Amoxicillin

Description

Amoxicillin is a semisynthetic antibiotic, an analog of ampicillin, with a broad spectrum of bactericidal activity against many Gram-positive and Gram-negative microorganisms. Chemically, amoxicillin is (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, and its molecular weight is 419.45 g/mol. Each film-coated tablet contains either 500 mg or 875 mg of amoxicillin USP as the trihydrate. The 500 mg tablets are pink, capsule-shaped, film-coated, and debossed with “A” on one side and “66” on the other side. The 875 mg tablets are also pink, capsule-shaped, film-coated, and debossed with “A” on one side and feature a score line between “6” and “7” on the other side. Inactive ingredients 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 are a penicillin-class antibacterial indicated for the treatment of infections caused by susceptible strains of designated microorganisms. This medication is specifically indicated for infections of the ear, nose, throat, genitourinary tract, skin and skin structure, and lower respiratory tract.

Additionally, amoxicillin tablets are indicated in combination with other therapies for the treatment of Helicobacter pylori infection and duodenal ulcer disease.

Amoxicillin tablets should be utilized only for infections that are proven or strongly suspected to be bacterial in origin. This approach is essential to reduce the development of drug-resistant bacteria and to maintain the effectiveness of amoxicillin tablets 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. For neonates and infants aged 3 months or younger, the maximum dosage is 30 mg per kilogram of body weight per day, divided and administered every 12 hours.

In the treatment of Helicobacter pylori infection, two therapeutic regimens are recommended. For triple therapy, the regimen 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, for dual therapy, the 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 is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis or Stevens-Johnson syndrome, to amoxicillin tablets or other beta-lactam antibiotics, 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 receiving penicillin therapy. Healthcare professionals should be vigilant for signs of anaphylaxis, which necessitate immediate emergency treatment and supportive measures. It is critical to assess the patient's history for any prior allergic reactions to penicillin or related antibiotics before initiating therapy.

In addition, Clostridium difficile-associated diarrhea (CDAD) has been observed in patients treated with penicillin, with manifestations ranging from mild diarrhea to potentially fatal colitis. If a patient develops diarrhea during or after treatment, it is essential to evaluate the situation promptly. Monitoring for gastrointestinal symptoms is recommended to ensure timely intervention if CDAD is suspected.

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 potentially 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.

Other significant adverse reactions include interstitial nephritis, which has been reported in a small number of patients following amoxicillin overdosage, potentially resulting in oliguric renal failure. Crystalluria has also been noted, with some cases leading to renal failure in both adult and pediatric patients after overdosage.

Drug Interactions

Probenicid, when administered concurrently with amoxicillin, decreases the renal tubular secretion of amoxicillin. This interaction may lead to elevated blood levels of amoxicillin, necessitating careful monitoring of amoxicillin concentrations and potential dosage adjustments.

The concomitant use of amoxicillin with oral anticoagulants has been associated with an increased prolongation of prothrombin time. Clinicians should monitor prothrombin time closely and consider adjusting the dosage of anticoagulants as needed to maintain therapeutic efficacy and safety.

Coadministration of amoxicillin with allopurinol has been reported to increase the risk of rash. Patients receiving both medications should be monitored for dermatological reactions, and appropriate management should be initiated if a rash develops.

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

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

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 indicate no 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 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 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. 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 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 an overdosage, it is imperative to discontinue the medication immediately. Symptomatic treatment should be initiated, and supportive measures should be implemented as necessary to ensure patient safety and comfort.

A prospective study indicates that overdosages of amoxicillin below 250 mg/kg typically do not result in significant clinical symptoms. However, it is important to remain vigilant, as cases of crystalluria have been documented, which in some instances may lead to renal failure in both adult and pediatric patients.

To mitigate the risk of crystalluria associated with amoxicillin overdosage, maintaining adequate fluid intake and promoting diuresis are essential. This approach helps to ensure proper renal function and reduces the likelihood of complications.

It is also noteworthy that patients with impaired renal function may experience elevated blood levels of amoxicillin due to decreased renal clearance. In such cases, hemodialysis may be employed as a method to remove amoxicillin from circulation effectively.

Healthcare professionals should monitor patients closely and provide appropriate interventions based on the severity of symptoms and the patient's overall 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 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.

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 3 g human dose based on body surface area.

Postmarketing Experience

Postmarketing experience has identified several adverse events reported voluntarily or through surveillance programs.

Infections and infestations include cases of mucocutaneous candidiasis. Gastrointestinal events have been noted, such as black hairy tongue and hemorrhagic or pseudomembranous colitis, with the onset of pseudomembranous colitis symptoms potentially occurring during or after antibacterial treatment.

Hypersensitivity reactions have been reported, including anaphylaxis, serum sickness-like reactions, erythematous maculopapular rashes, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, hypersensitivity vasculitis, and urticaria.

Liver-related findings include a moderate rise in AST and/or ALT levels, the significance of which remains unknown. Additionally, hepatic dysfunction such as cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis has been documented.

Renal events include reports of crystalluria. Hemic and lymphatic system reactions have encompassed anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis. These reactions are typically reversible upon discontinuation of therapy and are considered to be hypersensitivity phenomena.

Central nervous system effects have included reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and/or dizziness.

Miscellaneous reports have indicated tooth discoloration (brown, yellow, or gray staining), primarily in pediatric patients. In most cases, discoloration was reduced or eliminated with brushing or dental cleaning.

Patient Counseling

Healthcare providers should advise patients that amoxicillin tablets are intended solely for the treatment of infections that are proven or strongly suspected to be caused by bacteria. This approach is crucial to reduce the development of drug-resistant bacteria and to maintain the effectiveness of amoxicillin and other antibacterial drugs.

When culture and susceptibility information is available, it should be taken into account when selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may assist in the empirical selection of therapy.

Patients should be informed that treatment with amoxicillin should continue for a minimum of 48 to 72 hours after they become asymptomatic or after evidence of bacterial eradication has been obtained. For infections caused by Streptococcus pyogenes, it is recommended that treatment lasts at least 10 days to prevent the occurrence of acute rheumatic fever. In certain cases, therapy may be required for several weeks, and clinical and/or bacteriological follow-up may be necessary for several months after the cessation of therapy.

For patients with impaired renal function, it is generally not necessary to reduce the dose unless the impairment is severe. Specifically, patients with a glomerular filtration rate (GFR) of less than 30 mL/min should not receive a 875 mg dose. Those with a GFR of 10 to 30 mL/min should receive either 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a GFR of less than 10 mL/min should receive 500 mg or 250 mg every 24 hours, also depending on the severity of the infection. Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, with an additional dose during and at the end of dialysis.

Healthcare providers should caution patients that a significant percentage of individuals with mononucleosis who receive amoxicillin may develop an erythematous skin rash, and therefore, amoxicillin should not be administered to patients with this condition. If Clostridium difficile associated diarrhea (CDAD) is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate management, including fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation, should be initiated as clinically indicated.

It is important to communicate to patients that prescribing amoxicillin in the absence of a proven or strongly suspected bacterial infection is unlikely to benefit them and may increase the risk of developing drug-resistant bacteria. Additionally, nursing mothers should be made aware that the use of amoxicillin may lead to sensitization of infants, and caution should be exercised when administering this medication to nursing women.

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 guidelines. 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)