Amoxicillin

Description

Formulated as an oral suspension, USP, this product contains amoxicillin, a semisynthetic antibiotic and 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.

The molecular formula for amoxicillin is C16H19N3O5S•3H2O, with a molecular weight of 419.45. Each 5 mL of the reconstituted suspension provides amoxicillin trihydrate equivalent to either 200 mg or 400 mg of anhydrous amoxicillin. Additionally, each 5 mL of both the 200 mg and 400 mg formulations contains 0.16 mEq (3.61 mg) of sodium.

Inactive ingredients include sucrose, sodium citrate, sodium benzoate, edetate disodium, FD&C Red No. 3, xanthan gum, bubble-gum flavor, and colloidal silicon dioxide.

Uses and Indications

Amoxicillin for oral suspension 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, as well as the lower respiratory tract. Additionally, amoxicillin is indicated in combination therapy for the treatment of Helicobacter pylori infection and duodenal ulcer disease.

There are no teratogenic or nonteratogenic effects associated with the use of amoxicillin for oral suspension.

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 mg to 45 mg per kilogram of body weight 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 per kilogram of body weight per day, divided and administered every 12 hours.

For the treatment of Helicobacter pylori infection, two therapeutic regimens are recommended. In the triple therapy regimen, the patient should receive 1 gram of amoxicillin, 500 mg of clarithromycin, and 30 mg of lansoprazole, all administered twice daily (every 12 hours) for a duration of 14 days. In the dual therapy regimen, the patient should receive 1 gram of amoxicillin and 30 mg of lansoprazole, each given three times daily (every 8 hours) for 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 for oral suspension or to 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 undergoing penicillin therapy. Healthcare professionals should remain vigilant for signs of anaphylaxis, which may include difficulty breathing, swelling of the face or throat, and rapid heartbeat. In the event of a serious anaphylactic reaction, immediate emergency treatment is essential, including the administration of epinephrine and supportive measures.

Additionally, Clostridium difficile-associated diarrhea (CDAD) has been observed in patients receiving penicillin. This condition can range from mild diarrhea to severe, potentially fatal colitis. It is crucial for healthcare providers to evaluate any patient who presents with diarrhea during or after treatment with penicillin. Monitoring for symptoms of CDAD should be a standard practice, and appropriate diagnostic tests should be conducted if indicated.

Side Effects

Patients receiving treatment with amoxicillin may experience a range of adverse reactions. Common adverse reactions reported include diarrhea, rash, vomiting, and nausea.

Serious adverse reactions, although less frequent, can occur. Notably, serious and occasionally fatal anaphylactic reactions have been documented in patients undergoing penicillin therapy. Such reactions necessitate immediate emergency treatment along with supportive measures. Additionally, patients should be monitored for Clostridium difficile-associated diarrhea, which can manifest as mild diarrhea but may progress to fatal colitis; it is important to evaluate any instances of diarrhea that arise during treatment.

There are also important considerations regarding patients with a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to amoxicillin or other beta-lactams, including penicillins and cephalosporins. Furthermore, interstitial nephritis leading to oliguric renal failure has been reported in a small number of patients following amoxicillin overdosage. Crystalluria, which in some cases has resulted in renal failure, has also been observed after overdosage in both adult and pediatric patients.

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.

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 anticoagulants as needed.

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

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

Pregnancy Category B. Reproduction studies conducted in mice and rats at doses up to 2000 mg/kg, which are 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, because 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 the 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 lactating mothers may lead to sensitization of breastfed infants. Therefore, caution should be exercised when administering amoxicillin to a nursing woman.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to this patient population.

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 considered as part of standard clinical practice.

Overdosage

In the event of an overdosage, it is imperative to discontinue the medication immediately and initiate 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, it is important to note that there have been reports of interstitial nephritis leading to oliguric renal failure in a small number of patients following amoxicillin overdosage. Additionally, crystalluria has been documented, which in some instances has resulted in renal failure among 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 also noteworthy that patients with pre-existing renal impairment 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.

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 amoxicillin and clavulanic acid mixture demonstrated non-mutagenic properties 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, 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 several adverse reactions reported voluntarily or through surveillance programs. These include anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS). Additionally, cases of Clostridium difficile-associated diarrhea, hepatic dysfunction, renal impairment, hemolytic anemia, thrombocytopenia, agranulocytosis, and allergic reactions such as urticaria and angioedema have been documented.

Further safety information from postmarketing experience indicates reports of seizures in patients with renal impairment, interstitial nephritis, and elevated liver enzymes. It is important to note that these adverse reactions may not have been reported in clinical trials and may occur in a broader patient population.

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 amoxicillin or other antibacterial drugs ineffective in the future.

Patients should also be counseled that diarrhea is a common side effect associated with antibiotics, typically resolving once the antibiotic is discontinued. It is crucial for patients to be aware that they may develop 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 essential for patients to report any history of allergies to penicillin or related medications to their healthcare provider.

Storage and Handling

The dry powder is supplied in a tight container to ensure its integrity. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F). Proper storage conditions are essential to maintain the quality and efficacy of the product.

Additional Clinical Information

When available, clinical microbiology laboratories should provide cumulative in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas. These periodic reports should describe the susceptibility profiles of both nosocomial and community-acquired pathogens. Quantitative methods, such as dilution techniques, are employed to determine the minimum inhibitory concentrations (MICs) of antimicrobial compounds, which should be assessed using standardized test methods, either broth or agar. Additionally, diffusion techniques can yield reproducible estimates of bacterial susceptibility based on zone diameter measurements.

Clinicians may infer susceptibility to amoxicillin for Enterococcus spp., Enterobacteriaceae, and H. influenzae by testing ampicillin, while susceptibility for Staphylococcus spp. and beta-hemolytic Streptococcus spp. can be inferred through penicillin testing. It is noteworthy that most ampicillin or amoxicillin-resistant Enterococcus spp. isolates produce a TEM-type beta-lactamase, and a beta-lactamase test can quickly determine resistance. For Streptococcus pneumoniae (non-meningitis isolates), susceptibility to amoxicillin may also be inferred by testing penicillin or oxacillin.

FDA Insert (PDF)

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

View full prescribing information (PDF)