Amoxicillin

Description

Formulations of Amoxicillin Powder for Oral Suspension, USP contain amoxicillin, a semisynthetic antibiotic and an analog of ampicillin, exhibiting a broad spectrum of bactericidal activity against various Gram-positive and Gram-negative microorganisms. The chemical structure of amoxicillin 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 is C16H19N3O5S•3H2O, with a molecular weight of 419.45.

The powder for oral suspension is available in reconstituted forms containing 125 mg, 200 mg, 250 mg, or 400 mg of amoxicillin per 5 mL. Each of these formulations also contains 0.1898 mEq (4.3635 mg) of sodium per 5 mL. Inactive ingredients include colloidal silicon dioxide, hypromellose, sodium benzoate, sucrose, trisodium citrate dihydrate, tutti frutti flavor, and xanthan gum.

Uses and Indications

Amoxicillin Powder for Oral Suspension, USP is indicated for the treatment of infections caused by susceptible strains of designated microorganisms. This medication is effective in managing infections of the ear, nose, throat, genitourinary tract, skin and skin structure, as well as the lower respiratory tract. Additionally, it is indicated for use in combination therapy for the treatment of Helicobacter pylori infection and duodenal ulcer disease.

There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

In adults, the recommended dosage is 750 to 1750 mg per day, administered in divided doses every 8 to 12 hours. For pediatric patients over 3 months of age, the dosage ranges from 20 to 45 mg/kg per day, also given in divided doses every 8 to 12 hours.

For the treatment of gonorrhea, a single oral dose of 3 grams is indicated. In neonates and infants aged 3 months or younger, the maximum dosage is 30 mg/kg per day, divided and administered every 12 hours.

In the context of H. pylori infection, the following regimens are recommended: for triple therapy, the combination consists of 1 gram of amoxicillin, 500 mg of clarithromycin, and 30 mg of lansoprazole, all taken twice daily (every 12 hours) for a duration of 14 days. For dual therapy, the regimen includes 1 gram of amoxicillin and 30 mg of lansoprazole, each administered 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) of less than 30 mL/min.

Contraindications

Use of this product 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 undergoing penicillin therapy. Healthcare professionals should remain vigilant for signs of anaphylaxis, which may include difficulty breathing, swelling of the face or throat, and rapid heartbeat. In the event of a serious anaphylactic reaction, immediate emergency treatment is essential, along with appropriate supportive measures.

Additionally, there is a risk of Clostridium difficile-associated diarrhea, which can range from mild diarrhea to severe, potentially fatal colitis. It is crucial for healthcare providers to evaluate patients for diarrhea during and after treatment with penicillin. Prompt assessment and management are necessary to mitigate the risks associated with this condition.

Side Effects

Patients receiving treatment with 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 medical intervention.

Serious adverse reactions, although less frequent, can occur and necessitate immediate medical attention. Notably, serious and occasionally fatal anaphylactic reactions have been documented in patients undergoing penicillin therapy. Such reactions require prompt emergency treatment and supportive measures. Additionally, Clostridium difficile-associated diarrhea has been observed, with manifestations ranging from mild diarrhea to potentially fatal colitis. It is crucial to evaluate any patient who presents with diarrhea 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 due to the risk of severe reactions.

Overdosage of amoxicillin has been associated with serious adverse effects, including interstitial nephritis leading to oliguric renal failure, which has been reported in a small number of patients. Crystalluria, which in some cases has resulted in renal failure, has also been noted following overdosage in both adult and pediatric patients. Monitoring for these conditions is advised in cases of suspected overdose.

Drug Interactions

Probenicid, when administered concurrently with amoxicillin, decreases the renal tubular secretion of amoxicillin. This interaction may lead to elevated blood levels of amoxicillin, necessitating careful monitoring of amoxicillin concentrations and potential dosage adjustments based on clinical response.

The concomitant use of amoxicillin with oral anticoagulants has been associated with an increased prolongation of prothrombin time. Patients receiving this combination should be monitored closely for changes in coagulation parameters, and dosage adjustments of the anticoagulant may be required to maintain therapeutic efficacy and safety.

Coadministration of amoxicillin with allopurinol has been reported to increase the risk of rash. Clinicians should be vigilant for the development of skin reactions in patients receiving this combination and consider alternative therapies if necessary.

