Amoxicillin

Description

Formulations of amoxicillin tablets, USP contain 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.

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

Inactive ingredients in the formulations 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 is indicated for the treatment of infections caused by susceptible (only β-lactamase–negative) strains of designated microorganisms in the following conditions:

Infections of the Ear, Nose, and Throat Amoxicillin is indicated for infections due to Streptococcus spp. (α- and β-hemolytic strains only), S. pneumoniae, Staphylococcus spp., or H. influenzae.

Infections of the Genitourinary Tract This drug is indicated for infections caused by E. coli, P. mirabilis, or E. faecalis.

Infections of the Skin and Skin Structure Amoxicillin is indicated for infections due to Streptococcus spp. (α- and β-hemolytic strains only), Staphylococcus spp., or E. coli.

Infections of the Lower Respiratory Tract This drug is indicated for infections caused by Streptococcus spp. (α- and β-hemolytic strains only), S. pneumoniae, Staphylococcus spp., or H. influenzae.

Gonorrhea Amoxicillin is indicated for the treatment of acute uncomplicated ano-genital and urethral infections due to N. gonorrhoeae in both males and females.

H. pylori Eradication Amoxicillin, in combination with clarithromycin and lansoprazole as triple therapy, is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or with a 1-year history of a duodenal ulcer) to eradicate H. pylori. Additionally, amoxicillin, in combination with lansoprazole delayed-release capsules as dual therapy, is indicated for patients with H. pylori infection and duodenal ulcer disease (active or with a 1-year history of a duodenal ulcer) who are allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected.

Dosage and Administration

Capsules, chewable tablets, and oral suspensions of amoxicillin may be administered without regard to meals. However, the 400 mg suspension, 400 mg chewable tablet, and the 875 mg tablet have been studied only when given at the start of a light meal.

For neonates and infants aged ≤12 weeks (≤3 months), the recommended upper dose of amoxicillin is 30 mg/kg/day, divided every 12 hours.

Adults and Pediatric Patients >3 Months:

Ear/Nose/Throat:

• For mild to moderate infections, the usual adult dose is 500 mg every 12 hours or 250 mg every 8 hours. The usual dose for children is 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours.

• For severe infections, the usual adult dose is 875 mg every 12 hours or 500 mg every 8 hours. The usual dose for children is 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours.

Lower Respiratory Tract:

• For both mild/moderate and severe infections, the usual adult dose is 875 mg every 12 hours or 500 mg every 8 hours. The usual dose for children is 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours.

Skin/Skin Structure:

• For mild to moderate infections, the usual adult dose is 500 mg every 12 hours or 250 mg every 8 hours. The usual dose for children is 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours.

• For severe infections, the usual adult dose is 875 mg every 12 hours or 500 mg every 8 hours. The usual dose for children is 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours.

Genitourinary Tract:

• For mild to moderate infections, the usual adult dose is 500 mg every 12 hours or 250 mg every 8 hours. The usual dose for children is 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours.

• For severe infections, the usual adult dose is 875 mg every 12 hours or 500 mg every 8 hours. The usual dose for children is 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours.

Gonorrhea Acute, Uncomplicated Ano-genital and Urethral Infections:

• The usual adult dose is 3 grams as a single oral dose. For prepubertal children, the usual dose is 50 mg/kg of amoxicillin combined with 25 mg/kg of probenecid as a single dose. Note that probenecid is contraindicated in children under 2 years.

Dosing Recommendations for Adults with Impaired Renal Function:

• Patients with a glomerular filtration rate of <30 mL/min should not receive the 875 mg tablet.

• For patients with a glomerular filtration rate of 10 to 30 mL/min, the recommended dose is 500 mg or 250 mg every 12 hours, depending on the severity of the infection.

• For patients with a glomerular filtration rate of <10 mL/min, the recommended dose is 500 mg or 250 mg every 24 hours, depending on the severity of the infection.

• Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on the severity of the infection, with an additional dose during and at the end of dialysis.

Contraindications

A history of allergic reaction to any penicillins is a contraindication for use.

