Amoxicillin

Description

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

Amoxicillin is available in dosage forms including capsules, tablets, and powder for oral suspension, all intended for oral administration. Each amoxicillin capsule features a yellow opaque cap and body, containing either 250 mg or 500 mg of amoxicillin as the trihydrate. The 250 mg capsule is imprinted with AMOX 250 on one side and GG 848 on the other, while the 500 mg capsule is imprinted with AMOX 500 on one side and GG 849 on the other. Inactive ingredients include yellow ferric oxide, titanium dioxide, gelatin, black ferric oxide for the capsule shells, and cellulose microcrystalline and magnesium stearate for the capsule contents. The formulation meets the USP Dissolution Test 2.

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 active duodenal ulcer disease or a history of duodenal ulcer within the past year. Additionally, amoxicillin, in combination with lansoprazole delayed-release capsules as dual therapy, is indicated for patients with H. pylori infection and duodenal ulcer disease who are allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected.

Dosage and Administration

Capsules, tablets, and oral suspensions of amoxicillin may be administered without regard to meals. However, the 400 mg suspension and the 875 mg tablet have been studied only when given at the start of a light meal.

For neonates and infants aged ≤12 weeks (≤3 months), the recommended upper dose is 30 mg/kg/day, divided every 12 hours.

Usual Adult Dose:

• Ear/Nose/Throat:

  • Mild/Moderate: 500 mg every 12 hours or 250 mg every 8 hours

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

• Lower Respiratory Tract:

  • Mild/Moderate or Severe: 875 mg every 12 hours or 500 mg every 8 hours

• Skin/Skin Structure:

  • Mild/Moderate: 500 mg every 12 hours or 250 mg every 8 hours

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

• Genitourinary Tract:

  • Mild/Moderate: 500 mg every 12 hours or 250 mg every 8 hours

  • Severe: 875 mg every 12 hours or 250 mg every 8 hours

• Gonorrhea: 3 grams as a single oral dose.

Usual Dose for Children Over 3 Months:

• Ear/Nose/Throat:

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

  • Severe: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours

• Lower Respiratory Tract:

  • Severe: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours

• Skin/Skin Structure:

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

  • Severe: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours

• Genitourinary Tract:

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

  • Severe: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours

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.

For patients with impaired renal function, the following adjustments are recommended:

• Patients with a glomerular filtration rate of less than 30 mL/minute should not receive the 875 mg tablet.

• Patients with a glomerular filtration rate of 10 to 30 mL/minute should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection.

• Patients with a glomerular filtration rate of less than 10 mL/minute 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.

Contraindications

A history of allergic reaction to any of the penicillins is a contraindication for use. Due to the potential for severe hypersensitivity reactions, patients with this history should not be administered this product.

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.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including amoxicillin, and can range from mild to life-threatening in severity. It is crucial to consider this diagnosis in patients who present with diarrhea following the administration of antibacterial agents. The use of antibacterial agents can disrupt the normal flora of the colon, potentially leading to an overgrowth of Clostridium difficile. This organism produces a toxin that is a primary cause of antibiotic-associated colitis. Upon establishing a diagnosis of pseudomembranous colitis, appropriate therapeutic measures should be initiated. Mild cases typically respond to the discontinuation of the offending drug alone, while moderate-to-severe cases may require management with fluids, electrolytes, protein supplementation, and treatment with an antibacterial agent effective against C. difficile colitis.

For patients undergoing prolonged therapy with amoxicillin, periodic assessment of renal, hepatic, and hematopoietic function is recommended. Additionally, all patients diagnosed with gonorrhea should undergo a serologic test for syphilis at the time of diagnosis. A follow-up serologic test for syphilis should be conducted three months after treatment with amoxicillin.

In summary, if an allergic reaction occurs, amoxicillin should be discontinued, and appropriate therapy should be initiated. Emergency medical assistance should be sought immediately for serious anaphylactic reactions.

Side Effects

Serious adverse reactions associated with the use of amoxicillin include hypersensitivity reactions, which can be severe and occasionally fatal. Anaphylactic reactions have been reported, particularly in patients with a history of penicillin hypersensitivity or sensitivity to multiple allergens. These reactions are more common following parenteral therapy but can also occur in patients receiving oral formulations. Immediate emergency treatment with epinephrine is required for serious anaphylactic reactions, along with oxygen, intravenous steroids, and airway management as necessary.

Pseudomembranous colitis has been observed with nearly all antibacterial agents, including amoxicillin, and can range from mild to life-threatening. Clinicians should consider this diagnosis in patients who develop diarrhea following the administration of antibacterial agents.

Common gastrointestinal adverse reactions reported include nausea, vomiting, diarrhea, and hemorrhagic or pseudomembranous colitis.

Hypersensitivity reactions may manifest as 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-related adverse reactions include moderate elevations in AST (SGOT) and/or ALT (SGPT), hepatic dysfunction such as cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis.

Renal adverse reactions may present as crystalluria.

Hemic and lymphatic system effects include anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis.

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

Additionally, miscellaneous adverse reactions such as tooth discoloration (brown, yellow, or gray staining) have been noted.

Drug Interactions

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

The use of chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with the bactericidal activity of penicillin. While this interaction has been demonstrated in vitro, its clinical significance remains inadequately documented. Caution is recommended when these agents are used concomitantly with penicillin.

