Amoxicillin

Description

Amoxicillin capsules, 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 capsule is available in two strengths: 250 mg and 500 mg of amoxicillin USP 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. Amoxicillin capsules meet the USP Dissolution Test 2 criteria.

Uses and Indications

Amoxicillin capsules 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 capsules 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 minimize the development of drug-resistant bacteria and to preserve the efficacy of amoxicillin capsules 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 upper limit of dosing is 30 mg/kg/day, divided and administered every 12 hours.

In the treatment of Helicobacter 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 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, including anaphylaxis or Stevens-Johnson syndrome, to amoxicillin capsules 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 remain vigilant for signs of anaphylaxis. Should any allergic reaction occur, amoxicillin must be discontinued immediately.

Severe cutaneous adverse reactions (SCAR) have also been associated with amoxicillin use. Patients should be monitored closely for the development of rashes, and if any rash progresses, amoxicillin should be discontinued without delay.

Additionally, drug-induced enterocolitis syndrome (DIES) has been documented in patients taking amoxicillin. In the event that DIES is suspected, it is crucial 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 any patient who presents with diarrhea during or after treatment with amoxicillin, as timely intervention may be necessary.

Side Effects

Serious adverse reactions associated with amoxicillin include anaphylactic reactions, which can be serious and occasionally fatal. Patients experiencing such reactions should have amoxicillin discontinued immediately. Severe cutaneous adverse reactions (SCAR) have also been reported; patients should be monitored closely, and amoxicillin should be discontinued if any rash progresses. Additionally, drug-induced enterocolitis syndrome (DIES) has been noted in patients using amoxicillin, necessitating discontinuation and appropriate therapeutic intervention if this condition arises. Clostridioides difficile-associated diarrhea (CDAD) can occur, presenting a spectrum from mild diarrhea to potentially fatal colitis, warranting evaluation if diarrhea develops.

Common adverse reactions observed in clinical trials include diarrhea, rash, vomiting, and nausea.

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 exercise caution when considering amoxicillin therapy.

In cases of overdosage, interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients. Crystalluria, which in some instances has led to renal failure, has also been documented following amoxicillin 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 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 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 to ensure adequate contraceptive protection.

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, genitourinary tract infections, skin and skin structure infections, and lower respiratory tract infections 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. Reproduction studies conducted in mice and rats at doses up to 2000 mg/kg, which is 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. Therefore, because animal reproduction studies are not always predictive of human response, amoxicillin should be used during pregnancy only if clearly needed. 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 lactating mothers may lead to sensitization of breastfed infants. Therefore, caution should be exercised when administering amoxicillin to a nursing woman.

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 of these patients.

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. Symptomatic treatment 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, caution is warranted, as 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.

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 reduce the likelihood of 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 to facilitate the removal of amoxicillin from the 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 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 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, 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

Postmarketing experience has identified several adverse reactions reported voluntarily or through surveillance programs. These include severe allergic reactions, such as anaphylaxis, and serious skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Additionally, cases of Clostridium difficile-associated diarrhea have been documented.

Hepatic dysfunction has been observed, characterized by elevated liver enzymes and jaundice. Renal impairment, specifically interstitial nephritis, has also been reported. Hematologic reactions, including thrombocytopenia, leukopenia, and hemolytic anemia, have been noted. Other reactions include angioedema and various hypersensitivity reactions.

Patient Counseling

Healthcare providers should advise patients 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. 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 2 or more months after 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 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; however, 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 amoxicillin or other antibacterial drugs ineffective in the future.

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. Proper storage conditions are essential to maintain the product's efficacy and 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 Aurobindo Pharma Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)