Amoxicillin

Description

Amoxicillin is a semisynthetic antibiotic, an analog of ampicillin, exhibiting a broad spectrum of bactericidal activity against various gram-positive and gram-negative microorganisms. The chemical structure 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, with a molecular weight of 419.45.

The drug is available in several dosage forms: each capsule for oral administration contains either 250 mg or 500 mg of amoxicillin as the trihydrate, with inactive ingredients including magnesium stearate and various coloring agents such as black iron oxide, D and C Yellow No. 10, and FD and C Red No. 40, among others. Each 5 mL of the oral suspension contains 125 mg or 250 mg of amoxicillin as the trihydrate, with inactive ingredients including FD and C Red No. 40, mixed berry flavoring, and sodium benzoate. Additionally, each chewable tablet contains 125 mg or 250 mg of amoxicillin as the trihydrate, with inactive ingredients such as cherry flavor, lactose, and magnesium stearate.

Uses and Indications

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

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

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

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

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

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

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

No specific teratogenic or nonteratogenic effects have been mentioned.

Dosage and Administration

Amoxicillin may be administered in the form of capsules, chewable tablets, or oral suspensions without regard to meals.

Neonates and Infants Aged ≤ 12 Weeks (≤ 3 Months): The recommended upper dose is 30 mg/kg/day, divided every 12 hours.

Adults and Pediatric Patients > 3 Months:

• Ear/Nose/Throat Infections:

  • Mild/Moderate:

    • Adults: 500 mg every 12 hours or 250 mg every 8 hours.

    • Children: 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours.

  • Severe:

    • Adults: 875 mg every 12 hours or 500 mg every 8 hours.

    • 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:

  • Mild/Moderate or Severe:

    • Adults: 875 mg every 12 hours or 500 mg every 8 hours.

    • 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:

  • Mild/Moderate:

    • Adults: 500 mg every 12 hours or 250 mg every 8 hours.

    • Children: 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours.

  • Severe:

    • Adults: 875 mg every 12 hours or 500 mg every 8 hours.

    • 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:

  • Mild/Moderate:

    • Adults: 500 mg every 12 hours or 250 mg every 8 hours.

    • Children: 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours.

  • Severe:

    • Adults: 875 mg every 12 hours or 500 mg every 8 hours.

    • 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):

  • Adults: 3 grams as a single oral dose.

  • Prepubertal children: 50 mg/kg amoxicillin combined with 25 mg/kg probenecid as a single dose (not to be used in children under 2 years).

For the oral suspension, after reconstitution, the required amount should be placed directly on the child’s tongue for swallowing or mixed with formula, milk, fruit juice, water, ginger ale, or cold drinks, and taken immediately. It is important to shake the oral suspension well before use and to discard any unused portion after 14 days. Refrigeration is preferable but not required.

Larger doses may be necessary for stubborn or severe infections.

Dosing Recommendations for Adults With Impaired Renal Function:

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

• For patients with a glomerular filtration rate of 10 to 30 mL/min: 500 mg or 250 mg every 24 hours, depending on severity.

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

Directions for Mixing Oral Suspension:Prepare the suspension at the time of dispensing by adding water for reconstitution as specified in the accompanying table. Each teaspoonful (5 mL) will contain either 125 mg or 250 mg of amoxicillin (as the trihydrate).

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 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 in its various formulations. The severity of CDAD can range from mild diarrhea to fatal colitis, as treatment with antibacterial agents disrupts the normal flora of the colon, leading to an overgrowth of C. difficile. This organism produces toxins A and B, which are implicated in the development of CDAD. Hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality, as these infections may be refractory to antimicrobial therapy and could necessitate colectomy. CDAD should be considered in all patients presenting with diarrhea following antibiotic use, and careful medical history is warranted, as CDAD can occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic therapy 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.

General precautions should be observed during therapy. The potential for superinfections with mycotic or bacterial pathogens must be considered. If superinfections occur, amoxicillin should be discontinued, and 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 without 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 is recommended during prolonged therapy with amoxicillin. Furthermore, all patients diagnosed with gonorrhea should undergo a serologic test for syphilis at the time of diagnosis, with a follow-up serologic test for syphilis recommended three months post-treatment with amoxicillin.

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

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 serious and occasionally fatal. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity or sensitivity to multiple allergens. Immediate emergency treatment with epinephrine, oxygen, intravenous steroids, and airway management is required for serious anaphylactic reactions. 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. If any allergic reaction occurs, amoxicillin should be discontinued unless the treating physician deems the condition being treated life-threatening and only amenable to amoxicillin therapy.

