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 in 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 exclusively 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 kg 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 upper limit of dosing is 30 mg per kg per day, divided and administered every 12 hours.

In the treatment of H. pylori infection in adults, two therapeutic regimens are available. The 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. Alternatively, the dual therapy involves 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) 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 and 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 discontinue amoxicillin immediately if any signs of an anaphylactic reaction occur.

Severe cutaneous adverse reactions (SCAR) have also been associated with amoxicillin use. Patients should be monitored closely for the development of rashes, and amoxicillin should be discontinued if the rash progresses.

Additionally, drug-induced enterocolitis syndrome (DIES) has been documented in patients taking amoxicillin. In the event that DIES is suspected, it is essential 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 patients for CDAD if they present with diarrhea during or after treatment with amoxicillin.

Side Effects

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

Common adverse reactions observed in clinical trials include diarrhea, rash, vomiting, and nausea. These reactions are generally mild and self-limiting.

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

In cases of overdosage, several adverse reactions have been reported. Interstitial nephritis resulting in oliguric renal failure has occurred in a small number of patients. Crystalluria, which in some instances has led to renal failure, has also been documented following overdosage in both adult and pediatric patients. It is noted that renal impairment appears to be reversible upon cessation of amoxicillin administration. Additionally, patients with impaired renal function may experience higher blood levels of amoxicillin due to decreased renal clearance. Amoxicillin can be removed from circulation by hemodialysis.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

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) see Dosage and Administration (2.3).

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 subjects. The findings from these analyses did not identify 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

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 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

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 is advised 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 amoxicillin overdosage, it is imperative to discontinue the medication immediately and implement symptomatic treatment alongside supportive measures as necessary.

Clinical observations from a prospective study indicate that overdosages of amoxicillin below 250 mg/kg typically do not result in significant clinical symptoms. However, healthcare professionals should remain vigilant for potential adverse effects, as interstitial nephritis leading to oliguric renal failure has been documented in a limited number of cases following overdosage. Additionally, crystalluria has been reported, which in some instances has progressed to renal failure in both adult and pediatric populations.

To mitigate the risk of crystalluria associated with amoxicillin overdosage, it is essential to ensure adequate fluid intake and maintain diuresis. This approach helps to facilitate the elimination of the drug and reduce the likelihood of renal complications. Notably, renal impairment observed in these cases appears to be reversible upon cessation of amoxicillin administration.

It is important to recognize that patients with pre-existing renal impairment may experience elevated blood levels of amoxicillin due to decreased renal clearance. In severe cases of overdosage, hemodialysis may be employed as a method to remove amoxicillin from circulation effectively. Healthcare professionals should monitor renal function closely and provide appropriate interventions as needed.

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

No specific postmarketing experience details have been reported. As such, there are no additional adverse events or rare case reports to summarize at this time.

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 may develop watery and bloody stools (with or without stomach cramps and fever) even as late as two months after taking 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 treatment course, 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 includes 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 RX, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)