Amoxicillin

Description

Amoxicillin, USP is a semisynthetic antibacterial agent, an analog of ampicillin, exhibiting a broad spectrum of bactericidal activity against various Gram-positive and Gram-negative microorganisms. Chemically, it is identified 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. The molecular formula of amoxicillin, USP is C16H19N3O5S•3H2O, with a molecular weight of 419.45.

The drug is available in capsule form for oral administration, with each capsule containing either 250 mg or 500 mg of amoxicillin, USP as the trihydrate. The inactive ingredients in each 250 mg capsule include magnesium stearate, sodium lauryl sulfate, D&C Yellow No. 10, FD&C Yellow No. 6, FD&C Blue No. 1, FD&C Red No. 3, titanium dioxide, and gelatin. The 500 mg capsule contains magnesium stearate, sodium lauryl sulfate, D&C Yellow No. 10, FD&C Yellow No. 6, titanium dioxide, and gelatin.

Uses and Indications

Amoxicillin is a penicillin-class antibacterial indicated for the treatment of infections caused by susceptible strains of designated microorganisms. This drug is specifically indicated for the following conditions:

• Upper Respiratory Tract Infections of the Ear, Nose, and Throat

• Infections of the Genitourinary Tract

• Infections of the Skin and Skin Structure

• Infections of the Lower Respiratory Tract

• Helicobacter pylori Infection and Duodenal Ulcer Disease (for adult patients only)

To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin capsules and other antibacterial drugs, amoxicillin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Dosage and Administration

In adults, the recommended dosage ranges from 750 mg to 1,750 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. Healthcare professionals should refer to the full prescribing information for specific dosing regimens tailored to individual patient needs.

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 in adults, 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 in those with a glomerular filtration rate (GFR) greater 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 receiving penicillin therapy, including amoxicillin. It is imperative that healthcare professionals remain vigilant for signs of anaphylaxis. Should any allergic reaction occur, amoxicillin must be discontinued immediately.

Severe cutaneous adverse reactions (SCAR) have also been associated with amoxicillin use. Patients should be monitored closely for the development of rashes, and if any rash progresses, amoxicillin should be discontinued without delay.

Additionally, drug-induced enterocolitis syndrome (DIES) has been documented in patients taking amoxicillin. In the event that DIES is suspected, it is crucial to discontinue amoxicillin and initiate appropriate therapeutic measures.

Clostridioides difficile-associated diarrhea (CDAD) can manifest in a spectrum ranging from mild diarrhea to severe, potentially fatal colitis. Healthcare professionals should evaluate any patient who presents with diarrhea during or after treatment with amoxicillin, as timely intervention may be necessary.

Side Effects

Patients receiving amoxicillin may experience a range of adverse reactions, which can be categorized into common and serious reactions.

Common adverse reactions reported include diarrhea, rash, vomiting, and nausea. These reactions are generally mild and may not require discontinuation of therapy.

Serious adverse reactions, however, warrant immediate attention. Anaphylactic reactions, which can be serious and occasionally fatal, have been reported in patients undergoing penicillin therapy, including amoxicillin. It is crucial to discontinue amoxicillin if such a reaction occurs. Additionally, severe cutaneous adverse reactions (SCAR) have been noted; patients should be monitored closely, and amoxicillin should be discontinued if the rash progresses. Drug-induced enterocolitis syndrome (DIES) has also been associated with amoxicillin use, necessitating discontinuation and appropriate therapeutic intervention if this condition arises. Furthermore, Clostridioides difficile-associated diarrhea (CDAD) can range from mild diarrhea to fatal colitis, and evaluation is recommended if diarrhea occurs.

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) should be treated with caution.

Overdosage of amoxicillin has been linked to interstitial nephritis, which may result in oliguric renal failure, as reported in a small number of patients. Crystalluria has also been observed, occasionally leading to renal failure in both adult and pediatric patients following overdosage.

Drug Interactions

Coadministration of amoxicillin with probenecid is not recommended due to potential interactions that may affect the pharmacokinetics of amoxicillin.

When amoxicillin is used concurrently with oral anticoagulants, there is an increased risk of prolongation of prothrombin time. Clinicians should monitor prothrombin time closely and consider dosage adjustments of the anticoagulant as necessary.