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, and it must be considered in all patients presenting with diarrhea following antibiotic use. Symptoms of CDAD may occur over two months after the administration of antibacterial agents, necessitating careful medical history assessment.

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

Infections and infestations, specifically mucocutaneous candidiasis, have been noted among patients.

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

Renal adverse reactions such as crystalluria have also been reported.

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.

Patients should be monitored for these adverse reactions, and appropriate management should be instituted as necessary.

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 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 similarly occur with amoxicillin, warranting careful monitoring of hormone levels in pregnant patients receiving this antibiotic.

Packaging & NDC

The table below lists all NDC Code configurations of Amoxicillin, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

In pediatric patients 12 weeks or younger (≤ 3 months), dosing of amoxicillin should be modified due to incompletely developed renal function. This developmental stage may result in delayed elimination of amoxicillin, necessitating careful consideration of dosing to ensure safety and efficacy.

Geriatric Use

An analysis of clinical studies involving amoxicillin included subjects aged 65 and over to assess potential differences in response compared to younger patients. Among the 1,811 subjects treated with amoxicillin capsules, 85% were under 60 years of age, while 15% were aged 61 years and older, including 7% who were 71 years and older. The findings from this analysis, along with other clinical experiences, have not indicated significant differences in responses between elderly patients and their younger counterparts. However, it is important to note that a greater sensitivity to the drug in some older individuals cannot be excluded.

Amoxicillin is primarily excreted by the kidneys, which raises concerns regarding the risk of toxic reactions, particularly in patients with impaired renal function. Given that elderly patients are more likely to experience decreased renal function, careful consideration should be given to dose selection in this population. It may be beneficial to monitor renal function in geriatric patients to mitigate the risk of adverse effects associated with renal impairment.

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. Given that 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 any possible risks when prescribing this medication to pregnant patients.

Lactation

Penicillins, including amoxicillin, have been shown to be excreted in human milk. The use of amoxicillin by nursing mothers may lead to sensitization of breastfed infants. Therefore, caution should be exercised when administering amoxicillin to lactating mothers.

Renal Impairment

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 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.

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.

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 provide some insights. This combination 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 combination was negative in the mouse micronucleus test and the dominant lethal assay in mice. Additionally, potassium clavulanate alone was 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, as reported voluntarily or through surveillance programs.

Clostridium difficile associated diarrhea (CDAD) has been documented with nearly all antibacterial agents, including amoxicillin formulations. The severity of CDAD can range from mild diarrhea to fatal colitis, attributed to the alteration of normal colonic flora leading to C. difficile overgrowth. The production of toxins A and B by C. difficile contributes to the development of CDAD, with hypertoxin-producing strains associated with increased morbidity and mortality. It is essential to consider CDAD in patients presenting with diarrhea following antibiotic use, as cases have been reported to 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 clinical management should be initiated.

Adverse reactions associated with penicillins, including amoxicillin, primarily involve sensitivity phenomena, particularly in individuals with a history of hypersensitivity to penicillins or other allergic conditions. Reported adverse reactions include:

• Infections and Infestations: Mucocutaneous candidiasis.

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

• Hypersensitivity Reactions: 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. These reactions may be managed with antihistamines and systemic corticosteroids, and amoxicillin should be discontinued unless deemed necessary for life-threatening conditions.

• Liver: Moderate elevations in AST (SGOT) and/or ALT (SGPT) have been noted, alongside reports of hepatic dysfunction, including cholestatic jaundice and acute cytolytic hepatitis.

• Renal: Crystalluria has been reported.

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

• Central Nervous System: Rare instances of reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and dizziness have been reported.

• Miscellaneous: Tooth discoloration (brown, yellow, or gray staining) has been infrequently reported, primarily in pediatric patients, with most cases showing improvement with dental hygiene practices.

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 capsules, amoxicillin for oral suspension, and amoxicillin tablets (chewable), are intended solely for the treatment of bacterial infections and are ineffective against viral infections, such as the common cold.

When prescribed amoxicillin for a bacterial infection, patients should be advised that it is common to feel better early in the course of therapy. However, they must 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 and other antibacterial drugs ineffective in the future.

Patients should also be made aware that diarrhea is a common side effect associated with antibiotic use, typically resolving upon discontinuation of the medication. They should be instructed to monitor for the development of watery and bloody stools, which may occur even up to 2 months after completing the antibiotic course, and to contact their physician immediately if such symptoms arise.

Storage and Handling

The product is supplied in a tight, light-resistant container that complies with the United States Pharmacopeia (USP) standards, featuring a child-resistant closure as required. It should be stored at a temperature range of 20°C to 25°C (68°F to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper handling and 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 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 three months post-treatment.

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)