Amoxicillin

Description

Amoxicillin Tablets, USP are semisynthetic antibacterial agents, specifically amoxicillin, which is an analog of ampicillin. These tablets exhibit 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 contains 875 mg of amoxicillin as the trihydrate. The tablets are capsule-shaped, white, and scored on one side, with the engraving WW951 on the opposite side. Inactive ingredients include colloidal silicone dioxide, crospovidone, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol-partially hydrolyzed, polyethylene glycol, sodium starch glycolate, talc, 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 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 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 includes 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 tablets 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 tablets immediately.

Healthcare professionals should monitor patients closely for the development of 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 tablets and initiate appropriate therapeutic measures.

Clostridioides difficile-associated diarrhea (CDAD) can occur in patients taking amoxicillin, presenting a spectrum of severity from mild diarrhea to 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 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 tablets 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 any rash progresses. Drug-induced enterocolitis syndrome (DIES) has also been reported with amoxicillin use, necessitating discontinuation of the medication 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 treated with caution.

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

Drug Interactions

Co-administration of amoxicillin tablets with probenicid is not recommended due to potential interactions that may affect the pharmacokinetics of amoxicillin.

When amoxicillin tablets are used concurrently with oral anticoagulants, there is an increased risk of prolongation of prothrombin time. Monitoring of prothrombin time is advised to ensure patient safety and appropriate anticoagulation management.

The concomitant use of amoxicillin tablets and allopurinol has been associated with an increased risk of rash. Caution is advised when these medications are prescribed together, and patients should be monitored for dermatological reactions.

Additionally, amoxicillin tablets may reduce the efficacy of oral contraceptives. Patients using both amoxicillin and oral contraceptives should be counseled on alternative or additional contraceptive methods 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

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 tablets 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 accordingly in 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 did not identify 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 geriatric 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 elderly patients to mitigate potential risks associated with the use of this medication.

Pregnancy

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 teratogenic effects or harm to the fetus due to amoxicillin. However, there are no adequate and well-controlled studies in pregnant women. Therefore, amoxicillin should be used during pregnancy only if clearly needed, as animal reproduction studies are not always predictive of human response. Healthcare professionals should weigh the potential benefits against the 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

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to 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 administration of amoxicillin tablets immediately. Symptomatic treatment should be initiated, and supportive measures should be instituted as necessary to manage the patient's condition.

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 remain vigilant for potential adverse effects, as interstitial nephritis leading to oliguric renal failure has been documented in a small number of cases following overdosage.

Crystalluria has also been reported in both adult and pediatric patients after amoxicillin overdosage, with some instances progressing to renal failure. To mitigate the risk of crystalluria, it is essential to maintain adequate fluid intake and promote diuresis. Renal impairment associated with overdosage appears to be reversible upon cessation of amoxicillin administration.

Healthcare professionals should be aware that patients with impaired renal function may experience elevated blood levels of amoxicillin due to decreased renal clearance. In cases of severe overdosage, 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.

In the Ames bacterial mutation assay and the yeast gene conversion assay, the combination of amoxicillin and potassium clavulanate demonstrated non-mutagenic properties. However, in the mouse lymphoma assay, the mixture was weakly positive, with a noted trend toward increased mutation frequencies occurring at doses that also resulted in decreased cell survival. Conversely, the mixture was negative in the mouse micronucleus test and the dominant lethal assay in mice.

Potassium clavulanate, when tested alone in the Ames bacterial mutation assay and the mouse micronucleus test, yielded negative results in both assays, indicating no mutagenic potential.

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 skin reactions have been noted, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Instances of hepatic dysfunction have been observed, characterized by elevated liver enzymes and jaundice. Renal impairment has also been reported, specifically interstitial nephritis.

Hematologic reactions, such as thrombocytopenia, leukopenia, and hemolytic anemia, have been documented. Additionally, allergic reactions, including anaphylaxis and angioedema, have been recorded. Gastrointestinal disorders, particularly Clostridium difficile-associated diarrhea, have also been reported in the postmarketing setting.

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 tablets 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 immediate treatment and increase the likelihood of bacteria developing resistance, rendering amoxicillin tablets or other antibacterial drugs ineffective in the future.

Storage and Handling

The product is supplied in a tight, light-resistant container, as defined by the United States Pharmacopeia (USP), and is equipped with a child-resistant closure to ensure safety. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper adherence to these storage conditions is essential for maintaining the integrity and efficacy 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 Hikma Pharmaceuticals USA Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)