Amoxicillin

Description

Amoxicillin is a semisynthetic antibacterial agent, structurally 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. The tablet formulation includes 500 mg or 875 mg of amoxicillin as the trihydrate, with each film-coated, capsule-shaped, pink tablet debossed with "AMOXIL" centered over the respective dosage. The 875 mg tablet is scored on the reverse side. Inactive ingredients for both tablet strengths include colloidal silicon dioxide, crospovidone, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, and titanium dioxide.

For oral suspension, each 5 mL of the reconstituted formulation contains either 200 mg or 400 mg of amoxicillin as the trihydrate. The 200 mg suspension contains 0.15 mEq (3.39 mg) of sodium, while the 400 mg suspension contains 0.19 mEq (4.33 mg) of sodium. Inactive ingredients in the oral suspension include flavorings, silica gel, sodium benzoate, sodium citrate, sucrose, and xanthan gum.

Chewable tablets are available in strengths of 125 mg, 200 mg, 250 mg, and 400 mg of amoxicillin as the trihydrate. The inactive ingredients for the 125 mg and 250 mg chewable tablets consist of mannitol, glycine, magnesium stearate, silica gel, flavorings, citric acid, saccharin sodium, and confectioner’s sugar. The 200 mg and 400 mg chewable tablets contain mannitol, crospovidone, flavorings, magnesium stearate, and aspartame.

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 and other antibacterial drugs, amoxicillin should be utilized exclusively for the treatment or prevention of 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 to 45 mg/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 upper limit of dosing is 30 mg/kg per day, divided and administered every 12 hours.

In the treatment of Helicobacter 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 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, it is imperative to discontinue amoxicillin immediately.

Healthcare professionals should monitor patients closely for the development of severe cutaneous adverse reactions (SCAR). If any rash progresses, amoxicillin should be discontinued without delay.

Additionally, drug-induced enterocolitis syndrome (DIES) has been associated with the use of amoxicillin. Should this condition arise, it is essential to discontinue amoxicillin and initiate appropriate therapeutic measures.

Clostridioides difficile-associated diarrhea (CDAD) can occur in patients taking amoxicillin, presenting with symptoms that may range 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, 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 such a reaction, amoxicillin should be discontinued promptly. Additionally, severe cutaneous adverse reactions (SCAR) have been observed; patients should be monitored closely, and treatment should be stopped if any rash progresses. Drug-induced enterocolitis syndrome (DIES) has also been associated with amoxicillin use; if this condition arises, amoxicillin should be discontinued, and appropriate therapy should be initiated. Clostridioides difficile-associated diarrhea (CDAD) can occur, presenting as mild diarrhea but potentially leading to fatal colitis; therefore, evaluation is necessary if diarrhea develops.

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.

Additional adverse reactions of note include interstitial nephritis, which has resulted in oliguric renal failure in a small number of patients following amoxicillin overdosage. Crystalluria, which in some cases has led to renal failure, has also been reported after 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. Monitoring of prothrombin time is advised to ensure patient safety and appropriate anticoagulation management.

The concomitant use of amoxicillin and allopurinol has been associated with an increased risk of rash. Caution is advised when these medications are prescribed together, and patients should be monitored for dermatological reactions.

Additionally, amoxicillin may reduce the efficacy of oral contraceptives. Patients using hormonal contraceptives should be counseled on the potential for decreased contraceptive effectiveness and may need 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 AMOXIL 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 AMOXIL 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 AMOXIL 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 ensure safe and effective use of the 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. Therefore, amoxicillin should be used during pregnancy only if clearly needed, as animal reproduction studies are not always predictive of human response.

The effects of amoxicillin during labor and delivery are not well understood, and it is unknown whether its use in humans at this time has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood of the necessity for obstetrical intervention. Healthcare professionals should weigh the potential benefits against the risks when considering amoxicillin for 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

The available data does not include specific information regarding dosing adjustments, monitoring, or precautions for patients with renal impairment. Therefore, healthcare professionals should refer to the prescribing information for guidance on the management of patients with reduced kidney function, including any necessary adjustments based on creatinine clearance or other relevant clinical findings. It is essential to evaluate each patient's renal function and consider individual factors when determining the appropriate therapeutic approach.

