Amoxicillin/Clavulanate potassium

Description

Amoxicillin and Clavulanate Potassium for Oral Suspension 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 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 beta-lactam that is structurally related to penicillins and has the capability to inactivate certain beta-lactamases by obstructing their active sites. The molecular formula for clavulanate potassium is C₈H₈KNO₅, with a molecular weight of 237.25 g/mol, 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 5 mL of the oral suspension contains 250 mg of amoxicillin as the trihydrate and 62.5 mg of clavulanic acid, equivalent to 74.5 mg of clavulanate potassium. Additionally, each 5 mL of the reconstituted suspension provides 0.31 mEq of potassium. Inactive ingredients include colloidal silicon dioxide, hypromellose, mannitol, orange flavor, silicon dioxide, saccharin sodium, and xanthan gum.

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, based on the amoxicillin component. It is advised to use the 125 mg/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 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 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, it is imperative to discontinue the medication immediately.

Healthcare professionals should remain vigilant for Severe Cutaneous Adverse Reactions (SCAR). Patients should be monitored closely for any signs of rash, and if the rash progresses, the medication must be discontinued.

Drug-induced enterocolitis syndrome (DIES) has been associated with the use of 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 are at increased risk for cholestatic jaundice. If any signs or symptoms of hepatitis develop, the medication should be discontinued. Additionally, liver function tests should be monitored in patients with pre-existing hepatic impairment to ensure safety.

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.

It is advised to avoid the use of Amoxicillin and Clavulanate Potassium for Oral Suspension in patients with mononucleosis, as these individuals are prone to developing skin rashes upon administration of this medication.

Finally, healthcare providers should be aware of the risk of superinfections due to overgrowth of fungal or bacterial pathogens during therapy. Monitoring for signs of such infections is recommended throughout the course of treatment.

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 imperative to discontinue the medication if such a reaction occurs. Severe cutaneous adverse reactions (SCAR) require close monitoring, and the medication should be discontinued if any rash progresses. Drug-induced enterocolitis syndrome (DIES) has been associated with the use of amoxicillin, necessitating discontinuation of Amoxicillin and Clavulanate Potassium for Oral Suspension and appropriate therapeutic intervention if this condition arises.

Hepatic dysfunction and cholestatic jaundice have been noted, with recommendations to discontinue the medication if signs or symptoms of hepatitis occur, and to monitor liver function tests in patients with pre-existing hepatic impairment. Clostridioides difficile-associated diarrhea (CDAD) should be evaluated in patients presenting with diarrhea during treatment. Additionally, patients with mononucleosis who receive this medication may develop skin rashes, and its use is contraindicated in these individuals.

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 for Oral Suspension or other beta-lactams (including penicillins or cephalosporins) is a critical consideration. Furthermore, a history of cholestatic jaundice or hepatic dysfunction associated with this medication should be noted.

Additional serious adverse reactions include interstitial nephritis, which has resulted in oliguric renal failure following overdosage, as well as crystalluria, which in some cases has led to renal failure in both adult and pediatric patients after overdosage with amoxicillin and clavulanate potassium.

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 for Oral Suspension 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 and effective anticoagulation.

The concomitant use of Amoxicillin and Clavulanate Potassium for Oral Suspension 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 any 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 advised to consider 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 Powder 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 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 ensure safety and efficacy.

Geriatric Use

In an analysis of clinical studies involving Amoxicillin and Clavulanate Potassium, 32% of the 3,119 patients evaluated 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, it is important to note that while clinical experience has not identified significant differences in responses between elderly and younger patients, greater sensitivity in some older individuals cannot be ruled out.

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

Pregnant patients should be informed that Amoxicillin and Clavulanate Potassium is classified as Pregnancy Category B. Reproductive studies conducted in pregnant rats and mice, using a 2:1 ratio formulation of amoxicillin to clavulanate at oral doses up to 1200 mg/kg/day, demonstrated no evidence of harm to the fetus. The doses administered in these studies were approximately 4 and 2 times the maximum recommended adult human oral dose for amoxicillin (875 mg every 12 hours) and approximately 9 and 4 times for clavulanate (125 mg every 8 hours), based on body surface area.

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 should be used during pregnancy only if clearly needed. Additionally, it is not known whether the use of this medication during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood of the necessity for obstetrical intervention. Healthcare providers should 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

There is no specific information regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

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 any necessary adjustments in therapy.

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.

Potential Symptoms and Complications Overdosage of amoxicillin and clavulanate potassium has been associated with interstitial nephritis, which can lead to oliguric renal failure. Additionally, crystalluria has been reported, occasionally resulting in renal failure in both adult and pediatric populations.

Management Recommendations To mitigate the risk of crystalluria following an overdosage, it is essential to maintain adequate fluid intake and promote diuresis. This approach helps to reduce the likelihood of crystallization in the renal system. It is also important to note that renal impairment observed in these cases appears to be reversible upon cessation of the drug.

Patients with pre-existing renal impairment may experience elevated blood levels of amoxicillin and clavulanate potassium due to decreased renal clearance. In such instances, hemodialysis may be employed to facilitate the removal of the drug from circulation.

Nonclinical Toxicology

Long-term studies in animals have not been conducted to assess the carcinogenic potential of Amoxicillin and Clavulanate Potassium. In mutagenicity testing, Amoxicillin and Clavulanate Potassium (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 doses that also resulted in decreased cell survival. The compound was found to be negative in the mouse micronucleus test and in the dominant lethal assay in mice.

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

In terms of reproductive toxicity, Amoxicillin and Clavulanate Potassium (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 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), when adjusted for body surface area.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions associated with the use of the product. Notably, severe cutaneous adverse reactions (SCAR) have been reported. Additionally, instances of diarrhea have been documented, which may include cases of watery and bloody stools. These gastrointestinal symptoms can occur even after the last dose has been administered, with some cases arising as late as two months following treatment.

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 to 3 days, patients should contact their physician promptly.

It is essential to counsel patients that antibacterial drugs, including amoxicillin and clavulanate potassium, 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, although they may feel better early in the treatment, it is vital 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, 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 for oral suspension is supplied in its original container and should be stored at a temperature range of 20° to 25°C (68° to 77°F). 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 keep this product 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 Cipla USA Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)