Amoxicillin

Description

Amoxicillin, USP is 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 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, with a molecular weight of 419.45. The structural formula is represented as C₁₆H₁₉N₃O₅S•3H₂O.

Amoxicillin is available in several dosage forms:

• Capsules: Each capsule for oral administration contains either 250 mg or 500 mg of amoxicillin, USP as the trihydrate. Inactive ingredients include magnesium stearate and talc. The capsule shell and print constituents consist of black iron oxide, D&C Yellow #10, D&C Yellow #10 Aluminum Lake, FD&C Blue #1 Aluminum Lake, FD&C Blue #2 Aluminum Lake, FD&C Red #40, FD&C Red #40 Aluminum Lake, gelatin, propylene glycol, shellac, and titanium dioxide. The 500 mg capsule shell may also contain methylparaben, potassium hydroxide, propylparaben, and sodium lauryl sulfate, while the 250 mg capsule shell includes D&C Red #28 and FD&C Blue #1.

• Oral Suspension: Each 5 mL of reconstituted suspension contains 125 mg or 250 mg of amoxicillin, USP as the trihydrate. Inactive ingredients in the suspension include FD&C Red #40, mixed berry flavoring, silicon dioxide, sodium benzoate, sodium citrate, sucrose, and xanthan gum.

• Chewable Tablets: Each chewable tablet for oral administration contains 125 mg or 250 mg of amoxicillin, USP as the trihydrate. Inactive ingredients consist of cherry flavor, lactose anhydrous, magnesium stearate, mannitol, microcrystalline cellulose, sodium citrate, and sucrose.

Uses and Indications

Amoxicillin is a penicillin-class antibacterial indicated for the treatment of infections caused by susceptible strains of designated microorganisms. It is effective in managing infections of the ear, nose, throat, genitourinary tract, skin and skin structure, and lower respiratory tract. Additionally, amoxicillin is indicated for use in combination therapy for the treatment of Helicobacter pylori infection and duodenal ulcer disease.

Amoxicillin should be prescribed only for infections that are proven or strongly suspected to be bacterial in origin. This approach is essential to reduce the development of drug-resistant bacteria and to maintain the effectiveness of amoxicillin and other antibacterial agents.

There are no teratogenic or nonteratogenic effects associated with amoxicillin as per the available data.

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 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 treatment of Helicobacter pylori infection, the following regimens are recommended: for triple therapy, administer 1 gram of amoxicillin, 500 mg of clarithromycin, and 30 mg of lansoprazole, all given twice daily (every 12 hours) for a duration of 14 days. For dual therapy, the regimen consists of 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.

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.

In addition, Clostridium difficile associated diarrhea, which can range from mild diarrhea to severe and potentially fatal colitis, has been observed in patients receiving this therapy. It is imperative to evaluate any occurrence of diarrhea promptly to determine the appropriate course of action.

No specific general precautions or laboratory tests have been identified in the current guidelines. However, the potential for serious adverse reactions underscores the importance of monitoring patients closely during treatment.

Side Effects

Patients receiving treatment with amoxicillin may experience a range of adverse reactions. Common adverse reactions include diarrhea, rash, vomiting, and nausea. These reactions are generally mild and self-limiting.

Serious adverse reactions have also been reported. Notably, anaphylactic reactions, which can be serious and occasionally fatal, have occurred in patients undergoing penicillin therapy. Such reactions necessitate immediate emergency treatment and supportive measures. Additionally, Clostridium difficile associated diarrhea has been observed, with manifestations ranging from mild diarrhea to potentially fatal colitis; therefore, it is important to evaluate any occurrence of diarrhea in patients.

Other significant adverse reactions include 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 resulting in oliguric renal failure has been documented in a small number of patients following amoxicillin overdosage. Crystalluria, which in some cases has led to renal failure, has also been reported after overdosage in both adult and pediatric patients.

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.

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 to ensure appropriate anticoagulation management.

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 prevent unintended pregnancy.

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

Clinical studies of amoxicillin have been analyzed to assess whether elderly patients, specifically those aged 65 and over, exhibit different responses compared to younger individuals. The findings from these analyses indicate no significant differences in responses between these age groups; however, it is important to note that a greater sensitivity to the drug in some older individuals cannot be entirely excluded.

Amoxicillin is primarily excreted through the kidneys, which raises concerns regarding the potential for toxic reactions, particularly in patients with impaired renal function. Given that geriatric 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 in elderly patients to mitigate the risk of adverse effects associated with renal impairment.

Pregnancy

Amoxicillin is classified as Pregnancy Category B. Reproduction studies conducted in mice and rats at doses up to 2000 mg/kg, which is 3 and 6 times the human dose of 3 g based on body surface area, have shown no evidence of harm to 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, amoxicillin should be used during pregnancy only if clearly needed. Healthcare professionals are advised to weigh the potential benefits against any possible risks when prescribing this medication to 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

There is no specific information available 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 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 outlined 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, it is essential to monitor for potential adverse effects, as interstitial nephritis leading to oliguric renal failure has been documented in a small number of cases following amoxicillin overdosage.

Crystalluria has also been reported in both adult and pediatric patients after amoxicillin overdosage, with some instances progressing to renal failure. To mitigate the risk of crystalluria, it is crucial to ensure adequate fluid intake and maintain diuresis.

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 decreased renal clearance.

In cases of severe overdosage, hemodialysis may be employed to facilitate the removal of amoxicillin from circulation. Healthcare professionals should remain vigilant and implement appropriate management strategies to address any complications arising from overdosage.

Nonclinical Toxicology

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of the compound. 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 a weakly positive response in the mouse lymphoma assay, where the observed trend toward increased mutation frequencies coincided with doses that also resulted in decreased cell survival. In contrast, the mixture was negative in the mouse micronucleus test and the dominant lethal assay in mice.

Potassium clavulanate alone was evaluated 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 human dose of 3 g based on body surface area.

Postmarketing Experience

Postmarketing experience has revealed that diarrhea is a frequently reported issue associated with antibiotic use, typically resolving upon discontinuation of the medication. Notably, patients may experience watery and bloody stools, with or without accompanying symptoms such as stomach cramps and fever, even up to two months after completing antibiotic treatment. In such instances, it is advised that patients contact their physician promptly.

Additionally, it is important for patients to be informed that amoxicillin, as a penicillin-class antibiotic, has the potential to elicit allergic reactions in certain individuals.

Patient Counseling

Patients should be advised that amoxicillin 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, are intended solely for the treatment of bacterial infections and do not address viral infections, such as the common cold. When amoxicillin is prescribed for a bacterial infection, patients should be informed that it is common to feel better early in the course of therapy; however, the medication must be taken 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 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 once the antibiotic is discontinued. It is important to inform patients that they 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 such symptoms occur, patients should be advised to contact their physician promptly.

Additionally, patients should be made aware that amoxicillin 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 that complies with USP standards and includes a child-resistant closure as required. 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 handling and storage conditions are essential to maintain the integrity of the product.

Additional Clinical Information

When available, the clinical microbiology laboratory should provide cumulative in vitro susceptibility test results for antimicrobial drugs utilized in local hospitals and practice areas. These periodic reports, which describe the susceptibility profiles of nosocomial and community-acquired pathogens, are intended to assist physicians in selecting the most effective antimicrobial therapy for their patients.

Standardized susceptibility test procedures necessitate the use of laboratory controls to monitor and ensure the accuracy and precision of the supplies and reagents employed in the assay, as well as the techniques of the individuals conducting the tests.

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)