Amoxicillin

Description

Formulations of amoxicillin capsules, 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 capsules are designed for oral administration, available in two strengths: 250 mg and 500 mg of amoxicillin as the trihydrate. The 250 mg capsule features a blue cap and a pink body, with the body imprinted with ‘A44’ in black ink. The 500 mg capsule also has a blue cap and a pink body, marked with ‘A45’ in black ink. Inactive ingredients include microcrystalline cellulose, D&C Red No. 28, FD&C Blue No. 1, FD&C Red No. 40, gelatin, magnesium stearate, titanium dioxide, and sodium lauryl sulfate. The formulation meets the USP Dissolution Test 2.

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.

Dual Therapy Amoxicillin, in combination with lansoprazole delayed-release capsules, 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.

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 Infections:

• For mild to moderate infections, the usual adult dose is 500 mg every 12 hours or 250 mg every 8 hours. The usual pediatric dose 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 pediatric dose 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 Infections:

• 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 pediatric dose is 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours.

Skin and Skin Structure Infections:

• For mild to moderate infections, the usual adult dose is 500 mg every 12 hours or 250 mg every 8 hours. The usual pediatric dose 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 pediatric dose is 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours.

Genitourinary Tract Infections:

• For mild to moderate infections, the usual adult dose is 500 mg every 12 hours or 250 mg every 8 hours. The usual pediatric dose 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 pediatric dose 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 (GFR) of <30 mL/min should not receive the 875 mg tablet.

• For patients with a GFR 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 GFR 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, 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. 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 reactions, including anaphylaxis, have been reported in patients undergoing penicillin therapy. While anaphylaxis is more commonly associated with parenteral administration, it has also occurred in patients receiving oral penicillins. Individuals with a history of penicillin hypersensitivity or sensitivity to multiple allergens are at an increased risk for such reactions. Prior to initiating therapy with amoxicillin, healthcare professionals should conduct a thorough inquiry regarding any previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. In the event of an allergic reaction, amoxicillin must be discontinued immediately, and appropriate therapeutic measures should be implemented.

In cases of serious anaphylactic reactions, immediate emergency treatment with epinephrine is essential. Additional supportive measures, including oxygen administration, intravenous steroids, and airway management (which may include intubation), should be provided 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 the use of antibacterial agents disrupts the normal colonic flora, leading to C. difficile overgrowth. 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 refractory 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 occur up to 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.

Healthcare professionals should remain vigilant for the possibility of superinfections with mycotic or bacterial pathogens during therapy. Should superinfections arise, 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 be avoided in these patients. 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 immediately, and appropriate therapy should be instituted. In cases of serious anaphylactic reactions, emergency medical assistance must be sought without delay.

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 require immediate emergency treatment with epinephrine, oxygen, intravenous steroids, and airway management. Other serious hypersensitivity reactions reported 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 important to note that these reactions may be more likely in individuals with a history of penicillin hypersensitivity or sensitivity to multiple allergens. If an allergic reaction occurs, amoxicillin should be discontinued, and appropriate therapy should be initiated.

Clostridium difficile-associated diarrhea (CDAD) has also been reported in patients treated with amoxicillin, as well as with nearly all antibacterial agents. The severity of CDAD can range from mild diarrhea to fatal colitis, and it may occur over two months after antibiotic administration. Symptoms of pseudomembranous colitis may arise during or after treatment, necessitating careful monitoring and management.

Common adverse reactions include gastrointestinal symptoms such as nausea, vomiting, diarrhea, and black hairy tongue. Hemorrhagic or pseudomembranous colitis has been noted, with the onset of symptoms potentially occurring during or after antibiotic treatment.

Patients may also experience mild to moderate liver-related adverse reactions, including a rise in AST (SGOT) and/or ALT (SGPT), the clinical significance of which remains unclear. Hepatic dysfunction, such as cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis, has been reported.

Renal adverse reactions, such as crystalluria, have been documented, while hematologic reactions may include anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis. These hematologic 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 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, and any serious or concerning symptoms should prompt immediate medical evaluation and intervention.

Drug Interactions

Concurrent administration of probenecid and amoxicillin may lead to increased and prolonged blood levels of amoxicillin due to the inhibition of renal tubular secretion by probenecid. 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. Caution is advised when these agents are used concurrently with penicillin.

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 hormonal 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. This potential for false-positive results may also apply to amoxicillin.

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 occur with amoxicillin, and monitoring of hormone levels may be considered in this population.

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 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 lactating mothers may lead to sensitization of breastfed infants. Therefore, caution should be exercised when administering amoxicillin to a nursing woman.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to 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 may be made to induce emesis or utilize other methods to remove the drug from the stomach.

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.

It is noteworthy that renal impairment resulting from overdosage appears to be reversible upon cessation of amoxicillin administration. Furthermore, patients with pre-existing renal dysfunction may experience elevated 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 demonstrated 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 conducted. While specific studies to evaluate the mutagenic potential of amoxicillin alone have not been performed, data from tests on a 4:1 mixture of amoxicillin and potassium clavulanate are available. 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 toward increased mutation frequencies in this assay occurred at doses that were also linked to decreased cell survival. The combination 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.

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with the use of 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 agents can lead to C. difficile overgrowth, with hypertoxin producing strains associated with increased morbidity and mortality. CDAD should be considered in patients presenting with diarrhea following antibiotic use, as it may occur over two months post-administration. If CDAD is suspected or confirmed, ongoing antibiotic therapy not targeting C. difficile may need to be discontinued, and appropriate management should be initiated.

Anaphylaxis has been reported, along with 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.

Hepatic events include a moderate rise in AST (SGOT) and/or ALT (SGPT), although the clinical significance remains unclear. Reports of hepatic dysfunction such as cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis have also been noted.

Crystalluria has been reported, particularly in cases of overdose, and may lead to renal failure. Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis, has been observed during therapy, typically resolving upon discontinuation of the drug and believed to be hypersensitivity reactions.

Neuropsychiatric effects such as reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and dizziness have been reported rarely. Tooth discoloration, specifically brown, yellow, or gray staining, has been infrequently noted, primarily in pediatric patients, with most cases improving with dental cleaning.

The most frequently reported adverse events in patients receiving triple therapy included diarrhea (7%), headache (6%), and taste perversion (5%). In patients receiving dual therapy of amoxicillin three times daily plus lansoprazole three times daily, diarrhea (8%) and headache (7%) were the most common events, 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. Renal impairment appears to be reversible upon cessation of amoxicillin, although high blood levels may occur in patients with impaired renal function due to decreased clearance. Hemodialysis may facilitate the removal of amoxicillin from circulation.

Patient Counseling

Patients should be advised 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 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 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 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 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° 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. Proper adherence to these storage conditions is essential for maintaining the product's efficacy and safety.

Additional Clinical Information

Periodic assessment of renal, hepatic, and hematopoietic function is recommended for patients undergoing prolonged therapy with this potent drug. Additionally, all patients diagnosed with gonorrhea should undergo a serologic test for syphilis at the time of diagnosis. Those treated with amoxicillin are advised to have a follow-up serologic test for syphilis 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)