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.

Amoxicillin is available in several dosage forms:

Amoxicillin Capsules USP: Each capsule for oral administration contains either 250 mg or 500 mg of amoxicillin as the trihydrate. Inactive ingredients include magnesium stearate and talc. The capsule shell and print constituents consist of black iron oxide, D&C Yellow #10, D&C Yellow #10 Aluminum Lake, FD&C Blue #1 Aluminum Lake, FD&C Blue #2 Aluminum Lake, FD&C Red #40, FD&C Red #40 Aluminum Lake, gelatin, propylene glycol, shellac, and titanium dioxide. The 500 mg capsule shell may also contain methylparaben, potassium hydroxide, propylparaben, and sodium lauryl sulfate, while the 250 mg capsule shell includes D&C Red #28 and FD&C Blue #1.

Amoxicillin for Oral Suspension USP: Each 5 mL of reconstituted suspension contains 125 mg or 250 mg of amoxicillin as the trihydrate. Inactive ingredients consist of FD&C Red #40, mixed berry flavoring, silicon dioxide, sodium benzoate, sodium citrate, sucrose, and xanthan gum.

Amoxicillin Tablets USP (Chewable): Each chewable tablet for oral administration contains 125 mg or 250 mg of amoxicillin as the trihydrate. Inactive ingredients include cherry flavor, lactose anhydrous, magnesium stearate, mannitol, microcrystalline cellulose, sodium citrate, and sucrose.

Uses and Indications

Amoxicillin is indicated to reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin and other antibacterial drugs by treating infections that are proven or strongly suspected to be caused by bacteria.

Amoxicillin is indicated in the treatment of infections due to susceptible (only β-lactamase–negative) isolates of the designated bacteria in the following conditions:

Infections of the Ear, Nose, and Throat: Amoxicillin is indicated for infections caused by Streptococcus species (α- and β-hemolytic isolates only), Streptococcus pneumoniae, Staphylococcus spp., or Haemophilus influenzae.

Infections of the Genitourinary Tract: Amoxicillin is indicated for infections due to Escherichia coli, Proteus mirabilis, or Enterococcus faecalis.

Infections of the Skin and Skin Structure: Amoxicillin is indicated for infections caused by Streptococcus spp. (α- and β-hemolytic isolates only), Staphylococcus spp., or E. coli.

Infections of the Lower Respiratory Tract: Amoxicillin is indicated for infections due to Streptococcus spp. (α- and β-hemolytic isolates only), S. pneumoniae, Staphylococcus spp., or H. influenzae.

Gonorrhea, Acute Uncomplicated: Amoxicillin is indicated for the treatment of ano-genital and urethral infections in males and females caused by Neisseria gonorrhoeae. It is not recommended for empiric treatment due to high rates of amoxicillin resistance and should be limited to known susceptible isolates.

Triple Therapy for Helicobacter pylori: Amoxicillin is indicated for use in combination with clarithromycin and lansoprazole for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or with a history of duodenal ulcer within the past year) to eradicate H. pylori, which has been shown to reduce the risk of duodenal ulcer recurrence.

Dual Therapy for Helicobacter pylori: Amoxicillin is indicated for use in combination with lansoprazole for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or with a history of duodenal ulcer within the past year) who are allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.

Dosage and Administration

Treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. For any infection caused by Streptococcus pyogenes, a minimum of 10 days of treatment is recommended to prevent the occurrence of acute rheumatic fever. In certain infections, therapy may be required for several weeks, and clinical and/or bacteriological follow-up may be necessary for several months after cessation of therapy.

For adult and pediatric patients over 3 months of age, the dosing recommendations are as follows:

Ear/Nose/Throat, Skin/Skin Structure, Genitourinary Tract:

• Mild/Moderate Infections:

  • Usual Adult Dose: 500 mg every 12 hours or 250 mg every 8 hours.

  • Usual Dose for Children > 3 Months: 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours.

• Severe Infections:

  • Usual Adult Dose: 875 mg every 12 hours or 500 mg every 8 hours.

  • Usual Dose for Children > 3 Months: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours.

Lower Respiratory Tract:

• Mild/Moderate or Severe Infections:

  • Usual Adult Dose: 875 mg every 12 hours or 500 mg every 8 hours.

  • Usual Dose for Children > 3 Months: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours.

Gonorrhea:

• Usual Adult Dose: 3 grams as a single oral dose.

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

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

For H. pylori infection, the dosing regimens are as follows:

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

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

In patients with renal impairment, dosing adjustments may be necessary. Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Severely impaired patients with a glomerular filtration rate (GFR) of < 30 mL/min should not receive a 875 mg dose. For patients with a GFR of 10 to 30 mL/min, the recommended doses are 500 mg or 250 mg every 12 hours, depending on the severity of the infection. For patients with a GFR less than 10 mL/min, the recommended doses are 500 mg or 250 mg every 24 hours, also depending on the severity of the infection. Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, with an additional dose both during and at the end of dialysis.

