Amoxicillin

Description

Amoxicillin is a semisynthetic antibacterial, an analog of ampicillin, with a broad spectrum of bactericidal activity against many Gram-positive and Gram-negative microorganisms. Chemically, it is (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 is C16H19N3O5S·3H2O, and its molecular weight is 419.45.

Amoxicillin is available in several dosage forms. Each tablet contains either 500 mg or 875 mg of amoxicillin as the trihydrate. The inactive ingredients in each 500 mg or 875 mg tablet include colloidal silicon dioxide, crospovidone, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, and titanium dioxide.

For the reconstituted suspension, each 5 mL contains either 200 mg or 400 mg of amoxicillin as the trihydrate. The 200-mg reconstituted suspension contains 0.15 mEq (3.39 mg) of sodium, while the 400-mg reconstituted suspension contains 0.19 mEq (4.33 mg) of sodium. Inactive ingredients in the suspension include flavorings, silica gel, sodium benzoate, sodium citrate, sucrose, and xanthan gum.

Chewable tablets of amoxicillin are available in strengths of 125 mg, 200 mg, 250 mg, and 400 mg as the trihydrate. The inactive ingredients in each 125 mg and 250 mg chewable tablet consist of mannitol, glycine, magnesium stearate, silica gel, flavorings, citric acid, saccharin sodium, and confectioner’s sugar. The 200 mg and 400 mg chewable tablets contain mannitol, crospovidone, flavorings, magnesium stearate, and aspartame.

Uses and Indications

AMOXICILLIN is 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 adults only

AMOXICILLIN 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 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 to 45 mg/kg 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/kg per day, divided and administered every 12 hours.

In the treatment of H. pylori infection in adults, two therapeutic regimens are recommended. 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 or cephalosporins.

Warnings and Precautions

Serious and occasionally fatal anaphylactic reactions have been reported in patients receiving penicillin therapy, including amoxicillin. In the event of an anaphylactic reaction, it is imperative to discontinue amoxicillin immediately.

Healthcare professionals should monitor patients closely for severe cutaneous adverse reactions (SCAR). If any rash progresses, amoxicillin should be discontinued without delay.

Additionally, drug-induced enterocolitis syndrome (DIES) has been associated with the use of amoxicillin. Should this condition arise, it is essential to discontinue amoxicillin and initiate appropriate therapeutic measures.

Clostridioides difficile-associated diarrhea (CDAD) can occur in patients taking amoxicillin, presenting with symptoms that may range from mild diarrhea to severe, potentially fatal colitis. If a patient experiences diarrhea during treatment, a thorough evaluation is warranted to determine the appropriate course of action.

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, although less common, warrant immediate attention. Anaphylactic reactions, which can be serious and occasionally fatal, have been reported in patients undergoing penicillin therapy, including amoxicillin. In the event of such a reaction, amoxicillin should be discontinued promptly. Additionally, severe cutaneous adverse reactions (SCAR) have been observed; patients should be monitored closely, and treatment should be stopped 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 occur, presenting a spectrum from mild diarrhea to potentially fatal colitis, and should be evaluated if diarrhea develops.

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) are at increased risk for allergic reactions.

Additional adverse reactions of note include interstitial nephritis, which has resulted in oliguric renal failure 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

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 prolonged 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 medications 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 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 AMOXIL 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 AMOXIL 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 AMOXIL should be modified for pediatric patients aged 12 weeks or younger (3 months or younger) to account for this developmental consideration.

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

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 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 infant exposure to amoxicillin through breast milk. Caution is advised when administering amoxicillin to nursing mothers to mitigate any potential risks to breastfed infants.

Renal Impairment

Patients with renal impairment have no specific information regarding dosage adjustments, special monitoring, or safety considerations provided in the text. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing to this population. Regular assessment of renal function may be warranted to ensure safe and effective use of the medication in patients with reduced kidney function.

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. Symptomatic treatment and supportive measures should be instituted as necessary to manage the patient's condition effectively.

