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. Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus, with a molecular formula of C8H8KNO5 and a molecular weight of 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, 500 mg, or 875 mg of amoxicillin USP as the trihydrate, and 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 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, patients with a history of cholestatic jaundice or hepatic dysfunction associated with the use of amoxicillin and clavulanate potassium tablets should not use this medication.

Warnings and Precautions

Serious hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving amoxicillin and clavulanate potassium. In the event of such a reaction, it is imperative to discontinue the medication immediately.

Severe Cutaneous Adverse Reactions (SCAR) may occur during treatment. Healthcare professionals should monitor patients closely for any signs of rash, and if the rash progresses, discontinuation of amoxicillin and clavulanate potassium is warranted.

Drug-induced enterocolitis syndrome (DIES) has been associated with the use of amoxicillin, a component of this combination therapy. Should symptoms indicative of DIES arise, it is essential to discontinue the medication and initiate appropriate therapeutic measures.

Patients with hepatic dysfunction are at increased risk for cholestatic jaundice. It is crucial to monitor liver function tests in these individuals, and if any signs or symptoms of hepatitis develop, amoxicillin and clavulanate potassium should be discontinued.

Clostridioides difficile-associated diarrhea (CDAD) is a potential complication of antibiotic therapy. If a patient presents with diarrhea during treatment, a thorough evaluation for CDAD is necessary.

In patients diagnosed with mononucleosis, the use of amoxicillin and clavulanate potassium is contraindicated due to the risk of developing a skin rash.

Additionally, healthcare providers should remain vigilant for the possibility of superinfections with fungal or bacterial pathogens during therapy, as overgrowth may occur. Regular assessment of the patient's clinical status is recommended to address any emerging infections promptly.

Side Effects

Common adverse reactions observed in patients include diarrhea or loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%), and vaginitis (1%).

Serious adverse reactions necessitate immediate attention and discontinuation of amoxicillin and clavulanate potassium if they occur. These include serious hypersensitivity reactions, which can be fatal, and severe cutaneous adverse reactions (SCAR), where close monitoring is required, and discontinuation is advised if the rash progresses. Drug-induced enterocolitis syndrome (DIES) has also been reported; in such cases, discontinuation of the medication and appropriate therapy should be initiated. Hepatic dysfunction and cholestatic jaundice may occur, and patients should be monitored for signs or symptoms of hepatitis, with discontinuation of the drug if these arise. Clostridioides difficile-associated diarrhea (CDAD) should be evaluated if diarrhea occurs. Additionally, patients with mononucleosis who receive this medication may develop skin rashes, and its use should be avoided in these individuals. 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. Similarly, a history of cholestatic jaundice or hepatic dysfunction associated with this medication is a significant concern. 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 interactions that may affect the pharmacokinetics of the drugs involved.

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 combination.

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, 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 a lactating mother.

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 immediately. Regular assessment of liver function is essential to ensure the safety and efficacy of the therapy in this patient population.

Overdosage

In the event of an overdosage, it is imperative to discontinue the medication immediately. Symptomatic treatment should be initiated, and supportive measures should be implemented as necessary to ensure patient safety and comfort.

A prospective study indicates that overdosages of amoxicillin below 250 mg/kg are generally not associated with significant clinical symptoms. However, caution is warranted, as more severe outcomes have been documented. Notably, interstitial nephritis leading to oliguric renal failure has been reported following overdosage with amoxicillin and clavulanate potassium. Additionally, crystalluria, which can result in renal failure, has been observed in both adult and pediatric patients after overdosage with these agents.

To mitigate the risk of crystalluria, 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 impaired renal function may experience higher blood levels of amoxicillin and clavulanate potassium due to decreased renal clearance.

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. Notably, severe cutaneous adverse reactions (SCAR) have been documented. Additionally, instances of diarrhea, including cases characterized by watery and bloody stools, have been reported, occurring as late as two or more months following the last dose of the antibacterial.

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 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 while it is common to feel improvement early in the treatment, 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 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 a tight container, adhering to USP guidelines. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature standards.

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. Additionally, the product must be kept 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 REMEDYREPACK INC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)