For the preparation of the oral suspension, the following directions should be followed: Tap the bottle until all powder flows freely. Add approximately one-third of the total amount of water for reconstitution and shake vigorously to wet the powder. Add the remainder of the water and shake vigorously again. After reconstitution, the required amount of suspension should be placed directly on the child’s tongue for swallowing or added to formula, milk, fruit juice, water, ginger ale, or cold drinks, and taken immediately. 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

Amoxicillin is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis or Stevens-Johnson syndrome, to amoxicillin or other β-lactam antibiotics, such as penicillins and cephalosporins. Due to the potential for severe allergic reactions, use in these patients is not recommended.

Warnings and Precautions

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving penicillin therapy, including amoxicillin. Anaphylaxis is more frequently observed following parenteral administration but can also occur in patients taking oral penicillins. Individuals with a history of penicillin hypersensitivity or sensitivity to multiple allergens are at a higher risk for these reactions. It is imperative to conduct a thorough inquiry regarding any previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens prior to initiating therapy with amoxicillin. Notably, patients with a history of penicillin hypersensitivity have experienced severe reactions when treated with cephalosporins.

Clostridium difficile associated diarrhea (CDAD) has been documented 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 antibacterial use, and careful medical history is essential, as CDAD can occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, it may be necessary to discontinue ongoing antibiotic use not directed against C. difficile. Clinicians should ensure appropriate management, including fluid and electrolyte replacement, protein supplementation, antibiotic treatment for C. difficile, and surgical evaluation as clinically indicated.

The potential for superinfections with fungal or bacterial pathogens should be taken into account during therapy with amoxicillin. Should superinfections occur, amoxicillin should be discontinued, and appropriate therapeutic measures should be initiated. It is important to note that prescribing amoxicillin in the absence of a proven or strongly suspected bacterial infection is unlikely to benefit the patient and may increase the risk of developing drug-resistant bacteria.

Additionally, a significant percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Therefore, amoxicillin should not be administered to patients diagnosed with mononucleosis.

Side Effects

The most common adverse reactions observed in clinical trials of amoxicillin capsules, tablets, or oral suspension, occurring in more than 1% of patients, included diarrhea, rash, vomiting, and nausea. In the context of triple therapy (amoxicillin/clarithromycin/lansoprazole), the frequently reported adverse events were diarrhea (7%), headache (6%), and taste perversion (5%). For patients receiving dual therapy (amoxicillin/lansoprazole), diarrhea was reported in 8% of participants, and headache in 7%.

Postmarketing experience has revealed additional adverse reactions across various systems. Infections and infestations may include mucocutaneous candidiasis. Gastrointestinal reactions can manifest as black hairy tongue and hemorrhagic or pseudomembranous colitis, with symptoms of pseudomembranous colitis potentially occurring during or after antibacterial treatment.

Hypersensitivity reactions are significant and can include 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-related adverse reactions have been noted, including a moderate rise in AST and/or ALT, the clinical significance of which remains unclear. Hepatic dysfunction, such as cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis, has also been reported.

Renal adverse reactions include crystalluria, which has been documented. Hemic and lymphatic system reactions may involve anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis; these reactions are typically reversible upon discontinuation of therapy and are thought to be hypersensitivity phenomena.

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

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving penicillin therapy, including amoxicillin, particularly in those with a history of penicillin hypersensitivity or sensitivity to multiple allergens. Clostridium difficile associated diarrhea (CDAD) has also been reported with the use of nearly all antibacterial agents, including amoxicillin, and can range from mild diarrhea to fatal colitis; CDAD should be considered in all patients presenting with diarrhea following antibacterial use.

In cases of overdosage, interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients. Crystalluria, which in some instances has led to renal failure, has also been documented following amoxicillin overdosage in both adult and pediatric patients.

Drug Interactions

Concurrent use of certain medications with amoxicillin may lead to significant drug interactions, which can affect therapeutic outcomes and safety. The interactions are categorized below based on their pharmacodynamic and pharmacokinetic properties.

Pharmacokinetic Interactions

Probenecid: The co-administration of probenecid decreases the renal tubular secretion of amoxicillin, potentially resulting in increased and prolonged blood levels of amoxicillin. Monitoring of amoxicillin levels may be warranted in patients receiving both medications.

Oral Anticoagulants: Patients taking amoxicillin alongside oral anticoagulants may experience abnormal prolongation of prothrombin time, indicated by an increased international normalized ratio (INR). It is essential to monitor INR closely and adjust the dosage of oral anticoagulants as necessary to maintain the desired anticoagulation effect.

Pharmacodynamic Interactions

Allopurinol: The concurrent use of allopurinol with amoxicillin has been associated with an increased incidence of rashes. The mechanism behind this interaction is not fully understood, and it remains unclear whether the increased rash incidence is due to allopurinol or the hyperuricemia in patients.

Oral Contraceptives: Amoxicillin may alter gut flora, which can lead to decreased reabsorption of estrogen and potentially reduce the efficacy of combined oral estrogen/progesterone contraceptives. Patients should be advised to consider alternative or additional contraceptive methods while on amoxicillin.

