Amoxicillin/Clavulanate potassium

Description

Amoxicillin and clavulanate potassium tablets, amoxicillin and clavulanate potassium for oral suspension, and amoxicillin and clavulanate potassium tablets (chewable) are oral antibacterial combinations. The semisynthetic antibiotic amoxicillin, USP is an analog of ampicillin, derived from the basic penicillin nucleus, 6–aminopenicillanic acid. Chemically, amoxicillin, USP 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, with a molecular formula of C16H19N3O5S•3H2O and a molecular weight of 419.45. Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. Chemically, clavulanate potassium, USP is potassium (Z)–(2R,5R)–3–(2-hydroxyethylidene)–7-oxo-4-oxa-1-azabicyclo3.2.0-heptane-2-carboxylate, with a molecular formula of C8H8KNO5 and a molecular weight of 237.25.

Each tablet contains 500 mg of amoxicillin, USP as the trihydrate, and 125 mg of clavulanic acid (equivalent to 149 mg of clavulanate potassium). Each tablet also contains 875 mg of amoxicillin, USP as the trihydrate, and 125 mg of clavulanic acid (equivalent to 149 mg of clavulanate potassium). Following reconstitution, each 5 mL of oral suspension contains 200 mg of amoxicillin, USP as the trihydrate, and 28.5 mg of clavulanic acid (equivalent to 34 mg of clavulanate potassium), or 400 mg of amoxicillin, USP as the trihydrate, and 57 mg of clavulanic acid (equivalent to 68 mg of clavulanate potassium). Each chewable tablet contains 200 mg of amoxicillin, USP as the trihydrate, and 28.5 mg of clavulanic acid (equivalent to 34 mg of clavulanate potassium), or 400 mg of amoxicillin, USP as the trihydrate, and 57 mg of clavulanic acid (equivalent to 68 mg of clavulanate potassium). Each tablet of amoxicillin and clavulanate potassium tablets, USP contains 0.63 mEq potassium. Each 5 mL of reconstituted 200 mg/28.5 mg oral suspension contains 0.14 mEq potassium, and each 5 mL of reconstituted 400 mg/57 mg oral suspension contains 0.29 mEq potassium. Each 200 mg/28.5 mg chewable tablet contains 0.14 mEq potassium, and each 400 mg/57 mg chewable tablet contains 0.29 mEq potassium.

Inactive ingredients for Amoxicillin and Clavulanate Potassium Tablets, USP include colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, sodium starch glycolate, titanium dioxide, and triacetin. Inactive ingredients for Amoxicillin and Clavulanate Potassium for Oral Suspension, USP include artificial raspberry powder, aspartame, citric acid, colloidal silicon dioxide, mannitol, hypromellose, natural orange flavor, sodium citrate, sodium saccharin, and xanthan gum. Inactive ingredients for Amoxicillin and Clavulanate Potassium Tablets, USP (Chewable) include aspartame, colloidal silicon dioxide, FD&C Red #40 lake, magnesium stearate, mannitol, microcrystalline cellulose, SA84 artificial ripe banana flavor, and artificial cherry flavor powder.

Uses and Indications

Amoxicillin and clavulanate potassium tablets, amoxicillin and clavulanate potassium for oral suspension, and amoxicillin and clavulanate potassium tablets (chewable) 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.

This drug should be used only to treat or prevent 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 as well as other antibacterial drugs.

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.

Healthcare professionals should ensure that the appropriate dosing regimen is 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/clavulanate potassium or 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/clavulanate potassium.

Warnings and Precautions

Serious hypersensitivity reactions, including fatal outcomes, have been associated with the use of amoxicillin and clavulanate potassium formulations. In the event of such a reaction, it is imperative to discontinue the medication immediately.

Severe Cutaneous Adverse Reactions (SCAR) may occur; therefore, patients should be monitored closely for any signs of rash. If the rash progresses, discontinuation of the medication is warranted.

Drug-induced enterocolitis syndrome (DIES) has been reported in patients receiving amoxicillin. Should this syndrome manifest, it is essential to discontinue the use of amoxicillin and clavulanate potassium tablets, oral suspension, or chewable tablets, and to initiate appropriate therapeutic measures.

Patients with hepatic dysfunction or those exhibiting signs of cholestatic jaundice should be closely monitored. If symptoms of hepatitis arise, discontinuation of the medication is necessary. Liver function tests should be conducted regularly in patients with pre-existing hepatic impairment.

Clostridioides difficile–associated diarrhea (CDAD) is a potential complication; therefore, healthcare professionals should evaluate patients who present with diarrhea during treatment.

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.

Additionally, the possibility of superinfections due to overgrowth of fungal or bacterial pathogens should be considered during the course of therapy. Regular assessment of the patient's condition is recommended to mitigate these risks.

Side Effects

Patients receiving amoxicillin and clavulanate potassium may experience a range of adverse reactions, which can be categorized into common and serious 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%). These reactions are generally mild and may not require discontinuation of therapy.

