Amoxicillin/Clavulanate potassium

Description

Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL is an oral antibacterial combination that includes the semisynthetic antibiotic amoxicillin and the β-lactamase inhibitor clavulanate potassium, the potassium salt of clavulanic acid. Amoxicillin, an analog of ampicillin, is derived from the basic penicillin nucleus, 6-aminopenicillanic acid, with a molecular formula of C₁₆H₁₉N₃O₅S•3H₂O and a molecular weight of 419.46 g/mol. 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 β-lactam that is structurally related to penicillins. It effectively inactivates a wide variety of β-lactamases by blocking their active sites, particularly those that are plasmid-mediated and responsible for drug resistance to penicillins and cephalosporins. The molecular formula for clavulanate potassium is C₈H₈KNO₅, with a molecular weight of 237.25 g/mol. Its chemical structure is characterized as potassium (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo3.2.0-heptane-2-carboxylate.

Uses and Indications

Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL is indicated for the treatment of pediatric patients with recurrent or persistent acute otitis media caused by specific pathogens. This formulation is effective against Streptococcus pneumoniae (penicillin minimum inhibitory concentrations MICs ≤ 2 mcg/mL), Haemophilus influenzae (including β-lactamase–producing strains), and Moraxella catarrhalis (including β-lactamase–producing strains). The targeted patient population includes those exhibiting risk factors such as antibiotic exposure for acute otitis media within the preceding 3 months, and either being aged ≤ 2 years or attending daycare.

For cases of acute otitis media solely due to S. pneumoniae, treatment with amoxicillin is appropriate. However, Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL is not indicated for the treatment of acute otitis media caused by S. pneumoniae with penicillin MIC ≥ 4 mcg/mL.

Therapy may be initiated prior to the results of bacteriological studies when there is a clinical suspicion that the infection may involve both S. pneumoniae (penicillin MIC ≤ 2 mcg/mL) and the aforementioned β-lactamase–producing organisms.

Dosage and Administration

Pediatric patients aged 3 months and older are recommended to receive a dose of 90 mg/kg/day, divided into two administrations every 12 hours, for a duration of 10 days. The specific dosage based on body weight is as follows:

• For a body weight of 8 kg, administer 3.0 mL twice daily.

• For a body weight of 12 kg, administer 4.5 mL twice daily.

• For a body weight of 16 kg, administer 6.0 mL twice daily.

• For a body weight of 20 kg, administer 7.5 mL twice daily.

• For a body weight of 24 kg, administer 9.0 mL twice daily.

• For a body weight of 28 kg, administer 10.5 mL twice daily.

• For a body weight of 32 kg, administer 12.0 mL twice daily.

• For a body weight of 36 kg, administer 13.5 mL twice daily.

Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL should be administered at the start of a meal. This timing is recommended to minimize gastrointestinal intolerance and to enhance the absorption of clavulanate potassium.

Contraindications

Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL is contraindicated in patients with a history of allergic reactions to any penicillin, due to the risk of severe hypersensitivity reactions. Additionally, it is contraindicated in individuals with a previous history of cholestatic jaundice or hepatic dysfunction associated with Amoxicillin and Clavulanate Potassium, as this may exacerbate liver-related complications. Furthermore, the use of ampicillin-class antibiotics is contraindicated in patients with mononucleosis, as it may lead to a higher incidence of rash and other adverse effects.

Warnings and Precautions

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients undergoing penicillin therapy. These reactions are more prevalent in individuals with a history of penicillin hypersensitivity and/or sensitivity to multiple allergens. Notably, there have been instances of severe reactions in patients with a history of penicillin hypersensitivity who were treated with cephalosporins. Prior to initiating therapy with Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL, a thorough inquiry regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens is essential. Should an allergic reaction occur, the administration of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL must be discontinued immediately, and appropriate therapeutic measures should be instituted.

