Amoxicillin/Clavulanate potassium

Description

Amoxicillin and clavulanate potassium for oral suspension, USP is an oral antibacterial combination comprising amoxicillin and clavulanate potassium, the potassium salt of clavulanic acid. Amoxicillin, an analog of ampicillin, is derived from the penicillin nucleus, 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 is produced through the fermentation of Streptomyces clavuligerus and is a beta-lactam that can inactivate certain beta-lactamases by obstructing their active sites. The molecular formula for clavulanate potassium is C8H8KNO5, with a molecular weight of 237.25, and its chemical structure is potassium (Z)(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo3.2.0-heptane-2-carboxylate.

Upon reconstitution, each teaspoonful (5 mL) of the suspension contains either 200 mg of amoxicillin as the trihydrate and 28.5 mg of clavulanic acid as the potassium salt, or 400 mg of amoxicillin as the trihydrate and 57 mg of clavulanic acid as the potassium salt. The 200 mg/28.5 mg formulation provides 0.14 mEq of potassium per 5 mL, while the 400 mg/57 mg formulation contains 0.29 mEq of potassium per 5 mL. The product appears as a white to off-white granular powder, which transforms into a white to pale yellow suspension with an orange flavor upon reconstitution.

Inactive ingredients include colloidal silicon dioxide, hypromellose, orange flavor, silicon dioxide, succinic acid, xanthan gum, and aspartame.

Uses and Indications

Amoxicillin and clavulanate potassium for oral suspension is indicated for the treatment of the following infections: lower respiratory tract infections, acute bacterial otitis media, sinusitis, skin and skin structure infections, and urinary tract infections.

There are no teratogenic or nonteratogenic effects associated with this medication.

Dosage and Administration

For adults and pediatric patients weighing more 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.

For pediatric patients aged 12 weeks (3 months) and older, the dosage should be calculated based on body weight, with a range of 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 under 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/31.25 mg per 5 mL oral suspension for this population.

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 for oral suspension or to other beta-lactams, including penicillins or cephalosporins. Additionally, it is contraindicated in individuals with a history of cholestatic jaundice or hepatic dysfunction associated with amoxicillin and clavulanate potassium for oral suspension.

Warnings and Precautions

Serious hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving amoxicillin and clavulanate potassium for oral suspension. If any signs of hypersensitivity occur, the medication should be discontinued immediately to prevent potentially fatal outcomes.

Patients with hepatic dysfunction are at an increased risk for cholestatic jaundice. It is essential to monitor liver function tests in these individuals. Should any signs or symptoms of hepatitis arise, the use of amoxicillin and clavulanate potassium for oral suspension must be discontinued.

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

In patients diagnosed with mononucleosis, the administration of amoxicillin and clavulanate potassium for oral suspension may lead to the development of a skin rash. Therefore, this medication should be avoided in individuals with mononucleosis to prevent adverse reactions.

Additionally, 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 for oral suspension. Monitoring for signs of superinfection is recommended to ensure patient safety.

Side Effects

Patients receiving amoxicillin and clavulanate potassium for oral suspension 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, it is crucial to discontinue the medication if such a reaction occurs. Hepatic dysfunction and cholestatic jaundice have been noted, necessitating discontinuation of the drug if signs or symptoms of hepatitis arise, along with monitoring of liver function tests in patients with pre-existing hepatic impairment. Additionally, Clostridium difficile-associated diarrhea (CDAD) should be evaluated if diarrhea occurs during treatment. It is important to note that patients with mononucleosis who are treated with amoxicillin and clavulanate potassium may develop skin rashes, and the use of this medication should be avoided in these individuals. 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. Furthermore, interstitial nephritis resulting in oliguric renal failure has been reported following overdosage, along with 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 for oral suspension with probenecid is not recommended due to potential interactions that may affect therapeutic outcomes.

When used concurrently with oral anticoagulants, amoxicillin and clavulanate potassium may lead to an increased prolongation of prothrombin time. Monitoring of prothrombin time is advised 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. Caution is advised when these medications are prescribed together.

Additionally, amoxicillin and clavulanate potassium for oral suspension may reduce the efficacy of oral contraceptives. Patients should be informed of this potential interaction and advised to consider alternative or additional contraceptive measures during treatment.

