Amoxicillin

Description

Amoxicillin, 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 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. Its molecular formula is C16H19N3O5S•3H2O, with a molecular weight of 419.45.

Amoxicillin for Oral Suspension, USP is available in reconstituted forms containing 125 mg and 250 mg of amoxicillin per 5 mL. Each 5 mL of the 125 mg and 250 mg reconstituted suspension also contains 0.1898 mEq (4.3635 mg) of sodium. The formulation includes inactive ingredients such as colloidal silicon dioxide, hypromellose, sodium benzoate, sucrose, trisodium citrate dihydrate, tutti frutti flavor, and xanthan gum.

Uses and Indications

Amoxicillin is a penicillin-class antibacterial indicated for the treatment of infections caused by susceptible strains of designated microorganisms. This drug is specifically indicated 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

To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin for oral suspension and other antibacterial drugs, it is essential that amoxicillin for oral suspension be used solely to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

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 per kg of body weight per day, divided and administered every 12 hours.

In the treatment of H. 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 and 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 remain vigilant for signs of anaphylaxis. Should any allergic reaction occur, amoxicillin must be discontinued immediately.

Severe cutaneous adverse reactions (SCAR) have also been associated with amoxicillin use. Patients should be monitored closely for the development of rashes, and if any rash progresses, amoxicillin should be discontinued without delay.

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 for oral suspension 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 any patient who presents with diarrhea during or after treatment with amoxicillin, as timely intervention may be necessary.

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 of the oral suspension and appropriate therapeutic intervention if this condition arises.

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.

Furthermore, 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 noted, as this may increase the risk of adverse reactions.

In cases of overdosage, interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients. Crystalluria, which can lead to renal failure, has also been documented following amoxicillin overdosage in both adult and pediatric patients.

Drug Interactions

Coadministration of amoxicillin with probenecid 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 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

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 pediatric patients aged 12 weeks or younger (3 months or younger), caution is advised due to incompletely developed renal function, which may delay the elimination of amoxicillin. Therefore, dosing should be modified accordingly in this age group 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 subjects. The findings from these analyses did not identify significant differences in responses between these age groups; however, it is important to note that a greater sensitivity to the drug 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 the drug.

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 teratogenic effects or harm to the fetus due to amoxicillin. However, there are no adequate and well-controlled studies in pregnant women. Therefore, amoxicillin should be used during pregnancy only if clearly needed, as animal reproduction studies are not always predictive of human response. Healthcare professionals should 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

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in 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 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 less than 250 mg/kg of amoxicillin 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 amoxicillin overdosage.

Additionally, crystalluria has been documented in both adult and pediatric patients, with some cases progressing to renal failure. To mitigate the risk of crystalluria, it is essential to maintain adequate fluid intake and promote diuresis. Renal impairment observed in these cases appears to be reversible upon cessation of amoxicillin administration.

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 instances, hemodialysis may be employed to facilitate the removal of amoxicillin from circulation. Healthcare providers should monitor renal function and ensure appropriate management strategies are in place for affected patients.

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, 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. Additionally, severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. Cases of hepatic dysfunction, including cholestatic jaundice and hepatitis, have also been observed.

Renal impairment, specifically interstitial nephritis, has been noted among the reported events. Hematologic reactions, including thrombocytopenia, leukopenia, and hemolytic anemia, have been recorded as well. Furthermore, Clostridium difficile-associated diarrhea (CDAD) has been reported. Other adverse reactions include nausea, vomiting, and rash.

Patient Counseling

Healthcare providers should 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 two months after their last dose of the antibacterial drug. If such symptoms occur, patients should contact their physician as soon as possible.

It is essential to inform patients 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 prescribed amoxicillin tablets, oral suspension, chewable tablets, or capsules for a bacterial infection, patients should be reminded that it is common to feel better early in the treatment. However, they must take the medication exactly as directed. Skipping doses or failing to complete the full course of therapy may decrease the effectiveness of the treatment and increase the likelihood of bacteria developing resistance, rendering amoxicillin or other antibacterial drugs ineffective in the future.

Patients should be counseled that while it is preferable to refrigerate amoxicillin suspensions, it is not mandatory. They should shake the oral suspension well before each use and keep the bottle tightly closed. When dosing a child with the suspension, a calibrated oral syringe should be used, and it is important 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 should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. While refrigeration is preferable, it is not a requirement for storage. Prior to use, the product must be shaken well to ensure proper consistency. Once reconstituted, the suspension should be discarded after 14 days to maintain safety and efficacy. It is essential to keep the container tightly closed when not in use to protect the integrity 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 Hikma Pharmaceuticals USA Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)