Amoxicillin/Clavulanate potassium

Description

Amoxicillin and clavulanate potassium for oral suspension, USP is an oral antibacterial combination comprising amoxicillin and the beta-lactamase inhibitor, 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 (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 structurally related to penicillins. It 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.

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. Each 5 mL of the reconstituted 200 mg/28.5 mg oral suspension contains 0.14 mEq of potassium, while each 5 mL of the 400 mg/57 mg formulation contains 0.29 mEq of potassium. 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 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 used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. 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. 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 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 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 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 (5.1).

Severe Cutaneous Adverse Reactions (SCAR) may occur during treatment. Healthcare professionals should monitor patients closely for any signs of rash, and the medication should be discontinued if the rash progresses (5.2).

Drug-induced enterocolitis syndrome (DIES) has been reported in patients receiving amoxicillin, a component of this formulation. Should symptoms of DIES arise, it is essential to discontinue amoxicillin and clavulanate potassium for oral suspension and initiate appropriate therapeutic measures (5.3).

Patients with hepatic dysfunction or those exhibiting signs of cholestatic jaundice should be closely monitored. If any signs or symptoms of hepatitis develop, the medication must be discontinued. Additionally, liver function tests should be performed in patients with pre-existing hepatic impairment to ensure safety (5.4).

Clostridioides difficile-associated diarrhea (CDAD) is a potential complication of antibiotic therapy. If a patient presents with diarrhea during treatment, a thorough evaluation is warranted to rule out CDAD (5.5).

Amoxicillin and clavulanate potassium for oral suspension should be avoided in patients with mononucleosis, as these individuals are at risk of developing a skin rash upon administration of the medication (5.6).

During therapy, the possibility of superinfections due to overgrowth of fungal or bacterial pathogens should be considered. Clinicians should remain vigilant for signs of such infections throughout the course of treatment (5.7).

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, although less frequent, warrant careful monitoring and prompt action. These include serious hypersensitivity reactions, which may be fatal; in such cases, amoxicillin and clavulanate potassium should be discontinued immediately. Severe cutaneous adverse reactions (SCAR) have also been reported, necessitating close monitoring and discontinuation if any rash progresses. Drug-induced enterocolitis syndrome (DIES) is another serious reaction that requires discontinuation of the medication and appropriate therapeutic intervention.

Patients may also experience hepatic dysfunction and cholestatic jaundice; if signs or symptoms of hepatitis occur, discontinuation of the drug is advised, along with monitoring of liver function tests, particularly in those with pre-existing hepatic impairment. Clostridioides difficile-associated diarrhea (CDAD) should be evaluated if diarrhea occurs during treatment. Additionally, patients with mononucleosis who receive this medication may develop skin rashes, and its use in these patients is not recommended.

The potential for superinfections with fungal or bacterial pathogens should be considered during therapy, particularly in the context of overgrowth. A history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to amoxicillin and clavulanate potassium or other beta-lactams (including penicillins or cephalosporins) is a significant risk factor. Furthermore, a history of cholestatic jaundice or hepatic dysfunction associated with this medication should be noted.

Rarely, interstitial nephritis resulting in oliguric renal failure has been reported following overdosage of amoxicillin and clavulanate potassium. Crystalluria, which in some cases has led to renal failure, has also been documented after overdosage 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 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. Clinicians should monitor prothrombin time closely and consider dosage adjustments of the anticoagulant as necessary.

The concomitant use of allopurinol with amoxicillin and clavulanate potassium is associated with an increased risk of rash. Patients should be monitored for dermatological reactions, and if a rash occurs, discontinuation of one or both medications should be considered.

Additionally, amoxicillin and clavulanate potassium for oral suspension may reduce the efficacy of oral contraceptives. Patients using hormonal contraceptives should be advised to consider alternative or additional non-hormonal 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 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 adult patients, 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 lead to 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 under 12 weeks (less than 3 months) of age to account for these developmental considerations.

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. 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, although this has not been definitively established in reported clinical experiences.

Amoxicillin and clavulanate potassium is primarily excreted via the kidneys, which raises concerns regarding the potential for 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 to ensure appropriate dosing and to mitigate 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. The amoxicillin doses in these studies were approximately 4 and 2 times the maximum recommended adult human oral dose (875 mg every 12 hours) for rats and mice, respectively. For clavulanate, the corresponding multiples were approximately 9 and 4 times the maximum recommended adult human oral dose (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 may not have specific dosage adjustments, special monitoring, or safety considerations outlined in the available data. Therefore, healthcare professionals should exercise caution when prescribing to this population, as the lack of information necessitates careful clinical judgment regarding the use of the medication in individuals with reduced kidney function. Regular monitoring of renal function is advisable to ensure patient safety and therapeutic efficacy.

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. Symptomatic treatment and supportive measures should be instituted as necessary to manage the patient's condition effectively.

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, caution is warranted, as more severe outcomes have been documented with higher doses.

Notably, interstitial nephritis leading to oliguric renal failure has been reported following overdosage with amoxicillin and clavulanate potassium. Additionally, crystalluria, which in some instances has progressed to renal failure, has been observed in both adult and pediatric populations after excessive doses of amoxicillin and clavulanate potassium.

To mitigate the risk of crystalluria associated with amoxicillin and clavulanate potassium overdosage, it is essential to maintain adequate fluid intake and promote diuresis. This approach helps to ensure proper renal function and reduce the likelihood of complications.

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.

In cases of severe overdosage, hemodialysis may be employed to facilitate the removal of amoxicillin and clavulanate potassium from the circulation, thereby aiding in the management of the patient's condition.

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 about 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 associated with the use of the antibacterial. Notably, severe cutaneous adverse reactions (SCAR) have been reported. Additionally, instances of diarrhea have been documented, including cases characterized by watery and bloody stools. These gastrointestinal events may occur even as late as two or more months following the discontinuation of the antibacterial.

Patient Counseling

Patients should be informed that amoxicillin and clavulanate potassium for oral suspension may be administered every 8 hours or every 12 hours, depending on the prescribed dosage. It is important that each dose is taken with a meal or snack to minimize the risk of gastrointestinal upset.

Healthcare providers should counsel patients regarding the potential for allergic reactions, as amoxicillin and clavulanate potassium contains a penicillin class drug. 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 initial signs or symptoms of skin rash, mucosal lesions, or other indications of hypersensitivity.

Patients should also be advised that diarrhea is a common side effect associated with antibacterial medications, typically resolving upon discontinuation of the drug. However, it is crucial to inform patients that they may experience watery and bloody stools, with or without accompanying stomach cramps and fever, even up to 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 promptly.

It is essential to counsel patients that antibacterial drugs, including amoxicillin and clavulanate potassium for oral suspension, 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, 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 advised to store the suspension in the refrigerator and to shake it well before use. When administering the suspension to a child, a calibrated oral syringe should be used, and it is important 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 medication should be discarded.

Storage and Handling

The dry powder 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. Any unused suspension should be discarded after 10 days to ensure safety and efficacy.

The product should be dispensed in its original container to maintain integrity. Additionally, it is essential to keep this medication 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 Aurobindo Pharma Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)