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 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. Its molecular formula is C16H19N3O5S • 3H2O, with a molecular weight of 419.45.

Amoxicillin is available in various dosage forms for oral administration, including capsules, tablets, and powder for oral suspension. Amoxicillin capsules contain amoxicillin trihydrate equivalent to either 250 mg or 500 mg of amoxicillin. The capsules also include Magnesium Stearate and Sodium Lauryl Sulfate as inactive ingredients, while the capsule shell is composed of D&C red No. 33, FD&C blue No. 1, FD&C red No. 40, FD&C yellow No. 6, Gelatin, Sodium Lauryl Sulfate, and Titanium Dioxide. Each 250 mg capsule contains up to 0.0027 mEq (0.062 mg) of sodium, and the 500 mg capsule contains up to 0.0052 mEq (0.119 mg) of sodium.

Amoxicillin tablets provide amoxicillin trihydrate equivalent to 875 mg. Inactive ingredients in the tablets include Sodium Starch Glycolate, Pregelatinized Starch, Colloidal Silicon Dioxide, Povidone, Magnesium Stearate, Polyvinyl Alcohol, Titanium Dioxide, Talc, Polyethylene Glycol, and Lecithin. Each tablet contains up to 0.032 mEq (0.74 mg) of sodium.

Amoxicillin for oral suspension is presented as a dry powder that, when reconstituted as directed, yields a suspension containing amoxicillin trihydrate equivalent to either 125 mg or 250 mg of amoxicillin per 5 mL. The oral suspension formulation includes flavors, casing color (FD&C red No. 40 and FD&C yellow No. 6), Microcrystalline Cellulose, Carboxymethylcellulose Sodium, Colloidal Silicon Dioxide, Sodium Citrate, Sodium Propionate, and Sucrose. Each 5 mL of the 125 mg reconstituted suspension contains up to 0.209 mEq (4.80 mg) of sodium, while each 5 mL of the 250 mg reconstituted suspension contains up to 0.417 mEq (9.60 mg) of sodium.

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 to reduce the risk of duodenal ulcer recurrence in patients with H. pylori infection.

Triple Therapy Amoxicillin is indicated in combination with clarithromycin and lansoprazole for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or with a 1-year history of a duodenal ulcer).

Dual Therapy Amoxicillin is indicated in combination with lansoprazole for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or with a 1-year history of a duodenal ulcer) who are allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected.

No teratogenic or nonteratogenic effects have been mentioned.

Dosage and Administration

Capsules, tablets, and oral suspensions of amoxicillin may be administered without regard to meals. The 875-mg tablet has been studied only when taken 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 for infections caused by less susceptible organisms should adhere to the recommendations for severe infections. Pediatric dosages are intended for individuals weighing less than 40 kg; those weighing 40 kg or more should be dosed according to adult recommendations.

After reconstitution, the required amount of suspension 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. Larger doses may be necessary for stubborn or severe infections. In cases of chronic urinary tract infections, frequent bacteriological and clinical evaluations are essential. Smaller doses than those recommended should not be utilized; higher doses may be required at times. Treatment should continue for a minimum of 48 to 72 hours after the patient becomes asymptomatic or evidence of bacterial eradication is obtained. For infections caused by Streptococcus pyogenes, a treatment duration of at least 10 days is recommended to prevent the occurrence of acute rheumatic fever.

For H. pylori eradication, the following regimens are recommended:

• Triple therapy: 1 gram of amoxicillin, 500 mg of clarithromycin, and 30 mg of lansoprazole, administered twice daily (every 12 hours) for 14 days.

• Dual therapy: 1 gram of amoxicillin and 30 mg of lansoprazole, each given three times daily (every 8 hours) for 14 days.

In patients with impaired renal function, a dose reduction is generally not required unless the impairment is severe. Patients with a glomerular filtration rate (GFR) of <30 mL/minute should not receive the 875 mg tablet. For those with a GFR of 10 to 30 mL/minute, a dose of 500 mg or 250 mg every 12 hours may be administered, depending on the severity of the infection. Patients with a GFR of <10 mL/minute should receive 500 mg or 250 mg every 24 hours, also based on infection severity. Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, with an additional dose during and at the end of dialysis.

For mixing the oral suspension, it is advised to prepare the suspension at the time of dispensing. Tap the bottle until all powder flows freely, then add approximately half of the total amount of water for reconstitution and shake vigorously to wet the powder. Add the remaining water and shake vigorously again. Each teaspoonful (5 mL) will contain either 125 mg or 250 mg of amoxicillin. It is important to shake the oral suspension well before use. Any unused portion of the reconstituted suspension must be discarded after 14 days. Refrigeration is preferable but not required.

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 cases 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. 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 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.

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 a prophylactic indication, is unlikely to benefit the patient and may increase the risk of developing drug-resistant bacteria.

As with any potent medication, periodic assessment of renal, hepatic, and hematopoietic function is recommended during prolonged therapy. 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 after treatment with amoxicillin.

Side Effects

Patients receiving treatment with amoxicillin may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

Serious adverse reactions include hypersensitivity reactions, which can manifest as 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. Anaphylactic reactions, while more common following parenteral therapy, have also been reported in patients receiving oral penicillins. These reactions are particularly 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.

