Amoxicillin/Clavulanate potassium

Description

Amoxicillin and clavulanate potassium tablets, USP are an oral antibacterial combination consisting of amoxicillin and the beta-lactamase inhibitor, clavulanate potassium (the potassium salt of clavulanic acid). Amoxicillin USP is an analog of ampicillin, derived from the basic penicillin nucleus, 6-aminopenicillanic acid. The molecular formula for amoxicillin is C16H19N3O5S•3H2O, with a molecular weight of 419.46 g/mol. Chemically, amoxicillin is described 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. The molecular formula for clavulanate potassium is C8H8KNO5, with a molecular weight of 237.25 g/mol. Clavulanate potassium is chemically defined as potassium (Z)(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo3.2.0-heptane-2-carboxylate. Each tablet contains 250 mg, 500 mg, or 875 mg of amoxicillin USP as the trihydrate, along with 125 mg of clavulanic acid (equivalent to 149 mg of clavulanate potassium). Inactive ingredients include colloidal silicon dioxide, crospovidone, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, surelease clear (aqueous ethyl cellulose dispersion), and titanium dioxide. Each tablet of amoxicillin and clavulanate contains 0.63 mEq potassium.

Uses and Indications

Amoxicillin and clavulanate potassium tablets are indicated for the treatment of the following infections in adults and pediatric patients: lower respiratory tract infections, acute bacterial otitis media, sinusitis, skin and skin structure infections, and urinary tract infections. These tablets should be utilized only for the treatment or prevention of infections that are proven or strongly suspected to be caused by bacteria.

Limitations of use include the recommendation that amoxicillin and clavulanate potassium tablets should not be used when susceptibility test results indicate susceptibility to amoxicillin, particularly in cases where there is no beta-lactamase production.

No teratogenic or nonteratogenic effects have been reported.

Dosage and Administration

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

In pediatric patients aged 12 weeks (3 months) and older, the dosage ranges from 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 dose.

For neonates and infants less than 12 weeks of age, the recommended dosage is 30 mg/kg/day, divided and administered every 12 hours, based on the amoxicillin component. It is advised to use the 125 mg/31.25 mg per 5 mL oral suspension for this population.

Healthcare professionals should ensure that the appropriate dosing regimen is selected based on the patient's weight, age, and clinical condition.

Contraindications

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

Warnings and Precautions

Serious hypersensitivity reactions, including those that may be fatal, have been associated with the use of amoxicillin and clavulanate potassium. In the event of such a reaction, it is imperative to discontinue the medication immediately (5.1).

Severe Cutaneous Adverse Reactions (SCAR) have also been reported. Healthcare professionals should monitor patients closely for any signs of rash, and if the rash progresses, discontinuation of amoxicillin and clavulanate potassium is necessary (5.2).

Drug-induced enterocolitis syndrome (DIES) has been documented in patients using amoxicillin, a component of this medication. Should symptoms of DIES arise, it is crucial to discontinue the use of amoxicillin and clavulanate potassium and initiate appropriate therapeutic measures (5.3).

Patients with hepatic dysfunction or those exhibiting signs of cholestatic jaundice should be closely monitored. If any signs or symptoms of hepatitis occur, the medication must be discontinued. Additionally, liver function tests should be performed in patients with pre-existing hepatic impairment to ensure safety (5.4).

Clostridioides difficile-associated diarrhea (CDAD) is a potential complication that requires evaluation if diarrhea develops during treatment. Clinicians should remain vigilant for this condition (5.5).

Amoxicillin and clavulanate potassium should be avoided in patients with mononucleosis, as these individuals are at risk of developing a skin rash upon administration of the medication (5.6).

Finally, the possibility of superinfections due to overgrowth of fungal or bacterial pathogens should be considered during the course of therapy with amoxicillin and clavulanate potassium (5.7).

Side Effects

Patients receiving amoxicillin and clavulanate potassium 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 have also been reported. These include serious hypersensitivity reactions, which may be fatal; therefore, amoxicillin and clavulanate potassium should be discontinued immediately if such a reaction occurs. Severe cutaneous adverse reactions (SCAR) require close monitoring, and discontinuation is advised if any rash progresses. Drug-induced enterocolitis syndrome (DIES) necessitates discontinuation of the medication and appropriate therapeutic intervention if it occurs. Hepatic dysfunction and cholestatic jaundice have been noted, with recommendations to discontinue treatment if signs or symptoms of hepatitis arise, and to monitor liver function tests in patients with pre-existing hepatic impairment. Clostridioides difficile-associated diarrhea (CDAD) should be evaluated if diarrhea develops during treatment. Additionally, patients with mononucleosis should avoid the use of amoxicillin and clavulanate potassium due to the risk of skin rash. The potential for superinfections with fungal or bacterial pathogens should also be considered during therapy.

It is important to note that a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to amoxicillin and clavulanate potassium or other beta-lactams (including penicillins or cephalosporins) may increase the risk of adverse reactions. A history of cholestatic jaundice or hepatic dysfunction associated with amoxicillin and clavulanate potassium is also a significant consideration. Furthermore, interstitial nephritis resulting in oliguric renal failure has been reported following overdosage of amoxicillin and clavulanate potassium. Crystalluria, which in some cases has led to renal failure, has been documented after overdosage in both adult and pediatric patients.

Drug Interactions

Co-administration of amoxicillin and clavulanate potassium with probenecid is not recommended due to potential pharmacokinetic interactions that may affect the efficacy and safety of the treatment.

When used concurrently with oral anticoagulants, amoxicillin and clavulanate potassium may lead to an increased prolongation of prothrombin time. Clinicians should monitor prothrombin time closely and consider dosage adjustments of the anticoagulant as necessary to maintain therapeutic levels.

