A Comprehensive Monograph on Amoxicillin: Pharmacology, Clinical Utility, and Safety Profile

Section 1: Drug Identification and Physicochemical Properties

This section serves as the foundational chemical and structural reference for Amoxicillin, consolidating identifiers from numerous international databases to create a single, unambiguous profile of the molecule. This comprehensive identification is essential for accurate research, clinical communication, and regulatory tracking, especially for a drug with such a long and widespread history of use.

1.1 Core Identification

Amoxicillin is a well-established antibiotic agent recognized globally under various nomenclature systems. Its core identifiers provide a standardized method for referencing the compound across scientific literature, clinical databases, and regulatory filings.

• Generic Name: The universally accepted non-proprietary name is Amoxicillin. Variant spellings and Latin forms, such as Amoxicilline and Amoxicillinum, are also documented.[1]
• DrugBank Accession Number: The unique identifier in the DrugBank database is DB01060.[1]
• Drug Type/Modality: Amoxicillin is classified as a Small Molecule drug, indicating it is a low molecular weight organic compound.[1]
• Drug Groups: It holds multiple statuses, being listed as Approved for general medical use, Investigational for ongoing studies into new uses or formulations, and Vet approved for use in veterinary medicine.[1] This broad classification highlights its extensive utility across different fields of medicine.

1.2 Chemical and Structural Data

The precise chemical and structural properties of amoxicillin define its physical characteristics, stability, and, most importantly, its biological activity.

• Chemical Formula: The molecular formula for the anhydrous form of amoxicillin is C16​H19​N3​O5​S.[1]
• Molecular Weight: The average molecular weight of anhydrous amoxicillin is 365.404 g/mol, with a monoisotopic mass of 365.104541423 Da.[1] It is critical to distinguish this from the commonly used trihydrate form, which has a molecular weight of 419.45 g/mol and a molecular formula of C16​H25​N3​O8​S.[4] This distinction is vital for accurate dosage calculations and pharmaceutical formulation.
• IUPAC Name: The systematic name according to the International Union of Pure and Applied Chemistry (IUPAC) is (2S,5R,6R)−6−{amino}−3,3−dimethyl−7−oxo−4−thia−1−azabicyclo[3.2.0]heptane−2−carboxylic acid.[1] The specific stereochemical descriptors— (2S,5R,6R) for the core bicyclic structure and (2R) for the side chain—are not merely chemical formalities. They describe the precise three-dimensional architecture of the molecule, which is the absolute determinant of its ability to bind to its bacterial targets. An alternative isomer, L-Amoxicillin, which has a (2S) configuration on the side chain, exists but is not used therapeutically, underscoring that the biological activity is intrinsically linked to this specific spatial arrangement.[6]
• CAS Number: The Chemical Abstracts Service (CAS) Registry Number for the anhydrous parent compound is 26787-78-0.[1] Other CAS numbers exist for its various salt and hydrate forms, such as 34642-77-8.[8]
• Chemical Structure: Amoxicillin is a semi-synthetic derivative of penicillin. Its structure is characterized by a core 4-thia-1-azabicyclo[3.2.0]heptane system, which consists of a β-lactam ring fused to a thiazolidine ring. Attached to this core at position 6 is an acyl side chain: a D-(-)-α-amino-p-hydroxyphenylacetyl group.[2] This side chain, particularly the hydroxyl group on the phenyl ring, distinguishes it from its predecessor, ampicillin, and is responsible for its improved oral absorption profile.
• Physical Properties: In its raw form, amoxicillin is typically supplied as a white, crystalline solid.[4]

1.3 Synonyms and External Identifiers

The long history and global use of amoxicillin have led to a vast number of synonyms, brand names, and database identifiers. This extensive nomenclature reflects its status as a generic commodity chemical but can also be a source of confusion in literature searches and clinical practice, highlighting the importance of using precise identifiers like the CAS number or DrugBank ID.

