Augmentin

Description

AUGMENTIN is an oral antibacterial combination that includes amoxicillin and clavulanate potassium, a beta-lactamase inhibitor. Amoxicillin, an analog of ampicillin, is derived from the penicillin nucleus, 6-aminopenicillanic acid. Its molecular formula is C16H19N3O5S•3H2O, with a molecular weight of 419.46. The chemical structure of amoxicillin is (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 beta-lactam related to penicillins that inactivates certain beta-lactamases by blocking their active sites. The molecular formula for clavulanate potassium is C8H8KNO5, with a molecular weight of 237.25, and its chemical structure is potassium (Z)(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo3.2.0-heptane-2-carboxylate.

AUGMENTIN is available in various formulations, including tablets, powders for oral suspension, and chewable tablets. The tablets contain inactive ingredients such as colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, and titanium dioxide, with each tablet containing 0.63 mEq of potassium. The powder for oral suspension is available in concentrations of 125 mg/5 mL and 250 mg/5 mL, containing ingredients like colloidal silicon dioxide, flavorings, xanthan gum, mannitol, succinic acid, silica gel, and sodium saccharin. The chewable tablets come in strengths of 125 mg, 250 mg, 200 mg, and 400 mg, with various inactive ingredients including flavorings, magnesium stearate, mannitol, and aspartame. Each 125-mg chewable tablet and each 5 mL of reconstituted 125/5 mL oral suspension contains 0.16 mEq of potassium, while the 250-mg chewable tablet and 5 mL of reconstituted 250/5 mL oral suspension contain 0.32 mEq of potassium. The 200-mg chewable tablet and 5 mL of reconstituted 200/5 mL oral suspension contain 0.14 mEq of potassium, and the 400-mg chewable tablet and 5 mL of reconstituted 400/5 mL oral suspension contain 0.29 mEq of potassium.

Uses and Indications

AUGMENTIN is indicated for the treatment of the following conditions: lower respiratory tract infections, acute bacterial otitis media, sinusitis, skin and skin structure infections, and urinary tract infections.

There are no teratogenic or nonteratogenic effects associated with AUGMENTIN.

Dosage and Administration

For adults and pediatric patients weighing more than 40 kg, the recommended dosage is either 500 mg or 875 mg administered every 12 hours, or alternatively, 250 mg or 500 mg given every 8 hours.

In pediatric patients aged 12 weeks (3 months) and older, the dosage should be calculated based on body weight, with a range of 25 to 45 mg/kg/day administered every 12 hours, or 20 to 40 mg/kg/day given every 8 hours, not exceeding the adult dosage.

For neonates and infants under 12 weeks of age, the recommended dosage is 30 mg/kg/day, divided and administered every 12 hours. It is advised to use the 125 mg/5 mL oral suspension for this age group to ensure accurate dosing and administration.

Contraindications

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

Warnings and Precautions

Serious hypersensitivity reactions, including those that may be fatal, have been reported in patients receiving AUGMENTIN. In the event of such a reaction, it is imperative to discontinue the medication immediately. (5.1)

Patients with hepatic dysfunction or those who develop cholestatic jaundice should be closely monitored. If any signs or symptoms of hepatitis arise, AUGMENTIN should be discontinued. Regular liver function tests are recommended for patients with pre-existing hepatic impairment to ensure safety during treatment. (5.2)

Clostridium difficile-associated diarrhea (CDAD) is a potential complication associated with antibiotic therapy. Healthcare professionals should evaluate patients for CDAD if they present with diarrhea during or following treatment with AUGMENTIN. (5.3)

AUGMENTIN is contraindicated in patients with mononucleosis, as these individuals are at an increased risk of developing a skin rash upon administration of the medication. Therefore, it is advised to avoid prescribing AUGMENTIN to this patient population. (5.4)

The possibility of superinfections, including those caused by fungal or bacterial pathogens, should be considered during AUGMENTIN therapy. Clinicians should remain vigilant for signs of overgrowth and manage accordingly. (5.5)

Side Effects

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

Common adverse reactions observed in clinical trials include diarrhea or loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%), and vaginitis (1%). These reactions were reported among participants and may vary in frequency.

Serious adverse reactions necessitate immediate attention and may require discontinuation of AUGMENTIN. These include serious hypersensitivity reactions, which can be fatal; hepatic dysfunction and cholestatic jaundice, where discontinuation is advised if signs or symptoms of hepatitis occur, and liver function tests should be monitored in patients with hepatic impairment. Clostridium difficile-associated diarrhea (CDAD) is another serious concern, and patients should be evaluated if diarrhea occurs. Additionally, patients with mononucleosis who receive AUGMENTIN are at risk of developing skin rashes, and its use should be avoided in this population. The potential for superinfections with fungal or bacterial pathogens should also be considered during therapy.

