagulant therapy.

Central nervous system effects, although rare, may include agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity.

Miscellaneous adverse reactions include tooth discoloration (brown, yellow, or gray staining), which has been rarely reported, primarily in pediatric patients.

Drug Interactions

Probenecid is known to decrease the renal tubular secretion of amoxicillin. The concurrent use of probenecid with AUGMENTIN ES-600 Powder for Oral Suspension may lead to increased and prolonged blood levels of amoxicillin. Therefore, co-administration of probenecid with this formulation is not recommended.

In patients receiving amoxicillin alongside oral anticoagulants, there have been rare reports of abnormal prolongation of prothrombin time, indicated by an increased international normalized ratio (INR). When these medications are prescribed together, appropriate monitoring of INR is advised. Adjustments to the dosage of oral anticoagulants may be necessary to maintain the desired anticoagulation levels.

The combination of allopurinol and ampicillin has been associated with a significantly higher incidence of rashes compared to patients receiving ampicillin alone. It remains unclear whether this increased incidence is attributable to allopurinol or the hyperuricemia present in these patients. There is currently no data available regarding the concurrent administration of allopurinol with AUGMENTIN ES-600 Powder for Oral Suspension.

Similar to other broad-spectrum antibiotics, amoxicillin/clavulanate may diminish the efficacy of oral contraceptives. Patients using oral contraceptives should be advised of this potential interaction.

Oral administration of AUGMENTIN results in high urine concentrations of amoxicillin. This can lead to false-positive results when testing for glucose in urine using CLINITEST®, Benedict’s Solution, or Fehling’s Solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions, such as CLINISTIX®, be utilized to avoid this issue.

In pregnant women administered ampicillin, a transient decrease in plasma concentrations of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been observed. This effect may also be applicable to amoxicillin and, consequently, AUGMENTIN ES-600 Powder for Oral Suspension.

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 efficacy of AUGMENTIN ES-600 Powder for Oral Suspension have not been established in infants younger than 3 months. In pediatric patients aged 3 months to 12 years, AUGMENTIN ES-600 has demonstrated safety and efficacy for the treatment of acute otitis media. Additionally, it has been shown to be safe and effective for treating acute bacterial sinusitis in the same age group.

Geriatric Use

Elderly patients may require special consideration when using AUGMENTIN ES-600 Powder for Oral Suspension. Caution is advised in this population, particularly for those with evidence of hepatic dysfunction, as hepatic toxicity associated with amoxicillin/clavulanate potassium is typically reversible. However, there have been rare reports of fatalities (less than 1 death per estimated 4 million prescriptions worldwide), primarily in patients with serious underlying conditions or those taking concomitant medications.

Hepatic dysfunction has been observed more frequently in elderly patients, males, and those undergoing prolonged treatment. A moderate increase in AST (SGOT) and/or ALT (SGPT) levels has been noted in patients treated with ampicillin-class antibiotics, although the clinical significance of these findings remains unclear. Therefore, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic function, is recommended for geriatric patients receiving therapy beyond the approved duration.

Additionally, the risk of superinfections with mycotic or bacterial pathogens should be considered during treatment. Should superinfections occur, typically involving Pseudomonas or Candida, discontinuation of the drug and initiation of appropriate therapy is warranted.

Elderly patients receiving amoxicillin in conjunction with oral anticoagulants may experience abnormal prolongation of prothrombin time, indicated by an increased international normalized ratio (INR). Close monitoring is essential when these medications are co-administered, and adjustments to the dosage of oral anticoagulants may be necessary to maintain the desired anticoagulation levels.

Renal impairment, which may occur in this population, is generally reversible upon cessation of the drug. However, elderly patients with impaired renal function may experience elevated blood levels of amoxicillin and clavulanate due to decreased renal clearance. It is important to note that both amoxicillin and clavulanate can be removed from circulation through hemodialysis.

