Amoxicillin

Description

Amoxicillin for oral suspension, USP is a semisynthetic antibacterial agent, specifically amoxicillin, which is an analog of ampicillin. It exhibits 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 contains 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 in the formulation 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 medication is specifically used for the following conditions:

• Upper Respiratory Tract Infections of the Ear, Nose, and Throat

• Infections of the Genitourinary Tract

• Infections of the Skin and Skin Structure

• Infections of the Lower Respiratory Tract

• Helicobacter pylori Infection and Duodenal Ulcer Disease in adult patients only

To reduce the development of drug-resistant bacteria and to maintain the effectiveness of amoxicillin for oral suspension and other antibacterial drugs, it is essential that this medication be used solely to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

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. Healthcare professionals should refer to the full prescribing information for specific dosing regimens tailored to individual patient needs.

For neonates and infants aged 3 months or younger, the upper limit of dosing is 30 mg/kg/day, divided and administered every 12 hours.

In the treatment of Helicobacter pylori infection in adults, two therapeutic regimens are recommended. The triple therapy consists of 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. Alternatively, the dual therapy includes 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) greater 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 receiving penicillin therapy, including amoxicillin. It is imperative that healthcare professionals remain vigilant for signs of anaphylaxis. Should any allergic reaction occur, amoxicillin must be discontinued immediately.

Severe cutaneous adverse reactions (SCAR) have also been associated with amoxicillin use. Patients should be monitored closely for the development of rashes, and if any rash progresses, amoxicillin should be discontinued without delay.

Additionally, drug-induced enterocolitis syndrome (DIES) has been documented in patients taking amoxicillin. In the event that DIES is suspected, it is crucial to discontinue amoxicillin and initiate appropriate therapeutic measures.

Clostridioides difficile-associated diarrhea (CDAD) can manifest in a spectrum ranging from mild diarrhea to severe, potentially fatal colitis. Healthcare professionals should evaluate any patient who presents with diarrhea during or after treatment with amoxicillin, as timely intervention may be necessary.

Side Effects

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

Common adverse reactions reported include diarrhea, rash, vomiting, and nausea. These reactions are generally mild and may not require discontinuation of therapy.

Serious adverse reactions, however, warrant immediate attention. Anaphylactic reactions, which can be serious and occasionally fatal, have been reported in patients undergoing penicillin therapy, including amoxicillin. It is crucial to discontinue amoxicillin if such a reaction occurs. Additionally, severe cutaneous adverse reactions (SCAR) have been noted; patients should be monitored closely, and amoxicillin should be discontinued if the rash progresses. Drug-induced enterocolitis syndrome (DIES) has also been associated with amoxicillin use, necessitating discontinuation and appropriate therapeutic intervention if this condition arises. Furthermore, Clostridioides difficile-associated diarrhea (CDAD) can range from mild diarrhea to fatal colitis, and evaluation is recommended if diarrhea occurs.

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) should be closely monitored or may need to avoid amoxicillin altogether.

In cases of overdosage, adverse reactions such as interstitial nephritis leading to oliguric renal failure have been reported in a small number of patients. Crystalluria, which in some instances has resulted in renal failure, has also been documented following amoxicillin overdosage in both adult and pediatric patients.

Drug Interactions

Co-administration of amoxicillin with probenicid is not recommended due to potential interactions that may affect the pharmacokinetics of amoxicillin.

When amoxicillin is used concurrently with oral anticoagulants, there is an increased risk of prolongation of prothrombin time. Monitoring of prothrombin time is advised to ensure patient safety and appropriate anticoagulation management.

The concomitant use of amoxicillin and allopurinol has been associated with an increased risk of rash. Caution is advised when these medications are prescribed together, and patients should be monitored for dermatological reactions.

Additionally, amoxicillin may reduce the efficacy of oral contraceptives. Patients using hormonal contraceptives should be counseled on the potential for decreased contraceptive effectiveness and may require alternative or additional contraceptive methods during treatment with amoxicillin.

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

The safety and effectiveness of amoxicillin have been established for the treatment of upper respiratory tract infections, as well as infections of the genitourinary tract, skin and skin structure, and lower respiratory tract in pediatric patients. However, the safety and effectiveness of amoxicillin for the treatment of H. pylori infection have not been established in this population.

