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 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, and its molecular weight is 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 0.63 mEq potassium. Inactive ingredients include colloidal silicon dioxide, ethylcellulose, hypromellose, magnesium stearate, microcrystalline cellulose, propylene glycol, sodium starch glycolate, 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 Amoxicillin and Clavulanate Potassium and other antibacterial agents.

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 875 mg administered every 12 hours. This dosage is based on the amoxicillin component of the formulation.

Healthcare professionals should ensure that the medication is taken at evenly spaced intervals to maintain optimal therapeutic levels. It is advisable to instruct patients to take the medication with or without food, as per individual tolerance and preference.

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 this medication 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 the use of Amoxicillin and Clavulanate Potassium Tablets.

Warnings and Precautions

Serious hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving Amoxicillin and Clavulanate Potassium Tablets. 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, the medication should be discontinued without delay.

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

Patients with hepatic dysfunction or those exhibiting signs of cholestatic jaundice should be closely monitored. If any signs or symptoms of hepatitis develop, Amoxicillin and Clavulanate Potassium Tablets must be discontinued. Regular liver function tests are recommended for patients with pre-existing hepatic impairment to ensure safety during treatment.

Clostridioides difficile-associated diarrhea (CDAD) is a potential complication of antibiotic therapy. Healthcare providers should evaluate patients for CDAD if they present with diarrhea during or following treatment.

In patients diagnosed with mononucleosis, the use of Amoxicillin and Clavulanate Potassium Tablets is contraindicated due to the risk of developing a skin rash.

Additionally, the possibility of superinfections, including those caused by fungal or bacterial pathogens, should be considered during therapy, particularly in patients who may be at risk for overgrowth. Monitoring for signs of superinfection is advised throughout the course of treatment.

Side Effects

Patients receiving Amoxicillin and Clavulanate Potassium Tablets 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 been reported and require immediate attention. These include serious hypersensitivity reactions, which may be fatal; therefore, Amoxicillin and Clavulanate Potassium Tablets should be discontinued if such a reaction occurs. Severe cutaneous adverse reactions (SCAR) necessitate close monitoring, and discontinuation is advised if any rash progresses. Drug-induced enterocolitis syndrome (DIES) has also been noted, and if this condition arises, the medication should be discontinued, and appropriate therapy initiated.

Hepatic dysfunction and cholestatic jaundice are serious concerns, with discontinuation recommended if signs or symptoms of hepatitis develop. Liver function tests should be monitored in patients with pre-existing hepatic impairment. Additionally, Clostridioides difficile-associated diarrhea (CDAD) should be evaluated in patients who present with diarrhea during treatment.

Patients with mononucleosis who are treated with Amoxicillin and Clavulanate Potassium Tablets may develop skin rashes; thus, the use of this medication in such patients is contraindicated. The potential for superinfections with fungal or bacterial pathogens should also be considered during therapy.

Other important considerations include a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to Amoxicillin and Clavulanate Potassium Tablets 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 overdose, 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 levels.

The concomitant use of Amoxicillin and Clavulanate Potassium Tablets with allopurinol has been associated with an increased risk of rash. Patients should be monitored for dermatological reactions when these medications are used together.

Additionally, Amoxicillin and Clavulanate Potassium Tablets may reduce the efficacy of oral contraceptives. Patients relying on hormonal contraceptives should be advised to consider 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 these formulations in children is derived from studies involving Amoxicillin and Clavulanate Potassium Tablets in adults, along with additional data from a study specifically examining the Oral Suspension in pediatric patients aged 2 months to 12 years with acute otitis media.

Dosing considerations are critical for pediatric patients, particularly those under 12 weeks of age (less than 3 months). In this age group, dosing of Amoxicillin and Clavulanate Potassium Tablets should be modified due to the incompletely developed renal function in neonates and young infants, which may result in delayed elimination of amoxicillin. It is important to note that the elimination of clavulanate is not affected in this age group.

Geriatric Use

In clinical studies involving Amoxicillin and Clavulanate Potassium Tablets, 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 greater sensitivity to the drug may be present in some older individuals, although this has not been definitively established in reported clinical experiences.

Amoxicillin and Clavulanate Potassium Tablets are primarily excreted through the kidneys, which raises concerns regarding the potential for adverse reactions in patients with impaired renal function. Given that elderly 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 geriatric patients to mitigate the risk of adverse effects and ensure appropriate dosing.

Pregnancy

Reproduction studies conducted in pregnant rats and mice administered Amoxicillin and Clavulanate Potassium Tablets (2:1 ratio formulation of amoxicillin:clavulanate) at oral doses up to 1200 mg/kg/day demonstrated no evidence of teratogenic effects on 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) for rats and mice, respectively. For clavulanate, the corresponding multiples 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 reproduction studies in predicting human response, Amoxicillin and Clavulanate Potassium Tablets 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 therapy based on the results of these evaluations.

Overdosage

In the event of an overdosage, it is imperative to discontinue the medication immediately and initiate symptomatic treatment along with supportive measures as necessary.

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 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, it is essential to maintain adequate fluid intake and promote diuresis. Renal impairment observed in these cases appears to be reversible upon cessation of the drug. It is also noteworthy that patients with impaired renal function may experience elevated blood levels of amoxicillin and clavulanate potassium due to decreased renal clearance.

For patients experiencing severe overdosage, hemodialysis may be employed to facilitate the removal of amoxicillin and clavulanate potassium from circulation.

Nonclinical Toxicology

Long-term studies in animals have not been conducted to assess the carcinogenic potential of Amoxicillin and Clavulanate Potassium Tablets. In mutagenicity testing, the formulation demonstrated non-mutagenic properties in both the Ames bacterial mutation assay and the yeast gene conversion assay. However, it exhibited a weakly positive response in the mouse lymphoma assay; this observation was associated with increased mutation frequencies at doses that also resulted in decreased cell survival. The formulation was negative in the mouse micronucleus test and the dominant lethal assay in mice.

Potassium clavulanate, when tested independently in the Ames bacterial mutation assay and the mouse micronucleus test, also yielded negative results in both assays.

In terms of reproductive toxicity, Amoxicillin and Clavulanate Potassium Tablets (2:1 ratio formulation) 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

No postmarketing experience details are available in the provided data.

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 for patients to take each dose with a meal or snack to minimize the risk of gastrointestinal upset.

Healthcare providers should counsel patients that Amoxicillin and Clavulanate Potassium Tablets contain a penicillin class drug, which can lead to allergic reactions in some individuals. Patients should be made aware of the signs and symptoms of serious skin manifestations. They should be instructed to discontinue the medication immediately and promptly report any 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 without delay.

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.

Patients should be advised to keep the suspension refrigerated and to shake it well before use. When administering the suspension to a child, a calibrated oral syringe should be used, and it is important to rinse the syringe after each use. Patients should follow their healthcare provider's instructions regarding the appropriate dosage and duration of treatment for their child, and any unused medicine should be discarded.

Storage and Handling

The product is supplied in a tight container that meets the specifications outlined in the United States Pharmacopeia (USP), featuring a child-resistant closure as required. 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. Healthcare professionals should advise patients to keep the product in a closed container to maintain its integrity and efficacy.

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 Hikma Pharmaceuticals USA Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)