• Common Synonyms: Amoxycillin, p-Hydroxyampicillin, AX, and the original research code BRL-2333 are frequently encountered.[1]
• Brand Names: Amoxicillin is marketed under numerous brand names worldwide, including Amoxil, Augmentin (in combination with clavulanic acid), Clavulin, Moxatag, Trimox, Polymox, and Wymox.[1] It is also a component of combination therapy packs such as Prevpac, Talicia, and Voquezna.[1]
• External Identifiers: To facilitate cross-database research, amoxicillin is cataloged with numerous external IDs, including:
• PubChem CID: 33613 [4]
• ChEBI ID: CHEBI:2676 [4]
• National Cancer Institute (NCI) ID: NSC-277174 [1]
• Human Metabolome Database (HMDB) ID: HMDB0243588 [3]

The following table provides a consolidated reference for the key identifiers and physicochemical properties of the anhydrous form of amoxicillin.

Property	Value	Source(s)
Generic Name	Amoxicillin	1
DrugBank ID	DB01060	1
CAS Number	26787-78-0	1
IUPAC Name	(2S,5R,6R)−6−{amino}−3,3−dimethyl−7−oxo−4−thia−1−azabicyclo[3.2.0]heptane−2−carboxylic acid	1
Molecular Formula	C16​H19​N3​O5​S	1
Average Molecular Weight	365.404 g/mol	1
Monoisotopic Mass	365.104541423 Da	1
Physical Form	White, Crystalline Solid	4
PubChem CID	33613	4

Section 2: Historical Context and Regulatory Milestones

Understanding the developmental and regulatory history of amoxicillin provides crucial context for its enduring role in modern medicine. Its journey from a second-generation penicillin derivative to a globally essential medicine reflects key trends in antibiotic development and the ongoing challenge of antimicrobial resistance.

2.1 Discovery and Development

Amoxicillin, known by its developmental research code BRL-2333, is a semi-synthetic aminopenicillin derived from the fundamental penicillin G nucleus.[1] It was first described in the scientific literature in 1972.[1] Its development was a direct effort to improve upon the properties of its immediate predecessor, ampicillin. While ampicillin had expanded the spectrum of activity of penicillins to include some Gram-negative bacteria, its oral bioavailability was limited. The primary goal in designing amoxicillin was to create a compound with a similar antibacterial spectrum but with significantly better absorption from the gastrointestinal tract, leading to higher and more reliable serum concentrations after oral administration.[1] This goal was achieved through the addition of a single hydroxyl group to the phenyl side chain of ampicillin.

2.2 Regulatory Approval

Following its successful development and clinical evaluation, amoxicillin was granted its initial approval by the U.S. Food and Drug Administration (FDA) on January 18, 1974.[1] This marks nearly half a century of continuous clinical use in the United States, a testament to its efficacy and relative safety. Its regulatory status is broad, with approvals for human medical use, veterinary applications, and a continuing designation as an investigational drug.[1]

The fact that a drug approved in 1974 remains the subject of active clinical trials in the 2020s is remarkable and demonstrates the dynamic nature of its clinical life. For instance, recent or ongoing trials include studies on its pharmacokinetics in children (NCT05340257), surveillance of bacterial resistance patterns in Jordan (NCT05106803), and the investigation of high-dose regimens (NCT04070469).[10] This continuous research is not aimed at re-proving its established efficacy. Instead, it reflects a necessary adaptation to modern challenges. The high-dose studies are a clear strategy to overcome rising minimum inhibitory concentrations (MICs) in less-susceptible pathogens—a classic pharmacokinetic/pharmacodynamic optimization approach. Bioequivalence studies, such as NCT01772238, are driven by the large global market for generic amoxicillin formulations.[13] Surveillance studies are critical for tracking the spread of resistance and informing local treatment guidelines. Thus, amoxicillin is not a static, historical artifact but a dynamic therapeutic tool that requires constant re-evaluation to maintain its relevance in the evolving war against bacterial pathogens.

Section 3: Clinical Pharmacology

The clinical utility of amoxicillin is rooted in its specific pharmacological properties: how it affects bacteria (pharmacodynamics) and how the human body processes the drug (pharmacokinetics). A thorough understanding of these principles is essential for its safe and effective use.

