Amoxicillin

Description

Formulations of amoxicillin 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. Its molecular formula is C16H19N3O5S • 3H2O, with a molecular weight of 419.45.

Amoxicillin Capsules, USP, are available in two strengths: 250 mg and 500 mg of amoxicillin as the trihydrate. The 250 mg capsule features a yellow opaque cap and body, imprinted with AMOX 250 on one side and GG 848 on the other. The 500 mg capsule also has a yellow opaque cap and body, imprinted with AMOX 500 on one side and GG 849 on the other. Inactive ingredients include yellow ferric oxide, titanium dioxide, gelatin, black ferric oxide, shellac, propylene glycol, potassium hydroxide, and ammonium hydroxide for the capsule shells, while the capsule contents consist of microcrystalline cellulose and magnesium stearate. Amoxicillin capsules meet the USP Dissolution Test 2.

Uses and Indications

Amoxicillin is 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, and 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 amoxicillin.

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.

For neonates and infants aged 3 months or younger, the maximum dosage is 30 mg per kilogram of body weight per day, divided and administered every 12 hours.

In the treatment of Helicobacter pylori infection, the following regimens are recommended:

• 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 a duration of 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 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 undergoing penicillin therapy. Healthcare professionals should be vigilant for signs of anaphylaxis, which may include difficulty breathing, swelling of the face or throat, and rapid heartbeat. In the event of a serious anaphylactic reaction, immediate emergency treatment is required, along with appropriate supportive measures.

Additionally, there is a risk of Clostridium difficile-associated diarrhea, which can range from mild diarrhea to severe, potentially fatal colitis. It is essential for healthcare providers to evaluate patients for diarrhea during and after treatment with penicillin. Prompt assessment and management are crucial to mitigate the risks associated with this condition.

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 medical intervention.

Serious adverse reactions, although less common, can occur and necessitate immediate medical attention. Notably, serious and occasionally fatal anaphylactic reactions have been documented in patients undergoing penicillin therapy. Such reactions require prompt emergency treatment and supportive measures. Additionally, Clostridium difficile-associated diarrhea has been observed, which can range from mild diarrhea to severe, potentially fatal colitis. It is important to evaluate any occurrence of diarrhea in patients receiving this medication.

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 exercise caution when considering amoxicillin therapy.

Overdosage of amoxicillin has been associated with serious adverse effects, including interstitial nephritis leading to oliguric renal failure in a small number of cases. Crystalluria, which may result in renal failure, has also been reported following overdosage in both adult and pediatric patients. Renal impairment due to overdosage appears to be reversible upon cessation of the drug. It is important to note that patients with impaired renal function may experience higher blood levels of amoxicillin due to decreased renal clearance. Hemodialysis can effectively remove amoxicillin from circulation.

Furthermore, caution is advised when administering amoxicillin to nursing mothers, as its use may lead to sensitization of infants.

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 associated with an increased prolongation of prothrombin time. Clinicians should monitor prothrombin time closely in patients receiving this combination and consider adjusting the dosage of the anticoagulant as needed.

Coadministration of amoxicillin with allopurinol has been reported to increase the 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

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 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 through 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 mitigate the risk of adverse effects associated with renal impairment.

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 human dose of 3 g 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 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 nursing women.

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 an 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 amoxicillin below 250 mg/kg are generally not associated with significant clinical symptoms. However, it is important to remain vigilant for potential adverse effects.

Reports have documented cases of interstitial nephritis leading to oliguric renal failure following amoxicillin overdosage in a limited number of patients. Additionally, crystalluria has been observed, which in some instances has resulted in renal failure among both adult and pediatric patients. To mitigate the risk of crystalluria, it is essential to ensure adequate fluid intake and maintain diuresis during an overdosage scenario.

Renal impairment resulting from overdosage appears to be reversible upon cessation of amoxicillin administration. It is noteworthy that patients with pre-existing renal dysfunction may experience elevated blood levels of the drug due to decreased renal clearance.

For patients experiencing severe overdosage, hemodialysis may be employed as a method to remove amoxicillin from circulation effectively.

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 clavulanate potassium provide relevant insights.

The combination of amoxicillin and clavulanate potassium was found to be nonmutagenic 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 combination was negative in the mouse micronucleus test and in the dominant lethal assay in mice.

Potassium clavulanate, when tested independently, was negative in the Ames bacterial mutation assay and in the mouse micronucleus test, 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 diarrhea as a common adverse event associated with the use of amoxicillin, typically resolving upon discontinuation of the antibiotic. Additionally, there have been reports of patients developing watery and bloody stools, with or without accompanying symptoms such as stomach cramps and fever, even up to two months after completing treatment. Patients experiencing these symptoms are advised to contact their physician promptly. Furthermore, amoxicillin, being a penicillin-class antibiotic, has been associated with allergic reactions in some individuals.

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 counseled that it is common to feel better early in the course of therapy. However, they must take the medication 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.

Patients should also be informed that diarrhea is a common side effect associated with antibiotics, including amoxicillin, and it typically resolves once the antibiotic is discontinued. However, patients should be made aware that they can develop watery and bloody stools, with or without stomach cramps and fever, even as late as two or more 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

Capsules are supplied in a tight container to ensure their integrity. They should be stored at a temperature range of 20° to 25°C (68° to 77°F) to maintain optimal quality and efficacy.

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 Cambridge Therapeutics Technologies, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)