Amoxicillin/Clavulanate 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 alternatively, 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 utilize 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 is necessary to rule out CDAD.

In patients with mononucleosis, the use of amoxicillin and clavulanate potassium may lead to the development of a skin rash. Therefore, it is advised to avoid prescribing this medication to individuals diagnosed with mononucleosis.

Additionally, healthcare providers should remain vigilant for the possibility of superinfections due to overgrowth of fungal or bacterial pathogens during therapy with amoxicillin and clavulanate potassium.

Side Effects

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 been reported, necessitating immediate discontinuation of amoxicillin and clavulanate potassium upon occurrence. These include serious hypersensitivity reactions, which may 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 noted; if this occurs, discontinuation of the medication and appropriate therapy should be initiated. Hepatic dysfunction and cholestatic jaundice are serious concerns, with discontinuation recommended if signs or symptoms of hepatitis arise, alongside monitoring of liver function tests in patients with pre-existing hepatic impairment. Clostridioides difficile-associated diarrhea (CDAD) should be evaluated in patients presenting with diarrhea.

Patients with mononucleosis who receive amoxicillin and clavulanate potassium may develop skin rashes, and its use is contraindicated in these individuals. Additionally, the potential for superinfections with fungal or bacterial pathogens should be considered during therapy due to the risk of overgrowth.

Important notes 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. 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. Patients should be monitored for dermatological reactions when these medications are prescribed together.

Additionally, amoxicillin and clavulanate potassium may reduce the efficacy of oral contraceptives. Patients using hormonal contraceptives should be advised to consider alternative or additional contraceptive methods during and after 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 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. 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 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, 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 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 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.

In cases of severe overdosage, hemodialysis may be employed to facilitate the removal of amoxicillin and clavulanate potassium from the circulation. Healthcare professionals should remain vigilant in monitoring renal function and managing any complications that may arise from 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 negative in both 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 the maximum recommended adult human oral dose of clavulanate (125 mg every 8 hours), when adjusted for body surface area.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, several events have been identified during the postmarketing use of amoxicillin and clavulanate potassium. These events were reported voluntarily from a population of unknown size, and estimates of frequency cannot be made. They have been included based on their seriousness, frequency of reporting, or potential causal connection to the medication.

Gastrointestinal events include drug-induced enterocolitis syndrome (DIES), indigestion, gastritis, stomatitis, glossitis, black “hairy” tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis. Symptoms of pseudomembranous colitis may occur during or after antibacterial treatment.

Immune-related events encompass hypersensitivity reactions, anaphylactic/anaphylactoid reactions (including shock), angioedema, serum sickness-like reactions (characterized by urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), and hypersensitivity vasculitis.

Skin and appendage reactions include rashes, pruritus, urticaria, erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), exfoliative dermatitis, and linear IgA bullous dermatosis.

Hepatic dysfunction has been reported, including hepatitis and cholestatic jaundice, as well as increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase. These events have been observed more frequently in elderly patients, males, or those undergoing prolonged treatment. Histologic findings on liver biopsy have shown predominantly cholestatic, hepatocellular, or mixed cholestatic hepatocellular changes. Signs and symptoms of hepatic dysfunction may arise during or several weeks after therapy has been discontinued. While the hepatic dysfunction can be severe, it is usually reversible, although fatalities have been reported.

Renal events include interstitial nephritis, hematuria, and crystalluria.

Hemic and lymphatic system reactions consist of anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis. These reactions are typically reversible upon discontinuation of therapy and are believed to be hypersensitivity phenomena. Thrombocytosis was noted in less than 1% of patients treated with amoxicillin and clavulanate potassium. Additionally, there have been reports of increased prothrombin time in patients receiving amoxicillin and clavulanate potassium alongside anticoagulant therapy.

Central nervous system events include agitation, anxiety, behavioral changes, aseptic meningitis, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity.

Miscellaneous reports include tooth discoloration (brown, yellow, or gray staining), primarily in pediatric patients. Discoloration was often reduced or eliminated with brushing or dental cleaning in most cases.

Patient Counseling

Healthcare providers should advise patients that amoxicillin and clavulanate potassium tablets can be taken without regard to meals; however, they may enhance the absorption of clavulanate potassium when administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, it is recommended that patients take the tablets at the beginning of a meal.

Providers should emphasize the importance of using amoxicillin and clavulanate potassium tablets only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. This approach is crucial to reduce the development of drug-resistant bacteria and to maintain the effectiveness of this medication and other antibacterial drugs.

When culture and susceptibility information is available, healthcare providers should consider these results in selecting or modifying antibacterial therapy. In cases where such data is not available, local epidemiology and susceptibility patterns may assist in the empiric selection of therapy.

Additionally, providers should inform patients that if susceptibility test results indicate susceptibility to amoxicillin, showing no beta-lactamase production, amoxicillin and clavulanate potassium tablets should not be used. This information is vital for ensuring the appropriate use of the medication and for optimizing treatment outcomes.

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 Aurobindo Pharma Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)