In pediatric patients aged 12 weeks or younger (3 months or younger), caution is advised due to incompletely developed renal function, which may delay the elimination of amoxicillin. Therefore, dosing should be modified accordingly in this age group to ensure safety and efficacy.

Geriatric Use

Clinical studies of amoxicillin have been analyzed to assess whether elderly patients, specifically those aged 65 and over, exhibit different responses compared to younger individuals. The findings from these analyses have not identified significant differences in responses between these age groups; however, it is important to note that a greater sensitivity to the drug in some older individuals cannot be entirely 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 geriatric patients are more likely to experience decreased renal function, careful consideration should be given to dose selection in this population. It is advisable to monitor renal function in elderly patients to mitigate the risk of adverse effects associated with renal impairment.

Pregnancy

Amoxicillin is classified as Pregnancy Category B. Reproductive 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. Due to the limitations of animal reproduction studies in predicting human response, amoxicillin should be used during pregnancy only if clearly needed. Healthcare professionals are advised to 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 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 amoxicillin 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 less than 250 mg/kg of amoxicillin typically do not result in significant clinical symptoms.

However, it is important to note that interstitial nephritis leading to oliguric renal failure has been documented in a limited number of cases following amoxicillin overdosage. Additionally, crystalluria, which may in some instances progress to renal failure, has been reported in both adult and pediatric populations after excessive doses of amoxicillin. To mitigate the risk of crystalluria, it is essential to ensure adequate fluid intake and maintain diuresis during the management of overdosage.

Renal impairment associated with amoxicillin overdosage appears to be reversible upon cessation of the drug. It is also noteworthy that patients with pre-existing renal dysfunction may experience elevated blood levels of amoxicillin due to reduced renal clearance. In such cases, hemodialysis can effectively remove amoxicillin from the circulation, providing an additional management option for severe overdosage scenarios.

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

Potassium clavulanate, when tested independently, also yielded negative results 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 twice 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 allergic reactions, such as anaphylaxis and serious skin reactions. Severe cutaneous adverse reactions (SCAR) have also been noted, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Additionally, hepatic dysfunction has been reported, characterized by elevated liver enzymes and jaundice. Renal impairment, specifically interstitial nephritis, has been observed as well. Hematologic reactions, including thrombocytopenia, leukopenia, and hemolytic anemia, have been documented. Gastrointestinal reactions, particularly Clostridium difficile-associated diarrhea, have also been reported. Other reactions include seizures and hyperactivity.

Patient Counseling

Patients should be advised that amoxicillin may be taken every 8 hours or every 12 hours, depending on the prescribed dosage. It is important to counsel patients that amoxicillin is a penicillin class drug, which can cause allergic reactions in some individuals.

Healthcare providers should inform patients about the signs and symptoms of serious skin manifestations associated with amoxicillin use. Patients must be instructed to stop taking the medication immediately and promptly report any signs or symptoms of skin rash, mucosal lesions, or other indications of hypersensitivity.

Patients should also be made aware that diarrhea is a common side effect of antibacterial drugs, including amoxicillin, and it typically resolves upon discontinuation of the medication. However, patients may develop watery and bloody stools (with or without stomach cramps and fever) even as late as two months after their last dose. If such symptoms occur, patients should contact their physician as soon as possible.

It is essential to counsel patients that antibacterial drugs, including amoxicillin, are intended solely for the treatment or prevention of bacterial infections and do not treat viral infections, such as the common cold. When prescribed amoxicillin for a bacterial infection, patients should be informed that it is common to feel better early in the treatment course; however, the medication must be taken exactly as directed. Skipping doses or failing to complete the full course of therapy may decrease the effectiveness of the treatment and increase the likelihood of bacteria developing resistance, rendering them untreatable by amoxicillin or other antibacterial drugs in the future.

For patients using amoxicillin suspensions, it is preferable to refrigerate the product, although this is not mandatory. Patients should be instructed to shake the oral suspension well before each use and to keep the bottle tightly closed. When dosing a child with the suspension, a calibrated oral syringe should be used, and it is important to rinse the syringe after each use. Patients should follow their doctor’s instructions regarding the appropriate amount to use and the duration of treatment required for their child. Any unused portion of the suspension should be discarded after 14 days.

Storage and Handling

The dry powder is supplied in a tight container to ensure its integrity and stability. 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) in accordance with USP Controlled Room Temperature guidelines.

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 Rising Pharma Holdings, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)