Amoxicillin/Clavulanate potassium

Description

Amoxicillin and Clavulanate Potassium is an oral antibacterial combination that includes the semisynthetic antibacterial amoxicillin and the beta-lactamase inhibitor, clavulanate potassium, which is the potassium salt of clavulanic acid. The molecular formula for amoxicillin is C16H19N3O5S•3H2O, with a molecular weight of 419.46 g/mol. Chemically, amoxicillin is described as (2S,5R,6R)-6-((R)-(-)-2-Amino-2-(p-hydroxyphenyl)acetamido-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo 3.2.0 heptane-2-carboxylic acid trihydrate. The molecular formula for clavulanate potassium is C8H8KNO5, and it has a molecular weight of 237.25 g/mol. Clavulanate potassium is chemically defined as potassium (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo3.2.0-heptane-2-carboxylate.

Each 5 mL of the oral suspension contains 600 mg of amoxicillin as the trihydrate and 42.9 mg of clavulanic acid, which is equivalent to 51.1 mg of clavulanate potassium. The formulation includes inactive ingredients such as aspartame, colloidal silicon dioxide, silicon dioxide, sodium carboxymethylcellulose, strawberry cream flavor, and xanthan gum. Additionally, each 5 mL of reconstituted Amoxicillin and Clavulanate Potassium (600 mg/42.9 mg) for Oral Suspension contains approximately 9 mg of potassium and 4 mg of sodium.

Uses and Indications

Amoxicillin and Clavulanate Potassium (600 mg/42.9 mg) for Oral Suspension is indicated for the treatment of pediatric patients aged 3 months to 12 years, weighing less than or equal to 40 kg, who present with recurrent or persistent acute otitis media. This indication specifically applies to cases caused by the following bacterial pathogens: Streptococcus pneumoniae (with penicillin minimum inhibitory concentrations MICs less than or equal to 2 mcg/mL), Haemophilus influenzae (including beta-lactamase-producing strains), and Moraxella catarrhalis (including beta-lactamase-producing strains).

The use of Amoxicillin and Clavulanate Potassium is particularly recommended for patients exhibiting certain risk factors, which include antibacterial exposure for acute otitis media within the preceding 3 months, being 2 years of age or younger, and attendance at daycare facilities.

Amoxicillin and Clavulanate Potassium should be utilized exclusively for the treatment or prevention of infections that are proven or strongly suspected to be of bacterial origin.

Dosage and Administration

Pediatric patients aged 3 months to 12 years who weigh less than or equal to 40 kg should receive a dosage of 90 mg/kg/day. This total daily dose should be divided into two administrations, given every 12 hours. The treatment duration is recommended for a total of 10 days.

Healthcare professionals are advised to calculate the exact dosage based on the patient's weight to ensure accurate administration.

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 and Clavulanate Potassium or any 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 fatal outcomes, have been associated with the use of Amoxicillin and Clavulanate Potassium for oral suspension. In the event of such a reaction, it is imperative to discontinue the medication immediately.

Severe Cutaneous Adverse Reactions (SCAR) have also been reported. Healthcare professionals should monitor patients closely for any signs of rash, and if the rash progresses, the medication should be discontinued without delay.

Drug-induced enterocolitis syndrome (DIES) has been documented in patients using amoxicillin, a component of this formulation. Should symptoms indicative of DIES arise, it is essential to discontinue Amoxicillin and Clavulanate Potassium for oral suspension and initiate appropriate therapeutic measures.

Patients with hepatic dysfunction or those exhibiting signs of cholestatic jaundice should be closely monitored. If any signs or symptoms of hepatitis occur, the medication must be discontinued. Additionally, liver function tests should be performed in patients with pre-existing hepatic impairment to ensure safety.

Clostridioides difficile-associated diarrhea (CDAD) can manifest in varying degrees, from mild diarrhea to severe colitis. It is crucial to evaluate patients who present with diarrhea during treatment, as this may indicate a serious condition requiring further intervention.

The use of Amoxicillin and Clavulanate Potassium for oral suspension is contraindicated in patients with mononucleosis, as these individuals are at risk of developing a skin rash upon administration of the drug.

Furthermore, it is important to note that high urine concentrations of amoxicillin may lead to false-positive results when testing for glucose in urine using CLINITEST®, Benedict's Solution, or Fehling's Solution. Therefore, it is recommended that glucose tests based on enzymatic glucose oxidase reactions be utilized to avoid misinterpretation of results.

Side Effects

Patients receiving Amoxicillin and Clavulanate Potassium for oral suspension may experience a range of adverse reactions. The most frequently reported adverse reactions include coughing, vomiting, contact dermatitis (such as diaper rash), fever, upper respiratory tract infections, and diarrhea.