In cases of serious anaphylactic reactions, immediate emergency treatment with epinephrine is required. Additional interventions may include the administration of oxygen, intravenous steroids, and airway management, including intubation, as clinically indicated.

Pseudomembranous colitis has been associated with nearly all antibacterial agents, including Amoxicillin/Clavulanate Potassium, and can range from mild to life-threatening in severity. Therefore, this diagnosis should be considered in patients who present with diarrhea following the administration of antibacterial agents.

Caution is advised when prescribing Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL to patients with evidence of hepatic dysfunction. While hepatic toxicity associated with this medication is generally reversible, rare cases of fatalities have been reported, typically in patients with serious underlying conditions or those receiving concomitant medications.

For patients undergoing therapy longer than the approved duration, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic function, is recommended. Additionally, a significant percentage of patients with mononucleosis who receive ampicillin may develop an erythematous skin rash; therefore, ampicillin-class antibiotics should not be administered to these patients. The potential for superinfections with mycotic or bacterial pathogens should also be considered during therapy. If superinfections occur, typically involving Pseudomonas or Candida, the drug should be discontinued, and appropriate therapy should be initiated.

Prescribing Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL in the absence of a proven or strongly suspected bacterial infection, or without a prophylactic indication, is unlikely to benefit the patient and may increase the risk of developing drug-resistant bacteria.

For patients receiving therapy for an extended period, regular laboratory tests to assess organ system functions, including renal, hepatic, and hematopoietic function, are advisable.

Side Effects

Adverse reactions associated with the use of amoxicillin/clavulanate potassium have been observed in clinical trials and postmarketing experiences.

Common adverse reactions occurring in patients include contact dermatitis (diaper rash) (3.5%), diarrhea (2.9%), vomiting (2.2%), moniliasis (1.4%), and rash (1.1%). Notably, diarrhea (2.5%) and vomiting (1.4%) were also reported as adverse reactions leading to withdrawal from treatment.

Gastrointestinal adverse reactions may include diarrhea, nausea, vomiting, indigestion, gastritis, stomatitis, glossitis, black “hairy” tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis. Symptoms of pseudomembranous colitis may arise during or after antibiotic treatment.

Hypersensitivity reactions have been documented, including skin rashes, pruritus, urticaria, angioedema, and serum sickness-like reactions characterized by urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever. Rare but serious reactions such as erythema multiforme, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, and exfoliative dermatitis (including toxic epidermal necrolysis) have also been reported. Serious and occasionally fatal anaphylactic reactions can occur with oral penicillin therapy.

Liver-related adverse reactions may involve a moderate rise in AST (SGOT) and/or ALT (SGPT), with infrequent reports of hepatic dysfunction characterized by increases in serum transaminases, serum bilirubin, and/or alkaline phosphatase. While hepatic dysfunction may be severe, it is typically reversible.

Renal adverse reactions, though rare, can include interstitial nephritis, hematuria, and crystalluria.

Hemic and lymphatic system reactions may consist of anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, agranulocytosis, slight thrombocytosis (less than 1%), and increased prothrombin time in patients receiving amoxicillin and clavulanate potassium alongside anticoagulant therapy.

Central nervous system reactions have been reported rarely and may include agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity.

Miscellaneous adverse reactions include rare occurrences of tooth discoloration (brown, yellow, or gray staining).

It is important to note that serious and occasionally fatal hypersensitivity reactions have been reported in patients undergoing penicillin therapy. Additionally, pseudomembranous colitis has been associated with nearly all antibacterial agents, including amoxicillin/clavulanate potassium, with severity ranging from mild to life-threatening. Hepatic toxicity linked to amoxicillin/clavulanate potassium is generally reversible, although rare fatalities have been reported, estimated at less than one death per four million prescriptions worldwide.

Drug Interactions

Probenecid decreases the renal tubular secretion of amoxicillin. The concurrent use of probenecid with Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL may lead to increased and prolonged blood levels of amoxicillin. Therefore, co-administration of probenecid is not recommended.