Pregnancy

The use of AUGMENTIN during pregnancy should be approached with caution. Oral ampicillin-class antibiotics, including AUGMENTIN, are generally poorly absorbed during labor. Animal studies have indicated that intravenous administration of ampicillin can decrease uterine tone, frequency, height, and duration of contractions. However, it remains unclear whether AUGMENTIN has any immediate or delayed adverse effects on the fetus when used during labor or delivery. There is also insufficient data to determine if its use prolongs labor or increases the likelihood of requiring obstetrical interventions, such as forceps delivery or resuscitation of the newborn.

Additionally, a single study involving women with premature rupture of fetal membranes suggested that prophylactic treatment with AUGMENTIN may be associated with an increased risk of necrotizing enterocolitis in neonates. Given these considerations, healthcare professionals should weigh the potential benefits against the risks when prescribing AUGMENTIN to pregnant patients, particularly during labor and delivery.

Lactation

Ampicillin-class antibiotics, including AUGMENTIN, are excreted in human milk. Therefore, caution should be exercised when administering AUGMENTIN to lactating mothers. The potential effects on breastfed infants have not been fully established, and healthcare professionals should consider the benefits of breastfeeding alongside the potential risks associated with the use of this medication in nursing women.

Renal Impairment

Patients with renal impairment should use AUGMENTIN ES-600 Powder for Oral Suspension with caution. It is important to monitor renal function closely in these individuals, particularly those with evidence of hepatic dysfunction. Dosing adjustments may be necessary based on the degree of renal impairment to ensure safety and efficacy.

Hepatic Impairment

Patients with hepatic impairment should use AUGMENTIN ES-600 Powder for Oral Suspension with caution. While hepatic toxicity associated with the use of amoxicillin/clavulanate potassium is typically reversible, it is important to monitor liver function closely in these patients.

Although rare, there have been reports of fatalities linked to the use of this medication, with less than one death reported per an estimated four million prescriptions worldwide. These cases have generally involved patients with serious underlying diseases or those taking concomitant medications that may exacerbate liver issues. Therefore, careful consideration and monitoring are advised for patients with compromised liver function when prescribing this medication.

Overdosage

Following an overdosage of AUGMENTIN ES-600 Powder for Oral Suspension, patients have primarily exhibited gastrointestinal symptoms, including stomach and abdominal pain, vomiting, and diarrhea. In a minority of cases, additional symptoms such as rash, hyperactivity, or drowsiness have been reported.

Management of Overdosage In the event of an overdosage, it is imperative to discontinue the administration of AUGMENTIN ES-600. Symptomatic treatment and supportive measures should be instituted 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.

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

Renal Considerations Renal impairment observed in the context of overdosage 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, which may be considered in cases of significant overdosage.

Nonclinical Toxicology

Reproduction studies conducted in pregnant rats and mice administered AUGMENTIN at oral dosages up to 1,200 mg/kg/day, which corresponds to 4.9 and 2.8 times the maximum adult human oral dose based on body surface area, demonstrated no evidence of teratogenic effects on the fetus. However, there are no adequate and well-controlled studies in pregnant women. Due to the limitations of animal reproduction studies in predicting human outcomes, AUGMENTIN should be used during pregnancy only if clearly needed.

In terms of non-teratogenic effects, AUGMENTIN administered at oral doses of up to 1,200 mg/kg/day, equivalent to 5.7 times the maximum adult human dose based on body surface area, did not adversely affect fertility or reproductive performance in rats treated with a 2:1 ratio formulation of amoxicillin:clavulanate.

Long-term studies in animals to assess the carcinogenic potential of AUGMENTIN have not been conducted. The mutagenic potential of the drug was evaluated through various in vitro assays, including the Ames test, a human lymphocyte cytogenetic assay, a yeast test, and a mouse lymphoma forward mutation assay, as well as in vivo assessments using mouse micronucleus tests and a dominant lethal test. All tests returned negative results, except for the in vitro mouse lymphoma assay, which indicated weak activity at very high, cytotoxic concentrations.

No additional specific details regarding animal pharmacology and toxicology are available beyond those presented in the nonclinical toxicology section.

Postmarketing Experience

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving penicillin therapy. These reactions are more frequently observed in individuals with a history of penicillin hypersensitivity or sensitivity to multiple allergens.

