Amoxicillin/Clavulanate potassium

Description

Amoxicillin and clavulanate potassium for oral suspension, USP is an oral antibacterial combination comprising amoxicillin and clavulanate potassium, the potassium salt of clavulanic acid, which serves as a beta-lactamase inhibitor. Amoxicillin, an analog of ampicillin, is derived from the penicillin nucleus, 6-aminopenicillanic acid, with a molecular formula of C16H19N3O5S•3H2O and a molecular weight of 419.46. 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 is produced through the fermentation of Streptomyces clavuligerus and is a beta-lactam that can inactivate certain beta-lactamases by obstructing 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.

Upon reconstitution, each teaspoonful (5 mL) of the suspension provides either 200 mg of amoxicillin as the trihydrate and 28.5 mg of clavulanic acid as the potassium salt or 400 mg of amoxicillin as the trihydrate and 57 mg of clavulanic acid as the potassium salt. The 200 mg/28.5 mg formulation contains 0.14 mEq of potassium per 5 mL, while the 400 mg/57 mg formulation contains 0.29 mEq of potassium per 5 mL. The product appears as a white to off-white granular powder, which transforms into a white to pale yellow suspension with an orange flavor upon reconstitution.

Inactive ingredients include colloidal silicon dioxide, hypromellose, orange flavor, silicon dioxide, succinic acid, xanthan gum, and aspartame.

Uses and Indications

Amoxicillin and clavulanate potassium for oral suspension 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 this medication.

Dosage and Administration

For adults and pediatric patients weighing more than 40 kg, the recommended dosage is either 500 mg/125 mg or 875 mg/125 mg administered every 12 hours, or alternatively, 250 mg/125 mg or 500 mg/125 mg every 8 hours.

For 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 given every 12 hours, or 20 to 40 mg/kg/day given every 8 hours, not exceeding the adult dosage.

In 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 utilize the 125 mg/31.25 mg per 5 mL oral suspension for this age group.

Contraindications

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

Warnings and Precautions

Serious hypersensitivity reactions, including those that may be fatal, have been reported in patients receiving amoxicillin and clavulanate potassium for oral suspension. 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 also discontinue the use of this medication if any signs or symptoms of hepatitis arise. It is recommended that liver function tests be monitored in patients with pre-existing hepatic impairment to ensure safety (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 treatment (5.3).

Amoxicillin and clavulanate potassium for oral suspension should be avoided in patients with mononucleosis, as these individuals are at an increased risk of developing a skin rash when treated with this medication (5.4).

Additionally, the possibility of superinfections due to overgrowth of fungal or bacterial pathogens should be considered during the course of therapy. Clinicians should remain vigilant for signs of such infections (5.5).

Side Effects

Patients receiving amoxicillin and clavulanate potassium for oral suspension may experience a range of adverse reactions. 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%).

Serious adverse reactions, although less frequent, warrant careful monitoring. These include serious hypersensitivity reactions, which can be fatal; patients should discontinue the medication if such a reaction occurs. Hepatic dysfunction and cholestatic jaundice have also been reported, necessitating discontinuation of the drug if signs or symptoms of hepatitis arise, along with monitoring of liver function tests in patients with pre-existing hepatic impairment. Additionally, Clostridium difficile-associated diarrhea (CDAD) should be evaluated if diarrhea occurs during treatment. It is important to note that patients with mononucleosis who are treated with amoxicillin and clavulanate potassium may develop skin rashes, and the use of this medication is contraindicated in these individuals. The potential for superinfections with fungal or bacterial pathogens should also be considered during therapy.

Other important considerations include a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to amoxicillin and clavulanate potassium or other beta-lactams, as well as a history of cholestatic jaundice or hepatic dysfunction associated with this medication. Furthermore, interstitial nephritis resulting in oliguric renal failure has been reported following overdosage, along with crystalluria, which in some cases has led to renal failure in both adult and pediatric patients.

Drug Interactions

Co-administration of amoxicillin and clavulanate potassium for oral suspension with probenecid is not recommended due to potential interactions that may affect therapeutic outcomes.

When used concurrently with oral anticoagulants, amoxicillin and clavulanate potassium may lead to an increased prolongation of prothrombin time. Monitoring of prothrombin time is advised to ensure patient safety and appropriate anticoagulation management.

The concomitant use of amoxicillin and clavulanate potassium with allopurinol has been associated with an increased risk of rash. Caution is advised when these medications are prescribed together.

Additionally, amoxicillin and clavulanate potassium for oral suspension may reduce the efficacy of oral contraceptives. Patients should be informed of this potential interaction and advised to consider alternative or additional contraceptive measures during treatment.

Packaging & NDC

The table below lists all NDC Code configurations of 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 amoxicillin and clavulanate potassium powder for oral suspension and chewable tablets have been established in pediatric patients. Evidence supporting the use of amoxicillin and clavulanate potassium for oral suspension in this population is derived from studies involving amoxicillin and clavulanate potassium tablets in adults, supplemented by data from a study specifically examining pediatric patients aged 2 months to 12 years with acute otitis media.

In neonates and young infants, renal function is not fully developed, which may lead to delayed elimination of amoxicillin; however, the elimination of clavulanate remains unchanged in this age group. Therefore, dosing of amoxicillin and clavulanate potassium for oral suspension should be adjusted for pediatric patients aged less than 12 weeks (less than 3 months).