3.1 Mechanism of Action and Pharmacodynamics

• Drug Class: Amoxicillin is classified as a β-lactam antibiotic, belonging to the aminopenicillin subclass.[1] The defining feature of this class is the four-membered β-lactam ring, which is the chemical cornerstone of its antibacterial activity.
• Primary Target and Molecular Action: The bactericidal effect of amoxicillin is achieved through the inhibition of bacterial cell wall synthesis. Its primary molecular targets are a set of bacterial enzymes known as Penicillin-Binding Proteins (PBPs), such as PBP-1A in Helicobacter pylori.[1] Amoxicillin acts as a competitive inhibitor of these proteins.[1] PBPs are essential for the final steps of peptidoglycan synthesis, a polymer that forms the rigid outer layer of bacterial cells. Specifically, PBPs catalyze the transpeptidase and glycosyltransferase reactions that create cross-links between peptidoglycan chains, providing the cell wall with its structural integrity.[1] By mimicking the structure of the D-Ala-D-Ala terminus of the peptidoglycan strands, amoxicillin binds to the active site of the PBP and acylates it, forming a stable, covalent bond. This effectively deactivates the enzyme.
• Resulting Effect: The inactivation of PBPs prevents the formation of new cross-links and disrupts the ongoing process of cell wall repair and maintenance. This leads to the accumulation of peptidoglycan precursors, which in turn activates bacterial autolytic enzymes (autolysins). The combination of a weakened cell wall and enzymatic degradation results in a loss of osmotic stability, leading to cell swelling, lysis, and ultimately, bacterial death.[9] This mechanism of killing bacteria, rather than simply inhibiting their growth, defines amoxicillin as a bactericidal agent.[1]
• Pharmacodynamic Profile: Amoxicillin exhibits a time-dependent killing mechanism, meaning its efficacy is best correlated with the duration of time that the drug concentration at the site of infection remains above the Minimum Inhibitory Concentration (MIC) of the target pathogen. Its duration of action is sufficient to allow for convenient twice-daily or thrice-daily oral dosing regimens.[1] Furthermore, it possesses a wide therapeutic index, indicating that a large gap exists between the dose required for a therapeutic effect and the dose that causes significant toxicity, making mild overdoses generally manageable.[1]

3.2 Pharmacokinetics: Absorption, Distribution, Metabolism, and Excretion (ADME)

The pharmacokinetic profile of amoxicillin is a key determinant of its clinical success, particularly as an orally administered agent for outpatient therapy. Its journey through the body—absorption, distribution, metabolism, and excretion—is characterized by efficiency and predictability in patients with normal organ function.

• Absorption: Amoxicillin is notably stable in the presence of gastric acid, a crucial property for an oral antibiotic. Following oral administration, it is rapidly absorbed from the gastrointestinal tract.[5] The absolute oral bioavailability is approximately 60%.[1] For immediate-release formulations (capsules, suspension, chewable tablets), the effect of food on absorption is minimal, and the drug may be administered without regard to meals.[5] However, taking the medication with food can help mitigate gastrointestinal side effects like nausea.[15] In contrast, extended-release formulations (e.g., Moxatag) are specifically designed to be taken with a meal to ensure proper absorption.[15]
• Quantitative Pharmacokinetics: Peak serum concentrations (Cmax) are typically reached 1 to 2 hours after administration.[5]
• A single 250 mg oral dose results in a Cmax of approximately 3.93 mg/L and a time to peak (Tmax) of 1.31 hours.[1]
• A single 875 mg oral dose results in a Cmax in the range of 11.21 to 13.8 mg/L, with a Tmax of about 1.5 hours.[1]
• Distribution: Once absorbed into the bloodstream, amoxicillin distributes effectively into various body tissues and fluids.
• Volume of Distribution: The central volume of distribution is approximately 27.7 L, indicating that the drug does not remain confined to the bloodstream and distributes into extravascular spaces.[1]
• Protein Binding: Amoxicillin exhibits low binding to serum proteins, with reported values around 17-20%.[1] This is a highly favorable characteristic, as only the unbound (free) fraction of a drug is pharmacologically active and available to penetrate tissues and exert its antibacterial effect.
• Tissue Penetration: Therapeutic concentrations are achieved in numerous sites, including respiratory secretions, middle ear fluid, and interstitial fluid.[5] The drug is also known to cross the placental barrier, a key consideration during pregnancy.[9]
• Metabolism: While a significant portion of amoxicillin is excreted unchanged, it does undergo some metabolism. Studies involving incubation with human liver microsomes have identified at least seven metabolites (designated M1 through M7).[1] The primary metabolic pathways include hydroxylation (M1), oxidative deamination (M2), oxidation of the drug's aliphatic chain (M3-M5), decarboxylation (M6), and conjugation with glucuronic acid (M7).[1] The major metabolite found in urine is penicilloic acid, which is microbiologically inactive. The parent drug remains the primary active moiety.
• Excretion: Amoxicillin is eliminated from the body primarily via the kidneys.[19]
• Primary Route and Rate: Approximately 60% to 78% of an orally administered dose is excreted unchanged in the urine within 6 to 8 hours through both glomerular filtration and active tubular secretion.[1] This rapid and high-concentration excretion of the active drug in the urine is what makes it particularly effective for treating urinary tract infections.
• Half-life: The elimination half-life in adults with normal renal function is short, approximately 61.3 minutes (about 1 hour).[1]
• Clearance: The mean total body clearance is approximately 21.3 L/h.[1]

