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. 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 is available in several dosage forms:

Capsules: Each amoxicillin capsule contains either 250 mg or 500 mg of amoxicillin as the trihydrate. The capsules have a yellow opaque cap and body, with the 250 mg capsule imprinted with AMOX 250 and GG 848, while the 500 mg capsule is imprinted with AMOX 500 and GG 849. Inactive ingredients include yellow ferric oxide, titanium dioxide, gelatin, black ferric oxide, shellac, propylene glycol, potassium hydroxide, ammonium hydroxide, cellulose microcrystalline, and magnesium stearate. The product meets USP Dissolution Test 2.

Tablets: Each film-coated tablet contains either 500 mg or 875 mg of amoxicillin as the trihydrate. The tablets are oval-shaped and range in color from white to yellowish. The 500 mg tablet is unscored and embossed with GG-961 on one side and 500 on the other, while the 875 mg tablet is scored and embossed with GG-962 on one side and 875 on the other. Inactive ingredients for both tablet strengths include colloidal silicon dioxide, crospovidone, ethylcellulose aqueous dispersion, hypromellose, magnesium stearate, microcrystalline cellulose, sodium starch glycolate, talc, triethyl citrate, and titanium dioxide.

Oral Suspension: Each 5 mL of the reconstituted oral suspension contains 125 mg, 200 mg, 250 mg, or 400 mg of amoxicillin as the trihydrate, with each dosage providing 0.30 mEq (6.95 mg) of sodium. The 125 mg, 200 mg, 250 mg, and 400 mg formulations are fruity flavored pink suspensions. Inactive ingredients include anhydrous citric acid, colloidal silicon dioxide, flavorings (raspberry, strawberry, refrachessement), FD&C Red 40, sodium benzoate, sodium citrate, sucrose, and xanthan gum.

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

Amoxicillin 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 kilogram 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 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, amoxicillin should be discontinued immediately.

Healthcare professionals should monitor patients closely for the development of severe cutaneous adverse reactions (SCAR). If any rash progresses, it is imperative to discontinue amoxicillin to prevent further complications.

Additionally, drug-induced enterocolitis syndrome (DIES) has been associated with the use of amoxicillin. Should this syndrome occur, amoxicillin must be discontinued, and appropriate therapeutic measures should be initiated.

Clostridiodes difficile-associated diarrhea (CDAD) can manifest in a spectrum ranging 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. It is crucial to discontinue amoxicillin if any signs of anaphylaxis occur. Additionally, severe cutaneous adverse reactions (SCAR) have been noted; patients should be monitored closely, and amoxicillin should be discontinued if a 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, Clostridiodes difficile-associated diarrhea (CDAD) can occur, presenting as mild diarrhea but potentially leading to fatal colitis; evaluation is recommended 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.

Overdosage of amoxicillin has been associated with serious adverse effects, including interstitial nephritis resulting in oliguric renal failure, reported in a small number of patients. Crystalluria, which in some cases has led to renal failure, has also been documented 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 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 to ensure safety and efficacy in this age group.

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 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 renal impairment.

Pregnancy

Pregnancy Category B. Reproduction studies have been conducted in mice and rats at doses up to 2000 mg/kg, which is 3 and 6 times the 3 g human dose based on body surface area. These studies did not demonstrate any 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 should 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 lactating mothers may lead to sensitization of breastfed infants. Therefore, caution should be exercised when administering amoxicillin to nursing women.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

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 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, data from tests on a 4:1 mixture of amoxicillin and clavulanate potassium provide relevant insights.

The combination of amoxicillin and clavulanate potassium was found to be nonmutagenic 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, the mixture 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

Postmarketing experience has identified several adverse reactions reported voluntarily or through surveillance programs. These include allergic reactions, such as anaphylaxis, and severe cutaneous adverse reactions (SCAR), which encompass Stevens-Johnson syndrome and toxic epidermal necrolysis. Instances of hepatic dysfunction have 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. Additionally, Clostridium difficile-associated diarrhea (CDAD) has been observed, which may occur during or after treatment with antibacterial agents. Other adverse reactions reported include nausea, vomiting, and rash.

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.

Healthcare providers should inform patients about the signs and symptoms of serious skin manifestations associated with amoxicillin. Patients must be instructed to stop taking the medication immediately and to 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, including amoxicillin, and that it typically resolves upon discontinuation of the medication. However, patients may develop watery and bloody stools (with or without stomach cramps and fever) even as late as two months after their last dose. If such symptoms occur, 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 informed 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 decrease the effectiveness of the treatment and increase the likelihood of bacterial resistance, rendering amoxicillin or other antibacterial drugs ineffective 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.

Storage and Handling

Capsules, tablets, and unreconstituted powder for oral suspension are supplied in a tight container. They should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines.

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

View full prescribing information (PDF)