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 powder for oral suspension and chewable tablets have been established in pediatric patients. Evidence supporting the use of amoxicillin and clavulanate potassium for oral suspension in this population is derived from studies involving amoxicillin and clavulanate potassium tablets in adults, along with additional data from a study specifically examining 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 for oral suspension should be modified due to the potential for altered pharmacokinetics. It is important to note that in neonates and young infants, the elimination of amoxicillin may be delayed due to incompletely developed renal function; however, the elimination of clavulanate remains unaltered in this age group.

Geriatric Use

In clinical studies involving amoxicillin and clavulanate potassium for oral suspension, 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, while other clinical experiences have not identified significant differences in responses between elderly and younger patients, it is important to note that greater sensitivity to the drug may be present in some older individuals.

Amoxicillin and clavulanate potassium is substantially excreted by the kidneys, which raises concerns regarding the risk of 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 may be beneficial to monitor renal function 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 for oral suspension (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 for oral suspension 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 of these patients.

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 patient population.

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, clinicians should remain vigilant for potential adverse effects associated with higher doses.

Notably, interstitial nephritis leading to oliguric renal failure has been documented in patients following overdosage with amoxicillin and clavulanate potassium. Additionally, crystalluria has been reported, which in some instances has progressed to renal failure in both adult and pediatric populations. 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 important to note that patients with pre-existing renal impairment 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. Healthcare professionals should monitor renal function and provide appropriate interventions as needed.

Nonclinical Toxicology

Long-term studies in animals have not been conducted to assess the carcinogenic potential of amoxicillin and clavulanate potassium for oral suspension. 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, also yielded negative results in the Ames bacterial mutation assay and the mouse micronucleus test.

In terms of reproductive toxicity, amoxicillin and clavulanate potassium for oral suspension (2:1 ratio formulation) was administered at oral doses of up to 1,200 mg/kg/day in rats, with no observed effects on fertility and reproductive performance. This dose 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 several adverse reactions reported voluntarily or through surveillance programs.

Hypersensitivity reactions have been noted, including cases of anaphylaxis, angioedema, and various skin reactions. Gastrointestinal disorders have also been reported, with diarrhea being a significant concern; this may be severe and can occur even after the completion of treatment.

Elevations in liver enzymes and instances of hepatitis have been classified under hepatic disorders. Renal disorders, specifically interstitial nephritis, have been documented as well.

Hematologic reactions include thrombocytopenia, leukopenia, and hemolytic anemia. Neurological events, such as seizures, have been observed, particularly in patients with renal impairment. Additionally, Clostridium difficile-associated diarrhea has been reported in patients receiving amoxicillin and clavulanate potassium.

Patient Counseling

Patients should be informed that amoxicillin and clavulanate potassium for oral suspension 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 reduce the possibility of gastrointestinal upset.

Healthcare providers should counsel patients that antibacterial drugs, including amoxicillin and clavulanate potassium for oral suspension, are indicated solely for the treatment of bacterial infections and are ineffective against viral infections, such as the common cold.

When amoxicillin and clavulanate potassium for oral suspension is prescribed for a bacterial infection, patients should be advised that it is common to feel better early in the course of therapy; however, the medication must be taken exactly as directed. Skipping doses or failing to complete the full course of therapy may decrease the effectiveness of the immediate treatment and increase the likelihood of bacterial resistance, rendering the bacteria unresponsive to amoxicillin and clavulanate potassium for oral suspension or other antibacterial drugs in the future.

Patients should be counseled that diarrhea is a common side effect associated with antibacterial use, typically resolving upon discontinuation of the medication. However, patients may experience watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more 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.

Patients should be advised to store the suspension in the refrigerator and to shake it well before use. When administering the suspension to a child, a dosing spoon or medicine dropper should be utilized, and it is important to rinse the spoon or dropper after each use. Bottles of amoxicillin and clavulanate potassium for oral suspension may contain more liquid than required; therefore, patients should follow their doctor’s instructions regarding the appropriate dosage and duration of treatment for their child, and any unused medicine should be discarded.

Lastly, patients should be made aware that amoxicillin and clavulanate potassium for oral suspension contains a penicillin-class drug, which can cause allergic reactions in some individuals.

Storage and Handling

The dry powder should be stored at a temperature range of 20º to 25ºC (68º to 77ºF). Once reconstituted, the suspension must be kept under refrigeration. Any unused suspension should be discarded after 10 days to ensure safety and efficacy. It is essential to dispense the product in its original container to maintain its integrity. Additionally, the product should be kept out of the reach of children to prevent accidental ingestion.

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 Aidarex Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)