Additionally, amoxicillin may reduce the efficacy of oral contraceptives. Patients using hormonal contraceptives should be advised to consider alternative or additional contraceptive methods during and after treatment with amoxicillin to ensure adequate contraceptive protection.

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

Pediatric patients, particularly neonates and young infants, may experience delayed elimination of amoxicillin due to incompletely developed renal function. Therefore, dosing of amoxicillin should be modified for pediatric patients aged 12 weeks or younger (≤ 3 months) 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 have not identified significant differences in responses between these age groups; however, it is important to note that a greater sensitivity in some older individuals cannot be entirely excluded.

Amoxicillin is primarily excreted through 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

Pregnant patients should be aware that amoxicillin is classified as 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 based on body surface area, have shown no evidence of teratogenic effects or harm to the fetus. However, there are no adequate and well-controlled studies in pregnant women. Therefore, while animal reproduction studies may not always predict human outcomes, 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

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to 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 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 an overdosage, it is imperative to discontinue the medication immediately and provide symptomatic treatment along with supportive measures as necessary.

A prospective study involving 51 pediatric patients at a poison control center indicated that overdosages of amoxicillin below 250 mg/kg typically do not result in significant clinical symptoms. However, it is important to note that there have been reports of interstitial nephritis leading to oliguric renal failure in a small number of patients following amoxicillin overdosage. Additionally, crystalluria has been documented, which in some instances has resulted in renal failure among both adult and pediatric patients.

To mitigate the risk of crystalluria associated with amoxicillin overdosage, it is essential to maintain adequate fluid intake and promote diuresis. Renal impairment observed in these cases appears to be reversible upon cessation of the drug. It is also noteworthy that patients with pre-existing renal impairment may experience elevated blood levels of amoxicillin due to decreased renal clearance.

For patients undergoing hemodialysis, it is important to recognize that amoxicillin can be effectively removed from circulation, which may aid in the management of overdosage.

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 coincided with doses that also resulted in 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 associated with the use of amoxicillin powder for oral suspension. Diarrhea has been reported as a common issue, typically resulting from antibiotic use and generally resolving upon discontinuation of the medication. Additionally, there have been cases of the development of watery and bloody stools, which may occur with or without accompanying symptoms such as stomach cramps and fever. These symptoms can manifest even two months or more after the last dose of the antibiotic. Patients experiencing such symptoms are advised to contact their physician promptly.

Furthermore, it is noted that amoxicillin, being a penicillin class drug, has the potential to elicit allergic reactions in some individuals.

Patient Counseling

Patients should be advised that amoxicillin powder for oral suspension may be taken every 8 hours or every 12 hours, depending on the dose prescribed. It is important for patients to understand that antibacterial drugs, including amoxicillin powder for oral suspension, are intended solely for the treatment of bacterial infections and do not address viral infections, such as the common cold.

When amoxicillin powder for oral suspension is prescribed for a bacterial infection, patients should be informed that it is common to feel better early in the course of therapy; however, the medication must be taken exactly as directed. Patients should be cautioned against skipping doses or failing to complete the full course of therapy, as this may decrease the effectiveness of the immediate treatment and increase the likelihood of bacteria developing resistance, rendering amoxicillin powder for oral suspension or other antibacterial drugs ineffective in the future.

Patients should also be counseled that diarrhea is a common side effect associated with antibiotics, typically resolving upon discontinuation of the medication. However, it is important to inform patients that they may experience watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after completing the antibiotic course. If this occurs, patients should be advised to contact their physician promptly.

Finally, patients should be made aware that amoxicillin powder for oral suspension contains a penicillin class drug, which can cause allergic reactions in some individuals. It is essential for patients to report any history of allergies to penicillin or related compounds to their healthcare provider.

Storage and Handling

The product is supplied in a tight, light-resistant container, as defined by the United States Pharmacopeia (USP), and is equipped with a child-resistant closure to ensure safety. It 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 integrity and efficacy of the product.

Additional Clinical Information

Laboratory tests for assessing susceptibility to amoxicillin can be conducted using ampicillin powder and a 10 mcg ampicillin disk. Clinicians should ensure that clinical microbiology provides periodic reports of in vitro susceptibility test results for antimicrobial drugs utilized in resident hospitals. Quantitative methods are employed to determine the minimum inhibitory concentrations (MICs) of these drugs, with both dilution and diffusion techniques being standard practices for susceptibility testing.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Amoxicillin as submitted by Aidarex Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)