Amoxicillin

Description

Amoxicillin tablets are formulated to 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-azabicyclo 3.2.0heptane-2-carboxylic acid trihydrate. The molecular formula is C16H19N3O5S•3H2O, with a molecular weight of 419.45.

These tablets are intended for oral administration. Each film-coated tablet contains 875 mg of amoxicillin as the trihydrate. The tablets are capsule-shaped, pink in color, scored on one side, and imprinted with WW951 on the opposite side. Inactive ingredients include carmine, colloidal silicon dioxide, crospovidone, FD&C Red #40 Lake, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol (partially hydrolyzed), polyethylene glycol, sodium starch glycolate, talc, and titanium dioxide.

Uses and Indications

Amoxicillin is indicated for the treatment of infections caused by susceptible (only α-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 is indicated to reduce the risk of duodenal ulcer recurrence in patients with H. pylori infection.

Triple Therapy Amoxicillin, in combination with clarithromycin and lansoprazole, 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.

Dual Therapy Amoxicillin, in combination with lansoprazole, 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) who are allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected.

No teratogenic or nonteratogenic effects have been mentioned.

Dosage and Administration

The 875-mg tablet of Amoxicillin should be administered at the start of a light meal to enhance absorption.

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

In adults and pediatric patients over 3 months, dosing varies by indication:

Ear/Nose/Throat:

• For mild to moderate infections: 500 mg every 12 hours or 250 mg every 8 hours.

• For severe infections: 875 mg every 12 hours or 500 mg every 8 hours.

Lower Respiratory Tract:

• For both mild to moderate and severe infections: 875 mg every 12 hours or 500 mg every 8 hours.

Skin/Skin Structure:

• For mild to moderate infections: 500 mg every 12 hours or 250 mg every 8 hours.

• For severe infections: 875 mg every 12 hours or 500 mg every 8 hours.

Genitourinary Tract:

• For mild to moderate infections: 500 mg every 12 hours or 250 mg every 8 hours.

• For severe infections: 875 mg every 12 hours or 500 mg every 8 hours.

Gonorrhea (Acute, Uncomplicated Ano-genital and Urethral Infections):

• In adults: 3 grams as a single oral dose.

• In prepubertal children: 50 mg/kg Amoxicillin combined with 25 mg/kg probenecid as a single dose (not to be used in children under 2 years).

For H. pylori eradication, the following regimens are recommended:

• Triple Therapy: 1 gram Amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all administered twice daily (every 12 hours) for 14 days.

• Dual Therapy: 1 gram Amoxicillin and 30 mg lansoprazole, each given three times daily (every 8 hours) for 14 days.

Dosing adjustments are necessary for adults with impaired renal function:

• For a glomerular filtration rate (GFR) <30 mL/min, the 875 mg tablet should not be used.

• For GFR 10 to 30 mL/min: administer 500 mg or 250 mg every 12 hours, depending on the severity of the infection.

• For GFR <10 mL/min: administer 500 mg or 250 mg every 24 hours, depending on the severity of the infection.

• In hemodialysis patients: administer 500 mg or 250 mg every 24 hours, with an additional dose during and at the end of dialysis.

Contraindications

A history of allergic reactions to any penicillins is a contraindication for use. Additionally, ampicillin-class antibiotics should not be administered to patients with mononucleosis due to the risk of severe complications associated with this condition.

Warnings and Precautions

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients undergoing penicillin therapy. Although anaphylaxis is more frequently associated with parenteral administration, it has also occurred in patients receiving oral penicillins. Individuals with a history of penicillin hypersensitivity and/or sensitivity to multiple allergens are at a higher risk for these reactions. Notably, there have been cases of severe reactions in patients with a history of penicillin hypersensitivity who were treated with cephalosporins. Prior to initiating therapy with amoxicillin, a thorough inquiry regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens is essential. Should an allergic reaction occur, amoxicillin must be discontinued immediately, and appropriate therapeutic measures should be instituted.

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

Clostridium difficile-associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including amoxicillin, and can range from mild diarrhea to fatal colitis. The alteration of normal colonic flora due to antibacterial treatment can lead to an overgrowth of C. difficile, which produces toxins A and B that 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 warranted, as CDAD can occur over two months after the administration of antibacterial agents. If 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.

General precautions should be observed during therapy. The potential for superinfections with mycotic or bacterial pathogens must be considered. If superinfections occur, amoxicillin should be discontinued, and appropriate therapy should be initiated. Additionally, a significant percentage of patients with mononucleosis who receive ampicillin develop an erythematous skin rash; therefore, ampicillin-class antibiotics should not be administered to patients 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.

Periodic assessment of renal, hepatic, and hematopoietic function is recommended during prolonged therapy with amoxicillin. Furthermore, all patients diagnosed with gonorrhea should undergo a serologic test for syphilis at the time of diagnosis, with a follow-up serologic test for syphilis recommended three months after treatment with amoxicillin.

In summary, if an allergic reaction occurs, amoxicillin should be discontinued immediately, and appropriate therapy should be instituted.

Side Effects

Patients receiving amoxicillin may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

Serious adverse reactions include hypersensitivity reactions such as anaphylaxis, which can be life-threatening and requires immediate emergency treatment with epinephrine, along with supportive measures such as oxygen and intravenous steroids. Anaphylaxis is more frequently observed following parenteral therapy but has also occurred in patients receiving oral formulations. Other serious hypersensitivity reactions include 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. It is advised that amoxicillin be discontinued in the event of such reactions unless the treating physician deems the condition being treated as life-threatening and only amenable to amoxicillin therapy.