In patients receiving amoxicillin alongside oral anticoagulants, there have been rare reports of abnormal prolongation of prothrombin time, indicated by an increased international normalized ratio (INR). When these medications are prescribed concurrently, appropriate monitoring of INR is advised, and adjustments in the dosage of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

The concurrent administration of allopurinol and ampicillin has been associated with a significantly higher incidence of rashes compared to patients receiving ampicillin alone. While it remains unclear whether this increased incidence is due to allopurinol or the hyperuricemia present in these patients, there are no data available regarding the concurrent use of allopurinol with Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL.

Similar to other broad-spectrum antibiotics, amoxicillin/clavulanate may reduce the efficacy of oral contraceptives. Patients using oral contraceptives should be advised of this potential interaction.

Oral administration of Amoxicillin and Clavulanate Potassium results in high urine concentrations of amoxicillin. These elevated urine concentrations may lead to false-positive results when testing for glucose in urine using CLINITEST®, Benedict’s Solution, or Fehling’s Solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions, such as CLINISTIX®, be utilized to avoid this issue.

Following the administration of ampicillin to pregnant women, a transient decrease in plasma concentrations of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been observed. This effect may also occur with amoxicillin and, consequently, with Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL.

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 efficacy of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL have not been established in infants younger than 3 months. However, this formulation has demonstrated safety and efficacy for the treatment of acute otitis media in infants and children aged 3 months to 12 years. Additionally, it has been shown to be safe and effective for treating acute bacterial sinusitis in pediatric patients within the same age range.

Geriatric Use

Elderly patients should be treated with Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL with caution, particularly those with evidence of hepatic dysfunction. While hepatic toxicity associated with this medication is generally reversible, there have been rare reports of fatalities (less than 1 death per estimated 4 million prescriptions worldwide), typically occurring in patients with serious underlying conditions or those taking concomitant medications. Healthcare providers should refer to the CONTRAINDICATIONS and ADVERSE REACTIONS—Liver sections for further details.

In clinical observations, a moderate increase in AST (SGOT) and/or ALT (SGPT) levels has been noted among patients treated with ampicillin-class antibiotics, including Amoxicillin and Clavulanate Potassium. Although the clinical significance of these findings remains unclear, hepatic dysfunction characterized by elevated serum transaminases, bilirubin, and/or alkaline phosphatase has been infrequently reported, with a higher incidence observed in elderly patients, males, and those undergoing prolonged treatment.

For geriatric patients receiving therapy for an extended duration, periodic assessment of organ system functions—including renal, hepatic, and hematopoietic functions—is advisable. It is important to note that renal impairment associated with this medication appears to be reversible upon cessation of drug administration. Elderly patients may experience higher blood levels of the drug due to decreased renal clearance of both amoxicillin and clavulanate. Additionally, both components of the medication are effectively removed from circulation by hemodialysis, necessitating careful monitoring in patients with renal impairment.

Pregnancy

The use of AMOXICILLIN AND CLAVULANATE POTASSIUM during pregnancy has not been well studied, and it is not known whether its administration during labor or delivery has immediate or delayed adverse effects on the fetus. There is insufficient data to determine if this medication prolongs the duration of labor or increases the likelihood of requiring obstetrical interventions, such as forceps delivery or resuscitation of the newborn.

In a single study involving women with premature rupture of fetal membranes, prophylactic treatment with AMOXICILLIN AND CLAVULANATE POTASSIUM was associated with an increased risk of necrotizing enterocolitis in neonates. Given these findings, healthcare professionals should weigh the potential benefits against the risks when considering the use of this medication in pregnant patients. Caution is advised, particularly in the context of premature rupture of membranes.

Lactation

Ampicillin-class antibiotics, including AMOXICILLIN AND CLAVULANATE POTASSIUM, are excreted in human milk. Caution should be exercised when administering this medication to lactating mothers due to the potential for exposure to breastfed infants. Healthcare professionals should consider the benefits of breastfeeding alongside the potential risks associated with the presence of the drug in breast milk.

