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. The film-coated tablets contain 500 mg or 875 mg of amoxicillin as the trihydrate and 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. These suspensions are fruity flavored and pink in color. Inactive ingredients in the oral suspension formulation include anhydrous citric acid, colloidal silicon dioxide, flavorings, 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 kg 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 maximum recommended dose is 30 mg per kg per 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. In the event of an anaphylactic reaction, amoxicillin should be discontinued immediately.

Severe cutaneous adverse reactions (SCAR) may occur in some patients. It is essential to monitor patients closely for any signs of rash, and if the rash progresses, amoxicillin should be discontinued.

Drug-induced enterocolitis syndrome (DIES) has also been associated with the use of amoxicillin. Should this condition arise, it is imperative 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. If a patient experiences diarrhea during treatment, a thorough evaluation is warranted to determine the appropriate course of action.

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 during treatment.

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.

In cases of overdosage, adverse reactions such as interstitial nephritis leading to oliguric renal failure have 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 the use of 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 who are 12 weeks or younger (3 months or younger).

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 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. Given that 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 lack 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 and provide symptomatic treatment along with supportive measures as necessary.

A prospective study indicates that overdosages of less than 250 mg/kg of amoxicillin 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 patients.

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. It is noteworthy that renal impairment observed in these cases appears to be reversible upon cessation of amoxicillin administration.

Patients with pre-existing renal impairment may experience elevated blood levels of amoxicillin due to decreased renal clearance, necessitating careful monitoring. In cases of severe overdosage, hemodialysis may be employed to facilitate the removal of amoxicillin from 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 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 skin reactions have been noted, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Instances of hepatic dysfunction have been observed, characterized by elevated liver enzymes and jaundice. Renal impairment, specifically interstitial nephritis, has also been reported.

Hematologic reactions, such as thrombocytopenia, leukopenia, and hemolytic anemia, have been documented. Additionally, allergic reactions, including anaphylaxis and angioedema, have been recorded. Gastrointestinal disorders, particularly Clostridium difficile-associated diarrhea, have been reported as well.

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 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 are supplied in a tight container to ensure their integrity and stability. 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. Proper storage conditions are essential to maintain the quality and efficacy 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 QPharma, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)