Other important notes regarding adverse reactions include a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to AUGMENTIN or other beta-lactams, including penicillins or cephalosporins. A history of cholestatic jaundice or hepatic dysfunction associated with AUGMENTIN is also significant. Furthermore, interstitial nephritis resulting in oliguric renal failure has been reported following overdosage with amoxicillin/clavulanate potassium. Crystalluria, which in some cases has led to renal failure, has also been documented after overdosage in both adult and pediatric patients.

Drug Interactions

Co-administration of AUGMENTIN with probenecid is not recommended due to potential interactions that may affect therapeutic outcomes.

When AUGMENTIN is used concurrently with oral anticoagulants, there is an increased risk of prolonged prothrombin time, necessitating careful monitoring of coagulation parameters in patients receiving both medications.

The concomitant use of AUGMENTIN and allopurinol has been associated with an elevated risk of rash. Clinicians should be vigilant for dermatological reactions in patients receiving this combination.

Additionally, AUGMENTIN may reduce the efficacy of oral contraceptives. Patients should be advised to consider alternative or additional contraceptive measures while on AUGMENTIN therapy to ensure adequate contraceptive protection.

Packaging & NDC

The table below lists all NDC Code configurations of Augmentin (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 Powder for Oral Suspension and Chewable Tablets have been established in pediatric patients. Evidence supporting the use of AUGMENTIN in this population includes studies conducted with AUGMENTIN Tablets in adults, supplemented by data from a study involving pediatric patients aged 2 months to 12 years with acute otitis media.

In pediatric patients, particularly those aged less than 12 weeks (less than 3 months), dosing of AUGMENTIN should be modified due to the incompletely developed renal function in neonates and young infants, which may delay the elimination of amoxicillin. It is important to note that the elimination of clavulanate remains unaltered in this age group.

Geriatric Use

In clinical studies of AUGMENTIN, 32% of the 3,119 patients analyzed were aged 65 years and older, with 14% being 75 years and older. No overall differences in safety or effectiveness were observed between these elderly patients and their younger counterparts. However, while other clinical experiences have not identified significant differences in responses between elderly and younger patients, it is important to note that greater sensitivity to the drug may be present in some older individuals.

AUGMENTIN is substantially excreted by the kidneys, which raises concerns regarding the risk of adverse reactions in patients with impaired renal function. Given that elderly patients are more likely to experience decreased renal function, careful consideration should be given to dose selection in this population. It may be beneficial to monitor renal function to ensure appropriate dosing and minimize the risk of adverse effects.

Pregnancy

Pregnant patients should be aware that AUGMENTIN is classified as Pregnancy Category B. Reproduction studies conducted in pregnant rats and mice, which received AUGMENTIN at oral doses up to 1200 mg/kg/day, demonstrated no evidence of harm to the fetus. The amoxicillin doses administered in these studies were approximately 4 and 2 times the maximum recommended adult human oral dose of 875 mg every 12 hours, while the doses for clavulanate were approximately 9 and 4 times the maximum recommended adult human oral dose of 125 mg every 8 hours.

Despite these findings, there are no adequate and well-controlled studies in pregnant women. Therefore, due to the limitations of animal reproduction studies in predicting human response, AUGMENTIN should be used during pregnancy only if clearly needed. Healthcare professionals are advised to weigh the potential benefits against any possible risks when considering AUGMENTIN for pregnant patients.

Lactation

Amoxicillin has been shown to be excreted in human milk. The use of amoxicillin/clavulanate potassium by nursing mothers may lead to sensitization of breastfed infants. Caution should be exercised when administering amoxicillin/clavulanate potassium to a lactating mother.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

Hepatic Impairment

Patients with hepatic impairment should be closely monitored for liver function tests. In the event that signs or symptoms of hepatitis occur, the treatment should be discontinued immediately. It is essential to assess liver function regularly to ensure the safety and efficacy of the therapy in this population.

Overdosage

In the event of an overdosage, it is imperative to discontinue the medication immediately and provide symptomatic treatment along with supportive measures as necessary. 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.

Potential Symptoms and Complications

Overdosage of amoxicillin/clavulanate potassium has been associated with interstitial nephritis, which can lead to oliguric renal failure. Additionally, crystalluria has been reported, which in some instances has resulted in renal failure in both adult and pediatric patients.

Management Recommendations

To mitigate the risk of crystalluria following an overdosage of amoxicillin/clavulanate potassium, it is essential to maintain adequate fluid intake and promote diuresis. This approach helps to reduce the likelihood of crystallization in the renal system.

