Amoxicillin

Description

Amoxicillin is a semisynthetic antibacterial, an analog of ampicillin, with a broad spectrum of bactericidal activity against many Gram-positive and Gram-negative microorganisms. Chemically, it is (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, and its molecular weight is 419.45.

Amoxicillin is available in several dosage forms. Each capsule contains either 250 mg or 500 mg of amoxicillin as the trihydrate. 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 the tablets are oval-shaped and white to yellowish.

For oral suspension, amoxicillin is available in concentrations of 125 mg/5 mL, 200 mg/5 mL, 250 mg/5 mL, and 400 mg/5 mL, presented as fruity flavored pink suspensions. Inactive ingredients in the oral suspension include anhydrous citric acid, colloidal silicon dioxide, flavorings, 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 medication is specifically utilized 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 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 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 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, 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 discontinue amoxicillin immediately if any signs of an anaphylactic reaction occur.

Severe cutaneous adverse reactions (SCAR) have also been associated with amoxicillin use. Patients should be monitored closely for the development of rashes, and amoxicillin should be discontinued if the rash progresses.

Additionally, drug-induced enterocolitis syndrome (DIES) has been documented in patients taking amoxicillin. In the event that DIES is suspected, it is essential to discontinue amoxicillin and initiate appropriate therapeutic measures.

Clostridiodes difficile-associated diarrhea (CDAD) can manifest in a spectrum ranging from mild diarrhea to potentially fatal colitis. Healthcare professionals should evaluate patients for CDAD if diarrhea occurs during or after treatment with amoxicillin.

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.

In cases of overdosage, adverse reactions may include interstitial nephritis leading to oliguric renal failure, which has been reported in a small number of patients. Crystalluria, which in some instances has resulted in renal failure, has also been documented following amoxicillin overdosage in both adult and pediatric patients.

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 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

Clinical studies of amoxicillin have been analyzed to assess whether patients aged 65 and older exhibit different responses compared to younger patients. The findings from these analyses did not identify significant differences in responses between elderly and younger patients; 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 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 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, including any changes in clearance or creatinine clearance thresholds. Healthcare professionals should consider this absence of information when treating patients with renal impairment.

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. Symptomatic treatment and supportive measures should be instituted as necessary to manage the patient's condition effectively.

A prospective study indicates that overdosages of amoxicillin below 250 mg/kg typically do not result in significant clinical symptoms. However, healthcare professionals should remain vigilant, 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 reduces the likelihood of complications.

It is important to note that patients with impaired renal function may experience elevated blood levels of amoxicillin due to decreased renal clearance. In such cases, hemodialysis may be employed as a method to remove amoxicillin from circulation effectively.

Healthcare professionals should monitor patients closely and provide appropriate interventions based on the severity of symptoms and the patient's overall clinical status.

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 mixture was negative in the mouse micronucleus test and 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, 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 allergic reactions, including anaphylaxis, have been documented. Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have also been reported. Instances of hepatic dysfunction, characterized by elevated liver enzymes and jaundice, have been noted. Renal impairment, including cases of interstitial nephritis, has been observed.

Hematologic reactions, including thrombocytopenia, leukopenia, and hemolytic anemia, have been reported. Gastrointestinal disorders, particularly Clostridium difficile-associated diarrhea, have been associated with the use of the product. Additionally, cases of superinfection due to antibiotic resistance have been documented.

Further safety updates from postmarketing experience include reports of seizures in patients with renal impairment.

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 important to use a calibrated oral syringe and to rinse the syringe after each use. Providers should also inform patients that bottles of amoxicillin suspension may contain more liquid than necessary and to 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. They should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines.

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)