Amoxicillin/Clavulanate potassium

Description

Amoxicillin and clavulanate potassium tablets, USP, are oral antibacterial formulations that combine amoxicillin, a penicillin analog, with clavulanate potassium, a beta-lactamase inhibitor. Amoxicillin is derived from 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, produced through the fermentation of Streptomyces clavuligerus, has a molecular formula of C8H8KNO5 and a molecular weight of 237.25. Its chemical structure is potassium (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo3.2.0-heptane-2-carboxylate.

The tablets are available in three strengths: 250 mg/125 mg, 500 mg/125 mg, and 875 mg/125 mg. Each tablet contains the following: 250 mg, 500 mg, or 875 mg of amoxicillin as the trihydrate, and 125 mg of clavulanic acid, which is equivalent to 149 mg of clavulanate potassium. Each tablet also contains 0.63 mEq of potassium.

Inactive ingredients include colloidal silicon dioxide, ethylcellulose, hypromellose, magnesium stearate, microcrystalline cellulose, propylene glycol, sodium starch glycolate, talc, 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. This approach is essential to reduce the development of drug-resistant bacteria and to maintain the effectiveness of this drug and other antibacterial agents.

There are no teratogenic or nonteratogenic effects associated with the use of amoxicillin and clavulanate potassium tablets.

Dosage and Administration

For adults and pediatric patients weighing greater than 40 kg, the recommended dosage is either 500 mg or 875 mg administered every 12 hours, or 250 mg or 500 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/5 mL oral suspension for this population.

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

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 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.

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 impairment require careful monitoring for signs of hepatic dysfunction and cholestatic jaundice. Liver function tests should be conducted regularly, 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 is necessary to rule out CDAD.

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.

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 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 considerations include a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to amoxicillin and clavulanate potassium or other beta-lactams, including penicillins and cephalosporins. A history of cholestatic jaundice or hepatic dysfunction associated with amoxicillin and clavulanate potassium is also significant. Furthermore, 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 tablets 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 tablets 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 management.

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

Additionally, amoxicillin and clavulanate potassium tablets may reduce the efficacy of oral contraceptives. Patients should be advised to consider alternative or additional contraceptive measures during treatment to prevent unintended pregnancy.

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 these formulations in children is derived from studies involving amoxicillin and clavulanate potassium tablets in adults, supplemented by data from a study specifically examining the oral suspension in 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 aged less than 12 weeks (less than 3 months) 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. 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, which cannot be entirely ruled out based on current data.

Amoxicillin and clavulanate potassium is primarily excreted through the kidneys, and the risk of adverse reactions may be heightened 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. It is advisable to monitor renal function in elderly patients to ensure appropriate dosing and minimize the risk of adverse effects.

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 fetal harm 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, amoxicillin and clavulanate potassium should be used during pregnancy only if clearly needed. Healthcare professionals are advised to weigh the potential benefits against the 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, discontinuation of treatment is recommended. It is essential to assess liver function regularly to ensure patient safety and to make any necessary adjustments to the treatment regimen.

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. However, it is essential to remain vigilant for potential adverse effects.

Notably, interstitial nephritis leading to oliguric renal failure has been documented in patients following an overdosage of amoxicillin and clavulanate potassium. Additionally, crystalluria, which in some instances has resulted in renal failure, has been reported in both adult and pediatric populations after overdosage with these agents.

To mitigate the risk of crystalluria associated with amoxicillin and clavulanate potassium, it is crucial to maintain adequate fluid intake and promote diuresis. This approach helps to reduce the likelihood of renal complications. Renal impairment observed in these cases appears to be reversible upon cessation of the drug.

It is important to note that patients with impaired renal function may experience elevated 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 the drug from circulation.

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

No specific postmarketing experience details are available. As such, there are no additional adverse events or rare case reports to summarize at this time.

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 its original container to ensure integrity and stability. It is essential to store the product 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 efficacy and prevent contamination. Additionally, it is crucial 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 Micro Labs Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)