Renal Impairment

Patients with renal impairment should use Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL with caution. It is important to monitor renal function closely in these individuals, particularly in those with evidence of hepatic dysfunction. Dosing adjustments may be necessary based on the degree of renal impairment to ensure safety and efficacy.

Hepatic Impairment

Patients with hepatic impairment should use Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL with caution. While hepatic toxicity associated with the use of this medication is typically reversible, it is important to monitor liver function closely in these patients.

Although rare, there have been reports of fatalities linked to the use of amoxicillin/clavulanate potassium, with less than one death reported per an estimated four million prescriptions worldwide. These cases have generally occurred in patients with serious underlying diseases or those taking concomitant medications that may exacerbate liver function. Therefore, careful consideration of the patient's overall health status and concurrent therapies is advised when prescribing this medication to individuals with compromised liver function.

Overdosage

In cases of overdosage with Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL, patients have primarily exhibited gastrointestinal symptoms, including stomach and abdominal pain, vomiting, and diarrhea. Additionally, a small number of patients have reported symptoms such as rash, hyperactivity, or drowsiness.

Recommended Actions Upon suspicion of overdosage, it is imperative to discontinue the administration of Amoxicillin and Clavulanate Potassium. Symptomatic treatment should be initiated, and supportive measures should be implemented as necessary. If the overdosage has occurred recently and there are no contraindications, healthcare professionals may consider inducing emesis or employing other methods to remove the drug from the stomach. A prospective study involving 51 pediatric patients at a poison control center indicated that overdosages of less than 250 mg/kg of amoxicillin are generally not associated with significant clinical symptoms and do not necessitate gastric emptying.

Potential Symptoms and Complications In addition to gastrointestinal disturbances, interstitial nephritis leading to oliguric renal failure has been documented in a limited number of cases following amoxicillin overdosage. Furthermore, crystalluria, which can result in renal failure, has been reported in both adult and pediatric patients. To mitigate the risk of crystalluria, it is essential to maintain adequate fluid intake and promote diuresis.

Management of Renal Impairment Renal impairment observed in the context of overdosage appears to be reversible upon cessation of the drug. It is important to note that patients with pre-existing renal dysfunction may experience elevated blood levels of amoxicillin and clavulanate due to decreased renal clearance. Both amoxicillin and clavulanate can be effectively removed from the circulation through hemodialysis, which may be considered in cases of significant overdosage or renal impairment.

Nonclinical Toxicology

Reproduction studies conducted in pregnant rats and mice administered AMOXICILLIN AND CLAVULANATE POTASSIUM at oral dosages up to 1,200 mg/kg/day (4.9 and 2.8 times the maximum adult human oral dose based on body surface area, respectively) demonstrated no evidence of teratogenic effects on the fetus. However, there are no adequate and well-controlled studies in pregnant women. Due to the limitations of animal reproduction studies in predicting human response, this drug should be used during pregnancy only if clearly needed.

In terms of non-teratogenic effects, AMOXICILLIN AND CLAVULANATE POTASSIUM, when given at oral doses of up to 1,200 mg/kg/day (5.7 times the maximum adult human dose based on body surface area), did not adversely affect fertility or reproductive performance in rats treated with a 2:1 ratio formulation of amoxicillin to clavulanate.

Long-term studies in animals have not been conducted to assess the carcinogenic potential of AMOXICILLIN AND CLAVULANATE POTASSIUM. The mutagenic potential of this compound was evaluated through various in vitro assays, including the Ames test, a human lymphocyte cytogenetic assay, a yeast test, and a mouse lymphoma forward mutation assay, as well as in vivo assessments using mouse micronucleus tests and a dominant lethal test. All tests returned negative results, except for the in vitro mouse lymphoma assay, which indicated weak activity at very high, cytotoxic concentrations.

