Amoxicillin

Description

Amoxicillin tablets, USP, are semisynthetic antibacterial agents derived from 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-azabicyclo3.2.0heptane-2-carboxylic acid trihydrate. The molecular formula is C16H19N3O5S • 3H2O, with a molecular weight of 419.45.

Each film-coated tablet is available in two strengths: 500 mg and 875 mg of amoxicillin USP as the trihydrate. The 500 mg tablets are pink, capsule-shaped, and debossed with “A” on one side and “66” on the other. The 875 mg tablets are also pink, capsule-shaped, and feature a debossed “A” on one side with a score line between “6” and “7” on the opposite side. Inactive ingredients include colloidal silicon dioxide, crospovidone, D&C Red No. 30 aluminum lake, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, and titanium dioxide.

Uses and Indications

Amoxicillin tablets are indicated for the treatment of infections caused by susceptible strains of designated microorganisms. This medication 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 adults only

Amoxicillin tablets should be utilized exclusively for the treatment or prevention of 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 tablets and other antibacterial agents.

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. 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/kg/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 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, including anaphylaxis or Stevens-Johnson syndrome, to amoxicillin tablets or other beta-lactam antibiotics, such as penicillins or cephalosporins. This contraindication is due to the potential for severe allergic reactions in these individuals.

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

Serious adverse reactions necessitate immediate medical attention and discontinuation of amoxicillin. Anaphylactic reactions, which can be serious and occasionally fatal, have been reported in patients undergoing penicillin therapy, including amoxicillin. Patients should be monitored closely for any signs of hypersensitivity, particularly those with a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to amoxicillin or other beta-lactams.

Severe cutaneous adverse reactions (SCAR) have also been observed; patients should be monitored for the progression of any rash, and amoxicillin should be discontinued if the rash worsens. Additionally, drug-induced enterocolitis syndrome (DIES) has been reported with amoxicillin use, and if this condition occurs, amoxicillin should be discontinued, and appropriate therapy should be initiated.

Clostridioides difficile-associated diarrhea (CDAD) can range from mild diarrhea to severe, potentially fatal colitis. Patients experiencing diarrhea should be evaluated for this condition.

Overdosage of amoxicillin has been associated with serious adverse effects, including interstitial nephritis leading to oliguric renal failure, as well as crystalluria, which in some cases has resulted in renal failure in both adult and pediatric patients.

Drug Interactions

Co-administration of amoxicillin with probenicid 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 hormonal contraceptives should be advised to consider alternative or additional contraceptive methods 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 pediatric patients aged 12 weeks or younger (3 months or younger), caution is advised due to incompletely developed renal function, which may delay the elimination of amoxicillin. Therefore, dosing should be modified for this age group 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 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 mitigate potential risks associated with the use of this medication.

Pregnancy

Pregnancy Category B indicates that reproduction studies conducted in mice and rats at doses up to 2000 mg/kg (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 lactating mothers may lead to sensitization of breastfed infants. Therefore, caution should be exercised when administering amoxicillin to a nursing woman.

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 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 amoxicillin 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 less than 250 mg/kg of amoxicillin typically do not result in significant clinical symptoms.

However, it is important to note that interstitial nephritis leading to oliguric renal failure has been documented in a limited number of cases following amoxicillin overdosage. Additionally, crystalluria, which can occasionally result in renal failure, has been reported in both adult and pediatric populations after excessive doses 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 associated with amoxicillin overdosage appears to be reversible upon cessation of the drug. It is also noteworthy that patients with pre-existing renal impairment 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 circulation.

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 in 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 two times the 3 g human dose 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 tablets 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 tablets 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 experience watery and bloody stools (with or without stomach cramps and fever) even as late as two months after their last dose. If such symptoms occur, patients should contact their physician as soon as possible.

It is essential to inform patients that antibacterial drugs, including amoxicillin tablets, are intended solely for the treatment or prevention of bacterial infections and do not address 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 reduce the effectiveness of the treatment and increase the risk of bacteria developing resistance, rendering amoxicillin and other antibacterial drugs ineffective in the future.

Storage and Handling

The product is supplied in a configuration that includes specific NDC numbers, which should be referenced for accurate identification. It is essential to store the product at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F) in accordance with USP Controlled Room Temperature guidelines.

Healthcare professionals are advised to inspect the packaging prior to use; the product should not be utilized if the blister is torn or broken to ensure safety and efficacy. Proper handling and storage conditions are critical to maintaining the integrity of the product.

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 American Health Packaging. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)