Ampicillin-class antibiotics should not be administered to patients with mononucleosis due to the risk of severe rash and other complications.

Prescribing amoxicillin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is contraindicated, as it is unlikely to benefit the patient and may increase the risk of developing drug-resistant bacteria.

Warnings and Precautions

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, have been reported in patients undergoing penicillin therapy. Anaphylaxis is more prevalent following parenteral administration but can also occur in patients receiving oral penicillins. Individuals with a history of penicillin hypersensitivity or multiple allergies are at a higher risk for these reactions. It is imperative to conduct a thorough inquiry regarding any previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens prior to initiating therapy with amoxicillin. Should an allergic reaction occur, amoxicillin must be discontinued immediately, and appropriate medical intervention should be initiated.

In the event of a serious anaphylactic reaction, immediate emergency treatment with epinephrine is essential. Additional measures may include the administration of oxygen, intravenous steroids, and airway management, including intubation, as clinically indicated.

Clostridium difficile-associated diarrhea (CDAD) has been documented with the use of nearly all antibacterial agents, including amoxicillin. The severity of CDAD can range from mild diarrhea to fatal colitis, as the use of antibacterial agents disrupts the normal colonic flora, leading to an overgrowth of C. difficile. This organism produces toxins A and B, which are implicated in the development of CDAD. Hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality, and infections may be resistant to antimicrobial therapy, potentially necessitating colectomy. CDAD should be considered in any patient presenting with diarrhea following antibiotic use, and careful medical history is warranted, as CDAD can manifest over two months post-antibiotic administration. If CDAD is suspected or confirmed, ongoing antibiotic therapy not targeting C. difficile may need to be discontinued. Management should include appropriate fluid and electrolyte replacement, protein supplementation, antibiotic treatment for C. difficile, and surgical evaluation as clinically indicated.

The potential for superinfections with mycotic or bacterial pathogens should be considered during therapy. In cases of superinfection, amoxicillin should be discontinued, and suitable alternative therapy should be initiated. Additionally, a significant proportion of patients with mononucleosis who receive ampicillin develop an erythematous skin rash; therefore, ampicillin-class antibiotics should not be prescribed to patients diagnosed with mononucleosis. Prescribing amoxicillin in the absence of a proven or strongly suspected bacterial infection, or without a prophylactic indication, is unlikely to benefit the patient and may increase the risk of developing drug-resistant bacteria.

To ensure patient safety during prolonged therapy, periodic assessment of renal, hepatic, and hematopoietic function is recommended. For patients diagnosed with gonorrhea, a serologic test for syphilis should be conducted at the time of diagnosis, with a follow-up serologic test for syphilis recommended three months post-treatment with amoxicillin.

In summary, if an allergic reaction occurs, amoxicillin should be discontinued, and appropriate therapy should be instituted. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be halted.

Side Effects

Adverse reactions associated with amoxicillin therapy have been observed across various systems, with some reactions categorized by seriousness and frequency.

Serious adverse reactions include hypersensitivity reactions such as anaphylaxis, which can be serious and occasionally fatal, particularly in patients with a history of penicillin hypersensitivity or multiple allergies. Other serious hypersensitivity reactions reported include serum sickness-like reactions, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, hypersensitivity vasculitis, and urticaria. In cases of allergic reactions, amoxicillin should be discontinued, and appropriate therapy initiated unless the treating physician deems the condition being treated life-threatening and solely amenable to amoxicillin.

Gastrointestinal adverse reactions are common and include nausea, vomiting, diarrhea, and black hairy tongue. Additionally, hemorrhagic or pseudomembranous colitis has been reported, with symptoms potentially arising during or after antibiotic treatment. Clostridium difficile-associated diarrhea (CDAD) has also been noted, which can range from mild diarrhea to fatal colitis, and may occur up to two months post-antibiotic administration.

Infections and infestations, specifically mucocutaneous candidiasis, have been reported among patients receiving amoxicillin.

Hepatic adverse reactions include a moderate rise in AST (SGOT) and/or ALT (SGPT), the significance of which remains unclear, as well as reports of hepatic dysfunction, including cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis.

