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

Amoxicillin is available in several dosage forms. Each tablet contains either 500 mg or 875 mg of amoxicillin, USP as the trihydrate. The reconstituted suspension provides 200 mg, 250 mg, or 400 mg of amoxicillin, USP per 5 mL. The 200 mg suspension contains 0.09 mEq (2.11 mg) of sodium, the 250 mg suspension contains 0.14 mEq (3.24 mg) of sodium, and the 400 mg suspension contains 0.12 mEq (2.69 mg) of sodium.

Chewable tablets are available in strengths of 125 mg or 250 mg of amoxicillin, USP as the trihydrate. Each capsule for oral administration contains either 250 mg or 500 mg of amoxicillin, USP as the trihydrate. Inactive ingredients vary by formulation; the 200 mg and 400 mg suspensions include colloidal silicon dioxide, FD&C Red No. 40, natural and artificial fruit gum flavor, sodium benzoate, sodium citrate, spray dried mask flavor, sucrose, and xanthan gum. The 250 mg suspension contains FD&C Red No. 40, mixed berry flavoring, silicon dioxide, sodium benzoate, sodium citrate, sucrose, and xanthan gum.

The chewable tablets contain cherry flavor, lactose anhydrous, magnesium stearate, mannitol, microcrystalline cellulose, sodium citrate, and sucrose. The capsules include magnesium stearate and talc, with the capsule shell composed of D&C Yellow No. 10, FD&C Red No. 40, gelatin, and titanium dioxide. The 250 mg capsules may also contain D&C Red No. 28 and FD&C Blue No. 1, while the 500 mg capsules may include methylparaben, propylparaben, and sodium lauryl sulfate. The printing ink for the capsules consists of black iron oxide, propylene glycol, shellac, and strong ammonia solution. Additionally, the 250 mg capsules may contain D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, and FD&C Red No. 40 Aluminum Lake, and the 500 mg capsules may also contain potassium hydroxide.

Uses and Indications

Amoxicillin is indicated for the treatment of infections caused by susceptible strains of designated microorganisms. This drug is utilized in the management of 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

To mitigate the development of drug-resistant bacteria and preserve the efficacy of amoxicillin and other antibacterial agents, it is essential that amoxicillin be prescribed solely for the treatment or prevention of infections that are confirmed or strongly suspected to be of bacterial origin.

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/kg/day, divided and administered every 12 hours.

In the treatment of H. 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 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 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 and appropriate therapeutic intervention if this condition arises. Furthermore, Clostridioides difficile-associated diarrhea (CDAD) can range from mild diarrhea to fatal colitis, and evaluation is recommended 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 linked to interstitial nephritis, which may result in oliguric renal failure, as well as crystalluria, which in some cases has led to renal failure 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.

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 analyzing the response of elderly patients, specifically those aged 65 and over, to amoxicillin have not identified significant differences in efficacy or safety compared to younger patients. However, it is important to note that a greater sensitivity to the drug may be present in some older individuals, warranting careful consideration during treatment.

Amoxicillin is primarily excreted by the kidneys, and the risk of toxic reactions may be heightened in patients with impaired renal function. Given that geriatric patients are more likely to experience decreased renal function, it is essential to exercise caution in dose selection for this population. Monitoring of renal function is advisable to ensure safe and effective use of the medication in elderly patients.

Pregnancy

Pregnant patients should be aware that amoxicillin is classified as Pregnancy Category B. Reproductive 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 harm to the fetus. However, there are no adequate and well-controlled studies in pregnant women to confirm the safety of amoxicillin during pregnancy.

Due to the limitations of animal reproduction studies in predicting human response, 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

There is no specific information regarding renal impairment, dosage adjustments, special monitoring, or safety considerations for patients with reduced kidney function. Healthcare professionals should exercise caution and consider individual patient factors when prescribing to patients with renal impairment, as the absence of detailed guidance necessitates careful clinical judgment.

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.

Clinical Symptoms and Risks

A prospective study indicates that overdosages of amoxicillin below 250 mg/kg typically do not result in significant clinical symptoms. However, there are notable risks associated with higher doses. Interstitial nephritis leading to oliguric renal failure has been documented in a limited number of cases following amoxicillin overdosage. Additionally, crystalluria has been reported, which in some instances has progressed to renal failure in both adult and pediatric patients.

Management Recommendations

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 crystallization in the renal system. It is also important to note that renal impairment observed in cases of overdosage appears to be reversible upon cessation of amoxicillin administration.

Patients with pre-existing renal impairment may experience elevated blood levels of amoxicillin due to decreased renal clearance, necessitating careful monitoring. In cases of severe overdosage, hemodialysis may be employed to facilitate the removal of amoxicillin from circulation.

Healthcare professionals should remain vigilant for signs of renal complications and manage them promptly 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 AUGMENTIN provide relevant insights.

AUGMENTIN 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. 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 two times the 3 g human dose based on body surface area.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions reported voluntarily or through surveillance programs. These include severe allergic reactions, such as anaphylaxis, and severe cutaneous adverse reactions (SCAR), which encompass Stevens-Johnson syndrome and toxic epidermal necrolysis.

Additionally, hepatic dysfunction has been noted, characterized by elevated liver enzymes and jaundice. Renal impairment, specifically interstitial nephritis, has also been reported. Hematologic reactions, including thrombocytopenia, leukopenia, and hemolytic anemia, have been documented.

Gastrointestinal disorders, particularly Clostridium difficile-associated diarrhea, have been observed. Other reactions reported include angioedema and serum sickness-like reactions.

Patient Counseling

Patients should be advised that amoxicillin tablets, amoxicillin for oral suspension, amoxicillin tablets (chewable), and amoxicillin capsules 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.

Healthcare providers should inform patients about the signs and symptoms of serious skin manifestations associated with amoxicillin use. Patients 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.

Patients should also be made aware that diarrhea is a common side effect of 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 up to 2 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 treat 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 bacterial resistance, making future infections harder to treat.

Patients should be informed 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 for their child. Any unused portion of the suspension should be discarded after 14 days.

Storage and Handling

The product is supplied in a tight, light-resistant container that complies with USP standards and includes a child-resistant closure as required. It is essential to store the product at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines.

Healthcare professionals are advised to ensure that this product, along with all medications, is kept out of the reach of children to prevent accidental ingestion or misuse.

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 QPharma, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)