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 of amoxicillin is C16H19N3O5S•3H2O, with a molecular weight of 419.46 g/mol. Chemically, 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. The molecular formula of clavulanate potassium is C8H8KNO5, and its molecular weight is 237.25 g/mol. Chemically, clavulanate potassium is potassium (Z)(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo3.2.0-heptane-2-carboxylate.

Each tablet contains 250 mg of amoxicillin USP as the trihydrate, and 125 mg of clavulanic acid (equivalent to 149 mg of clavulanate potassium). Additionally, each tablet is available in strengths of 500 mg and 875 mg of amoxicillin USP as the trihydrate, both containing 125 mg of clavulanic acid (equivalent to 149 mg of clavulanate potassium). Each tablet of amoxicillin and clavulanate contains 0.63 mEq 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.

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 exclusively for the treatment or prevention of infections that are proven or strongly suspected to be caused by bacteria.

There are no teratogenic or nonteratogenic effects associated with the use of this medication.

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.

For 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.

In 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 age group.

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, these tablets should not be administered to individuals with a history of cholestatic jaundice or hepatic dysfunction associated with their use.

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.

Healthcare professionals should remain vigilant for Severe Cutaneous Adverse Reactions (SCAR) during treatment. Close monitoring is essential, and the medication should be discontinued if any rash progresses.

Drug-induced enterocolitis syndrome (DIES) has been reported in patients receiving amoxicillin, a component of amoxicillin and clavulanate potassium tablets. Should this syndrome occur, it is crucial to discontinue the medication and initiate appropriate therapeutic measures.

Patients with hepatic dysfunction may experience cholestatic jaundice. In such cases, the medication should be discontinued if any signs or symptoms of hepatitis arise. Additionally, liver function tests should be monitored in patients with pre-existing hepatic impairment to ensure safety.

Clostridioides difficile-associated diarrhea (CDAD) is a potential complication of antibiotic therapy. If a patient develops diarrhea, a thorough evaluation is warranted to rule out this condition.

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.

Finally, healthcare providers should be aware of the possibility of superinfections due to overgrowth of fungal or bacterial pathogens during therapy. Monitoring for signs of such infections is recommended throughout the course of treatment.

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, alongside monitoring 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 who are treated with amoxicillin and clavulanate potassium may develop skin rashes, and its use is contraindicated in these individuals. The potential for superinfections with fungal or bacterial pathogens should also be considered during therapy.

Important notes regarding patient history include a prior serious hypersensitivity reaction to amoxicillin and clavulanate potassium or other beta-lactams, as well as a history of cholestatic jaundice or hepatic dysfunction associated with this medication. Interstitial nephritis resulting in oliguric renal failure has been reported following overdosage, as has 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 with probenecid is not recommended due to potential pharmacokinetic interactions that may affect the therapeutic efficacy of the antibiotic.

When used concurrently with oral anticoagulants, amoxicillin and clavulanate potassium may lead to an increased prolongation of prothrombin time. It is advisable to monitor prothrombin time closely in patients receiving this combination to ensure appropriate anticoagulation levels.

The concomitant use of amoxicillin and clavulanate potassium with allopurinol has been associated with an increased risk of rash. Clinicians should be vigilant for dermatological reactions in patients receiving both medications.

Additionally, amoxicillin and clavulanate potassium may reduce the efficacy of oral contraceptives. Patients should be counseled on the potential need for alternative or additional contraceptive methods during treatment with this antibiotic.

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 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 should be adjusted for pediatric patients under 12 weeks (less than 3 months) of age to ensure safety and efficacy.

Geriatric Use

In clinical studies involving amoxicillin and clavulanate potassium, 32% of the 3,119 patients analyzed were aged 65 years or older, and 14% were aged 75 years or older. No overall differences in safety or effectiveness were observed between these elderly patients and their younger counterparts. However, it is important to note that while clinical experience has not identified significant differences in responses between elderly and younger patients, greater sensitivity in some older individuals cannot be ruled out.

Given that this medication is substantially excreted by the kidneys, the risk of adverse reactions may be heightened 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 (2:1 ratio formulation) at oral doses up to 1200 mg/kg/day demonstrated no evidence of harm to the fetus attributable to the drug. 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, this medication should be used during pregnancy only if clearly needed. Healthcare professionals are advised to weigh the potential benefits against any possible risks when considering the use of amoxicillin and clavulanate potassium in 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

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 of these patients.

Hepatic Impairment

Patients with hepatic impairment should be closely monitored for liver function tests. In the event of hepatic dysfunction or the development of cholestatic jaundice, it is recommended to discontinue treatment if signs or symptoms of hepatitis occur. Regular 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. 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 cases of interstitial nephritis leading to oliguric renal failure have been documented following overdosage with amoxicillin and clavulanate potassium. Additionally, crystalluria has been reported, which in some instances has resulted in renal failure in both adult and pediatric patients.

To mitigate the risk of crystalluria associated with amoxicillin and clavulanate potassium overdosage, 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 in these cases appears to be reversible upon cessation of the drug.

Patients with pre-existing renal impairment may experience higher blood levels of amoxicillin and clavulanate potassium due to decreased renal clearance. In such cases, hemodialysis may be employed to facilitate the removal of the drug from circulation, thereby aiding in the management of overdosage.

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 4:1 ratio formulation of amoxicillin and clavulanate 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, 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 in the dominant lethal assay in mice.

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

In terms of reproductive toxicity, the 2:1 ratio formulation of amoxicillin and clavulanate potassium administered at oral doses of up to 1,200 mg/kg/day did not 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 higher than 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 product. Severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported. Additionally, hepatic dysfunction, characterized by cholestatic jaundice and hepatitis, has been observed.

Hypersensitivity reactions, such as anaphylaxis and angioedema, have also been documented. Gastrointestinal adverse reactions, including diarrhea, with specific cases of Clostridium difficile-associated diarrhea, have been noted. Renal adverse reactions, particularly interstitial nephritis, have been reported in the postmarketing setting.

Hematologic reactions, including thrombocytopenia and leukopenia, have been observed. Furthermore, there have been reports of seizures in patients with renal impairment who received high doses of amoxicillin and clavulanate potassium.

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 product. Patients should be made aware of the signs and symptoms of serious skin manifestations. 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 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 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 harder to treat with amoxicillin and clavulanate potassium tablets or other antibacterial drugs.

Storage and Handling

The product is supplied in a tight container, ensuring compliance with USP standards. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines.

Patients are advised to keep the product in a closed container to maintain its integrity. It is essential to use the product only if the inner seal is intact, ensuring safety and efficacy. Additionally, the product must 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 REMEDYREPACK INC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)