Amoxicillin

Description

Formulations of Amoxicillin capsules, USP contain amoxicillin USP, 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-azabicyclo3.2.0heptane­2-carboxylic acid trihydrate. The molecular formula is C16H19N3O5S•3H2O, with a molecular weight of 419.45. Each capsule is intended for oral administration and contains either 250 mg or 500 mg of amoxicillin as the trihydrate. Inactive ingredients include black iron oxide, gelatin, magnesium stearate, potassium hydroxide, propylene glycol, shellac, strong ammonia, talc, and titanium dioxide.

Uses and Indications

Amoxicillin capsules are a penicillin-class antibacterial indicated for the treatment of infections caused by susceptible strains of designated microorganisms. This drug is specifically indicated for infections of the ear, nose, throat, genitourinary tract, skin and skin structure, and lower respiratory tract.

Additionally, amoxicillin capsules are indicated in combination for the treatment of Helicobacter pylori infection and duodenal ulcer disease.

Amoxicillin capsules should be utilized only for infections that are proven or strongly suspected to be bacterial in origin. This approach is essential to reduce the development of drug-resistant bacteria and to maintain the effectiveness of amoxicillin capsules 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 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.

In the treatment of Helicobacter pylori infection, two therapeutic regimens are recommended. For triple therapy, the combination 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, for dual therapy, the regimen 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) 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 manifest in a spectrum from mild diarrhea to severe, potentially fatal colitis. Healthcare providers should evaluate patients for diarrhea, particularly in those who have recently been treated with antibiotics, and manage accordingly.

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 medical intervention.

Serious adverse reactions, although less frequent, can occur and necessitate immediate medical attention. Notably, serious and occasionally fatal anaphylactic reactions have been documented in patients undergoing penicillin therapy. Such reactions require prompt 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 severe and potentially fatal colitis, has also been reported. Patients experiencing diarrhea should be evaluated to determine the underlying cause.

Hypersensitivity reactions are of particular concern, especially in individuals with a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to amoxicillin or other beta-lactams, including penicillins and cephalosporins.

Additional adverse reactions have been noted in the context of amoxicillin overdosage. Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients. Furthermore, crystalluria, which in some cases has led to renal failure, has been observed in both adult and pediatric patients following overdosage.

Healthcare providers should monitor patients for these adverse reactions and manage them accordingly.

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 the anticoagulant as needed.

Co-administration 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 measures 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

Pediatric patients, particularly neonates and young infants, may experience delayed elimination of amoxicillin due to incompletely developed renal function. Therefore, dosing of amoxicillin capsules should be modified for pediatric patients aged 12 weeks or younger (≤ 3 months) to ensure appropriate therapeutic levels and minimize the risk of adverse effects. Careful consideration of renal function is essential when prescribing amoxicillin in this age group.

Geriatric Use

Clinical studies analyzing the response of elderly patients, specifically those aged 65 and over, to amoxicillin capsules have not identified significant differences in efficacy or safety compared to younger subjects. However, it is important to note that a greater sensitivity to the drug may be present in some older individuals, warranting careful consideration during treatment.

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, it is essential to exercise caution in dose selection for this population. Monitoring of renal function may be beneficial to ensure safe and effective dosing in elderly patients.

Pregnancy

Reproduction studies conducted in mice and rats at doses up to 2000 mg/kg, which is 3 and 6 times the human dose of 3 g 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. 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 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 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. 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, it is important to 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 observed in these cases appears to be reversible upon cessation of the drug.

It is noteworthy that patients with impaired renal function may experience elevated blood levels of amoxicillin due to decreased renal clearance. In such instances, hemodialysis may be employed to facilitate the removal of amoxicillin from circulation, thereby aiding in the management of overdosage.

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 clavulanate potassium provide relevant insights.

The combination of amoxicillin and clavulanate potassium 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 combination was negative in the mouse micronucleus test and the dominant lethal assay in mice.

Clavulanate potassium, when tested alone, was also negative in the Ames bacterial mutation assay and the mouse micronucleus test, indicating no mutagenic potential.

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, even up to two months after completing treatment. Patients experiencing these symptoms are advised to contact their physician promptly. Furthermore, it is noted that amoxicillin, being a penicillin class drug, has the potential to elicit allergic reactions in susceptible individuals.

Patient Counseling

Patients should be advised that amoxicillin capsules 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 capsules, are intended solely for the treatment of bacterial infections and are ineffective against viral infections, such as the common cold.

When prescribed amoxicillin capsules 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 capsules 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 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 capsules contain 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 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 storage conditions are essential to maintain the integrity and efficacy 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 Micro Labs Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)