Serious adverse reactions have also been observed. These include serious hypersensitivity reactions, which can be fatal; therefore, it is crucial to discontinue the medication if such a reaction occurs. Severe cutaneous adverse reactions (SCAR) require close monitoring, and the drug should be discontinued if any rash progresses. Drug-induced enterocolitis syndrome (DIES) has been reported with the use of amoxicillin, necessitating discontinuation of the medication and appropriate therapeutic intervention if this condition arises. Hepatic dysfunction and cholestatic jaundice are serious concerns, and the medication should be discontinued if signs or symptoms of hepatitis occur. Liver function tests should be monitored in patients with pre-existing hepatic impairment. Additionally, Clostridioides difficile-associated diarrhea (CDAD), which can range from mild diarrhea to fatal colitis, warrants evaluation if diarrhea occurs. It is advised to avoid the use of Amoxicillin and Clavulanate Potassium for oral suspension in patients with mononucleosis, as they may develop a skin rash.

Other important considerations include a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to Amoxicillin and Clavulanate Potassium or any other beta-lactams, including penicillins or cephalosporins. A history of cholestatic jaundice or hepatic dysfunction associated with this medication should also be noted.

In cases of overdosage, patients have primarily experienced gastrointestinal symptoms, including stomach and abdominal pain, vomiting, and diarrhea. Some patients have reported rash, hyperactivity, or drowsiness. Additionally, interstitial nephritis resulting in oliguric renal failure has been documented in a small number of patients following overdosage with amoxicillin. Crystalluria, which in some instances has led to renal failure, has also been reported in both adult and pediatric patients after amoxicillin 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 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 safe 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 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.

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 (600 mg/42.9 mg) for Oral Suspension have been established in pediatric patients aged 3 months to 12 years, weighing less than or equal to 40 kg, for the treatment of acute otitis media and acute bacterial sinusitis. However, the safety and effectiveness in pediatric patients younger than 3 months of age have not been established. Additionally, the use of this formulation in pediatric patients aged 3 months to 12 years who weigh more than 40 kg has not been evaluated.

Geriatric Use

Elderly patients may require special consideration when being prescribed Amoxicillin and Clavulanate Potassium (600 mg/42.9 mg) for Oral Suspension, as experience with this formulation in adults is limited. It is important to note that this oral suspension should not be administered to adults who have difficulty swallowing, as alternative formulations such as the 500 mg or 875 mg tablets are recommended.

In geriatric patients, particularly those with hepatic impairment, dosing should be approached with caution. Regular monitoring of hepatic function is advised, as hepatic dysfunction has been infrequently reported with the use of Amoxicillin and Clavulanate Potassium. This dysfunction may manifest as increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase levels. Notably, such hepatic dysfunction has been observed more frequently in elderly patients, males, and those undergoing prolonged treatment. While this condition is typically reversible, it can be severe, and there have been reports of fatalities associated with hepatic dysfunction.

Additionally, healthcare providers should remain vigilant for the potential development of superinfections with mycotic or bacterial pathogens during therapy, particularly in elderly patients who may have other underlying health issues that could complicate their clinical status.

Pregnancy

Available data from published epidemiologic studies and pharmacovigilance case reports over several decades of use with amoxicillin and clavulanate during pregnancy have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal outcomes. However, a study involving women with preterm prelabor rupture of membranes (PPROM) indicated that prophylactic treatment with amoxicillin and clavulanate may be associated with an increased risk of necrotizing enterocolitis in neonates.

Reproduction studies conducted in pregnant rodents, administered doses up to approximately 2 times the amount of amoxicillin and 15 times the amount of clavulanate in the Maximum Human Recommended Dose (MHRD) of Amoxicillin and Clavulanate Potassium (600 mg/42.9 mg) for Oral Suspension, revealed no evidence of harm to the fetus. Similarly, studies in pregnant rats and mice given amoxicillin and clavulanate at oral doses up to 1,200 mg/kg/day also showed no evidence of fetal harm.

It is important to note that the background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. A randomized, controlled trial involving 4,826 pregnant women with premature rupture of fetal membranes found that treatment with amoxicillin and clavulanate was associated with a significantly increased rate of proven neonatal necrotizing enterocolitis, with rates of 1.9% in the amoxicillin and clavulanate group compared to 0.5% in the placebo group.

Healthcare professionals should weigh the potential benefits against the risks when considering the use of amoxicillin and clavulanate in pregnant patients, particularly those with PPROM.

Lactation

Amoxicillin is present in human milk, as indicated by data from a published clinical lactation study. Lactating mothers should be aware that there have been reports of diarrhea, irritability, and rash in breastfed infants exposed to amoxicillin and clavulanate through breast milk. Therefore, it is recommended that infants exposed to Amoxicillin and Clavulanate Potassium be monitored for these symptoms.

Currently, there are no data available regarding the effects of amoxicillin and clavulanate on milk production. When considering the use of Amoxicillin and Clavulanate Potassium, healthcare professionals should weigh the developmental and health benefits of breastfeeding against the mother's clinical need for the medication and any potential adverse effects on the breastfed child, whether from the medication itself or from the underlying maternal condition.