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, and it should be considered in all patients who present with diarrhea following antibiotic use.

Common adverse reactions include gastrointestinal disturbances such as nausea, vomiting, diarrhea, and black hairy tongue. Additionally, patients may develop hemorrhagic or pseudomembranous colitis, with symptoms potentially arising during or after antibiotic treatment.

Hepatic adverse reactions may manifest as a moderate rise in AST (SGOT) and/or ALT (SGPT), as well as hepatic dysfunction, which can include cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis.

Renal effects such as crystalluria have also been reported. Hematological reactions may include anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis. These hematological reactions are generally reversible upon discontinuation of therapy and are believed to be hypersensitivity phenomena.

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

Miscellaneous reactions include tooth discoloration, which may present as brown, yellow, or gray staining, primarily in pediatric patients. This discoloration is often reduced or eliminated with brushing or dental cleaning.

Overall, while many adverse reactions are manageable, it is essential for healthcare providers to monitor patients closely for any signs of serious reactions, particularly hypersensitivity events.

Drug Interactions

Concurrent administration of probenecid with amoxicillin may lead to decreased renal tubular secretion of amoxicillin, resulting in increased and prolonged blood levels of the antibiotic. Monitoring of amoxicillin levels may be warranted in patients receiving this combination.

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

Amoxicillin, like other antibiotics, may disrupt gut flora, which can lead 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 treatment with amoxicillin.

High concentrations of ampicillin in urine may cause false-positive results in glucose testing using CLINITEST®, Benedict’s Solution, or Fehling’s Solution. This effect may also be observed with amoxicillin. It is recommended that glucose tests utilizing enzymatic glucose oxidase reactions, such as CLINISTIX®, be employed for accurate results.

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

In pediatric patients, particularly neonates and young infants, the elimination of amoxicillin may be delayed 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. Careful consideration of renal function is essential when prescribing this medication to this age group.

Geriatric Use

Clinical studies of amoxicillin included an analysis to assess whether patients aged 65 and older respond differently compared to younger patients. Among the 1,811 subjects treated with amoxicillin capsules, 85% were under 60 years of age, while 15% were aged 61 years and older, and 7% were aged 71 years and older. The analysis, along with other clinical experiences, did not reveal 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.

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. However, there are no adequate and well-controlled studies in pregnant women. As animal reproduction studies are not always predictive of human response, amoxicillin should be used during pregnancy only if clearly needed.

Given its Pregnancy Category B classification, healthcare professionals should weigh the potential benefits against any possible risks when considering the use of this medication 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 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 for the removal of 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 in both adult and pediatric populations. 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 the circulation.

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 amoxicillin and potassium clavulanate mixture 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 in the dominant lethal assay in mice.

Potassium clavulanate alone was evaluated 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 three times the human dose when adjusted for body surface area.

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with the use of antibacterial agents, including amoxicillin. Clostridium difficile associated diarrhea (CDAD) has been reported, which can range in severity from mild diarrhea to fatal colitis. The alteration of normal colonic flora due to antibacterial treatment can lead to C. difficile overgrowth, with hypertoxin producing strains associated with increased morbidity and mortality. Symptoms of CDAD may occur over two months post-antibiotic administration, necessitating careful medical history assessment in patients presenting with diarrhea following antibiotic use. If CDAD is suspected or confirmed, ongoing antibiotic therapy not targeting C. difficile may need to be discontinued, and appropriate management should be initiated.

Adverse reactions reported with penicillins include:

• Infections and Infestations: Mucocutaneous candidiasis.

• Gastrointestinal: Nausea, vomiting, diarrhea, black hairy tongue, and hemorrhagic/pseudomembranous colitis, with the onset of pseudomembranous colitis symptoms potentially occurring during or after treatment.

• Hypersensitivity Reactions: 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: Moderate elevations in AST (SGOT) and/or ALT (SGPT) have been noted, alongside reports of hepatic dysfunction, including cholestatic jaundice and acute cytolytic hepatitis.

• Renal: Crystalluria has been reported.

• Hemic and Lymphatic Systems: Anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis, typically reversible upon discontinuation of therapy and believed to be hypersensitivity phenomena.

• Central Nervous System: Rare reports of reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and dizziness.

• Miscellaneous: Tooth discoloration (brown, yellow, or gray staining), primarily in pediatric patients, with most cases improving with dental cleaning.

In clinical trials involving combination therapy with amoxicillin, clarithromycin, and lansoprazole, no unique adverse reactions were observed beyond those previously reported for the individual components. The most frequently reported adverse events in patients receiving triple therapy included diarrhea (7%), headache (6%), and taste perversion (5%), with no significant increase in treatment-emergent adverse events compared to dual therapy regimens. For patients on dual therapy with amoxicillin and lansoprazole, diarrhea (8%) and headache (7%) were the most common adverse events, 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 effective only for treating 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 advised that it is common to feel better early in the course of therapy; however, it is crucial to take the medication exactly as directed. Patients must understand that 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 once the antibiotic is discontinued. Additionally, they should be informed that it is possible to develop watery and bloody stools, with or without accompanying stomach cramps and fever, even as late as two or more months after completing the antibiotic course. In such cases, 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°-25°C (68°-77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the quality of the product.

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 undergo 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 a period of 3 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)