Amoxicillin

Description

Amoxicillin tablets, USP are formulated with amoxicillin, a semisynthetic antibiotic and 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. The molecular formula is C16H19N3O5S●3H2O, with a molecular weight of 419.45.

Each film-coated tablet is available in two strengths: 500 mg and 875 mg of amoxicillin as the trihydrate. The 500 mg tablets are pink, capsule-shaped, and debossed with “A” on one side and “66” on the other. The 875 mg tablets are also pink, capsule-shaped, and feature a score line between “6” and “7” on one side, with “A” debossed on the other side.

Inactive ingredients in the formulation include colloidal silicon dioxide, crospovidone, D&C Red No. 30 aluminum lake, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, and titanium dioxide.

Uses and Indications

Amoxicillin tablets, USP are indicated for the treatment of infections caused by susceptible strains of designated microorganisms. This includes infections of the ear, nose, throat, genitourinary tract, skin and skin structure, as well as the lower respiratory tract. Additionally, amoxicillin is indicated in combination therapy for the treatment of Helicobacter pylori infection and duodenal ulcer disease.

There are no teratogenic or nonteratogenic effects associated with the use of amoxicillin.

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.

For the treatment of gonorrhea, a single oral dose of 3 grams is indicated. In neonates and infants aged 3 months or younger, the maximum dosage is 30 mg/kg/day, divided and administered every 12 hours.

In the context of H. pylori infection, two therapeutic regimens are available:

• Triple Therapy: This 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.

• Dual Therapy: This regimen 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) of less than 30 mL/min.

Contraindications

Use of this product is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis or Stevens-Johnson syndrome, to amoxicillin tablets 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 undergoing penicillin therapy. Healthcare professionals should remain vigilant for signs of anaphylaxis, which may include difficulty breathing, swelling of the face or throat, and rapid heartbeat. Immediate emergency treatment, including supportive measures, is essential in the event of such reactions (5.1).

In addition, Clostridium difficile associated diarrhea (CDAD) has been observed in patients receiving penicillin. This condition can range from mild diarrhea to severe, potentially fatal colitis. It is crucial for healthcare providers to evaluate any patient who presents with diarrhea during or after treatment, as timely intervention may be necessary to manage this serious complication (5.2).

Side Effects

Patients receiving treatment with amoxicillin may experience a range of adverse reactions. Common adverse reactions reported include diarrhea, rash, vomiting, and nausea.

Serious adverse reactions, although less frequent, can occur and require immediate medical attention. Notably, serious and occasionally fatal anaphylactic reactions have been documented in patients undergoing penicillin therapy. Such reactions necessitate prompt emergency treatment and supportive measures. Additionally, Clostridium difficile associated diarrhea has been observed, which can vary in severity from mild diarrhea to fatal colitis; therefore, it is crucial to evaluate any instances of diarrhea that arise during treatment.

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 closely monitored.

Furthermore, interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients following amoxicillin overdosage. Crystalluria, which in some cases has led to renal failure, has also been noted after overdosage in both adult and pediatric patients. These additional adverse reactions highlight the importance of careful dosing and monitoring during treatment with amoxicillin.

Drug Interactions

Concomitant administration of amoxicillin with certain medications may lead to significant drug interactions that require careful consideration.

Pharmacokinetic Interactions

Probenicid has been shown to decrease the renal tubular secretion of amoxicillin, potentially resulting in elevated blood levels of amoxicillin. Clinicians should monitor amoxicillin levels and consider dosage adjustments as necessary to avoid toxicity.

Pharmacodynamic Interactions

The use of amoxicillin alongside oral anticoagulants may enhance the prolongation of prothrombin time. It is advisable to monitor prothrombin time closely and adjust anticoagulant dosages as needed to maintain therapeutic efficacy and safety.

Coadministration of amoxicillin with allopurinol is associated with an increased risk of rash. Patients should be monitored for dermatological reactions, and if a rash occurs, consideration should be given to discontinuing one of the medications.

Additionally, amoxicillin may reduce the efficacy of oral contraceptives. Patients using hormonal contraceptives should be counseled on the potential for decreased contraceptive effectiveness and 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

Pediatric patients, particularly neonates and young infants, may experience delayed elimination of amoxicillin due to incompletely developed renal function. Therefore, dosing of amoxicillin should be modified for pediatric patients aged 12 weeks or younger (≤ 3 months) to ensure safety and efficacy.

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 did not identify 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. Reproduction studies 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, 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, because 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 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 may not have specific information regarding dosage adjustments, special monitoring, or safety considerations outlined in the prescribing information. Therefore, healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment and individualized patient assessment. Regular monitoring of renal function is advisable to ensure patient safety and therapeutic efficacy.

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 an 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 note that interstitial nephritis leading to oliguric renal failure has been documented in a small number of cases following amoxicillin overdosage. Additionally, crystalluria has been reported, which in some instances has resulted in renal failure among both adult and pediatric patients.

To mitigate the risk of crystalluria associated with amoxicillin overdosage, it is essential to maintain adequate fluid intake and promote diuresis. 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 impairment may experience elevated blood levels of amoxicillin due to decreased renal clearance.

For patients experiencing severe overdosage, hemodialysis may be employed as a method to remove amoxicillin from circulation effectively.

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. In contrast, the mixture was negative in the mouse micronucleus test and the dominant lethal assay in mice.

Potassium clavulanate, when tested alone, 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 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 serious reactions such as anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS). Additionally, cases of Clostridium difficile-associated diarrhea, hepatic dysfunction, renal dysfunction, hemolytic anemia, thrombocytopenia, and agranulocytosis have been documented.

Other reported adverse reactions encompass a range of allergic responses, including urticaria and angioedema, as well as non-serious events such as rash, nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, fatigue, fever, arthralgia, myalgia, insomnia, anxiety, depression, confusion, and seizures.

It is important to note that these adverse reactions were reported during postmarketing surveillance and may not be directly related to the use of amoxicillin.

Patient Counseling

Patients should be advised that amoxicillin may be taken every 8 hours or every 12 hours, depending on the dose prescribed. It is important for patients to understand that antibacterial drugs, including amoxicillin, are intended solely for the treatment of bacterial infections and do not have any effect on viral infections, such as the common cold.

When amoxicillin is prescribed for a bacterial infection, patients should be informed that it is common to feel better early in the course of therapy; however, the medication must be taken exactly as directed. Patients should be cautioned against skipping doses or failing to complete the full course of therapy, as this 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.

Patients should also be counseled that diarrhea is a common side effect associated with antibiotic use, typically resolving once the antibiotic is discontinued. They should be made aware that in some cases, patients may develop watery and bloody stools, with or without accompanying stomach cramps and fever, even as late as two months after completing the antibiotic course. If this occurs, patients should be instructed to contact their physician promptly.

Finally, patients should be informed that amoxicillin contains a penicillin class drug, which can cause allergic reactions in some individuals. It is essential for patients to report any history of allergies to penicillin or related medications to their healthcare provider.

Storage and Handling

The product is supplied in a tight container to ensure integrity and stability. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F) as defined by USP Controlled Room Temperature. Proper adherence to these storage conditions is essential for maintaining the product's efficacy and safety.

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 Aidarex Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)