Amoxicillin

Description

Amoxicillin is a semisynthetic antibiotic, structurally related to ampicillin, exhibiting a broad spectrum of bactericidal activity against various gram-positive and gram-negative microorganisms. The chemical designation is (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 structural formula is represented as C₁₆H₁₉N₃O₅S•3H₂O.

Amoxicillin is available in several dosage forms for oral administration. Each capsule contains either 250 mg or 500 mg of amoxicillin as the trihydrate, with inactive ingredients including magnesium stearate and various constituents in the capsule shell such as black iron oxide, D&C Yellow #10, FD&C Red #40, gelatin, propylene glycol, shellac, sodium lauryl sulfate, and titanium dioxide. The 250 mg capsule shell may also contain D&C Red #28 and FD&C Blue #1, while the 500 mg capsule shell may include FD&C Blue #1.

The oral suspension formulation contains 125 mg or 250 mg of amoxicillin per 5 mL, with inactive ingredients comprising FD&C Red #40, mixed berry flavoring, silicon dioxide, sodium benzoate, sodium citrate, sucrose, and xanthan gum. Additionally, each chewable tablet formulation contains 125 mg or 250 mg of amoxicillin as the trihydrate, with inactive ingredients including cherry flavor, lactose, magnesium stearate, mannitol, microcrystalline cellulose, sodium citrate, and sucrose.

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.

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:

  • 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.

• For severe infections:

  • 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:

• For both mild/moderate and severe infections:

  • 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:

• For mild to moderate infections:

  • 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.

• For severe infections:

  • 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:

• For mild to moderate infections:

  • 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.

• For severe infections:

  • 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 (probenecid is contraindicated 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.

For adults with impaired renal function:

• Patients with a glomerular filtration rate of < 30 mL/min should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection.

• Patients with a glomerular filtration rate 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.

Directions for mixing the oral suspension include preparing 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 potential for severe adverse reactions.

Warnings and Precautions

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients undergoing penicillin therapy. Although anaphylaxis is more frequently associated with parenteral administration, it has also occurred in patients receiving oral penicillins. Individuals with a history of penicillin hypersensitivity and/or sensitivity to multiple allergens are at a higher risk for these reactions. Notably, there have been instances of severe reactions in patients with a history of penicillin hypersensitivity who were treated with cephalosporins. Prior to initiating therapy with amoxicillin, a thorough inquiry regarding any previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens is essential. Should an allergic reaction occur, amoxicillin must be discontinued immediately, and appropriate therapeutic measures should be instituted.

In the event of serious anaphylactic reactions, immediate emergency treatment with epinephrine is required. Additional interventions may include the administration of oxygen, intravenous steroids, and airway management, including intubation, as clinically indicated.

Clostridium difficile-associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including amoxicillin in its various formulations (capsules, oral suspension, and chewable tablets). 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 manifest 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.

Healthcare professionals should remain vigilant for the possibility of superinfections with mycotic or bacterial pathogens during therapy. In cases where superinfections occur, amoxicillin should be discontinued, and suitable alternative therapy should be initiated. It is also important to note that a significant percentage of patients with mononucleosis who receive ampicillin develop an erythematous skin rash; therefore, ampicillin-class antibiotics should not be prescribed 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, as with any potent drug. Additionally, all patients diagnosed with gonorrhea should undergo serologic testing 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 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 in individuals with a history of penicillin hypersensitivity or sensitivity to multiple allergens. Immediate emergency treatment with epinephrine is required for serious anaphylactic reactions, along with oxygen, intravenous steroids, and airway management as necessary. 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. In cases of hypersensitivity reactions, 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 amoxicillin, which may range from mild diarrhea to fatal colitis. Symptoms of CDAD can occur over two months after antibiotic administration, necessitating careful medical history assessment in patients presenting with diarrhea following treatment.

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

Patients may also experience various reactions affecting the hemic and lymphatic systems, including anemia (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.

Liver-related adverse reactions have been noted, including a moderate rise in AST (SGOT) and/or ALT (SGPT), the significance of which remains unknown. Reports of hepatic dysfunction, such as cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis, have also been documented.

Renal adverse reactions include crystalluria.

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

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

Overall, while many adverse reactions are manageable, careful monitoring and appropriate intervention are essential for patients receiving amoxicillin.