Pseudomembranous colitis has been documented with nearly all antibacterial agents, including amoxicillin/clavulanate potassium, with severity ranging from mild to life-threatening.

Hepatic dysfunction, characterized by increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been infrequently reported with AUGMENTIN. This condition has been more commonly observed in elderly patients, males, or those undergoing prolonged treatment. The onset of hepatic dysfunction may occur during therapy or several weeks after discontinuation, and while it can be severe, it is usually reversible.

On rare occasions, deaths have been reported, with an estimated incidence of less than one death per four million prescriptions worldwide. These cases have generally involved patients with serious underlying diseases or those taking concomitant medications.

Interstitial nephritis and hematuria have been reported rarely, along with crystalluria. Hematological reactions, including anemia (notably hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis, have also been associated with penicillin therapy. These reactions are typically reversible upon discontinuation of the medication and are believed to be hypersensitivity phenomena.

Neuropsychiatric events such as agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity have been reported rarely. Additionally, tooth discoloration (brown, yellow, or gray staining) has been noted, primarily in pediatric patients, with most cases showing improvement or resolution following dental cleaning or brushing.

Patient Counseling

Healthcare providers should advise patients that AUGMENTIN ES-600 Powder for Oral Suspension should be taken every 12 hours with a meal or snack to minimize the risk of gastrointestinal upset. Patients should be informed that diarrhea is a common side effect associated with antibiotic use, and if they experience severe diarrhea or if it lasts more than 2 or 3 days, they should contact their doctor.

It is important to counsel patients that, although diarrhea typically resolves after discontinuation of the antibiotic, they should be vigilant for the development of watery and bloody stools, which may occur even weeks after completing the treatment. If such symptoms arise, patients should seek medical attention promptly.

Patients should be instructed to keep the suspension refrigerated and to shake the bottle well before each use. When administering the suspension to a child, healthcare providers should recommend using a dosing spoon or medicine dropper, ensuring that it is rinsed after each use. Additionally, patients should be reminded that the bottle may contain more liquid than necessary, and they should adhere to their doctor’s instructions regarding the appropriate dosage and duration of treatment, discarding any unused medication.

It is essential to communicate that AUGMENTIN ES-600 Powder for Oral Suspension is an antibacterial medication intended solely for the treatment of bacterial infections and is ineffective against viral infections, such as the common cold. Patients should be cautioned that even if they start to feel better early in the treatment, it is crucial to take the medication exactly as prescribed. Skipping doses or failing to complete the full course of therapy may reduce the effectiveness of the treatment and increase the risk of bacterial resistance, making future infections harder to treat.

Lastly, healthcare providers should inform patients who are phenylketonurics that each 5 mL of the 600 mg/42.9 mg per 5 mL suspension contains 7 mg of phenylalanine.

Storage and Handling

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

Additional Clinical Information

High urine concentrations of amoxicillin may lead to false-positive results for glucose in urine when using CLINITEST, Benedict’s Solution, or Fehling’s Solution. Clinicians are advised to utilize glucose tests based on enzymatic glucose oxidase reactions, such as CLINISTIX, for accurate results.

AUGMENTIN ES-600 Powder for Oral Suspension should be administered every 12 hours with a meal or snack to minimize gastrointestinal upset. Patients should be informed that if diarrhea occurs and is severe or persists for more than 2 to 3 days, they should contact their healthcare provider. It is important to note that antibiotic-associated diarrhea may occur, sometimes leading to watery and bloody stools even weeks after treatment has ended, necessitating prompt medical attention. The suspension must be refrigerated and shaken well before use. When dosing children, a dosing spoon or medicine dropper should be used, and any unused medicine should be discarded as per the physician's instructions. Patients should be counseled that AUGMENTIN ES-600 is effective only against bacterial infections and not viral infections, emphasizing the importance of adhering to the prescribed regimen to prevent reduced effectiveness and antibiotic resistance. Additionally, each 5 mL of the suspension contains 7 mg of phenylalanine, which is relevant for phenylketonurics.

FDA Insert (PDF)

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

View full prescribing information (PDF)