Amoxicillin

Description

Formulations of Amoxicillin for Oral Suspension, USP contain Amoxicillin, a semisynthetic antibiotic and an analog of ampicillin, exhibiting a broad spectrum of bactericidal activity against various Gram-positive and Gram-negative microorganisms. The chemical structure of Amoxicillin is defined as (2S,5R,6R)-6-((R)-(-)-2-amino-2-(p-hydroxyphenyl)acetamido-3,3-dimethyl-7-oxo-4-thia-1-zabicyclo3.2.0heptane-2-carboxylic acid trihydrate. The molecular formula is C16H19N3O5S•3H2O, with a molecular weight of 419.45.

For the Oral Suspension, each 5 mL of the reconstituted formulation contains 125 mg, 200 mg, 250 mg, or 400 mg of Amoxicillin as the trihydrate. Additionally, each 5 mL of the 125 mg, 200 mg, 250 mg, and 400 mg reconstituted suspension contains 0.1898 mEq (4.3635 mg) of sodium. Inactive ingredients include colloidal silicon dioxide, hypromellose, sodium benzoate, sucrose, trisodium citrate dihydrate, tutti frutti flavor, and xanthan gum.

Uses and Indications

Amoxicillin for Oral Suspension, USP is a penicillin-class antibacterial indicated for the treatment of infections caused by susceptible strains of designated microorganisms. This medication is specifically indicated for infections of the ear, nose, throat, genitourinary tract, skin and skin structure, and lower respiratory tract.

Additionally, Amoxicillin for Oral Suspension is indicated in combination with other therapies for the treatment of Helicobacter pylori infection and duodenal ulcer disease.

There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

In adults, the recommended dosage ranges from 750 mg to 1750 mg per day, administered in divided doses every 8 to 12 hours. For pediatric patients over 3 months of age, the dosage is 20 mg to 45 mg per kilogram of body weight per day, also given in divided doses every 8 to 12 hours.

For the treatment of gonorrhea, a single oral dose of 3 grams is indicated. In neonates and infants aged 3 months or younger, the maximum dosage is 30 mg per kilogram of body weight per day, divided and administered every 12 hours.

In the context of H. pylori infection, two therapeutic regimens are recommended:

• Triple therapy consists of 1 gram of Amoxicillin, 500 mg of clarithromycin, and 30 mg of lansoprazole, all administered twice daily (every 12 hours) for a duration of 14 days.

• Dual therapy includes 1 gram of Amoxicillin and 30 mg of lansoprazole, each given three times daily (every 8 hours) for 14 days.

It is essential to reduce the dosage in patients with severe renal impairment, specifically those with a glomerular filtration rate (GFR) of less than 30 mL/min.

Contraindications

Use is contraindicated in patients with a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to Amoxicillin or other beta-lactams, including penicillins or cephalosporins. Due to the potential for severe allergic reactions, administration in these cases poses significant risk.

Warnings and Precautions

Serious and occasionally fatal anaphylactic reactions have been reported in patients undergoing penicillin therapy. Healthcare professionals should be vigilant for signs of anaphylaxis, which necessitates immediate emergency treatment and supportive measures. It is imperative that patients with a known history of penicillin allergy are carefully assessed prior to initiating therapy.

In addition, Clostridium difficile-associated diarrhea (CDAD) has been observed in patients receiving penicillin. This condition can range from mild diarrhea to severe, potentially fatal colitis. Healthcare providers should evaluate any patient who develops diarrhea during or after treatment with penicillin, as timely diagnosis and management are crucial to prevent complications associated with CDAD. Monitoring for gastrointestinal symptoms is recommended to ensure patient safety and effective management of potential adverse effects.

Side Effects

Patients receiving treatment with Amoxicillin may experience a range of adverse reactions. Common adverse reactions reported include diarrhea, rash, vomiting, and nausea.