The concomitant use of amoxicillin and clavulanate potassium with allopurinol has been associated with an increased risk of rash. Patients should be monitored for dermatological reactions, and if a rash occurs, discontinuation of one or both medications should be considered.

Additionally, amoxicillin and clavulanate potassium may reduce the efficacy of oral contraceptives. Patients using hormonal contraceptives should be advised to consider alternative or additional non-hormonal contraceptive methods 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 for oral suspension and chewable tablets have been established in pediatric patients. Evidence supporting the use of amoxicillin and clavulanate potassium tablets in this population is derived from studies conducted in adults, supplemented by data from a study involving pediatric patients aged 2 months to 12 years with acute otitis media.

In neonates and young infants, renal function is incompletely developed, which may lead to delayed elimination of amoxicillin; however, the elimination of clavulanate remains unaffected in this age group. Therefore, dosing of amoxicillin and clavulanate potassium 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, 32% of the 3,119 patients analyzed were aged 65 years or older, with 14% being 75 years or older. Overall, no significant differences in safety or effectiveness were observed between elderly patients and their younger counterparts. However, it is important to note that greater sensitivity to the drug may be present in some older individuals, although this has not been definitively established through clinical experience.

Amoxicillin and clavulanate potassium is primarily excreted via the kidneys, which raises concerns regarding the potential for adverse reactions in patients with impaired renal function. Given that geriatric patients are more likely to experience decreased renal function, careful consideration should be given to dose selection in this population. Monitoring of renal function may be beneficial to ensure safe and effective use of the medication in elderly patients.

Pregnancy

Pregnancy Category B. Reproduction studies conducted in pregnant rats and mice administered amoxicillin and clavulanate potassium (2:1 ratio formulation) at oral doses up to 1200 mg/kg/day demonstrated no evidence of teratogenic effects or harm to the fetus. The doses of amoxicillin in these studies were approximately 4 and 2 times the maximum recommended adult human oral dose (875 mg every 12 hours), while the doses of clavulanate were approximately 9 and 4 times the maximum recommended adult human oral dose (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 studies in predicting human outcomes, amoxicillin and clavulanate potassium 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 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. Symptomatic treatment and supportive measures should be instituted as necessary to manage the patient's condition effectively.

A prospective study indicates that overdosages of amoxicillin below 250 mg/kg are generally not associated with significant clinical symptoms. However, it is important to note that interstitial nephritis leading to oliguric renal failure has been documented in patients following an overdosage of amoxicillin and clavulanate potassium. Additionally, crystalluria has been reported, which in some instances has resulted in renal failure among both adult and pediatric patients.

To mitigate the risk of crystalluria, it is essential to maintain adequate fluid intake and promote diuresis. It should be noted that patients with impaired renal function may experience elevated blood levels of amoxicillin and clavulanate potassium due to decreased renal clearance, necessitating careful monitoring.

In cases of severe overdosage, hemodialysis may be employed to facilitate the removal of amoxicillin and clavulanate potassium from circulation, thereby aiding in the management of the patient's condition.

Nonclinical Toxicology

Long-term studies in animals have not been conducted to assess the carcinogenic potential of amoxicillin and clavulanate potassium. In mutagenicity testing, the combination of amoxicillin and clavulanate potassium (4:1 ratio formulation) demonstrated non-mutagenic properties in both the Ames bacterial mutation assay and the yeast gene conversion assay. However, it exhibited weakly positive results in the mouse lymphoma assay, where the observed trend toward increased mutation frequencies coincided with doses that also resulted in decreased cell survival. The compound was found to be negative in the mouse micronucleus test and in 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 (2:1 ratio formulation) administered at oral doses of up to 1,200 mg/kg/day did not adversely affect fertility or reproductive performance in rats. 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 reported voluntarily or through surveillance programs. These include severe allergic reactions, such as anaphylaxis, and serious skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Instances of hepatic dysfunction have been noted, characterized by jaundice and elevated liver enzymes. Hematologic reactions, including thrombocytopenia, leukopenia, and agranulocytosis, have also been reported.

Gastrointestinal disorders, particularly Clostridium difficile-associated diarrhea, have been observed. Additionally, renal impairment, specifically interstitial nephritis, has been documented. Other reactions include hypersensitivity reactions and angioedema.

Patient Counseling

Patients should be informed that amoxicillin and clavulanate potassium tablets 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 regarding the potential for allergic reactions, as amoxicillin and clavulanate potassium tablets contain a penicillin class drug. Patients should be made aware of the signs and symptoms of serious skin reactions. They should be instructed to discontinue the medication immediately and report any initial signs or symptoms of skin rash, mucosal lesions, or other indications of hypersensitivity.

Patients should also be advised that diarrhea is a common side effect associated with antibacterial medications, typically resolving upon discontinuation of the drug. However, it is crucial to inform patients that they may experience watery and bloody stools, with or without accompanying stomach cramps and fever, even up to two months after completing the course of treatment. If diarrhea is severe or persists for more than 2 to 3 days, patients should contact their physician promptly.

It is essential to counsel patients that antibacterial drugs, including amoxicillin and clavulanate potassium tablets, are effective only against bacterial infections and do not treat viral infections, such as the common cold. When prescribed for a bacterial infection, patients should be reminded that it is common to feel better early in the treatment. However, they must 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 risk of bacterial resistance, making future infections more difficult to treat with amoxicillin and clavulanate potassium tablets or other antibacterial agents.

Storage and Handling

The product is supplied in blister packaging. Each blister must be inspected prior to use; do not use if the blister is torn or broken.

For optimal storage, the product should be maintained at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. It is essential to keep the product out of the reach of children to ensure safety.

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 American Health Packaging. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)