Clinical Symptoms

A prospective study indicates 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 overdosage. Additionally, crystalluria has been documented, which in some instances has progressed to renal failure in both adult and pediatric populations.

Management Recommendations

To mitigate the risk of crystalluria associated with amoxicillin overdosage, it is essential to maintain adequate fluid intake and promote diuresis. This approach helps to ensure proper renal function and reduces the likelihood of complications.

Patients with impaired renal function may experience elevated blood levels of amoxicillin due to decreased renal clearance. Therefore, careful monitoring of renal function is advised in these individuals.

In cases of severe overdosage, hemodialysis may be employed as a method to remove amoxicillin from circulation, thereby aiding in the management of the patient's condition.

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 (AUGMENTIN) provide relevant insights.

AUGMENTIN 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 occurred at doses that were also associated with decreased cell survival. In contrast, AUGMENTIN was negative in the mouse micronucleus test and in the dominant lethal assay in mice. Potassium clavulanate, when tested alone in the Ames bacterial mutation assay and the mouse micronucleus test, also yielded 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 are available in the extracted data. As such, there are no additional adverse events or rare case reports to summarize at this time.

Patient Counseling

Patients should be advised that amoxicillin 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 and instructed to stop taking amoxicillin immediately and promptly report any signs or symptoms of skin rash, mucosal lesions, or other indications of hypersensitivity.

Patients should also be made aware that diarrhea is a common side effect associated with antibacterial drugs, typically resolving upon discontinuation of the medication. However, they should be cautioned that watery and bloody stools, with or without stomach cramps and fever, may occur even as late as two months after the last dose. In such cases, patients should contact their physician as soon as possible.

It is essential to counsel patients that antibacterial drugs, including amoxicillin, 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 informed that while it is common to feel better early in the treatment, 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, making them untreatable by amoxicillin or other antibacterial drugs in the future.

For patients using amoxicillin suspensions, it is preferable to refrigerate the product, although this is not mandatory. Patients should be instructed to shake the oral suspension well before each use and to keep the bottle tightly closed. When dosing a child with the suspension, a calibrated oral syringe should be used, and it is important to rinse the syringe after each use. Patients should follow their doctor’s instructions regarding the appropriate amount to use and the duration of treatment required for their child. Any unused portion of the suspension should be discarded after 14 days.

Additionally, patients with phenylketonuria should be counseled that each 200 mg chewable tablet contains 1.82 mg of phenylalanine, while each 400 mg chewable tablet contains 3.64 mg of phenylalanine.

Storage and Handling

The product is supplied in a tight container to ensure its integrity and stability. It should be stored at or below 25° C (77° F) to maintain optimal conditions. Proper handling and storage are essential to preserve the quality of the product.

Additional Clinical Information

Patients should be advised on the administration of amoxicillin, which can be taken every 8 or 12 hours based on the prescribed dosage. It is important to inform patients that amoxicillin is a penicillin-class drug that may cause allergic reactions. They should be educated on the signs and symptoms of severe cutaneous adverse reactions (SCAR) and instructed to discontinue use and report any rash, mucosal lesions, or other hypersensitivity signs immediately.

Diarrhea is a common side effect associated with antibacterial drugs, including amoxicillin, and may persist even after treatment has ended. Patients should be aware that watery or bloody stools, potentially accompanied by stomach cramps and fever, can occur up to two months post-treatment, necessitating prompt medical consultation. Additionally, patients must understand that amoxicillin is effective only against bacterial infections and should not be used for viral infections. Adherence to the prescribed regimen is crucial to prevent reduced effectiveness and the development of antibacterial resistance.

For storage, amoxicillin suspensions are preferably refrigerated, shaken well before use, and kept tightly closed. When administering the suspension to children, a calibrated oral syringe should be used, and any unused portion should be discarded after 14 days. Patients with phenylketonuria should be informed that the 200 mg chewable tablet contains 1.82 mg of phenylalanine, while the 400 mg chewable tablet contains 3.64 mg.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Amoxicillin as submitted by REMEDYREPACK INC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)