Serious adverse reactions, although less frequent, can occur and require immediate medical attention. Notably, serious and occasionally fatal anaphylactic reactions have been documented in patients undergoing penicillin therapy. Such reactions necessitate prompt emergency treatment and supportive measures. Additionally, Clostridium difficile-associated diarrhea has been observed, which can vary in severity from mild diarrhea to fatal colitis; therefore, it is crucial to evaluate any instances of diarrhea in patients.

There are also important considerations regarding patients with a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to Amoxicillin or other beta-lactams, including penicillins and cephalosporins.

Furthermore, interstitial nephritis leading to oliguric renal failure has been reported in a small number of patients following Amoxicillin overdosage. Crystalluria, which in some cases has resulted in renal failure, has also been noted after overdosage in both adult and pediatric patients. Monitoring and appropriate management of these adverse reactions are essential for patient safety.

Drug Interactions

Probenicid, when administered concurrently with Amoxicillin, decreases the renal tubular secretion of Amoxicillin. This interaction may lead to elevated blood levels of Amoxicillin, necessitating careful monitoring of Amoxicillin concentrations and potential dosage adjustments based on clinical response.

The concomitant use of Amoxicillin with oral anticoagulants has been associated with an increased prolongation of prothrombin time. Clinicians should monitor prothrombin time closely in patients receiving this combination and consider adjusting the dosage of the anticoagulant as needed to maintain therapeutic levels.

Coadministration of Amoxicillin with allopurinol has been reported to increase the risk of rash. Patients should be monitored for dermatological reactions, and if a rash occurs, consideration should be given to discontinuing one of the medications.

Additionally, Amoxicillin may reduce the efficacy of oral contraceptives. Patients using oral contraceptives should be advised to consider alternative or additional contraceptive methods during treatment with Amoxicillin to ensure adequate contraceptive protection.

Packaging & NDC

The table below lists all NDC Code configurations of Amoxicillin, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Pediatric patients, particularly neonates and young infants, may experience delayed elimination of Amoxicillin due to incompletely developed renal function. Therefore, dosing of Amoxicillin should be modified for pediatric patients aged 12 weeks or younger (≤ 3 months) to ensure safety and efficacy.

Geriatric Use

An analysis of clinical studies of Amoxicillin has been conducted to evaluate the response of subjects aged 65 and over compared to younger subjects. The findings from these analyses did not identify significant differences in responses between elderly patients and their younger counterparts; however, it is important to note that a greater sensitivity to the drug in some older individuals cannot be ruled out.

Amoxicillin is substantially excreted by the kidneys, which raises concerns regarding the risk of toxic reactions, particularly 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 in geriatric patients to mitigate potential risks associated with the use of this medication.

Pregnancy

Pregnancy Category B. Reproduction studies conducted in mice and rats at doses up to 2000 mg/kg, which is 3 and 6 times the 3 g human dose based on body surface area, have shown no evidence of harm to the fetus due to Amoxicillin. However, there are no adequate and well-controlled studies in pregnant women. Given that animal reproduction studies are not always predictive of human response, Amoxicillin should be used during pregnancy only if clearly needed. Healthcare professionals are advised to weigh the potential benefits against any possible risks when considering the use of Amoxicillin in pregnant patients.

Lactation

Penicillins, including Amoxicillin, have been shown to be excreted in human milk. The use of Amoxicillin by nursing mothers may lead to sensitization of breastfed infants. Therefore, caution should be exercised when administering Amoxicillin 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 have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

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, there are notable risks associated with higher doses. Interstitial nephritis leading to oliguric renal failure has been documented in a limited number of cases following Amoxicillin overdosage. Additionally, crystalluria, which can occasionally progress to renal failure, has been reported in both adult and pediatric populations after excessive intake of Amoxicillin. To mitigate the risk of crystalluria, it is essential to ensure adequate fluid intake and maintain diuresis during the management of overdosage.

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 dysfunction may experience elevated blood levels of Amoxicillin due to reduced renal clearance. In such cases, hemodialysis may be employed to facilitate the removal of Amoxicillin from the bloodstream.

