Amoxicillin/Clavulanate potassium

Uses and Indications

Amoxicillin and Clavulanate Potassium for Oral Suspension is 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 utilized only 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 this medication.

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.

Pediatric patients aged 12 weeks (3 months) and older should receive a dosage of 25 to 45 mg/kg/day divided into two doses every 12 hours, or 20 to 40 mg/kg/day divided into three doses 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 into two doses every 12 hours, based on the amoxicillin component. It is advised to use the 125 mg/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 and age, and that the method of administration is consistent with the recommended guidelines.

Contraindications

Use of this product is contraindicated in patients with a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to amoxicillin and clavulanate potassium or to other beta-lactams, including penicillins and 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 those that may be fatal, have been associated with the use of amoxicillin and clavulanate potassium. In the event of such a reaction, it is imperative to discontinue the medication immediately.

Severe Cutaneous Adverse Reactions (SCAR) have also been reported. Patients should be monitored closely for any signs of rash, and if the rash progresses, amoxicillin and clavulanate potassium should be discontinued without delay.

Drug-induced enterocolitis syndrome (DIES) has been documented in patients receiving 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 or those exhibiting signs of cholestatic jaundice must be closely monitored. If any signs or symptoms of hepatitis occur, the use of amoxicillin and clavulanate potassium should be discontinued, and liver function tests should be conducted in patients with pre-existing hepatic impairment.

Clostridioides difficile-associated diarrhea (CDAD) is a potential complication of antibiotic therapy. Healthcare professionals should evaluate patients for CDAD if diarrhea develops during treatment.

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

Finally, the possibility of superinfections due to overgrowth of fungal or bacterial pathogens should be considered during the course of therapy with amoxicillin and clavulanate potassium. Continuous assessment of the patient's condition is recommended to address any emerging infections promptly.

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, although less frequent, require immediate attention. These include serious hypersensitivity reactions, which may be fatal; patients should discontinue the medication if such a reaction occurs. Severe cutaneous adverse reactions (SCAR) have also been reported, necessitating close monitoring and discontinuation if the rash progresses. Drug-induced enterocolitis syndrome (DIES) is another serious concern; if this condition arises, amoxicillin and clavulanate potassium should be discontinued, and appropriate therapy should be initiated.

Hepatic dysfunction and cholestatic jaundice have been noted, with recommendations to discontinue the medication 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 presenting with diarrhea during treatment.

Patients with mononucleosis who are treated with amoxicillin and clavulanate potassium may develop skin rashes, and the use of this medication is contraindicated in such cases. 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 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. Clinicians should be vigilant for any 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 these formulations in children is derived from studies involving amoxicillin and clavulanate potassium tablets in 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 pediatric patients, particularly those aged less than 12 weeks (less than 3 months), dosing of amoxicillin and clavulanate potassium should be modified due to the potential for delayed elimination of amoxicillin resulting from incompletely developed renal function in neonates and young infants. It is important to note that the elimination of clavulanate remains unaltered in this age group.

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 excluded 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, 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

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 less than 250 mg/kg of amoxicillin typically do not result in significant clinical symptoms.

However, it is important to note that interstitial nephritis leading to oliguric renal failure has been documented in patients following an overdosage of amoxicillin/clavulanate potassium. Additionally, crystalluria, which in some instances has progressed to renal failure, has been reported in both adult and pediatric patients after overdosage with amoxicillin and clavulanate potassium. 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 also noteworthy that patients with pre-existing renal impairment 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 amoxicillin and clavulanate potassium from the 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 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

No specific postmarketing experience details have been reported. 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 may be taken every 8 hours or every 12 hours, depending on the prescribed dose. Each dose should be taken with a meal or snack to minimize the risk of gastrointestinal upset.

Healthcare providers should counsel patients that amoxicillin and clavulanate potassium contains 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 stop taking amoxicillin and clavulanate potassium immediately and promptly report any initial signs or symptoms of skin rash, mucosal lesions, or other indications of hypersensitivity.

It is important to inform patients that diarrhea is a common side effect associated with antibacterial medications, typically resolving upon discontinuation of the drug. However, patients should be cautioned that they may experience watery and bloody stools (with or without stomach cramps and fever) even as late as 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 without delay.

Patients should be advised that antibacterial drugs, including amoxicillin and clavulanate potassium, 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, it is crucial to 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 also 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 essential 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 dry powder formulation is supplied in its original container and should be stored at a temperature range of 20º to 25ºC (68º to 77ºF), in accordance with USP Controlled Room Temperature guidelines. Once reconstituted, the suspension must be stored under refrigeration. It is important to discard any unused suspension after 10 days to ensure safety and efficacy. Additionally, this product should be kept out of the reach of children to prevent accidental ingestion.

Additional Clinical Information

For laboratory test interpretive criteria and associated test methods and quality control standards recognized by the FDA for amoxicillin and clavulanate potassium, clinicians are directed to refer to the FDA's website at https://www.fda.gov/STIC.

Amoxicillin and clavulanate potassium may be administered every 8 or 12 hours, depending on the prescribed dosage, and should be taken with food to minimize gastrointestinal upset. Clinicians should counsel patients on the potential for allergic reactions due to the penicillin component, advising them to recognize and report any signs of serious skin reactions or hypersensitivity, such as rashes or mucosal lesions. Patients should be informed that diarrhea is a common side effect of antibacterial therapy, typically resolving after discontinuation of the medication; however, they should seek medical advice if diarrhea is severe or persists beyond 2 to 3 days. It is crucial to emphasize that this medication is effective only against bacterial infections and not viral ones, and patients must adhere to the prescribed regimen to prevent reduced efficacy and the development of antibiotic resistance. Additionally, patients should be instructed to store the suspension in the refrigerator, shake well before use, and utilize a calibrated oral syringe for dosing. Any unused medication should be discarded.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Amoxicillin and Clavulanate Potassium as submitted by Devatis, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)