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 individuals 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 patient safety and to make any necessary adjustments to the treatment regimen.

Overdosage

Following an overdosage of Amoxicillin and Clavulanate Potassium, patients have primarily exhibited gastrointestinal symptoms, which include stomach and abdominal pain, vomiting, and diarrhea. Additionally, a small number of patients have reported experiencing rash, hyperactivity, or drowsiness.

In the event of an overdosage, it is recommended to discontinue the administration of Amoxicillin and Clavulanate Potassium. Symptomatic treatment should be initiated, and supportive measures should be implemented as necessary. A prospective study indicates that overdosages of less than 250 mg/kg of amoxicillin are generally not associated with significant clinical symptoms and do not necessitate gastric emptying.

However, it is important to note that interstitial nephritis resulting in oliguric renal failure has been documented in a limited number of cases following amoxicillin overdosage. Furthermore, crystalluria, which can lead to renal failure, has also been reported in both adult and pediatric patients after amoxicillin overdosage.

To mitigate the risk of crystalluria, it is essential to maintain adequate fluid intake and promote diuresis. It should be noted that patients with impaired renal function may experience higher blood levels of the drug due to decreased renal clearance of both amoxicillin and clavulanate. In cases of severe overdosage, hemodialysis can effectively remove both amoxicillin and clavulanate from the circulation.

Nonclinical Toxicology

Long-term studies in animals have not been conducted to assess the carcinogenic potential of amoxicillin and clavulanate. In mutagenicity testing, amoxicillin and clavulanate (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 decreased cell survival at the tested concentrations. Additionally, amoxicillin and clavulanate were negative in the mouse micronucleus test and the dominant lethal assay in mice.

Clavulanate potassium, when tested independently in the Ames bacterial mutation assay and the mouse micronucleus test, also yielded negative results in both assays.

In terms of reproductive toxicity, amoxicillin and clavulanate (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, when adjusted for body surface area based on a 20 kg child, is approximately twice the recommended clinical dose of amoxicillin and clavulanate potassium (600 mg/42.9 mg) for oral suspension, which is 90/6.4 mg/kg/day. For clavulanate, the dose multiple is approximately 15 times higher than the recommended clinical daily dose, also calculated based on body surface area.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions reported voluntarily or through surveillance programs. Serious skin reactions have been noted, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Hepatic dysfunction has also been reported, encompassing cholestatic jaundice and hepatitis. Hematologic reactions, such as thrombocytopenia, leukopenia, and agranulocytosis, have been documented. Additionally, renal impairment, specifically interstitial nephritis, has been observed. Anaphylaxis and other allergic reactions have been reported, along with cases of Clostridium difficile-associated diarrhea.

Patient Counseling

Patients should be informed to take Amoxicillin and Clavulanate Potassium (600 mg/42.9 mg) for Oral Suspension every 12 hours with a meal or snack to minimize the risk of gastrointestinal upset. They should be advised to contact their doctor if they experience severe diarrhea that lasts more than 2 or 3 days.

It is important to counsel patients that Amoxicillin and Clavulanate Potassium contains a penicillin class drug, which may cause allergic reactions in some individuals. 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 signs or symptoms of skin rash, mucosal lesions, or other indications of hypersensitivity promptly.

Patients should also be counseled that diarrhea is a common side effect associated with antibacterial drugs, including Amoxicillin and Clavulanate Potassium. This side effect typically resolves upon discontinuation of the medication. However, patients should be informed that they may develop watery and bloody stools (with or without stomach cramps and fever) even weeks after completing the course of the antibacterial drug. If such symptoms occur, patients should seek medical attention as soon as possible.

For patients with phenylketonuria, it should be noted that each 5 mL of Amoxicillin and Clavulanate Potassium (600 mg/42.9 mg) for Oral Suspension contains 7 mg of phenylalanine.

Patients must be counseled that antibacterial drugs, including Amoxicillin and Clavulanate Potassium, are indicated solely for the treatment of bacterial infections and are ineffective against 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, they must 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 be instructed to keep the suspension refrigerated and to shake it well before use. When administering the suspension to a child, a dosing spoon or medicine dropper should be used, and it is essential to rinse the spoon or dropper after each use. Patients should follow their doctor’s instructions regarding the appropriate dosage and duration of treatment, and any unused medicine should be discarded.

Storage and Handling

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

Additional Clinical Information

High urine concentrations of amoxicillin may lead to false-positive results for glucose when using CLINITEST®, Benedict's Solution, or Fehling's Solution. Clinicians are advised to utilize glucose tests that rely on enzymatic glucose oxidase reactions for accurate results. Additionally, administration of amoxicillin in pregnant women has been associated with a temporary reduction in plasma concentrations of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol.

FDA Insert (PDF)

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

View full prescribing information (PDF)