Other Antibacterials: The use of chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with the bactericidal effects of penicillin, including amoxicillin. While this interaction has been demonstrated in vitro, its clinical significance remains uncertain.

Drug/Laboratory Interactions

High urine concentrations of amoxicillin may lead to false-positive results for glucose when using tests such as 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.

Special Populations

In pregnant women, administration of ampicillin or amoxicillin has been associated with a transient decrease in plasma concentrations of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol. Monitoring of hormone levels may be considered in this population.

Packaging & NDC

The table below lists all NDC Code configurations of Amoxicillin (amoxicillin powder, for suspension), 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 see Dosage and Administration (2.2).

Geriatric Use

An analysis of clinical studies of amoxicillin has been conducted to evaluate the response of subjects aged 65 and over compared to younger subjects. The findings from these analyses have not identified significant differences in responses between elderly patients and their younger counterparts; however, it is important to note that a greater sensitivity to the drug in some older individuals cannot be ruled out.

Amoxicillin is substantially 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 ensure safe and effective use of the medication.

Pregnancy

Amoxicillin is classified as Pregnancy Category B. Reproduction studies conducted in mice and rats at doses up to 2000 mg/kg, which is 3 and 6 times the human dose based on body surface area, have shown no evidence of harm to the fetus. However, there are no adequate and well-controlled studies in pregnant women. Therefore, amoxicillin should be used during pregnancy only if clearly needed, as animal reproduction studies are not always predictive of human response.

The effects of amoxicillin use during labor or delivery on fetal outcomes remain unknown. It is unclear whether its use may have immediate or delayed adverse effects on the fetus, prolong the duration of labor, or increase the likelihood of the necessity for obstetrical intervention. Healthcare professionals should weigh the potential benefits against the risks when considering amoxicillin for 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 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. A prospective study involving 51 pediatric patients at a poison-control center indicated that overdosages of amoxicillin below 250 mg/kg typically do not result in significant clinical symptoms.

However, there are notable risks associated with higher doses. Interstitial nephritis leading to oliguric renal failure has been documented in a limited number of cases following amoxicillin overdosage. Additionally, crystalluria, which can occasionally progress to renal failure, has been reported in both adult and pediatric populations after excessive amoxicillin intake. To mitigate the risk of crystalluria, it is essential to ensure adequate fluid intake and maintain diuresis.

Renal impairment resulting from overdosage appears to be reversible upon cessation of the drug. It is important to note that patients with pre-existing renal dysfunction may experience elevated blood levels of amoxicillin due to reduced renal clearance. In such cases, hemodialysis may be employed to facilitate the removal of amoxicillin from the bloodstream.

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 coincided with doses that also resulted in decreased cell survival. In contrast, the mixture was negative in the mouse micronucleus test and the dominant lethal assay in mice.

Potassium clavulanate, when tested independently in the Ames bacterial mutation assay and the mouse micronucleus test, yielded 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 twice the human dose of 3 g based on body surface area.

Postmarketing Experience

Postmarketing experience has identified several adverse events reported voluntarily or through surveillance programs.

Infections and infestations have included cases of mucocutaneous candidiasis. Gastrointestinal events reported include black hairy tongue and hemorrhagic or pseudomembranous colitis, with the onset of pseudomembranous colitis symptoms potentially occurring during or after antibacterial treatment.

Hypersensitivity reactions have been noted, including 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-related findings have included a moderate rise in AST and/or ALT levels, the significance of which remains unknown. Reports of hepatic dysfunction have encompassed cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis.

Renal events have included crystalluria.

Hemic and lymphatic system reactions have involved anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis. These reactions are typically reversible upon discontinuation of therapy and are considered to be hypersensitivity phenomena.

Central nervous system effects have included reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and/or dizziness.

Miscellaneous reports have noted tooth discoloration (brown, yellow, or gray staining), primarily in pediatric patients. In most cases, discoloration was reduced or eliminated with brushing or dental cleaning.

Patient Counseling

Patients should be advised that amoxicillin may be taken every 8 hours or every 12 hours, depending on the dose prescribed. It is important for patients to understand that antibacterial drugs, including amoxicillin, are intended solely for the treatment of bacterial infections and are ineffective against 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, the medication must be taken exactly as directed. Patients should be cautioned that skipping doses or failing to complete the full course of therapy may decrease the effectiveness of the immediate treatment and increase the likelihood of bacteria developing resistance, rendering amoxicillin or other antibacterial drugs ineffective in the future.

Patients should also be counseled that diarrhea is a common side effect associated with antibiotic use, typically resolving upon discontinuation of the medication. They should be made aware that, in some cases, patients may develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after completing the antibiotic course. If this occurs, patients should contact their physician promptly.

Additionally, patients should be informed that amoxicillin contains a penicillin class drug product, which can cause allergic reactions in some individuals. It is essential for patients to report any history of allergies to penicillin or related medications to their healthcare provider.

Storage and Handling

The product is supplied in a tight, light-resistant container that complies with USP standards and includes a child-resistant closure as required. 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 handling and storage conditions are essential to maintain the integrity of the product.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)