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. A similar effect may also occur with amoxicillin.

In pregnant women, administration of ampicillin has been associated with a transient decrease in plasma concentrations of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol. This effect may also be observed with amoxicillin, warranting careful monitoring of hormonal 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 differential responses compared to younger individuals. Among the 1,811 subjects treated with amoxicillin capsules, 85% were younger than 60 years, 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 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 associated with renal impairment.

Pregnancy

Pregnancy Category B. 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 the risks when considering the use of this medication in pregnant patients.

Lactation

Penicillins, including amoxicillin, have been shown to be excreted in human milk. The use of amoxicillin by 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 may not have specific information regarding dosage adjustments, special monitoring, or safety considerations outlined in the prescribing information. Therefore, healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment and individualized patient assessment. Regular monitoring of renal function is advisable to ensure patient safety and therapeutic 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 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, healthcare professionals may consider inducing emesis or employing other methods to remove the drug from the stomach.

A prospective study involving 51 pediatric patients at a poison-control center indicated that overdosages of amoxicillin below 250 mg/kg are generally not associated with significant clinical symptoms and typically do not necessitate gastric emptying.

Potential complications from amoxicillin overdosage include interstitial nephritis, which can lead to oliguric renal failure, although this has been reported in a limited number of cases. Additionally, crystalluria has been documented, occasionally resulting in renal failure in both adult and pediatric populations. 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 important to note that patients with pre-existing renal dysfunction may experience elevated blood levels of the drug due to decreased renal clearance.

For patients experiencing severe overdosage, hemodialysis may be employed as a method to remove amoxicillin from circulation effectively.

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. In contrast, the mixture was negative in the mouse micronucleus test and in the dominant lethal assay in mice.

Potassium clavulanate alone was evaluated 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

Pseudomembranous colitis has been reported in association with nearly all antibacterial agents, including amoxicillin, and may vary in severity from mild to life-threatening. It is essential to consider this diagnosis in patients presenting with diarrhea following the administration of antibacterial agents. The use of antibacterial agents can disrupt the normal flora of the colon, potentially allowing for the overgrowth of Clostridia. Research indicates that a toxin produced by Clostridium difficile is a primary cause of antibiotic-associated colitis. Upon establishing a diagnosis of pseudomembranous colitis, appropriate therapeutic measures should be initiated. Mild cases typically respond to the discontinuation of the drug alone, while moderate-to-severe cases may require management with fluids, electrolytes, protein supplementation, and treatment with an antibacterial agent effective against C. difficile colitis.

Adverse reactions associated with the use of penicillins include gastrointestinal events such as nausea, vomiting, diarrhea, and hemorrhagic/pseudomembranous colitis, with symptoms of pseudomembranous colitis potentially occurring during or after antibiotic treatment. Hypersensitivity reactions have been reported, including 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. Hepatic events include moderate elevations in AST (SGOT) and/or ALT (SGPT), with the clinical significance of these findings remaining unclear. Reports of hepatic dysfunction, such as cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis, have also been noted. Renal adverse events include crystalluria, while hematologic reactions encompass anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis, which are generally reversible upon discontinuation of therapy and are thought to be hypersensitivity phenomena.

Central nervous system effects, although rare, include reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and dizziness. Miscellaneous reports include tooth discoloration (brown, yellow, or gray staining), primarily in pediatric patients, with most cases showing improvement or resolution following dental cleaning or brushing.

In clinical trials involving combination therapy with amoxicillin plus clarithromycin and lansoprazole, as well as amoxicillin plus lansoprazole, no unique adverse reactions were observed. Adverse reactions reported were consistent with those previously documented for amoxicillin, clarithromycin, or lansoprazole. The most frequently reported adverse events in patients receiving triple therapy included diarrhea (7%), headache (6%), and taste perversion (5%), with no significant increase in treatment-emergent adverse events compared to dual therapy regimens. For patients receiving amoxicillin three times daily plus lansoprazole three times daily, the most frequently reported adverse events were diarrhea (8%) and headache (7%), with no significant increase in treatment-emergent adverse events compared to lansoprazole alone.

Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients following amoxicillin overdosage. Additionally, crystalluria, which in some cases has led to renal failure, has been reported after amoxicillin overdosage in both adult and pediatric patients.

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 prescribing amoxicillin for a bacterial infection, healthcare providers should emphasize the importance of adhering to the prescribed regimen. Patients should be informed that while it is common to feel better early in the course of therapy, it is crucial to take the medication exactly as directed. Skipping doses or failing to complete the full course of therapy may reduce the effectiveness of the treatment and increase the risk of bacteria developing resistance, which could render amoxicillin or other antibacterial drugs ineffective in the future.

Additionally, healthcare providers should ensure that all patients diagnosed with gonorrhea undergo a serologic test for syphilis at the time of diagnosis. Patients treated with amoxicillin should also be advised to have a follow-up serologic test for syphilis after 3 months to monitor their health status.

Storage and Handling

Capsules are supplied in a tight container to ensure their integrity and stability. They should be stored at a temperature range of 20°-25°C (68°-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. Additionally, all patients diagnosed with gonorrhea should receive a serologic test for syphilis at the time of diagnosis. For those treated with amoxicillin, a follow-up serologic test for syphilis is advised after three months.

FDA Insert (PDF)

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

View full prescribing information (PDF)