Amoxicillin

Description

Amoxicillin, USP 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, USP is C16H19N3O5S·3H2O, with a molecular weight of 419.45.

For the oral suspension formulation, each 5 mL of the reconstituted suspension contains either 125 mg or 250 mg of amoxicillin as the trihydrate. The 125 mg reconstituted suspension provides 0.11 mEq (2.51 mg) of sodium per 5 mL, while the 250 mg reconstituted suspension contains 0.15 mEq (3.36 mg) of sodium per 5 mL. Inactive ingredients in the formulation include microcrystalline cellulose, carboxymethylcellulose sodium, sucrose, colloidal silicon dioxide, sodium citrate, sodium propionate, artificial cream flavor, FD&C Red # 40, and FD&C Yellow # 6.

Uses and Indications

Amoxicillin for oral suspension is indicated for the treatment of infections caused by susceptible strains of designated microorganisms. This medication is appropriate for use in both adults and pediatric patients 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

In adult patients specifically, amoxicillin for oral suspension is also indicated for the treatment of Helicobacter pylori infection and duodenal ulcer disease.

Amoxicillin for oral suspension should be utilized only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. This approach is essential to reduce the development of drug-resistant bacteria and to maintain the effectiveness 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 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 in adults, the following regimens are recommended: for 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. For dual therapy, the regimen consists of 1 gram of amoxicillin and 30 mg of lansoprazole, to be taken 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 for oral suspension should be discontinued immediately.

Healthcare professionals should also be vigilant for severe cutaneous adverse reactions (SCAR). Close monitoring of patients is essential, and amoxicillin should be discontinued if any rash progresses.

Additionally, there is a risk of Clostridioides difficile-associated diarrhea (CDAD), which can range from mild diarrhea to potentially fatal colitis. If a patient experiences diarrhea during treatment, a thorough evaluation is warranted to assess the severity and potential underlying causes.

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, although less common, warrant immediate attention. Anaphylactic reactions, which can be serious and occasionally fatal, have been reported in patients undergoing penicillin therapy, including amoxicillin. In the event of an anaphylactic reaction, amoxicillin for oral suspension should be discontinued promptly. Additionally, severe cutaneous adverse reactions (SCAR) have been observed; patients should be monitored closely, and the medication should be discontinued if any rash progresses. Clostridioides difficile-associated diarrhea (CDAD) is another serious concern, with manifestations ranging from mild diarrhea to potentially fatal colitis. Patients experiencing diarrhea should be evaluated for this condition.

It is important to note that 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) may be at increased risk for adverse reactions.

Overdosage of amoxicillin has been associated with serious complications. Reports indicate that interstitial nephritis resulting in oliguric renal failure has occurred in a small number of patients following overdosage. Additionally, crystalluria, which in some cases has led to renal failure, has been documented in both adult and pediatric patients after amoxicillin overdosage.

Drug Interactions

Coadministration of amoxicillin for oral suspension with probenecid is not recommended due to potential interactions that may affect the pharmacokinetics of amoxicillin.

When used concurrently with oral anticoagulants, amoxicillin for oral suspension may lead to an increased prolongation of prothrombin time. It is advisable to monitor prothrombin time closely in patients receiving both medications to ensure safe and effective anticoagulation.

The concomitant use of amoxicillin for oral suspension and allopurinol has been associated with an increased risk of rash. Clinicians should be vigilant for dermatological reactions in patients receiving this combination.

Additionally, amoxicillin for oral suspension may reduce the efficacy of oral contraceptives. Patients should be counseled on the potential need for 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) see Dosage and Administration (2.3).

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 ensure safe and effective use of the medication.

Pregnancy

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. Given that 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 the risks when considering the use of amoxicillin in pregnant patients.

Lactation

There are no adequate and well-controlled studies in lactating mothers. Amoxicillin should be used during lactation only if clearly needed. The effects of amoxicillin on breastfed infants are not well characterized, and caution is advised when administering this medication to nursing mothers.

Renal Impairment

Patients with renal impairment have no specific information regarding dosage adjustments, special monitoring, or safety considerations provided in the text. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing to this population. Regular monitoring of renal function may be warranted in patients with reduced kidney function to ensure safety and efficacy.

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 considered as a method to remove amoxicillin from circulation effectively.

Healthcare professionals should monitor patients closely for any signs of adverse effects and manage them accordingly, ensuring that all necessary interventions are implemented promptly.

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 potassium clavulanate provide relevant insights.

The combination of amoxicillin and potassium clavulanate was found to be non-mutagenic 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. Additionally, this combination was negative in the mouse micronucleus test and in the dominant lethal assay in mice.

Potassium clavulanate alone was tested 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 two times the 3 g human dose based on body surface area.

Postmarketing Experience

No specific postmarketing experience details are available. As such, there are no additional adverse events or rare case reports to summarize at this time.

Patient Counseling

Advise patients that amoxicillin for oral suspension 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. They should be instructed to stop taking amoxicillin immediately and promptly report any signs or symptoms of skin rash, mucosal lesions, or other indications of hypersensitivity.

Counsel patients that diarrhea is a common side effect associated with antibacterial drugs, typically resolving upon discontinuation of the medication. However, patients should be made aware that they may develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 months after their last dose of the antibacterial drug. If such symptoms occur, patients should contact their physician as soon as possible.

Patients should be reminded 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 it is common to feel better early in the treatment course; 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 bacteria developing resistance, making them untreatable by amoxicillin or other antibacterial drugs in the future.

It is preferable to refrigerate amoxicillin suspensions, although this 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, a calibrated oral syringe should be used, and patients should be reminded 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

Unreconstituted powder should be stored at a temperature range of 20°C to 25°C (68°F to 77°F), in accordance with USP Controlled Room Temperature guidelines. It is essential to dispense the product in a tight, light-resistant container as specified by the USP, ensuring that it includes a child-resistant closure as required. Additionally, it is crucial to keep this medication, along with all other medications, out of the reach of children.

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 Chartwell RX, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)