Serious adverse reactions, although less frequent, necessitate immediate attention. Patients may experience serious hypersensitivity reactions, including anaphylaxis and Stevens–Johnson syndrome, which require discontinuation of amoxicillin and clavulanate potassium products. Severe cutaneous adverse reactions (SCAR) have also been reported; patients should be monitored closely, and treatment should be discontinued if any rash progresses. Drug-induced enterocolitis syndrome (DIES) has been associated with the use of amoxicillin, and if this occurs, discontinuation of the medication and appropriate therapy should be initiated.

Hepatic dysfunction and cholestatic jaundice have been noted, with recommendations to discontinue treatment if signs or symptoms of hepatitis arise. Liver function tests should be monitored in patients with pre-existing hepatic impairment. Clostridioides difficile-associated diarrhea (CDAD) is another serious concern; patients presenting with diarrhea should be evaluated for this condition.

Additionally, patients with mononucleosis who receive amoxicillin and clavulanate potassium may develop skin rashes, and the use of this medication in such patients should be avoided. 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 to amoxicillin/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

Coadministration of amoxicillin/clavulanate potassium with probenecid is not recommended due to potential interactions that may affect therapeutic outcomes.

When used concurrently with oral anticoagulants, amoxicillin/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 use of amoxicillin/clavulanate potassium alongside allopurinol has been associated with an elevated risk of rash. Clinicians should be vigilant for dermatological reactions in patients receiving both medications.

Additionally, amoxicillin/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 these formulations in children is derived from studies involving adults, supplemented by data from a study of 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 for oral suspension and chewable tablets should be adjusted for pediatric patients under 12 weeks of age (less than 3 months).

Geriatric Use

In clinical studies involving amoxicillin/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 greater sensitivity to the drug may be present in some older individuals, although this has not been definitively established in reported clinical experiences.

Amoxicillin/clavulanate potassium is primarily excreted by 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/clavulanate potassium (2:1 ratio formulation) at oral doses up to 1200 mg/kg/day demonstrated no evidence of teratogenic effects on the fetus. 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 outcomes, amoxicillin/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/clavulanate potassium by nursing mothers may lead to sensitization of breastfed infants. Therefore, caution should be exercised when administering amoxicillin/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, discontinuation of treatment is recommended. It is essential to assess liver function regularly to ensure the safety and efficacy of the therapy in this population.

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, higher doses may lead to serious complications. Notably, interstitial nephritis resulting in oliguric renal failure has been documented following overdosage with amoxicillin/clavulanate potassium. Additionally, crystalluria has been reported, which in some instances has progressed to 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 important to note that patients with pre-existing renal impairment may experience elevated blood levels of amoxicillin/clavulanate potassium due to decreased renal clearance.

For patients experiencing severe overdosage, hemodialysis may be employed to facilitate the removal of amoxicillin/clavulanate potassium from circulation. Continuous monitoring and appropriate management are crucial to ensure patient safety and recovery.

Nonclinical Toxicology

Long-term studies in animals have not been conducted to assess the carcinogenic potential of amoxicillin/clavulanate potassium. In mutagenicity testing, amoxicillin/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 formulations, including tablets, oral suspension, and chewable tablets (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 approximately nine times the maximum recommended adult human oral dose of clavulanate (125 mg every 8 hours), based on body surface area calculations.

Postmarketing Experience

Postmarketing experience has identified serious skin manifestations, including severe cutaneous adverse reactions (SCAR), in patients receiving amoxicillin and clavulanate potassium. Patients are advised to discontinue the medication immediately and report any signs or symptoms of skin rash, mucosal lesions, or other indications of hypersensitivity.

Additionally, diarrhea, which may present as watery or bloody stools, has been reported as a common adverse reaction. This gastrointestinal effect can occur even 2 or more months after the cessation of antibacterial treatment. Patients experiencing severe diarrhea or symptoms lasting more than 2 or 3 days are encouraged to contact their physician promptly.

Patient Counseling

Patients should be informed that amoxicillin and clavulanate potassium tablets, amoxicillin and clavulanate potassium for oral suspension, and amoxicillin and clavulanate potassium tablets (chewable) 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 these medications contain a penicillin class drug product. 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, they should be informed that watery and bloody stools may occur, even up to two months after completing the 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, amoxicillin and clavulanate potassium for oral suspension, and amoxicillin and clavulanate potassium tablets (chewable), are effective only against bacterial infections and do not treat viral infections, such as the common cold. Patients should be advised to adhere strictly to the prescribed regimen, as skipping doses or failing to complete the full course of therapy may reduce the effectiveness of treatment and increase the risk of bacterial resistance.

Patients should be instructed 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 medication should be discarded.

Storage and Handling

The product is supplied in original containers that are tight and light-resistant, as defined by the USP, and equipped with a child-resistant closure where 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.

Once reconstituted, the suspension must be stored under refrigeration. Any unused suspension should be discarded after 10 days to ensure safety and efficacy. It is crucial to keep this product, along with all medications, out of the reach of children.

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

View full prescribing information (PDF)