The concomitant use of amoxicillin and allopurinol has been associated with an increased risk of rash. Patients should be monitored for dermatological reactions, and if a rash occurs, discontinuation of one or both agents may be warranted.

Additionally, amoxicillin may reduce the efficacy of oral contraceptives. Patients using oral contraceptives should be advised to consider alternative or additional contraceptive measures during treatment with amoxicillin.

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

The safety and effectiveness of amoxicillin have been established for the treatment of upper respiratory tract infections, as well as infections of the genitourinary tract, skin and skin structure, and lower respiratory tract in pediatric patients. However, the safety and effectiveness of amoxicillin for the treatment of H. pylori infection have not been established in this population.

In neonates and young infants, renal function is incompletely developed, which may lead to delayed elimination of amoxicillin. Therefore, dosing of amoxicillin should be modified for pediatric patients aged 12 weeks or younger (3 months or younger) to account for this developmental consideration.

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 have not identified 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 ensure safe and effective use of the medication.

Pregnancy

Reproduction studies have been conducted in mice and rats at doses up to 2,000 mg/kg, which is 3 and 6 times the 3 g human dose based on body surface area. These studies did not demonstrate any evidence of harm to the fetus attributable to amoxicillin. However, there are no adequate and well-controlled studies in pregnant women. Due to the limitations of animal reproduction studies in predicting human outcomes, 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

Nursing mothers should be aware of the potential for excretion of amoxicillin in breast milk. There is a risk of adverse effects in breastfed infants; therefore, caution should be exercised when administering amoxicillin to a nursing mother.

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 amoxicillin 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 indicates that overdosages of amoxicillin below 250 mg/kg are generally not associated with significant clinical symptoms. However, it is important to note that more severe outcomes can occur with higher doses. Notably, interstitial nephritis leading to oliguric renal failure has been documented following amoxicillin overdosage. Additionally, crystalluria has been reported, which in some instances has resulted in renal failure among both adult and pediatric patients.

To mitigate the risk of crystalluria, it is essential to maintain adequate fluid intake and promote diuresis in patients who have experienced an overdosage. This is particularly crucial as high blood levels of amoxicillin may develop more readily in individuals with impaired renal function due to decreased renal clearance of the drug.

For patients experiencing severe overdosage, hemodialysis may be employed as a method to remove amoxicillin from circulation, thereby aiding in the management of the overdose.

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 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 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 identified several adverse reactions reported voluntarily or through surveillance programs. Serious allergic reactions, including anaphylaxis, have been documented. Additionally, severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been observed.

Hepatic dysfunction, characterized by elevated liver enzymes and jaundice, has also been reported. Cases of renal impairment, including interstitial nephritis, have been noted. Hematologic reactions, including thrombocytopenia, leukopenia, and hemolytic anemia, have been recorded as well.

Furthermore, Clostridium difficile-associated diarrhea has been reported among other adverse reactions, which include nausea, vomiting, and rash.

Patient Counseling

Healthcare providers should advise patients that amoxicillin capsules may be taken every 8 hours or every 12 hours, depending on the prescribed dosage. It is important to counsel patients that amoxicillin is a penicillin class drug, which can cause allergic reactions in some individuals.

Patients should be informed about the signs and symptoms of serious skin manifestations. They should be instructed to stop taking amoxicillin immediately and promptly report any signs or symptoms of skin rash, mucosal lesions, or other indications of hypersensitivity.

Additionally, healthcare providers should counsel patients that diarrhea is a common side effect associated with antibacterial drugs, typically resolving upon discontinuation of the medication. However, patients should be made aware that they can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after their last dose of the antibacterial drug. If such symptoms occur, patients should contact their physician as soon as possible.

It is essential to inform patients that antibacterial drugs, including amoxicillin, are intended solely for the treatment or prevention of bacterial infections and do not treat viral infections, such as the common cold. When prescribed amoxicillin for a bacterial infection, patients should be reminded that it is common to feel better early in the course of therapy, but 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 them untreatable by amoxicillin or other antibacterial drugs in the future.

Storage and Handling

The product is supplied in a tight, light-resistant container that complies with USP standards and features a child-resistant closure as required. It is essential to store the product at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. Additionally, it is crucial to keep this medication, along with all other medications, out of the reach of children to ensure safety.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)