Amoxicillin

Description

Amoxicillin capsules, USP, are formulated to 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-azabicyclo3.2.0heptane-2-carboxylic acid trihydrate. The molecular formula is C16H19N3O5S•3H2O, with a molecular weight of 419.45.

Each capsule is available in two strengths: 250 mg and 500 mg of amoxicillin as the trihydrate. The 250 mg capsule features a blue cap and a pink body, with the body imprinted with ‘A44’ in black ink. The 500 mg capsule also has a blue cap and a pink body, marked with ‘A45’ in black ink. Inactive ingredients include D&C Red No. 28, FD&C Blue No. 1, FD&C Red No. 40, gelatin, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, and titanium dioxide. This formulation meets the USP Dissolution Test 2.

Uses and Indications

Amoxicillin capsules, USP are indicated for the treatment of infections caused by susceptible strains of designated microorganisms. This includes infections of the ear, nose, throat, genitourinary tract, skin and skin structure, as well as the lower respiratory tract. Additionally, amoxicillin is indicated in combination therapy for the treatment of Helicobacter pylori infection and duodenal ulcer disease.

There are no teratogenic or nonteratogenic effects associated with the use of amoxicillin capsules, USP.

Dosage and Administration

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

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

• 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.

• Dual Therapy: Administer 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 of this product is contraindicated in patients with a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to amoxicillin capsules 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. Healthcare professionals should be vigilant for signs of anaphylaxis, which necessitate immediate emergency treatment and supportive measures. It is critical to assess the patient's history for any prior allergic reactions to penicillin or related antibiotics before initiating therapy.

In addition, Clostridium difficile associated diarrhea (CDAD) has been observed in patients treated with penicillin, with manifestations ranging from mild diarrhea to potentially fatal colitis. If a patient develops diarrhea during or after treatment, it is essential to evaluate the situation promptly. Clinicians should consider the possibility of CDAD and take appropriate action, which may include discontinuation of the antibiotic and further diagnostic testing as necessary.

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 may not require medical intervention.

Serious adverse reactions, although less common, can occur and necessitate immediate medical attention. Notably, serious and occasionally fatal anaphylactic reactions have been reported in patients undergoing penicillin therapy. Such reactions require prompt emergency treatment and supportive measures. Additionally, Clostridium difficile associated diarrhea can manifest, ranging from mild diarrhea to severe, potentially fatal colitis; therefore, it is crucial to evaluate any occurrence of diarrhea in patients.

Patients with a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to amoxicillin capsules or other beta-lactams (including penicillins or cephalosporins) should be closely monitored.

Furthermore, interstitial nephritis resulting in oliguric renal failure has been documented in a small number of patients following amoxicillin overdosage. Crystalluria, which in some instances has led to renal failure, has also been reported in both adult and pediatric patients after overdosage with amoxicillin.

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 observed to increase the prolongation of prothrombin time. Clinicians should monitor prothrombin time closely in patients receiving this combination to ensure appropriate anticoagulation levels.

Coadministration of amoxicillin with allopurinol has been associated with an increased 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 hormonal contraceptives should be advised to consider alternative or additional contraceptive methods during and after 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

An analysis of clinical studies of amoxicillin has been conducted to evaluate the response of subjects aged 65 and over compared to younger patients. The findings from these analyses did not identify significant differences in responses between elderly and younger patients; 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

Amoxicillin is classified as Pregnancy Category B. Reproductive 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. 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

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 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 initiate 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 important to note that there have been reports of interstitial nephritis leading to oliguric renal failure in a small number of patients following amoxicillin overdosage. Additionally, crystalluria has been documented, which in some instances has resulted in renal failure among both adult and pediatric patients.

To mitigate the risk of crystalluria associated with amoxicillin overdosage, it is essential to maintain adequate fluid intake and promote diuresis. Renal impairment observed in these cases 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 decreased renal clearance.

For patients experiencing severe overdosage, hemodialysis may be employed as a method to remove amoxicillin from circulation effectively. Continuous monitoring and appropriate management are crucial to ensure patient safety and recovery.

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

Patients have reported the occurrence of watery and bloody stools, which may present with or without accompanying symptoms such as stomach cramps and fever. These events have been noted to arise even as late as two months or more following the last dose of the antibiotic. In such instances, it is advised that patients contact their physician promptly for further evaluation and management.

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 are ineffective against 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. Patients should be cautioned that 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 upon discontinuation of the medication. However, 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 contact their physician promptly.

Additionally, patients should be made aware that amoxicillin contains a penicillin class drug product, which can cause allergic reactions in some individuals. It is essential 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 container to ensure integrity and stability. It should be stored 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) as defined by USP Controlled Room Temperature guidelines.

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 Aidarex Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)