Amoxicillin

Description

Amoxicillin, USP is 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 is defined as (2S,5R,6R)-6-((R)-(-)-2-amino-2-(p-hydroxyphenyl)acetamido-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo3.2.0heptane-2-carboxylic acid trihydrate, with a molecular formula of C16H19N3O5S•3H2O and a molecular weight of 419.45.

Amoxicillin is available in several dosage forms. The capsules are presented in two variants: one with a blue opaque cap and pink opaque body containing either 250 mg or 500 mg of amoxicillin as the trihydrate, and the other with a white opaque cap and body containing 500 mg of amoxicillin as the trihydrate. The imprints on the capsules indicate their respective dosages, with "AMOXIL®" over "250" for the 250 mg and "AMOXIL®" over "500" for the 500 mg capsules. Inactive ingredients for the blue and pink capsules include D&C Red No. 28, FD&C Blue No. 1, FD&C Red No. 40, gelatin, magnesium stearate, and titanium dioxide, while the white capsules contain gelatin, magnesium stearate, and titanium dioxide.

Amoxicillin is also available as an oral suspension, with each 5 mL of the reconstituted suspension containing either 125 mg or 250 mg of amoxicillin as the trihydrate. The 125 mg formulation contains 0.11 mEq (2.51 mg) of sodium, and the 250 mg formulation contains 0.15 mEq (3.36 mg) of sodium. Inactive ingredients in the oral suspension include FD&C Red No. 3, flavorings, silica gel, sodium benzoate, sodium citrate, sucrose, and xanthan gum.

Uses and Indications

Amoxicillin is indicated for the treatment of infections caused by susceptible strains of designated microorganisms. This includes infections of the ear, nose, throat, genitourinary tract, skin and skin structure, and lower respiratory tract. Additionally, amoxicillin is indicated in combination therapy for the treatment of Helicobacter pylori infection and duodenal ulcer disease.

Amoxicillin should be utilized exclusively for the treatment or prevention of infections that are proven or strongly suspected to be caused by bacteria. This approach is essential to reduce the development of drug-resistant bacteria and to maintain the effectiveness of amoxicillin and other antibacterial agents.

Dosage and Administration

In adults, the recommended dosage ranges from 750 mg to 1750 mg per day, administered in divided doses every 8 to 12 hours. For pediatric patients over 3 months of age, the dosage is 20 to 45 mg/kg per day, also given in divided doses every 8 to 12 hours. For neonates and infants aged 3 months or younger, the maximum dosage is 30 mg/kg per day, divided and administered every 12 hours.

For the treatment of H. pylori infection, the following regimens are recommended:

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

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

It is essential to reduce the dosage in patients with severe renal impairment, specifically those with a glomerular filtration rate (GFR) of less than 30 mL/min.

Contraindications

Use is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis or Stevens-Johnson syndrome, to Amoxicillin or other beta-lactams, such as penicillins or cephalosporins. This contraindication is due to the potential for severe allergic reactions in these individuals.

Warnings and Precautions

Serious and occasionally fatal anaphylactic reactions have been reported in patients receiving penicillin therapy. Healthcare professionals should be vigilant for signs of anaphylaxis, which necessitate immediate emergency treatment and supportive measures.

Drug-induced enterocolitis syndrome (DIES) has been associated with the use of amoxicillin. In the event that DIES is suspected, it is imperative to discontinue amoxicillin and initiate appropriate therapeutic interventions.

Clostridium difficile-associated diarrhea can occur in patients treated with amoxicillin, presenting a spectrum of severity from mild diarrhea to potentially fatal colitis. Healthcare providers should evaluate any patient who develops diarrhea during or after treatment with amoxicillin to determine the appropriate course of action.

Side Effects

Patients receiving amoxicillin may experience a range of adverse reactions, which can be categorized into common and serious reactions.

Common adverse reactions include diarrhea, rash, vomiting, and nausea. These reactions are generally mild and may not require medical intervention.

Serious adverse reactions have also been reported. Anaphylactic reactions, which can be serious and occasionally fatal, have been documented in patients undergoing penicillin therapy. Such reactions necessitate immediate emergency treatment and supportive measures. Additionally, drug-induced enterocolitis syndrome (DIES) has been associated with amoxicillin use; if this condition arises, it is imperative to discontinue amoxicillin and initiate appropriate therapy. Clostridium difficile-associated diarrhea, which can range from mild diarrhea to fatal colitis, has also been observed. Patients should be evaluated if they experience diarrhea during treatment.

