Amoxicillin

Description

Amoxicillin is a semisynthetic antibacterial agent, an analog of ampicillin, exhibiting a broad spectrum of bactericidal activity against various Gram-positive and Gram-negative microorganisms. Its chemical structure 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 of amoxicillin is C16H19N3O5S • 3H2O, with a molecular weight of 419.45.

Amoxicillin is available in several dosage forms. Each capsule, characterized by a yellow opaque cap and body, contains either 250 mg or 500 mg of amoxicillin as the trihydrate. The inactive ingredients in these capsules include yellow ferric oxide, titanium dioxide, gelatin, black ferric oxide, shellac, propylene glycol, potassium hydroxide, and ammonium hydroxide. The film-coated tablets contain 500 mg or 875 mg of amoxicillin as the trihydrate, presented in an oval shape and white to yellowish in color. Inactive ingredients in the tablets consist of colloidal silicon dioxide, crospovidone, ethylcellulose aqueous dispersion, hypromellose, magnesium stearate, microcrystalline cellulose, sodium starch glycolate, talc, triethyl citrate, and titanium dioxide.

For oral suspension, amoxicillin is available in reconstituted forms containing 125 mg, 200 mg, 250 mg, or 400 mg of amoxicillin per 5 mL. These suspensions are fruity flavored and pink in color. The inactive ingredients in the oral suspension include anhydrous citric acid, colloidal silicon dioxide, flavorings (raspberry, strawberry, refrachessement), FD&C Red 40, sodium benzoate, sodium citrate, sucrose, and xanthan gum.

Uses and Indications

Amoxicillin is indicated for the treatment of infections caused by susceptible strains of designated microorganisms. This drug is utilized in the management of 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 prescribed 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 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 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 and cephalosporins.

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.

Clostridiodes difficile-associated diarrhea (CDAD) can manifest in a spectrum ranging from mild diarrhea to severe, potentially fatal colitis. Healthcare professionals should evaluate any patient presenting with diarrhea during or after treatment with amoxicillin, as timely assessment and intervention are essential.

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, however, warrant immediate attention. Anaphylactic reactions, which can be serious and occasionally fatal, have been reported in patients undergoing penicillin therapy, including amoxicillin. It is crucial to discontinue amoxicillin 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 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, Clostridiodes difficile-associated diarrhea (CDAD) can range from mild diarrhea to fatal colitis, and evaluation is recommended 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 closely monitored or may need to avoid amoxicillin altogether.

Overdosage of amoxicillin has been linked to serious complications, including interstitial nephritis resulting in oliguric renal failure, which has been reported in a small number of patients. Crystalluria, which in some cases has led to renal failure, has also been documented following 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 agents 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 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 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 amoxicillin should be modified for pediatric patients aged 12 weeks or younger (3 months or younger) to account for this developmental consideration.

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 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 indicates that reproduction studies conducted in mice and rats at doses up to 2000 mg/kg (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, while 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

The available data does not include specific information regarding dosing adjustments, monitoring, or precautions for patients with renal impairment. Therefore, healthcare professionals should refer to the prescribing information for guidance on the management of patients with reduced kidney function, including any necessary adjustments based on creatinine clearance or other relevant clinical findings. It is essential to evaluate renal function prior to initiating treatment and to monitor it regularly throughout the course of therapy to ensure patient safety and efficacy of the medication.

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 and implement symptomatic treatment alongside supportive measures as necessary.

Clinical observations from a prospective study indicate that overdosages of amoxicillin below 250 mg/kg typically do not result in significant clinical symptoms. However, it is essential to remain vigilant for potential adverse effects, as interstitial nephritis leading to oliguric renal failure has been documented following amoxicillin overdosage. Additionally, crystalluria has been reported, 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 crucial to ensure adequate fluid intake and maintain diuresis. This approach helps to facilitate the elimination of the drug and reduce the likelihood of renal complications. Notably, renal impairment resulting from overdosage appears to be reversible upon cessation of amoxicillin administration.

Healthcare professionals should also be aware that patients with pre-existing renal impairment may experience elevated blood levels of amoxicillin due to decreased renal clearance. In cases of 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 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

Postmarketing experience has identified several adverse reactions reported voluntarily or through surveillance programs. These include allergic reactions, with cases of anaphylaxis noted. Severe cutaneous adverse reactions (SCAR) have also been reported, including instances of Stevens-Johnson syndrome and toxic epidermal necrolysis.

Additionally, hepatic dysfunction has been observed, characterized by elevated liver enzymes and jaundice. Renal dysfunction, specifically interstitial nephritis, has been documented as well. Hematologic reactions such as thrombocytopenia, leukopenia, and hemolytic anemia have been reported.

Gastrointestinal disorders, including Clostridium difficile-associated diarrhea, have been noted in the postmarketing data. Furthermore, cases of superinfection due to antibiotic resistance have been identified.

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 of the antibacterial drug. 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 course, 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 risk of bacteria developing resistance, rendering amoxicillin or other antibacterial drugs ineffective in the future.

Patients should be advised that it is preferable to refrigerate amoxicillin suspensions, although this is not mandatory. They should shake the oral suspension well before each use and 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.

Storage and Handling

Capsules, tablets, and unreconstituted powder for oral suspension are supplied in a tight container. The recommended storage temperature for these products is between 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. It is essential to maintain these conditions to ensure the integrity and efficacy of the products.

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 REMEDYREPACK INC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)