Postmarketing Experience

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving penicillin therapy. These reactions are more frequently observed in individuals with a history of penicillin hypersensitivity and/or sensitivity to multiple allergens.

Pseudomembranous colitis has been documented with nearly all antibacterial agents, including amoxicillin/clavulanate potassium, with severity ranging from mild to life-threatening.

Hepatic dysfunction, characterized by increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been infrequently reported in association with amoxicillin and clavulanate potassium. This condition has been noted more commonly in elderly patients, males, or those undergoing prolonged treatment. The onset of hepatic dysfunction may occur during therapy or several weeks after discontinuation, and while it can be severe, it is usually reversible.

On rare occasions, deaths have been reported, with an estimated incidence of less than one death per four million prescriptions worldwide. These cases have generally involved patients with serious underlying diseases or those taking concomitant medications.

Interstitial nephritis and hematuria have been reported rarely, along with crystalluria.

Hematological reactions, including anemia (notably hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis, have been observed during therapy with penicillins. These reactions are typically reversible upon discontinuation of therapy and are believed to be hypersensitivity phenomena.

Neuropsychiatric effects such as agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity have been reported rarely.

Tooth discoloration, including brown, yellow, or gray staining, has been reported infrequently, primarily in pediatric patients. In most cases, discoloration was reduced or eliminated through brushing or dental cleaning.

Patient Counseling

Healthcare providers should advise patients to take Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL every 12 hours with a meal or snack to minimize the risk of gastrointestinal upset. Patients should be informed that diarrhea is a common side effect associated with antibiotic use, and if they experience severe diarrhea or if it lasts more than 2 or 3 days, they should contact their doctor. It is important to note that patients may develop watery and bloody stools, with or without stomach cramps and fever, even up to 2 months after completing the antibiotic course. In such cases, patients should seek medical attention promptly.

Patients should be instructed to keep the suspension refrigerated and to shake the bottle well before each use. When administering the suspension to a child, healthcare providers should recommend using a dosing spoon or medicine dropper, ensuring that the spoon or dropper is rinsed after each use. It is essential to follow the physician's instructions regarding the appropriate dosage and duration of treatment, as bottles may contain more liquid than necessary. Any unused medicine should be discarded.

Healthcare providers should emphasize that Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL is indicated solely for the treatment of bacterial infections and is ineffective against viral infections, such as the common cold. Patients should be counseled that even if they feel better early in the treatment, it is crucial to take the medication exactly as prescribed. 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.

Additionally, healthcare providers should inform patients who are phenylketonurics that each 5 mL of the suspension contains 7 mg of phenylalanine.

Storage and Handling

The reconstituted suspension must be stored under refrigeration. Any unused suspension should be discarded after 10 days to ensure safety and efficacy. The dry powder for oral suspension should be stored at or below 25°C (77°F). It is essential to dispense the product in its original container to maintain its integrity and stability.

Additional Clinical Information

Oral administration of Amoxicillin and Clavulanate Potassium 600 mg/42.9 mg per 5 mL results in high urine concentrations of amoxicillin, which may lead to false-positive glucose test results when using CLINITEST, Benedict’s Solution, or Fehling’s Solution. Clinicians are advised to utilize glucose tests based on enzymatic glucose oxidase reactions, such as CLINISTIX, to avoid this issue.

Patients should take Amoxicillin and Clavulanate Potassium every 12 hours with a meal or snack to minimize gastrointestinal upset. It is important to counsel patients about the potential for diarrhea, which is common with antibiotic use and may persist even after treatment has ended. Patients should seek medical attention if they experience severe diarrhea or develop watery and bloody stools. The suspension should be refrigerated, shaken well before use, and administered with a dosing spoon or medicine dropper. Additionally, patients should be informed that this antibiotic is effective only against bacterial infections and that completing the full course of therapy is crucial to prevent resistance. Each 5 mL of the suspension contains 7 mg of phenylalanine, which is relevant for phenylketonurics.

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)