Renal adverse reactions include crystalluria and interstitial nephritis, which has resulted in oliguric renal failure in a small number of patients following overdose. Renal impairment appears to be reversible upon cessation of amoxicillin, although high blood levels may occur more readily in patients with impaired renal function due to decreased clearance.

Hemic and lymphatic system reactions include anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis. These reactions are generally reversible upon discontinuation of therapy and are believed to be hypersensitivity phenomena.

Central nervous system reactions, although reported rarely, include reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and dizziness.

Miscellaneous adverse reactions include tooth discoloration (brown, yellow, or gray staining), which has been rarely reported, primarily in pediatric patients. Most cases of discoloration were reduced or eliminated with brushing or dental cleaning.

Patients should be monitored for these adverse reactions, and appropriate management should be instituted as necessary.

Drug Interactions

Concurrent use of probenecid and amoxicillin may lead to increased and prolonged blood levels of amoxicillin due to probenecid's inhibition of renal tubular secretion. It is advisable to monitor amoxicillin levels when these medications are used together.

Antibiotics such as chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with the bactericidal activity of penicillin, including amoxicillin. While this interaction has been demonstrated in vitro, its clinical significance remains unclear.

Amoxicillin, like other antibiotics, can alter gut flora, potentially leading to decreased reabsorption of estrogen and reduced efficacy of combined oral estrogen/progesterone contraceptives. Patients using these contraceptives should be advised to consider alternative or additional contraceptive methods during and after treatment with amoxicillin.

High concentrations of ampicillin in urine may cause false-positive results for glucose when using tests such as CLINITEST®, Benedict’s Solution, or Fehling’s Solution. It is recommended to utilize glucose tests based on enzymatic glucose oxidase reactions, such as CLINISTIX®, to avoid this issue.

In pregnant women administered ampicillin, a transient decrease in plasma concentrations of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been observed. This effect may also be applicable to amoxicillin, warranting careful monitoring of hormone levels in pregnant patients receiving this antibiotic.

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 account for this developmental consideration. Careful monitoring and adjustment of dosage are recommended to ensure safety and efficacy in this age group.

Geriatric Use

An analysis of clinical studies involving amoxicillin included subjects aged 65 and over to assess any differences in response compared to younger individuals. Among the 1,811 subjects treated with amoxicillin capsules, 85% were under 60 years of age, while 15% were aged 61 years and older, with 7% being 71 years or older. The findings from this analysis, along with additional clinical experience, have not indicated 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 excluded.

Amoxicillin is primarily excreted by the kidneys, which raises concerns regarding the potential for 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 mitigate the risk of adverse effects and ensure appropriate dosing.

Pregnancy

Reproduction studies conducted in mice and rats at doses up to 10 times the human dose have shown no evidence of impaired fertility or harm to the fetus due to amoxicillin. This medication is classified as Pregnancy Category B. 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 are advised to weigh the potential benefits against any possible risks when considering the use of this drug 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 a nursing woman.

Renal Impairment

There is no specific information 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 indicated 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. If the overdosage has occurred very recently and there are no contraindications, an attempt to induce emesis or utilize other methods to remove the drug from the stomach may be considered.

A prospective study involving 51 pediatric patients at a poison-control center indicated that overdosages of amoxicillin less than 250 mg/kg are generally not associated with significant clinical symptoms and do not necessitate gastric emptying. However, it is important to monitor for potential complications.

Reports have documented cases of interstitial nephritis leading to oliguric renal failure following amoxicillin overdosage in a small number of patients. Additionally, crystalluria has been observed, which in some instances has resulted in renal failure among both adult and pediatric patients. To mitigate the risk of crystalluria, it is essential to maintain adequate fluid intake and promote diuresis.

Renal impairment resulting from overdosage appears to be reversible upon cessation of amoxicillin administration. It is noteworthy that patients with impaired renal function may experience higher blood levels of the drug due to decreased renal clearance. In cases of severe overdosage, hemodialysis may be employed to facilitate the removal of amoxicillin from circulation.