Nonclinical Toxicology

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Amoxicillin. While specific studies to detect the mutagenic potential of Amoxicillin alone have not been conducted, data from tests on a 4:1 mixture of Amoxicillin and potassium clavulanate provide relevant insights.

The combination of Amoxicillin and potassium clavulanate was found to be non-mutagenic 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 occurred at doses that were also associated with decreased cell survival. In contrast, the combination was negative in the mouse micronucleus test and the dominant lethal assay in mice.

Potassium clavulanate alone was tested in the Ames bacterial mutation assay and the mouse micronucleus test, yielding negative results in both assays.

In a multi-generation reproduction study conducted in rats, no impairment of fertility or other adverse reproductive effects were observed at doses up to 500 mg/kg, which is approximately twice the 3 g human dose based on body surface area.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions associated with the use of the product. Diarrhea has been reported, which is a common issue linked to antibiotic use and typically resolves upon discontinuation of the antibiotic. Additionally, patients may experience watery and bloody stools, which can occur with or without accompanying symptoms such as stomach cramps and fever. These symptoms may manifest even two months or more after the last dose of the antibiotic. In such cases, it is advised that patients contact their physician promptly.

Furthermore, it is noted that amoxicillin for oral suspension, being a penicillin class drug, has the potential to cause allergic reactions in certain individuals.

Patient Counseling

Patients should be advised that Amoxicillin for oral suspension may be taken every 8 hours or every 12 hours, depending on the dose prescribed. It is important for patients to understand that antibacterial drugs, including Amoxicillin for oral suspension, are intended solely for the treatment of bacterial infections and are ineffective against viral infections, such as the common cold.

When Amoxicillin for oral suspension is prescribed for a bacterial infection, patients should be informed that it is common to feel better early in the course of therapy. However, they must take the medication exactly as directed. Skipping doses or failing to complete the full course of therapy may decrease the effectiveness of the immediate treatment and increase the likelihood of bacteria developing resistance, rendering Amoxicillin for oral suspension or other antibacterial drugs ineffective in the future.

Patients should also be counseled that diarrhea is a common side effect associated with antibiotics, typically resolving upon discontinuation of the medication. However, it is important to note that some patients may experience watery and bloody stools, with or without stomach cramps and fever, even as late as two months after completing the antibiotic course. If this occurs, patients should contact their physician promptly.

Additionally, patients should be made aware that Amoxicillin for oral suspension contains a penicillin class drug, which can cause allergic reactions in some individuals. It is crucial for patients to report any history of allergies to penicillin or related medications to their healthcare provider.

Storage and Handling

The product is supplied in a tight, light-resistant container, as defined by the United States Pharmacopeia (USP), and is equipped with a child-resistant closure to ensure safety. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper adherence to these storage conditions is essential for maintaining the integrity and efficacy of the product.

Additional Clinical Information

Laboratory tests for determining susceptibility to Amoxicillin can utilize ampicillin powder and a 10 mcg ampicillin disk. Clinical microbiology should provide periodic reports to physicians detailing the in vitro susceptibility profiles of nosocomial and community-acquired pathogens when available. Quantitative methods, such as dilution techniques, are employed to ascertain antimicrobial minimum inhibitory concentrations (MICs), while diffusion techniques measure zone diameters to estimate bacterial susceptibility to antimicrobial agents. Quality control measures necessitate the use of laboratory control microorganisms to ensure the reliability of standardized procedures.

For patient counseling, a report indicating “Susceptible” suggests that the pathogen is likely to be inhibited if the antimicrobial compound reaches achievable blood concentrations. An “Intermediate” report denotes an equivocal result, warranting a repeat test if the microorganism is not fully susceptible to alternative treatments. Conversely, a “Resistant” report indicates that the pathogen is unlikely to be inhibited at achievable blood concentrations, suggesting that other therapeutic options should be considered.

FDA Insert (PDF)

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

View full prescribing information (PDF)