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, produced by the fermentation of Streptomyces clavuligerus, is a beta-lactam that inactivates certain beta-lactamases by blocking 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.

In 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 dosage.

For neonates and infants under 12 weeks of age, the recommended dosage is 30 mg/kg/day, divided and administered every 12 hours. It is advised to use the 125 mg/31.25 mg per 5 mL oral suspension for this age group.

Healthcare professionals should ensure that the appropriate formulation and dosing schedule is selected based on the patient's age, weight, and clinical condition.

Contraindications

Use of amoxicillin and clavulanate potassium for oral suspension 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 the use of amoxicillin and clavulanate potassium.

Warnings and Precautions

Serious hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving amoxicillin and clavulanate potassium for oral suspension. In the event of such a reaction, the medication should be discontinued immediately. Healthcare professionals are advised to monitor patients closely for any signs of hypersensitivity during treatment (5.1).

Patients with pre-existing hepatic dysfunction are at an increased risk for developing cholestatic jaundice. If any signs or symptoms of hepatitis arise, amoxicillin and clavulanate potassium should be discontinued. It is essential to monitor liver function tests in patients with hepatic impairment to ensure safe use of this medication (5.2).

Clostridium difficile-associated diarrhea (CDAD) has been associated with the use of antibiotics, including amoxicillin and clavulanate potassium. If a patient presents with diarrhea during or after treatment, a thorough evaluation for CDAD should be conducted to rule out this serious condition (5.3).

In patients diagnosed with mononucleosis, the use of amoxicillin and clavulanate potassium has been linked to the development of skin rashes. Therefore, it is recommended to avoid prescribing this medication to patients with mononucleosis to prevent adverse skin reactions (5.4).

During therapy with amoxicillin and clavulanate potassium, there is a potential risk for the overgrowth of non-susceptible organisms, including fungal or bacterial pathogens. Healthcare professionals should remain vigilant for signs of superinfection and manage accordingly (5.5).

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; patients should 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. Clostridium difficile-associated diarrhea (CDAD) is another serious concern, and patients should be evaluated if diarrhea occurs during treatment. Additionally, patients with mononucleosis who are treated with amoxicillin and clavulanate potassium may develop skin rashes, and the use of this medication is contraindicated in these individuals. The potential for superinfections with fungal or bacterial pathogens should also be considered during therapy.

Other 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, and crystalluria, which in some cases has led to renal failure, has also been documented in both adult and pediatric patients after overdosage.

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 safe and effective anticoagulation management.

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, and patients should be monitored for dermatological reactions.

Additionally, amoxicillin and clavulanate potassium for oral suspension may reduce the efficacy of oral contraceptives. Patients using hormonal contraceptives should be informed of this potential interaction and may require alternative or additional contraceptive methods 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 adults, supplemented by data from a study specifically examining 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 result in 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 should be adjusted for pediatric patients aged less than 12 weeks (less than 3 months).

Geriatric Use

In clinical studies involving amoxicillin and clavulanate potassium for oral suspension, 32% of the 3,119 patients analyzed were aged 65 years and older, with 14% being 75 years and older. No overall differences in safety or effectiveness were observed between these elderly patients and their younger counterparts. However, while clinical experience has not identified significant differences in responses between elderly and younger patients, it is important to consider that some older individuals may exhibit greater sensitivity to the drug.

Amoxicillin and clavulanate potassium is primarily 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 is advisable to monitor renal function in geriatric patients to ensure appropriate dosing and to mitigate potential risks associated with renal impairment.

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. 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 any possible 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 lactating mothers.

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, it is recommended to discontinue treatment. Careful assessment of liver function is essential to ensure patient safety and to guide therapeutic decisions.

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, it is important to note that overdosage with amoxicillin and clavulanate potassium has been associated with serious adverse effects. Specifically, interstitial nephritis leading to oliguric renal failure has been documented in patients following such overdosage. Additionally, crystalluria, which in some instances has progressed to renal failure, has been reported in both adult and pediatric populations.

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 also noteworthy that patients with pre-existing renal impairment may experience elevated blood levels of the drug due to decreased renal clearance.

For patients experiencing severe overdosage, hemodialysis may be employed as a method to remove amoxicillin and clavulanate potassium from circulation effectively.

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, 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 also negative in the Ames bacterial mutation assay and the mouse micronucleus test.

In terms of reproductive toxicity, amoxicillin and clavulanate potassium for oral suspension, at a 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 dosage corresponds to approximately four times the maximum recommended adult human oral dose of amoxicillin (875 mg every 12 hours) and about nine times higher than the maximum recommended adult human oral dose of clavulanate (125 mg every 8 hours), based on body surface area.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions associated with the use of amoxicillin and clavulanate potassium. Reports received voluntarily or through surveillance programs have documented the occurrence of anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme. Additionally, cases of drug reaction with eosinophilia and systemic symptoms (DRESS), hepatic dysfunction, renal dysfunction, hemolytic anemia, thrombocytopenia, and agranulocytosis have been noted. Furthermore, Clostridium difficile-associated diarrhea (CDAD) has also been reported in patients receiving this medication.

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 dosage. Each dose should be taken with a meal or snack to minimize the risk 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 treatment course; 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, potentially rendering the bacteria untreatable by amoxicillin and clavulanate potassium or other antibacterial agents in the future.

Patients should be counseled that diarrhea is a frequent side effect associated with antibacterial use, typically resolving upon discontinuation of the medication. However, they should be made aware that watery and bloody stools, with or without accompanying stomach cramps and fever, can occur even up to 2 months after completing the treatment. If diarrhea is severe or persists for more than 2 to 3 days, patients should contact their physician.

It is important to advise patients 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 essential to rinse the spoon or dropper after each use. Patients should be informed that bottles of the suspension may contain more liquid than necessary, and they should adhere to their physician's instructions regarding the appropriate dosage and duration of treatment for their child. Any unused medication should be discarded.

Lastly, patients should be made aware that amoxicillin and clavulanate potassium for oral suspension contains a penicillin-class drug, which may 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)