The pharmacokinetic profile of amoxicillin—specifically the combination of its rapid oral absorption, low protein binding, and primary, rapid renal excretion of the active drug—is the key to its success as an outpatient antibiotic. These properties synergize to ensure that high concentrations of the free, biologically active drug quickly reach the bloodstream and are then efficiently delivered to and concentrated in the urinary tract, making it a highly effective agent for common infections like streptococcal pharyngitis and uncomplicated UTIs.

However, the fact that amoxicillin is "substantially excreted by the kidney" is a double-edged sword that dictates its entire risk management strategy.[19] While beneficial for treating UTIs, this reliance on renal clearance is the direct causal reason for the most critical dosing adjustments and population-specific warnings. The explicit need for dose reduction in patients with renal impairment, the specific caution advised for elderly patients (who are more likely to have age-related decline in renal function), and the modified dosing schedules for neonates (due to their "incompletely developed renal function") all stem directly from this single pharmacokinetic characteristic.[20] If the primary elimination pathway is impaired, the drug will accumulate, leading to supratherapeutic concentrations and an increased risk of toxicity, such as crystalluria and CNS effects. This illustrates a core principle of clinical pharmacology: a drug's route of elimination is often the primary determinant of its safety profile in special populations.

Section 4: Clinical Efficacy and Therapeutic Indications

Amoxicillin's broad utility in clinical practice stems from its effectiveness against a range of common bacterial pathogens and its adaptability for use in combination regimens to overcome resistance and treat complex infections.

4.1 Approved Indications for Monotherapy

When used alone, amoxicillin is indicated for the treatment of infections caused by susceptible strains of designated microorganisms. Its spectrum of activity is primarily focused on Gram-positive bacteria, particularly streptococci, and some Gram-negative respiratory and enteric pathogens.

• Ear, Nose, and Throat (ENT) Infections: Amoxicillin is a first-line agent for infections such as pharyngitis, tonsillitis, and acute otitis media caused by Streptococcus species (including α- and β-hemolytic strains like S. pyogenes), Streptococcus pneumoniae, susceptible Staphylococcus species, and Haemophilus influenzae.[1]
• Lower Respiratory Tract Infections (LRTI): It is indicated for LRTIs, including community-acquired pneumonia and acute bacterial exacerbations of chronic bronchitis, caused by the same spectrum of pathogens as in ENT infections.[1]
• Genitourinary (GU) Tract Infections: Amoxicillin is effective for treating GU infections, such as cystitis, caused by susceptible strains of Escherichia coli, Proteus mirabilis, and Enterococcus faecalis.[1]
• Skin and Skin Structure Infections: It is used for skin infections caused by Streptococcus spp., susceptible Staphylococcus spp., and E. coli.[1]
• Acute Uncomplicated Gonorrhea: In the past, amoxicillin was indicated for ano-genital and urethral infections caused by Neisseria gonorrhoeae, although widespread resistance has now limited this use.[5]

4.2 Role in Combination Therapies

The clinical indications for amoxicillin reveal a clear bifurcation in its strategic deployment. As a monotherapy, it serves as a narrow-spectrum workhorse for highly susceptible, common pathogens. In contrast, its role in combination therapy is to function as a broad-spectrum agent, either by being protected from bacterial resistance mechanisms or by acting as part of a multi-pronged assault to prevent the emergence of resistance during treatment.