Geriatric Use

In clinical studies involving amoxicillin and clavulanate potassium for oral suspension, 32% of the 3,119 patients analyzed were aged 65 years or older, and 14% were aged 75 years or older. The data indicated no overall differences in safety or effectiveness between elderly patients and their younger counterparts. However, it is important to note that while clinical experience has not identified significant differences in responses between these age groups, the possibility of greater sensitivity in some older individuals cannot be excluded.

Given that this medication is substantially excreted by the kidneys, there is an increased risk of adverse reactions in patients with impaired renal function. Elderly patients are more likely to experience decreased renal function; therefore, careful consideration should be given to dose selection in this population. It may be beneficial to monitor renal function to ensure safe and effective use of the drug in geriatric patients.

Pregnancy

Pregnancy Category B. Reproduction studies conducted in pregnant rats and mice administered amoxicillin and clavulanate potassium for oral suspension (2:1 ratio formulation) at oral doses up to 1200 mg/kg/day demonstrated no evidence of harm to the fetus. The amoxicillin doses in these studies were approximately 4 and 2 times the maximum recommended adult human oral dose of 875 mg every 12 hours, while the clavulanate doses 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, amoxicillin and clavulanate potassium for oral suspension should be used during pregnancy only if clearly needed. Healthcare professionals are advised to weigh the potential benefits against any possible risks when considering this medication for pregnant patients.

Lactation

Amoxicillin has been shown to be excreted in human milk. The use of amoxicillin and clavulanate potassium by nursing mothers may lead to sensitization of breastfed infants. Therefore, caution should be exercised when administering amoxicillin and clavulanate potassium to lactating mothers.

Renal Impairment

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

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 any necessary adjustments in therapy.

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 typically do not result in significant clinical symptoms. However, more severe cases have been documented. Notably, interstitial nephritis leading to oliguric renal failure has been reported following overdosage with amoxicillin and clavulanate potassium. Additionally, crystalluria, which in some instances has progressed to renal failure, has been observed in both adult and pediatric patients after overdosage with these agents.

To mitigate the risk of crystalluria associated with amoxicillin and clavulanate potassium overdosage, it is essential to maintain adequate fluid intake and promote diuresis. Renal impairment resulting from overdosage appears to be reversible upon cessation of the drug. It is important to note that patients with pre-existing renal impairment may experience elevated blood levels of the drug due to decreased renal clearance.

For patients experiencing severe overdosage, hemodialysis may be employed as a method to remove amoxicillin and clavulanate potassium from circulation effectively.

Nonclinical Toxicology

Long-term studies in animals have not been conducted to assess the carcinogenic potential of amoxicillin and clavulanate potassium for oral suspension. In mutagenicity testing, the formulation demonstrated non-mutagenic properties in both the Ames bacterial mutation assay and the yeast gene conversion assay. However, it exhibited a weakly positive response in the mouse lymphoma assay, where the observed trend toward increased mutation frequencies coincided with doses that also resulted in decreased cell survival. The formulation was negative in the mouse micronucleus test and the dominant lethal assay in mice.

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

In terms of reproductive toxicity, amoxicillin and clavulanate potassium for oral suspension, at a 2:1 ratio formulation, 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 about nine times the maximum recommended adult human oral dose of clavulanate (125 mg every 8 hours), when adjusted for body surface area.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions associated with the use of the antibacterial. Diarrhea has been reported, which may be severe and can occur even as late as two or more months after the last dose of the antibacterial. Additionally, patients may experience watery and bloody stools, which can occur with or without accompanying symptoms such as stomach cramps and fever, following the initiation of treatment with antibacterials.

Patient Counseling

Patients should be informed that amoxicillin and clavulanate potassium for oral suspension 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 amoxicillin and clavulanate potassium for oral suspension, are intended solely for the treatment of bacterial infections and are ineffective against viral infections, such as the common cold.

When prescribed for a bacterial infection, patients should be advised that it is common to feel better early in the course of therapy; however, the medication must be taken exactly as directed. Skipping doses or failing to complete the full course of therapy may reduce the effectiveness of the treatment and increase the risk of bacteria developing resistance, which could render amoxicillin and clavulanate potassium for oral suspension or other antibacterial drugs ineffective in the future.

Patients should be made aware that diarrhea is a common side effect associated with antibacterial use, typically resolving upon discontinuation of the medication. However, they should be informed that watery and bloody stools, with or without stomach cramps and fever, can occur even up to 2 months after completing the treatment. If diarrhea is severe or persists for more than 2 to 3 days, patients should contact their physician.

It is essential to advise patients to keep the suspension refrigerated and to shake it well before use. When administering the suspension to a child, a dosing spoon or medicine dropper should be used, and it is important to rinse the spoon or dropper after each use. Patients should follow their doctor’s instructions regarding the appropriate amount to use and the duration of treatment required for their child, and any unused medicine should be discarded.

Lastly, patients should be informed that amoxicillin and clavulanate potassium for oral suspension contains a penicillin-class drug, which may cause allergic reactions in some individuals.

Storage and Handling

The dry powder formulation is supplied in its original container and should be stored at a temperature range of 20º to 25ºC (68º to 77ºF), in accordance with USP Controlled Room Temperature guidelines. Once reconstituted, the suspension must be stored under refrigeration. It is important to discard any unused suspension after 10 days to ensure safety and efficacy. Additionally, this product should be kept out of the reach of children to prevent accidental ingestion.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Amoxicillin and Clavulanate Potassium as submitted by Aidarex Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)