It is important to note that patients with a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to amoxicillin or other beta-lactams (including penicillins or cephalosporins) may be at increased risk for adverse reactions.

In cases of overdosage, several serious reactions have been reported. Interstitial nephritis resulting in oliguric renal failure has occurred in a small number of patients. Crystalluria, which in some instances has led to renal failure, has also been noted following amoxicillin overdosage in both adult and pediatric patients. To mitigate the risk of crystalluria, it is essential to maintain adequate fluid intake and diuresis. Renal impairment resulting from overdosage appears to be reversible upon cessation of the drug. Furthermore, patients with impaired renal function may experience higher blood levels of amoxicillin due to decreased renal clearance. Hemodialysis may be effective in removing amoxicillin from circulation.

Drug Interactions

Probenicid, when administered concurrently with amoxicillin, decreases the renal tubular secretion of amoxicillin. This interaction may lead to elevated blood levels of amoxicillin, necessitating careful monitoring of amoxicillin concentrations and potential dosage adjustments based on clinical response.

The concomitant use of amoxicillin with oral anticoagulants has been associated with an increased prolongation of prothrombin time. Clinicians should monitor prothrombin time closely in patients receiving this combination and consider adjusting the dosage of the anticoagulant as needed to maintain therapeutic levels.

Coadministration of amoxicillin with allopurinol has been reported to increase the risk of rash. Patients should be monitored for dermatological reactions, and if a rash occurs, discontinuation of one or both medications may be warranted.

Additionally, amoxicillin may reduce the efficacy of oral contraceptives. Patients using oral contraceptives should be advised to consider alternative or additional contraceptive methods during treatment with amoxicillin to ensure adequate contraceptive protection.

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 of amoxicillin has been conducted to evaluate the response of subjects aged 65 and over compared to younger subjects. The findings from these analyses did not identify 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

Pregnancy Category B indicates that reproduction studies conducted in mice and rats at doses up to 2000 mg/kg (3 and 6 times the 3 g human dose, based on body surface area) have shown no evidence of harm to the fetus due to amoxicillin. However, there are no adequate and well-controlled studies in pregnant women. Therefore, while animal reproduction studies are not always predictive of human response, amoxicillin should be used during pregnancy only if clearly needed. Healthcare professionals should weigh the potential benefits against any possible risks when considering the use of amoxicillin 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 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. Symptomatic treatment and supportive measures should be instituted as necessary to manage the patient's condition effectively.

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, healthcare professionals should remain vigilant, as there have been reports of interstitial nephritis leading to oliguric renal failure in a small number of patients following amoxicillin overdosage.

Crystalluria has also been documented in both adult and pediatric patients after amoxicillin overdosage, with some cases progressing to renal failure. 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.

In cases of severe overdosage, hemodialysis may be employed to facilitate the removal of amoxicillin from the circulation, thereby aiding in the management of the patient's condition.

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 (AUGMENTIN) provide relevant insights.

AUGMENTIN 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, AUGMENTIN yielded negative results in the mouse micronucleus test and the dominant lethal assay in mice.

Potassium clavulanate, when tested independently, was also negative in the Ames bacterial mutation assay and the mouse micronucleus test.

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 two times the 3 g human dose based on body surface area.

Postmarketing Experience

Postmarketing experience has identified diarrhea as a common adverse event associated with the use of amoxicillin, typically resolving upon discontinuation of the antibiotic. Additionally, there have been reports of patients developing watery and bloody stools, with or without accompanying symptoms such as stomach cramps and fever, which may occur even two months or more after the last dose of the antibiotic. In such cases, it is advised that patients contact their physician promptly. Furthermore, amoxicillin, being a penicillin-class drug, has been associated with allergic reactions in some individuals.

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, they must take the medication exactly as directed. Skipping doses or failing to complete the full course of therapy may decrease the effectiveness of the immediate treatment and increase the likelihood of bacteria developing resistance, rendering them untreatable by amoxicillin or other antibacterial drugs in the future.

Patients should also be counseled that diarrhea is a common side effect associated with antibiotics, typically resolving upon discontinuation of the medication. However, it is important to note that patients 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 contact their physician promptly.

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

Storage and Handling

The product is supplied in a tight container as defined by the United States Pharmacopeia (USP). It should be stored at a controlled room temperature of 20°C to 25°C (68°F to 77°F) to maintain its integrity and efficacy.

Healthcare professionals are advised to ensure that this product, along with all medications, is kept out of the reach of children to prevent accidental ingestion or misuse.

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 USAntibiotics, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)