Drug Interactions

Concurrent use of probenecid with amoxicillin may lead to increased and prolonged blood levels of amoxicillin due to the inhibition of renal tubular secretion. It is advisable to monitor amoxicillin levels and consider dosage adjustments as necessary.

Antibiotics such as chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with the bactericidal activity of penicillin, including amoxicillin. While this interaction has been demonstrated in vitro, its clinical significance remains unclear. Caution is recommended when these agents are used concomitantly.

Amoxicillin, in various formulations including capsules, oral suspension, and chewable tablets, may disrupt gut flora, potentially leading to decreased reabsorption of estrogen and reduced efficacy of combined oral estrogen/progesterone contraceptives. Patients should be advised to consider alternative contraceptive methods during treatment.

High concentrations of ampicillin in urine can cause false-positive results for glucose 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 effect may also be applicable 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 during 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 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, with 7% being 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 potential for toxic reactions, particularly in patients with impaired renal function. Given that geriatric 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 elderly patients to mitigate the risk of adverse effects associated with renal impairment.

Pregnancy

Amoxicillin is classified as a pregnancy category B medication. Reproductive 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. However, there are no adequate and well-controlled studies available in pregnant women.

Due to the limitations of animal reproduction studies in predicting human outcomes, 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 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 these patients to ensure safety and efficacy.

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 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 interstitial nephritis leading to oliguric renal failure in a small subset 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 excessive doses of amoxicillin. 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 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 outcomes, the use of this drug during pregnancy should be considered only when clearly necessary.

Long-term studies to assess the carcinogenic potential of amoxicillin have not been performed. While specific mutagenicity studies for amoxicillin alone have not been conducted, data from a 4:1 mixture of amoxicillin and potassium clavulanate provide some insights. This combination was found to be non-mutagenic in both the Ames bacterial mutation assay and the yeast gene conversion assay. In the mouse lymphoma assay, it exhibited weakly positive results; however, this trend towards increased mutation frequencies occurred 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. Potassium clavulanate alone was tested in the Ames bacterial mutation assay and the mouse micronucleus test, yielding negative results in both assays. Additionally, a multi-generation reproduction study in rats indicated no impairment of fertility or other adverse reproductive effects at doses up to 500 mg/kg, which is approximately three times the human dose in mg/m².

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with the use of amoxicillin and other penicillins, 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, as treatment with antibacterial agents disrupts the normal colonic flora, leading to C. difficile overgrowth. The organism produces toxins A and B, which are implicated in CDAD development. 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 essential, 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 management should be initiated.

Serious hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving penicillin therapy. While anaphylaxis is more common with parenteral administration, it has also occurred in patients taking oral penicillins. Individuals with a history of penicillin hypersensitivity or multiple allergen sensitivities are at greater risk. Severe reactions have been noted in patients with a history of penicillin allergy treated with cephalosporins. In the event of an allergic reaction, amoxicillin should be discontinued, and emergency treatment with epinephrine, oxygen, intravenous steroids, and airway management should be provided as necessary.

Additional adverse reactions associated with penicillin use 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 if necessary. Amoxicillin should be discontinued unless the treating physician deems the condition life-threatening and solely treatable with amoxicillin.

• Liver: Moderate elevations in AST (SGOT) and/or ALT (SGPT) have been observed, though the clinical significance remains unclear. Reports of hepatic dysfunction, including cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis, have also been noted.

• Renal: Crystalluria has been reported.

• Hemic and Lymphatic Systems: Anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been documented during penicillin therapy. These reactions are typically reversible upon discontinuation and are thought to be hypersensitivity-related.

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

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

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 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 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 reduce the effectiveness of the immediate treatment and increase the risk of bacteria developing resistance, which could render 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 cautioned that in some cases, patients may experience watery and bloody stools, with or without stomach cramps and fever, even up to 2 months after completing the antibiotic course. If such symptoms occur, patients should be advised to contact their physician promptly.

Storage and Handling

The product is supplied in a tight, light-resistant container that complies with the specifications outlined in the United States Pharmacopeia (USP). Each container is equipped with a child-resistant closure as mandated.

For optimal storage, the product should be maintained at a temperature range of 20°C to 25°C (68°F to 77°F), in accordance with USP Controlled Room Temperature guidelines. It is essential to adhere to these storage conditions to ensure the integrity and efficacy 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 after three months.

FDA Insert (PDF)

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

View full prescribing information (PDF)