Amoxicillin

Description

Amoxicillin for oral suspension, USP is a semisynthetic antibacterial agent, specifically an analog of ampicillin, exhibiting a broad spectrum of bactericidal activity against various Gram-positive and Gram-negative microorganisms. The 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 g/mol.

The reconstituted suspension is available in two strengths: each 5 mL contains either 125 mg or 250 mg of amoxicillin as the trihydrate. Additionally, each 5 mL of both the 125 mg and 250 mg formulations contains 0.12 mEq (2.8 mg) of sodium. Inactive ingredients include art bubble gum flavor, colloidal silicon dioxide, edetate disodium, FD&C Red No. 3, silicon dioxide, sodium benzoate, sodium citrate, sucrose, and xanthan gum.

Uses and Indications

Amoxicillin for oral suspension is indicated for the treatment of infections caused by susceptible strains of designated microorganisms. This formulation 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 adult patients only

Amoxicillin for oral suspension 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. It is essential to 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 recommended dosage is 30 mg per kg per day, divided and administered every 12 hours.

In the treatment of Helicobacter 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 important 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, including anaphylaxis or Stevens-Johnson syndrome, to amoxicillin for oral suspension or to other beta-lactams, such as penicillins or cephalosporins. This contraindication is due to the potential for severe allergic reactions in these individuals.

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 and discontinue amoxicillin immediately if such a reaction occurs.

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 any rash progresses.

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.

Clostridioides difficile-associated diarrhea (CDAD) can manifest in a spectrum ranging from mild diarrhea to severe, 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, 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. 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, Clostridioides difficile-associated diarrhea (CDAD) can range from mild diarrhea to severe, potentially fatal colitis, and should be evaluated 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 associated with serious adverse effects, including interstitial nephritis leading to oliguric renal failure in a small number of patients. Crystalluria, which in some cases has resulted in renal failure, has also been reported following overdosage in both adult and pediatric patients.

Drug Interactions

Co-administration of amoxicillin with probenicid is not recommended due to potential interactions that may affect the pharmacokinetics of amoxicillin.

When amoxicillin is used concurrently with oral anticoagulants, there is an increased risk of prolongation of prothrombin time. Clinicians should monitor prothrombin time closely and consider dosage adjustments of the anticoagulant as necessary.

The concomitant use of amoxicillin and allopurinol has been associated with an increased risk of rash. Patients should be monitored for dermatological reactions, and if a rash occurs, discontinuation of one or both medications may be warranted.

Additionally, amoxicillin may reduce the efficacy of oral contraceptives. Patients using oral contraceptives should be advised to consider 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) 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 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

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 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 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 remain vigilant, as there have been reports of interstitial nephritis leading to oliguric renal failure in a small number of cases 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, maintaining adequate fluid intake and promoting diuresis are essential. 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 dysfunction may experience elevated blood levels of amoxicillin due to reduced renal clearance.

For patients experiencing severe overdosage, hemodialysis may be employed as a method to remove amoxicillin from circulation, thereby aiding in the management of the overdose. Continuous monitoring and appropriate interventions are crucial to ensure patient safety and recovery.

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 amoxicillin and clavulanic acid mixture demonstrated non-mutagenic properties 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. Notably, the mixture was negative in the mouse micronucleus test and the dominant lethal assay in mice.

Potassium clavulanate, when tested independently, also yielded negative results 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 reported voluntarily or through surveillance programs. Serious allergic reactions, including anaphylaxis, have been documented. Additionally, severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.

Hepatic dysfunction, characterized by elevated liver enzymes and jaundice, has also been observed. Renal impairment, including interstitial nephritis, has been noted among patients. Hematologic reactions, such as thrombocytopenia, leukopenia, and hemolytic anemia, have been recorded as well.

Clostridium difficile-associated diarrhea (CDAD) has been reported, which can occur during or after treatment with antibacterial agents. Other adverse reactions include nausea, vomiting, and rash.

Patient Counseling

Advise patients that amoxicillin may be taken every 8 hours or every 12 hours, depending on the dose prescribed. It is important for patients to understand the dosing schedule to ensure optimal effectiveness of the medication.

Counsel patients that amoxicillin contains a penicillin class drug product, which can cause allergic reactions in some individuals. Patients should be informed about the potential for allergic reactions and encouraged to report any history of allergies to penicillin or related drugs.

Patients should be made aware of the signs and symptoms of serious skin manifestations. Instruct patients to stop taking amoxicillin immediately and promptly report the first signs or symptoms of skin rash, mucosal lesions, or any other indication of hypersensitivity.

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

Patients should be counseled that antibacterial drugs, including amoxicillin, are intended solely for the treatment or prevention of bacterial infections and do not treat viral infections, such as the common cold. When amoxicillin is prescribed for a bacterial infection, patients should be advised that it is common to feel better early in the course of therapy; however, the medication must be taken exactly as directed. Skipping doses or failing to complete the full course of therapy may decrease the effectiveness of the immediate treatment and increase the likelihood of bacteria developing resistance, rendering amoxicillin or other antibacterial drugs ineffective in the future.

It is preferable to refrigerate amoxicillin suspensions, although this is not a strict requirement. Patients should be instructed to shake oral suspensions 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

The dry powder is supplied in a tight container to ensure its integrity and stability. 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 quality 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 Aurobindo Pharma Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)