Amoxicillin

Description

Formulations of amoxicillin capsules, USP contain amoxicillin, a semi-synthetic antibiotic and an analog of ampicillin, exhibiting a broad spectrum of bactericidal activity against various gram-positive and gram-negative microorganisms. The chemical structure of amoxicillin is defined as (2S, 5R, 6R)-6-((R)-(-)-2-amino-2-(p-hydroxyphenyl)acetamido-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo 3.2.0 heptane-2-carboxylic acid trihydrate. The molecular formula is C16H19N3O5S∙3H2O, with a molecular weight of 419.45.

Amoxicillin capsules are intended for oral administration, available in two strengths: 250 mg and 500 mg of amoxicillin. The 250 mg capsules feature a caramel opaque cap and buff opaque body, imprinted with AA and 820, respectively. Inactive ingredients in the 250 mg formulation include magnesium stearate, sodium lauryl sulfate, D&C Yellow No. 10, FD&C Yellow No. 6, FD&C Blue No. 1, FD&C Red No. 3, titanium dioxide, and gelatin. The 500 mg capsules have a buff opaque cap and buff opaque body, imprinted with AA and 825, and contain similar inactive ingredients, excluding FD&C Blue No. 1 and FD&C Red No. 3.

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 is indicated for the eradication of H. pylori to reduce the risk of duodenal ulcer recurrence. It is used in combination with clarithromycin and lansoprazole as triple therapy for patients with H. pylori infection and duodenal ulcer disease (active or with a 1-year history of a duodenal ulcer). Additionally, amoxicillin is indicated in combination with lansoprazole delayed-release capsules as dual therapy for 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

Amoxicillin capsules may be administered without regard to meals.

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 of age, dosing varies by infection type:

Ear/Nose/Throat Infections:

• For mild to moderate infections:

  • Usual adult dose: 500 mg every 12 hours or 250 mg every 8 hours.

  • Usual dose for children: 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours.

• For severe infections:

  • Usual adult dose: 875 mg every 12 hours or 500 mg every 8 hours.

  • Usual dose for children: 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:

  • Usual adult dose: 875 mg every 12 hours or 500 mg every 8 hours.

  • Usual dose for children: 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:

  • Usual adult dose: 500 mg every 12 hours or 250 mg every 8 hours.

  • Usual dose for children: 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours.

• For severe infections:

  • Usual adult dose: 875 mg every 12 hours or 500 mg every 8 hours.

  • Usual dose for children: 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:

  • Usual adult dose: 500 mg every 12 hours or 250 mg every 8 hours.

  • Usual dose for children: 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours.

• For severe infections:

  • Usual adult dose: 875 mg every 12 hours or 500 mg every 8 hours.

  • Usual dose for children: 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):

• Usual adult dose: 3 grams as a single oral dose.

• Usual dose for 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).

General recommendations indicate that treatment should continue for a minimum of 48 to 72 hours beyond the time the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. For infections caused by Streptococcus pyogenes, a minimum of 10 days of treatment is recommended to prevent the occurrence of acute rheumatic fever.

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

• Patients 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 should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection.

• Patients with a GFR of < 10 mL/min should 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, 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 (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 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. If superinfections occur, amoxicillin should be discontinued, and appropriate therapy should be initiated. Additionally, a significant percentage of patients with mononucleosis who receive ampicillin develop an erythematous skin rash; therefore, ampicillin-class antibiotics should not be administered to patients with mononucleosis. Prescribing amoxicillin in the absence of a proven or strongly suspected bacterial infection or 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 promptly.

Side Effects

Serious adverse reactions associated with the use of amoxicillin include anaphylaxis, which can be serious and occasionally fatal. Patients experiencing such hypersensitivity reactions require immediate emergency treatment with epinephrine, along with oxygen, intravenous steroids, and airway management as necessary. Additionally, Clostridium difficile-associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including amoxicillin, and may range in severity from mild diarrhea to fatal colitis. CDAD should be considered in all patients who present with diarrhea following antibiotic use.

Common adverse reactions observed in clinical trials and postmarketing experiences include gastrointestinal disturbances such as nausea, vomiting, diarrhea, and black hairy tongue. Hemorrhagic or pseudomembranous colitis may occur, with symptoms potentially arising during or after antibiotic treatment.

Hypersensitivity reactions are notable and may 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. These 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 life-threatening and only amenable to amoxicillin therapy.

Liver-related adverse reactions include a moderate rise in AST (SGOT) and/or ALT (SGPT), as well as hepatic dysfunction characterized by cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis. Renal adverse reactions may manifest as crystalluria.

Hematological reactions can 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 may present as reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and, although reported rarely, dizziness.

