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 contains either 250 mg or 500 mg of amoxicillin as the trihydrate. The inactive ingredients in amoxicillin capsules include yellow ferric oxide, titanium dioxide, gelatin, black ferric oxide, shellac, propylene glycol, potassium hydroxide, and ammonium hydroxide. Each film-coated tablet contains 500 mg or 875 mg of amoxicillin as the trihydrate, and these tablets are oval-shaped, appearing white to yellowish.

For oral suspension, amoxicillin is provided in concentrations of 125 mg, 200 mg, 250 mg, or 400 mg per 5 mL of reconstituted suspension. The oral suspension is a fruity flavored pink liquid. 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 a penicillin-class antibacterial 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

To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin and other antibacterial drugs, amoxicillin should be utilized exclusively for the treatment or prevention of infections that are proven or strongly suspected to be caused by bacteria.

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/kg/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 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. 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 who presents with diarrhea during or after treatment with amoxicillin, as timely intervention may be necessary.

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 treated with caution.

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

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

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 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

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 did not reveal 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 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 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 teratogenic effects or harm to the fetus due to amoxicillin. However, there are no adequate and well-controlled studies in pregnant women. Therefore, due to the limitations of animal reproduction studies in predicting 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 nursing mothers may lead to sensitization of breastfed infants. Therefore, caution should be exercised when administering amoxicillin to lactating mothers.

Renal Impairment

There are no specific dosing adjustments, monitoring requirements, or precautions indicated for patients with renal impairment. The prescribing information does not provide details regarding the management of patients with reduced kidney function. As such, healthcare professionals should consider the absence of guidance when treating 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 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.

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 monitor for potential adverse effects, as interstitial nephritis leading to oliguric renal failure has been documented in a limited number of cases following 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, maintaining adequate fluid intake and promoting diuresis are essential. 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.

Healthcare professionals should be aware 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 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 also negative in the Ames bacterial mutation assay and the mouse micronucleus test.

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 associated with the use of the product. These include anaphylaxis, serious skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis, hepatic dysfunction characterized by cholestatic jaundice, and renal impairment including interstitial nephritis. Hematologic reactions have also been reported, notably thrombocytopenia and agranulocytosis, as well as Clostridium difficile-associated diarrhea. Additionally, allergic reactions such as urticaria and angioedema have been documented.

Further adverse reactions reported include nausea, vomiting, rash, diarrhea, abdominal pain, and headache. These reactions were reported voluntarily from a population of uncertain size; therefore, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

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. Providers should inform patients about the signs and symptoms of serious skin manifestations and instruct them to stop taking amoxicillin immediately and report any signs or symptoms of skin rash, mucosal lesions, or other indications of hypersensitivity.

Patients should be made aware that diarrhea is a common side effect associated with antibacterial drugs, typically resolving upon discontinuation of the medication. Additionally, healthcare providers should inform patients that they may develop watery and bloody stools, with or without stomach cramps and fever, even as late as 2 months after completing the course of the antibacterial drug. If such symptoms occur, patients should be advised to contact their physician promptly.

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 reminded that it is common to feel better early in the treatment; however, 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 bacterial resistance, making future infections harder to treat.

For patients receiving amoxicillin in suspension form, healthcare providers should recommend refrigerating the suspension, although it 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, it is advisable to use a calibrated oral syringe and to rinse the syringe after each use. Providers should clarify that bottles of amoxicillin suspension may contain more liquid than necessary and that patients should follow their doctor’s instructions regarding the appropriate amount and duration of treatment 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 to ensure product integrity. These formulations should be stored at a controlled room temperature of 20° to 25°C (68° to 77°F), in accordance with USP guidelines. Proper storage conditions are essential to maintain the efficacy and safety 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 REMEDYREPACK INC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)