Amoxicillin

Description

Formulations of amoxicillin powder for oral suspension 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. This formulation is specifically intended for oral administration.

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 This drug is indicated for the eradication of H. pylori to reduce the risk of duodenal ulcer recurrence.

No specific teratogenic or nonteratogenic effects have been mentioned.

Dosage and Administration

Amoxicillin oral suspensions may be administered without regard to meals. The 400 mg suspension has been evaluated only when given at the start of a light meal; however, food effect studies have not been conducted with the 200 mg formulation.

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

In adults and pediatric patients over 3 months of age, the dosing recommendations are as follows:

Ear/Nose/Throat:

• Mild/Moderate: 500 mg every 12 hours or 250 mg every 8 hours

• Severe: 875 mg every 12 hours or 500 mg every 8 hours

Lower Respiratory Tract:

• Mild/Moderate or Severe: 875 mg every 12 hours or 500 mg every 8 hours

Skin/Skin Structure:

• Mild/Moderate: 500 mg every 12 hours or 250 mg every 8 hours

• Severe: 875 mg every 12 hours or 500 mg every 8 hours

Genitourinary Tract:

• Mild/Moderate: 500 mg every 12 hours or 250 mg every 8 hours

• Severe: 875 mg every 12 hours or 500 mg every 8 hours

Gonorrhea:

• Adults: 3 grams as a single oral dose

• Prepubertal children: 50 mg/kg amoxicillin, combined with 25 mg/kg probenecid as a single dose (Note: Probenecid is contraindicated in children under 2 years).

After reconstitution, the required amount of suspension should be placed directly on the child’s tongue for swallowing. Alternatively, the suspension may be added to formula, milk, fruit juice, water, ginger ale, or cold drinks, which should be consumed in their entirety.

For patients with impaired renal function:

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

• Patients with a GFR of 10 to 30 mL/min may receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection.

• Patients with a GFR of < 10 mL/min may receive 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, with an additional dose during and at the end of dialysis.

For the eradication of H. pylori, the recommended adult oral doses are as follows:

• 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.

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 adverse reactions.

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 instances 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 any 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 cases 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. The severity of CDAD can range from mild diarrhea to fatal colitis, as treatment with antibacterial agents disrupts the normal flora of the colon, 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, 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. Appropriate management should include 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 suitable 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 a prophylactic indication is unlikely to benefit the patient and may increase the risk of developing drug-resistant bacteria.

Laboratory tests are recommended to monitor patient safety during prolonged therapy. Periodic assessment of renal, hepatic, and hematopoietic function should be conducted. 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.

Side Effects

Adverse reactions associated with the use of the medication include a range of serious and common events, as detailed below.

Serious adverse reactions include hypersensitivity reactions such as anaphylaxis, serum sickness–like reactions, and severe skin reactions including erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis. Patients may also experience hypersensitivity vasculitis and urticaria. It is important to note that these hypersensitivity reactions may be managed with antihistamines and, if necessary, systemic corticosteroids. Amoxicillin should be discontinued in the event of such reactions unless the treating physician deems the condition being treated to be life-threatening and only amenable to amoxicillin therapy.

Gastrointestinal adverse reactions are common and include nausea, vomiting, diarrhea, and black hairy tongue. Additionally, hemorrhagic or pseudomembranous colitis may occur, with symptoms potentially arising during or after antibiotic treatment. 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 development of CDAD is linked to alterations in the normal flora of the colon, leading to overgrowth of C. difficile, which produces toxins contributing to the condition. It is crucial to consider CDAD in any patient presenting with diarrhea following antibiotic use, as it may occur up to two months after treatment. If CDAD is suspected or confirmed, ongoing antibiotic therapy not targeting C. difficile may need to be discontinued.

Infections and infestations, such as mucocutaneous candidiasis, have also been reported.

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

Renal adverse reactions include crystalluria.

Hemic and lymphatic system reactions may manifest as 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 effects, although reported rarely, may 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. In most cases, discoloration was reduced or eliminated with brushing or dental cleaning.

Overall, careful monitoring for these adverse reactions is recommended during treatment.

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. 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 unclear.

Amoxicillin, like other antibiotics, may disrupt gut flora, which can result in 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

In pediatric patients, particularly neonates and young infants, renal function is not fully developed, which may lead to delayed elimination of amoxicillin. Therefore, dosing of amoxicillin should be adjusted for pediatric patients aged 12 weeks or younger (≤ 3 months) to account for this altered pharmacokinetics. Caution is advised when prescribing amoxicillin to this age group to ensure safe and effective use.

Geriatric Use

An analysis of clinical studies involving amoxicillin included subjects aged 65 and over to assess potential 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, and 7% were aged 71 years and 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 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 is advisable 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 associated with amoxicillin, which is classified as Pregnancy Category B. However, there are no adequate and well-controlled studies in pregnant women. Due to the limitations of animal reproduction studies in predicting 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 prescribing this medication to 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 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 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, as interstitial nephritis leading to oliguric renal failure has been documented in a small number of cases following amoxicillin overdosage. Additionally, crystalluria, which in some instances has resulted in renal failure, has been reported in both adult and pediatric populations.

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 noteworthy that patients with impaired renal function may experience higher 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. Continuous monitoring and appropriate management are crucial to ensure patient safety and recovery.

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. The drug is classified as Pregnancy Category B. However, there are no adequate and well-controlled studies in pregnant women, and since animal reproduction studies may not always predict human response, amoxicillin should be used during pregnancy only if clearly needed.

Long-term studies to evaluate the carcinogenic potential of amoxicillin have not been performed. While specific mutagenicity studies on amoxicillin alone have not been conducted, data from a 4:1 mixture of amoxicillin and potassium clavulanate provide some insights. This mixture was found to be non-mutagenic in the Ames bacterial mutation assay and the yeast gene conversion assay. It exhibited weakly positive results in the mouse lymphoma assay; however, this trend towards increased mutation frequencies occurred at doses that also resulted in decreased cell survival. The mixture was negative in the mouse micronucleus test and the dominant lethal assay in mice. Potassium clavulanate alone was also tested in the Ames bacterial mutation assay and the mouse micronucleus test, yielding negative results in both assays. In a multi-generation reproduction study 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 in mg/m².

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. 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 associated with penicillins include:

• Infections and Infestations: Mucocutaneous candidiasis.

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

• Hypersensitivity Reactions: Reports include 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 such as cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis.

• Renal: Crystalluria has been reported, with some cases leading to renal failure, particularly following overdosage.

• Hemic and Lymphatic Systems: Anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been observed, typically reversible upon discontinuation of therapy.

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

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

Additionally, interstitial nephritis resulting in oliguric renal failure has been documented in a small number of patients following amoxicillin overdosage. In cases of overdosage, maintaining adequate fluid intake and diuresis is recommended to mitigate the risk of crystalluria.

Patient Counseling

Healthcare providers should advise patients that amoxicillin may be taken every 8 hours or every 12 hours, depending on the strength of the product prescribed. It is important to counsel patients 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 informed 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 develop 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 this occurs, patients should be advised 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 H. J. Harkins Company, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)