Nonclinical Toxicology

Reproduction studies conducted in mice and rats at doses up to 10 times the human dose have shown no evidence of impaired fertility or teratogenic effects associated with amoxicillin. However, there are no adequate and well-controlled studies in pregnant women. Due to the limitations of animal reproduction studies in predicting human responses, the use of this drug during pregnancy should be considered only when clearly necessary.

In a multi-generation reproduction study involving rats, no adverse reproductive effects or impairment of fertility were observed at doses up to 500 mg/kg, which is approximately three times the human dose based on mg/m².

Long-term studies in animals to assess the carcinogenic potential of amoxicillin have not been performed. While specific studies to evaluate the mutagenic potential of amoxicillin alone have not been conducted, data from tests on a 4:1 mixture of amoxicillin and potassium clavulanate provide some insights. This combination was found to be non-mutagenic in both the Ames bacterial mutation assay and the yeast gene conversion assay. It exhibited weakly positive results in the mouse lymphoma assay; however, the observed trend of increased mutation frequencies in this assay occurred at doses that were also linked to decreased cell survival. The mixture was negative in the mouse micronucleus test and the dominant lethal assay in mice. Potassium clavulanate, when tested alone in the Ames bacterial mutation assay and the mouse micronucleus test, also yielded negative results in both assays.

Postmarketing Experience

Clostridium difficile associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including amoxicillin. The severity of CDAD can range from mild diarrhea to fatal colitis, as treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile. This organism produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality, as these infections may be refractory to antimicrobial therapy and could necessitate colectomy. CDAD should be considered in all patients presenting with diarrhea following antibiotic use, and careful medical history is essential, as cases have been reported to occur over two months after the administration of antibacterial agents.

In cases where CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Management should include appropriate fluid and electrolyte replacement, protein supplementation, antibiotic treatment for C. difficile, and surgical evaluation as clinically indicated.

Anaphylaxis has been reported (see WARNINGS). Additionally, 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 have also been documented.

A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted, although the significance of this finding remains unclear. Reports of hepatic dysfunction, including cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis, have been observed.

Crystalluria has been reported, particularly in the context of overdose. Hematological reactions such as anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been associated with penicillin therapy. These reactions are typically reversible upon discontinuation of therapy and are believed to be hypersensitivity phenomena.

Rarely, reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and/or dizziness have been reported. Tooth discoloration (brown, yellow, or gray staining) has been infrequently noted, primarily in pediatric patients, with most cases showing improvement or resolution with dental cleaning or brushing.

In clinical studies, the most frequently reported adverse events among patients receiving triple therapy included diarrhea (7%), headache (6%), and taste perversion (5%). No treatment-emergent adverse events were observed at significantly higher rates with triple therapy compared to any dual therapy regimen. For patients receiving amoxicillin three times daily plus lansoprazole three times daily, the most frequently reported adverse events were diarrhea (8%) and headache (7%), with no significant differences in treatment-emergent adverse events compared to lansoprazole alone.

Patient Counseling

Patients should be informed that amoxicillin may be taken every 8 hours or every 12 hours, depending on the strength of the product prescribed. It is essential to emphasize that antibacterial drugs, including amoxicillin, are intended solely for the treatment of bacterial infections and are ineffective against viral infections, such as the common cold.

When amoxicillin is prescribed for a bacterial infection, patients should be advised that it is common to feel better early in the course of therapy. However, they must be instructed to take the medication exactly as directed. Skipping doses or failing to complete the full course of therapy 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 made aware that diarrhea is a common side effect associated with antibiotic use, which typically resolves upon discontinuation of the medication. They should be cautioned that, in some cases, they may experience watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after completing the antibiotic course. If such symptoms occur, patients should be instructed to contact their physician as soon as possible.

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.

Additional Clinical Information

Periodic assessment of renal, hepatic, and hematopoietic function is recommended for patients undergoing prolonged therapy. Additionally, all patients diagnosed with gonorrhea should receive a serologic test for syphilis at the time of diagnosis. For those treated with amoxicillin, a follow-up serologic test for syphilis is advised after three months.

FDA Insert (PDF)

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

View full prescribing information (PDF)