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 amoxicillin below 250 mg/kg typically do not result in significant clinical symptoms. However, it is important to remain vigilant for potential adverse effects, as interstitial nephritis leading to oliguric renal failure has been documented in a small number of cases following overdosage. Additionally, crystalluria, which may progress to renal failure, has been reported in both adult and pediatric populations after excessive doses of amoxicillin.

To mitigate the risk of crystalluria, it is essential to maintain adequate fluid intake and promote diuresis. This approach helps to reduce the likelihood of renal complications associated with amoxicillin overdosage. Notably, renal impairment observed in these cases appears to be reversible upon cessation of the drug.

Healthcare professionals should also be aware that patients with pre-existing renal impairment may experience elevated blood levels of amoxicillin due to decreased renal clearance. In severe cases of overdosage, hemodialysis may be employed to facilitate the removal of amoxicillin from the 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, relevant data is available from tests on a 4:1 mixture of amoxicillin and potassium clavulanate, known as AUGMENTIN.

AUGMENTIN was found to be non-mutagenic in both the Ames bacterial mutation assay and the yeast gene conversion assay. However, it exhibited a weakly positive response 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, AUGMENTIN was negative in the mouse micronucleus test and in 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.

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

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

Patient Counseling

Patients should be advised 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. Patients should be informed about the signs and symptoms of serious skin manifestations and instructed to stop taking amoxicillin immediately and promptly report any signs or symptoms of skin rash, mucosal lesions, or other indications of hypersensitivity.

Patients should also be made aware that diarrhea is a common side effect associated with antibacterial drugs, typically resolving upon discontinuation of the medication. However, they should be informed that watery and bloody stools, with or without stomach cramps and fever, can occur even as late as two months after the last dose of the antibacterial drug. In such cases, patients should contact their physician as soon as possible.

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 course, but 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.

For patients using amoxicillin suspensions, it is preferable to refrigerate the product, 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 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.

Lastly, patients with phenylketonuria should be counseled that each 200 mg chewable tablet contains 1.82 mg of phenylalanine, while each 400 mg chewable tablet contains 3.64 mg of phenylalanine.

Storage and Handling

The product is supplied in a tight container to ensure integrity and stability. It should be stored at or below 25° C (77° F) to maintain its efficacy and safety. Proper storage conditions are essential to prevent degradation and ensure optimal performance.

Additional Clinical Information

Patients should be advised on the administration of amoxicillin, which may be taken every 8 or 12 hours based on the prescribed dosage. It is important to inform patients that amoxicillin is a penicillin-class drug, which can lead to allergic reactions in some individuals. They should be made aware of the signs and symptoms of severe cutaneous adverse reactions (SCAR) and instructed to discontinue use and report any skin rash, mucosal lesions, or other hypersensitivity signs immediately.

Patients may experience diarrhea as a common side effect of antibacterial drugs, which typically resolves upon discontinuation. However, they should be cautioned that watery or bloody stools may occur even weeks after treatment, necessitating prompt medical consultation. Additionally, patients should understand that antibacterial drugs, including amoxicillin, are effective only against bacterial infections and not viral ones. They must complete the full course of therapy as directed to prevent reduced effectiveness and the potential development of antibacterial resistance.

For storage, amoxicillin suspensions are preferably refrigerated but do not require it. Patients should shake the suspension well before use, keep the bottle tightly closed, and use a calibrated oral syringe for dosing children, ensuring it is rinsed after each use. Any unused suspension should be discarded after 14 days. Lastly, patients with phenylketonuria should be informed that the 200 mg chewable tablet contains 1.82 mg of phenylalanine, while the 400 mg chewable tablet contains 3.64 mg.

FDA Insert (PDF)

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

View full prescribing information (PDF)