Amoxicillin

Description

Formulations of amoxicillin for oral suspension, 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 for oral suspension is intended for oral administration. Each 5 mL of the reconstituted suspension contains amoxicillin trihydrate equivalent to either 200 mg or 400 mg of anhydrous amoxicillin. Additionally, each 5 mL of both the 200 mg and 400 mg formulations contains 0.16 mEq (3.61 mg) of sodium. The reconstituted suspensions are bubble-gum flavored pink liquids. Inactive ingredients include sucrose, sodium citrate, sodium benzoate, edetate disodium, FD&C Red No. 3, xanthan gum, bubble-gum flavor, and colloidal silicon dioxide.

Uses and Indications

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

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

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

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

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

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

Helicobacter pylori Infection 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. Eradication has been shown to reduce the risk of duodenal ulcer recurrence.

In 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, amoxicillin in combination with lansoprazole delayed-release capsules as dual therapy is indicated. This regimen also aims to eradicate H. pylori and reduce the risk of duodenal ulcer recurrence.

Dosage and Administration

Oral suspensions of amoxicillin may be administered without regard to meals; however, the 400 mg suspension has been studied specifically when given at the start of a light meal.

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 Infections:

• For mild to moderate infections:

  • 500 mg every 12 hours or 250 mg every 8 hours

  • Alternatively, 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours

• For severe infections:

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

  • Alternatively, 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:

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

  • Alternatively, 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours

Skin/Skin Structure Infections:

• For mild to moderate infections:

  • 500 mg every 12 hours or 250 mg every 8 hours

  • Alternatively, 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours

• For severe infections:

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

  • Alternatively, 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:

  • 500 mg every 12 hours or 250 mg every 8 hours

  • Alternatively, 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours

• For severe infections:

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

  • Alternatively, 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):

• 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 to ensure the full dosage is received.

For adults with impaired renal function, dosing adjustments are necessary:

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

• For patients with a glomerular filtration rate of less than 10 mL/min: 500 mg or 250 mg every 24 hours, depending on the severity of the infection.

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

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. Anaphylaxis is more prevalent following parenteral administration but can also occur in patients receiving oral penicillins. Individuals with a history of penicillin hypersensitivity or sensitivity to multiple allergens are at a higher risk for these reactions. It is imperative to conduct a thorough inquiry regarding any previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens prior to initiating therapy with amoxicillin. Should an allergic reaction manifest, amoxicillin must be discontinued immediately, and appropriate therapeutic measures should be implemented.

In the event of a serious anaphylactic reaction, immediate emergency treatment with epinephrine is essential. Additional supportive measures, including oxygen administration, intravenous steroids, and airway management (which may involve intubation), should be provided as clinically indicated.

Clostridium difficile-associated diarrhea (CDAD) has been documented with the use of nearly all antibacterial agents, including amoxicillin. The severity of CDAD can range from mild diarrhea to fatal colitis, as the use of antibacterial agents disrupts the normal colonic flora, leading to 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 resistant to antimicrobial therapy, potentially necessitating colectomy. CDAD should be considered in any patient presenting with diarrhea following antibiotic use, and careful medical history is warranted, as CDAD can occur up to two months post-administration of antibacterial agents. 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 confirmed or strongly suspected bacterial infection, or without a prophylactic indication, is unlikely to benefit the patient and may increase the risk of developing drug-resistant bacteria.

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

In summary, if an allergic reaction occurs, amoxicillin should be discontinued, and appropriate therapy should be instituted. Immediate medical assistance should be sought for serious anaphylactic reactions, which require urgent intervention.

Side Effects

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

Serious adverse reactions include hypersensitivity reactions such as anaphylaxis, which can be serious and occasionally fatal. These reactions are more likely to occur in patients with a history of penicillin hypersensitivity or sensitivity to multiple allergens. In the event of an allergic reaction, amoxicillin should be discontinued, and appropriate therapy should be initiated. Other serious hypersensitivity reactions reported include serum sickness-like reactions, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, hypersensitivity vasculitis, and urticaria. Management of these reactions may involve antihistamines and, if necessary, systemic corticosteroids, although amoxicillin should only be continued in life-threatening situations where it is deemed essential by the physician.

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

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

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

Renal adverse reactions include crystalluria, which has been reported and, in some cases, has led to renal failure, particularly following overdosage. Interstitial nephritis resulting in oliguric renal failure has also been documented in a small number of patients after amoxicillin overdosage.

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

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

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

Overall, careful monitoring for these adverse reactions is advised, particularly in patients with known hypersensitivities or those receiving prolonged therapy.

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 plasma 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 when using 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 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 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 under 60 years of age, while 15% were aged 61 years and older, with 7% being 71 years or older. The findings from this analysis, along with additional clinical experience, have not indicated significant differences in responses between elderly patients and their younger counterparts. However, it is important to note that a greater sensitivity to the drug in some older individuals cannot be excluded.

Amoxicillin is primarily excreted by the kidneys, which raises concerns regarding the potential for toxic reactions, particularly in patients with impaired renal function. Given that elderly patients are more likely to experience decreased renal function, careful consideration should be given to dose selection in this population. It 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 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. Healthcare professionals are advised to weigh the potential benefits against the 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 lactating mothers may lead to sensitization of breastfed infants. Therefore, caution should be exercised when administering amoxicillin to nursing women.

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 for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In the event of an overdosage, it is imperative to discontinue the medication immediately and provide symptomatic treatment along with supportive measures as necessary. If the overdosage has occurred very recently and there are no contraindications, an attempt to induce emesis or utilize other methods to remove the drug from the stomach may be considered.

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

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

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

Nonclinical Toxicology

Reproduction studies conducted in mice and rats at doses up to 10 times the human dose have shown no evidence of impaired fertility or teratogenic effects associated with amoxicillin. This 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.

In a multi-generation reproduction study involving 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 based on mg/m².

Long-term studies in animals to evaluate the carcinogenic potential of amoxicillin have not been performed. While specific studies to assess the mutagenic potential of amoxicillin alone have not been conducted, data from tests on a 4:1 mixture of amoxicillin and potassium clavulanate provide some insights. This 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, with increased mutation frequencies observed 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 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, including amoxicillin, can lead 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, and CDAD should be considered in any patient presenting with diarrhea following antibiotic use, even if it occurs over two months post-administration.

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

Other reported adverse events include anaphylaxis, serum sickness–like reactions, various skin reactions such as erythematous maculopapular rashes, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, hypersensitivity vasculitis, and urticaria.

Hepatic events have been noted, including 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 documented.

Crystalluria has been reported, particularly in cases of overdosage, 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 related to hypersensitivity.

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 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 with amoxicillin and lansoprazole, 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 amoxicillin overdosage. Renal impairment appears to be reversible upon cessation of the drug, although high blood levels may occur more readily in patients with impaired renal function due to decreased clearance. Hemodialysis may be effective in removing 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 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 antibiotics, 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 promptly.

Healthcare providers should ensure that periodic assessments of renal, hepatic, and hematopoietic function are conducted during prolonged therapy with amoxicillin. Additionally, all patients diagnosed with gonorrhea should undergo a serologic test for syphilis at the time of diagnosis. Those treated with amoxicillin should have a follow-up serologic test for syphilis after 3 months to ensure proper management of their condition.

Storage and Handling

The dry powder is supplied in a configuration that adheres to the National Drug Code (NDC) specifications. 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) in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the integrity 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 receive a serologic test for syphilis at the time of diagnosis. For those treated with amoxicillin, a follow-up serologic test for syphilis is advised after three months.

FDA Insert (PDF)

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

View full prescribing information (PDF)