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.

Helicobacter 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 studied 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, dosing varies by indication:

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 immediately. Larger doses may be necessary for stubborn or severe infections.

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.

• For a GFR of < 10 mL/min, the dosing is 500 mg or 250 mg every 24 hours, based on severity.

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

To prepare the oral suspension, add water for reconstitution as specified for each bottle size at the time of dispensing. Each teaspoonful (5 mL) will contain:

• 125 mg amoxicillin (for the 125 mg/5 mL formulation)

• 200 mg amoxicillin (for the 200 mg/5 mL formulation)

• 250 mg amoxicillin (for the 250 mg/5 mL formulation)

• 400 mg amoxicillin (for the 400 mg/5 mL formulation)

Shake the oral suspension well before use. Any unused portion of the reconstituted suspension must be discarded after 14 days. Refrigeration is preferable but not required.

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 potential for 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 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 use of antibacterial agents disrupts the normal flora of the colon, leading to an overgrowth of C. difficile, which produces toxins A and B that contribute to 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.

Healthcare professionals should remain vigilant for the possibility of superinfections with mycotic or bacterial pathogens during therapy. In cases of superinfection, 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 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 should be conducted during prolonged therapy with amoxicillin, as with any potent drug. Furthermore, all patients diagnosed with gonorrhea should undergo a serologic test for syphilis at the time of diagnosis, and those treated with amoxicillin should have a follow-up serologic test for syphilis after three months.

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

Side Effects

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

Serious adverse reactions primarily involve hypersensitivity reactions, which can be severe and occasionally fatal. Anaphylaxis has been reported in patients receiving penicillin therapy, with a higher incidence following parenteral administration. However, cases have also occurred in patients on oral penicillins, particularly in individuals with a history of penicillin hypersensitivity or sensitivity to multiple allergens. 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 recommended that amoxicillin be discontinued in the event of such reactions unless the treating physician deems the condition life-threatening and only amenable to amoxicillin therapy.

Gastrointestinal adverse reactions are also notable, with nausea, vomiting, diarrhea, and black hairy tongue being commonly reported. Additionally, hemorrhagic or pseudomembranous colitis may occur, with symptoms potentially arising during or after antibiotic treatment. Clostridium difficile-associated diarrhea (CDAD) has been documented with 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 C. difficile overgrowth, necessitating consideration of CDAD in patients presenting with diarrhea following antibiotic use.

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

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

Renal adverse reactions, such as crystalluria, have been reported as well.

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 effects, 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. In most cases, discoloration was reduced or eliminated with brushing or dental cleaning.

Overall, while many adverse reactions are manageable, careful monitoring and consideration of patient history are essential in the administration of amoxicillin.

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. It is advisable to monitor amoxicillin levels and consider dosage adjustments as necessary.

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 inadequately documented.

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 hormonal contraceptives should be advised to consider alternative or additional contraceptive methods during treatment with amoxicillin.

In terms of laboratory test interactions, high urine concentrations of ampicillin may cause false-positive results for glucose when using CLINITEST®, Benedict’s Solution, or Fehling’s Solution. This effect may also be observed with amoxicillin. Therefore, it is recommended to utilize glucose tests based on enzymatic glucose oxidase reactions, such as CLINISTIX®.

Additionally, administration of ampicillin to pregnant women has been associated with a transient decrease in plasma concentrations of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol. This effect may also be applicable to amoxicillin, warranting careful monitoring of hormone levels in pregnant patients receiving treatment.

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 these physiological differences. Careful consideration of renal function is essential when prescribing amoxicillin in this age group to ensure safety and efficacy.

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 younger than 60 years, 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 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 associated with renal impairment.

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. Given that animal reproduction studies are not always predictive of human response, amoxicillin should be used during pregnancy only if clearly needed. Pregnant patients should be informed of the potential risks and benefits of treatment, and healthcare providers should exercise caution when prescribing this medication to women of childbearing potential.

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 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, 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.

In cases of severe overdosage, hemodialysis may be employed to facilitate the removal of amoxicillin from circulation, thereby aiding in the management of the patient's condition.

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 of amoxicillin alone have not been conducted, data from 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, 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 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 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

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. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued, and appropriate management should be instituted as clinically indicated.

Anaphylaxis has been reported (see WARNINGS). Other 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.

A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted, although the significance of this finding remains unknown. Hepatic dysfunction, including cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis, has also been reported. Crystalluria has been documented, particularly in cases of overdose.

Hematological reactions such as anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported during therapy with penicillins. These reactions are typically reversible upon discontinuation of therapy and are believed to be hypersensitivity phenomena.

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

The most frequently reported adverse events in patients receiving triple therapy were 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. In 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.

Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients following overdose with amoxicillin. Crystalluria, in some instances leading to renal failure, has also been reported after amoxicillin overdose in both adult and pediatric patients.

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 antibiotics, which typically resolves upon discontinuation of the medication. They should be cautioned that, in some cases, patients 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 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 and efficacy 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 Aidarex Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)