Miscellaneous adverse reactions include tooth discoloration (brown, yellow, or gray staining), which has been rarely reported, particularly in pediatric patients. In most cases, discoloration was reduced or eliminated with brushing or dental cleaning.

Drug Interactions

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

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

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 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. 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 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

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 subjects. 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 other clinical experiences, have not identified 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

Pregnancy Category B indicates that 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.

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 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 a nursing woman.

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 of these patients.

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 cases of interstitial nephritis leading to oliguric renal failure following amoxicillin overdosage in a small number of patients. 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

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of the compound. While specific studies to detect the mutagenic potential of amoxicillin alone have not been conducted, data from tests on a 4:1 mixture of amoxicillin and potassium clavulanate provide relevant insights.

The combination of amoxicillin and potassium clavulanate was found to be non-mutagenic in both the Ames bacterial mutation assay and the yeast gene conversion assay. However, it exhibited weakly positive results in the mouse lymphoma assay, where the observed trend toward increased mutation frequencies occurred at doses that were also associated with decreased cell survival. Additionally, this combination 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 conducted in rats, no impairment of fertility or other adverse reproductive effects were observed at doses up to 500 mg/kg, which is approximately three times the human dose when adjusted for body surface area.

Postmarketing Experience

Clostridium difficile associated diarrhea (CDAD) has been reported in association 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 an 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.

The following adverse reactions have been reported in association with the use of penicillins:

Infections and Infestations: Mucocutaneous candidiasis.

Gastrointestinal: Nausea, vomiting, diarrhea, black hairy tongue, and hemorrhagic/pseudomembranous colitis. Symptoms of pseudomembranous colitis may occur during or after antibiotic treatment.

Hypersensitivity Reactions: Anaphylaxis, serum sickness-like reactions, erythematous maculopapular rashes, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, hypersensitivity vasculitis, and urticaria have been reported. These reactions may be managed with antihistamines and, if necessary, systemic corticosteroids. Amoxicillin should be discontinued unless the physician deems the condition being treated life-threatening and amenable only to amoxicillin therapy.

Liver: A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted, though the significance of this finding remains unclear. Reports of hepatic dysfunction, including cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis, have also been documented.

Renal: Crystalluria has been reported, with some cases leading to renal failure.

Hemic and Lymphatic Systems: 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.

Central Nervous System: Rare reports of reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and/or dizziness have been noted.

Miscellaneous: Tooth discoloration (brown, yellow, or gray staining) has been rarely reported, primarily in pediatric patients. Discoloration was often reduced or eliminated with brushing or dental cleaning.

Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients following overdosage with amoxicillin. Crystalluria, which in some cases has led to renal failure, has also been reported after amoxicillin overdosage in both adult and pediatric patients. In cases of overdosage, maintaining adequate fluid intake and diuresis is recommended to reduce the risk of crystalluria. Renal impairment appears to be reversible with cessation of drug administration. High blood levels of amoxicillin may occur more readily in patients with impaired renal function due to decreased renal clearance. Amoxicillin may be removed from circulation by hemodialysis.

Patient Counseling

Patients should be informed that amoxicillin may be taken every 8 hours or every 12 hours, depending on the strength of the product prescribed. It is essential to emphasize that antibacterial drugs, including amoxicillin, are effective only for treating bacterial infections and do not have any effect on viral infections, such as the common cold.

When amoxicillin is prescribed for a bacterial infection, patients should be advised that it is common to feel better early in the course of therapy; however, it is crucial to take the medication exactly as directed. Patients must understand that skipping doses or failing to complete the full course of therapy may decrease the effectiveness of the immediate treatment and increase the likelihood of bacteria developing resistance, rendering amoxicillin or other antibacterial drugs ineffective in the future.

Patients should also be made aware that diarrhea is a common side effect associated with antibiotic use, which typically resolves once the antibiotic is discontinued. Additionally, they should be informed that it is possible to develop watery and bloody stools, with or without accompanying stomach cramps and fever, even as late as two or more months after completing the antibiotic course. In such cases, patients should be instructed to contact their physician as soon as possible.

Storage and Handling

Capsules are supplied in a package configuration that includes NDC numbers for identification. It is essential to store the capsules at a temperature range of 20°C to 25°C (68°F to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions must be maintained to ensure the integrity and efficacy of the product.

Additional Clinical Information

Patients undergoing prolonged therapy should have periodic assessments of renal, hepatic, and hematopoietic function to monitor for potential adverse effects. Additionally, all patients diagnosed with gonorrhea are recommended to 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 to ensure proper management and care.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Amoxicillin as submitted by Bi-Coastal Pharma International LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)