Renal impairment observed due to overdosage is typically reversible upon cessation of the drug. It is important to note that patients with pre-existing renal impairment may experience elevated blood levels of amoxicillin/clavulanate potassium due to decreased renal clearance. In cases of severe overdosage, hemodialysis may be employed to facilitate the removal of the drug from circulation.

Nonclinical Toxicology

Long-term studies in animals have not been conducted to assess the carcinogenic potential of AUGMENTIN. In mutagenicity testing, AUGMENTIN (4:1 ratio formulation of amoxicillin:clavulanate) demonstrated non-mutagenic properties in both the Ames bacterial mutation assay and the yeast gene conversion assay. However, it exhibited weak positivity in the mouse lymphoma assay, where the observed trend toward increased mutation frequencies coincided with decreased cell survival at the tested doses. AUGMENTIN was found to be negative in the mouse micronucleus test and in the dominant lethal assay in mice.

Potassium clavulanate, when tested independently in the Ames bacterial mutation assay and the mouse micronucleus test, also yielded negative results in both assays.

In terms of reproductive toxicity, AUGMENTIN (2:1 ratio formulation of amoxicillin:clavulanate) was administered at oral doses of up to 1,200 mg/kg/day in rats, with no observed effects on fertility and reproductive performance. This dosage corresponds to approximately four times the maximum recommended adult human oral dose of amoxicillin (875 mg every 12 hours) and approximately nine times the maximum recommended adult human oral dose of clavulanate (125 mg every 8 hours), when adjusted for body surface area.

Postmarketing Experience

Diarrhea has been reported as a common adverse event associated with the use of antibacterials, typically resolving upon discontinuation of the medication. Notably, there have been instances where patients developed watery and bloody stools, with or without accompanying symptoms such as stomach cramps and fever, even up to two months after the last dose of the antibacterial. In cases of severe diarrhea lasting more than 2 to 3 days, it is advised that patients seek medical attention. Additionally, it is important for patients to be informed that AUGMENTIN contains a penicillin-class drug, which may lead to allergic reactions in susceptible individuals.

Patient Counseling

Patients should be informed that AUGMENTIN may be taken every 8 hours or every 12 hours, depending on the prescribed dosage. It is important that each dose is taken with a meal or snack to minimize the risk of gastrointestinal upset.

Healthcare providers should counsel patients that antibacterial drugs, including AUGMENTIN, are intended solely for the treatment of bacterial infections and are ineffective against viral infections, such as the common cold. When AUGMENTIN is prescribed for a bacterial infection, patients should be advised that it is common to feel better early in the treatment. However, it is crucial to take the medication exactly as directed. Skipping doses or failing to complete the full course of therapy may reduce the effectiveness of the treatment and increase the likelihood of bacteria developing resistance, making them unresponsive to AUGMENTIN or other antibacterial drugs in the future.

Patients should be made aware that diarrhea is a common side effect associated with antibacterial medications, typically resolving upon discontinuation of the drug. However, in some cases, patients may experience watery and bloody stools (with or without stomach cramps and fever) even weeks after completing the course of treatment. If diarrhea is severe or persists for more than 2 or 3 days, patients should be instructed to contact their physician.

For those receiving the suspension form of AUGMENTIN, patients should be advised to keep the medication refrigerated and to shake it well before use. When administering the suspension to a child, a dosing spoon or medicine dropper should be utilized, and it is important to rinse the spoon or dropper after each use. Patients should follow their doctor’s instructions regarding the appropriate dosage and duration of treatment for their child, and any unused medicine should be discarded.

Lastly, patients should be informed that AUGMENTIN contains a penicillin-class drug, which may cause allergic reactions in some individuals.

Storage and Handling

Tablets and dry powder should be stored at or below 25°C (77°F). Once reconstituted, the suspension must be kept under refrigeration. Any unused suspension should be discarded after 10 days to ensure safety and efficacy. It is essential to dispense the product in its original container to maintain integrity. Additionally, the product should be kept out of the reach of children to prevent accidental ingestion.

Additional Clinical Information

Patients should be informed that AUGMENTIN Chewable tablets and AUGMENTIN Powder for Oral Solution contain aspartame, which includes phenylalanine. Specifically, each 200-mg chewable tablet contains 2.1 mg of phenylalanine, while each 400-mg chewable tablet contains 4.2 mg. Additionally, each 5 mL of either the 200 mg/5 mL or 400 mg/5 mL oral suspension contains 7 mg of phenylalanine. It is important to note that other formulations of AUGMENTIN do not contain phenylalanine.

No further information is available regarding laboratory tests, abuse potential, route, method, and frequency of administration, or postmarketing experience.

FDA Insert (PDF)

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

View full prescribing information (PDF)