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 may occur over two months after antibiotic administration. Symptoms of pseudomembranous colitis may arise during or after treatment, necessitating careful monitoring and potential discontinuation of ongoing antibiotic therapy not directed against C. difficile.

Common adverse reactions include gastrointestinal disturbances such as nausea, vomiting, diarrhea, and black hairy tongue. Hemorrhagic or pseudomembranous colitis may also occur. Additionally, patients may experience mucocutaneous candidiasis.

Hepatic adverse reactions have been noted, including moderate rises in AST (SGOT) and/or ALT (SGPT), as well as hepatic dysfunction characterized by cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis. Renal effects such as crystalluria have also been reported.

Hematological 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 may include reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and, though rarely, dizziness.

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

Patients should be monitored closely for these adverse reactions, and appropriate management should be instituted as clinically indicated.

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 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

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. Careful consideration of renal function is essential when prescribing this medication to this age group.

Geriatric Use

An analysis of clinical studies involving amoxicillin included subjects aged 65 and over to assess any differential responses 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, and 7% were aged 71 years and older. The findings from this analysis, along with additional clinical experience, have not indicated significant differences in responses between elderly patients and their younger counterparts. However, it is important to note that a greater sensitivity to the drug in some older individuals cannot be excluded.

Amoxicillin is primarily excreted through 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 associated with renal impairment.

Pregnancy

Reproduction studies conducted in mice and rats at doses up to ten 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.

Given the Pregnancy Category B classification, healthcare professionals should 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

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.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In the event of an overdosage, it is imperative to discontinue the medication immediately and provide symptomatic treatment along with supportive measures as necessary. If the overdosage has occurred very recently and there are no contraindications, an attempt 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, as interstitial nephritis leading to oliguric renal failure has been documented in a small number of cases following amoxicillin overdosage. Additionally, crystalluria, which in some instances has resulted in renal failure, has been reported in both adult and pediatric patients.

To mitigate the risk of crystalluria associated with amoxicillin overdosage, it is essential to maintain adequate fluid intake and promote diuresis. Renal impairment observed in these cases appears to be reversible upon cessation of the drug. It is noteworthy that patients with impaired renal function may experience elevated blood levels of amoxicillin due to decreased renal clearance.

For patients experiencing severe overdosage, hemodialysis may be employed as a method to remove amoxicillin from circulation effectively. Continuous monitoring and appropriate management are crucial to ensure patient safety and recovery.

Nonclinical Toxicology

Reproduction studies conducted in mice and rats at doses up to ten times the human dose have shown 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 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 assess the carcinogenic potential of amoxicillin have not been performed. While specific studies to evaluate 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 combination was found to be non-mutagenic in both the Ames bacterial mutation assay and the yeast gene conversion assay. It exhibited weakly positive results in the mouse lymphoma assay; however, the observed trend toward increased mutation frequencies in this assay occurred at doses that were also linked to decreased cell survival. The combination was negative in the mouse micronucleus test and 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 antibacterial agents, including 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 treatment can lead to C. difficile overgrowth, with hypertoxin producing strains associated with increased morbidity and mortality. Symptoms of CDAD may occur over two months post-antibiotic administration, necessitating careful medical history assessment. If CDAD is suspected or confirmed, ongoing antibiotic use not targeting C. difficile may need to be discontinued, and appropriate management should be initiated.

Additional adverse reactions reported with penicillins include:

• Infections and Infestations: Mucocutaneous candidiasis.

• Gastrointestinal: Nausea, vomiting, diarrhea, black hairy tongue, and hemorrhagic/pseudomembranous colitis, with the onset of pseudomembranous colitis symptoms 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.

• Liver: Moderate rises 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, typically reversible upon discontinuation of therapy.

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

• Miscellaneous: Tooth discoloration (brown, yellow, or gray staining), primarily in pediatric patients, with most cases improving with dental cleaning.

In clinical trials involving combination therapy with amoxicillin, clarithromycin, and lansoprazole, as well as amoxicillin and lansoprazole alone, no unique adverse reactions were observed beyond those previously reported for the individual agents.

For patients receiving triple therapy, the most frequently reported adverse events included diarrhea (7%), headache (6%), and taste perversion (5%). No significant differences in treatment-emergent adverse events were noted compared to dual therapy regimens.

In dual therapy with amoxicillin and lansoprazole, the most common adverse events were diarrhea (8%) and headache (7%), with no significant increase in treatment-emergent adverse events compared to lansoprazole alone.

Patient Counseling

Healthcare providers should advise patients 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 take the medication exactly as directed. Emphasize the importance of not skipping doses or discontinuing the medication prematurely, as this 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, healthcare providers should inform patients that they may experience watery and bloody stools, with or without stomach cramps and fever, even as late as two months after completing the antibiotic course. If such symptoms occur, patients should be instructed to contact their physician promptly.

Storage and Handling

The product is supplied in a tight container to ensure integrity and stability. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the quality and efficacy of the product.

Additional Clinical Information

Periodic assessment of renal, hepatic, and hematopoietic function is recommended for patients undergoing prolonged therapy with potent drugs. Additionally, all patients diagnosed with gonorrhea should 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 three months.

FDA Insert (PDF)

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

View full prescribing information (PDF)