• With β-Lactamase Inhibitors (Clavulanic Acid): The most common combination is with clavulanic acid (co-amoxiclav), marketed as Augmentin and Clavulin.[1] Many bacteria develop resistance to amoxicillin by producing β-lactamase enzymes, which destroy the antibiotic's active β-lactam ring. Clavulanic acid is a β-lactamase inhibitor; it has little antibacterial activity on its own but binds to and inactivates these bacterial enzymes, effectively acting as a "shield" that allows amoxicillin to reach its PBP targets unimpeded. This combination dramatically broadens amoxicillin's spectrum to include β-lactamase-producing strains of H. influenzae, Moraxella catarrhalis, S. aureus, E. coli, and Klebsiella species. Indications for this combination include more severe or resistant infections such as acute bacterial sinusitis, community-acquired pneumonia, animal bites, and complicated skin or urinary tract infections.[1] Clinical trials such as NCT05340257 have investigated this combination for pediatric pneumonia and sinusitis.[10]
• For Helicobacter pylori Eradication: Amoxicillin is a cornerstone of multi-drug regimens for the eradication of H. pylori, the bacterium responsible for most cases of peptic ulcer disease and a risk factor for gastric cancer.[1] Its low rate of primary resistance in H. pylori makes it a reliable component. Standard regimens include:
• Standard Triple Therapy: 1 gram amoxicillin, 500 mg clarithromycin, and a proton pump inhibitor (PPI) such as 30 mg lansoprazole or omeprazole, with all drugs given twice daily for 14 days.[1]
• Standard Dual Therapy: 1 gram amoxicillin and 30 mg lansoprazole, with each given three times daily for 14 days.[15]
• Alternative and Salvage Regimens: The existence of numerous, complex, multi-drug regimens for H. pylori is a direct consequence of rising antimicrobial resistance to other agents in the cocktail, particularly clarithromycin. The failure of its partner drugs in many regions necessitates the use of alternative regimens to maintain high eradication rates. These include combinations of amoxicillin with other agents like levofloxacin, rifabutin, or the potassium-competitive acid blocker vonoprazan.[1] This positions amoxicillin as the reliable anchor in a failing system, whose own utility is threatened not by its own shortcomings, but by the failure of the drugs upon which it depends. This illustrates a critical concept in combination therapy: the entire regimen is only as strong as its weakest link.

4.3 Analysis of Clinical Trial Data

The landscape of modern clinical trials involving amoxicillin further illuminates its current clinical role. These studies are focused on optimization, surveillance, and market dynamics rather than establishing primary efficacy.

• Phase 1 studies often focus on pharmacokinetics and bioequivalence, such as NCT01772238, which compared different formulations of amoxicillin/clavulanic acid to ensure they perform identically, a necessary step for generic drug approval.[13]
• Phase 2 studies, like the withdrawn trial NCT05340257 for pediatric CAP and ABRS, explore efficacy in specific patient populations or indications.[10]
• Phase 4 (post-marketing) studies are crucial for refining use in the real world. For example, trial NCT04070469 investigated the plasma concentrations achieved with high-dose amoxicillin, providing data to support dosing strategies aimed at overcoming bacteria with elevated MICs.[12]
• Observational and surveillance studies, such as NCT05106803 in Jordan, are essential for monitoring local antibiotic resistance patterns.[11] This data is critical for updating regional treatment guidelines and practicing effective antimicrobial stewardship.

Section 5: Dosage, Formulations, and Administration

The practical application of amoxicillin in a clinical setting requires a detailed understanding of its available forms, dosing regimens for different age groups and indications, and necessary adjustments for specific patient populations. The availability of multiple formulations and flexible dosing schedules is a key driver of amoxicillin's high utility, particularly in pediatrics, as it allows for precise weight-based dosing and accommodates the practical challenges of administering medication to children, thereby improving adherence and clinical outcomes.

5.1 Available Formulations and Strengths

Amoxicillin is available in a variety of oral formulations to suit different patient needs:

• Capsules: 250 mg, 500 mg [14]
• Tablets (Immediate-Release): 500 mg, 875 mg [21]
• Chewable Tablets: 125 mg, 200 mg, 250 mg, 400 mg [14]
• Powder for Oral Suspension: 125 mg/5 mL, 200 mg/5 mL, 250 mg/5 mL, 400 mg/5 mL [14]
• Tablets (Extended-Release, e.g., Moxatag): 775 mg [15]

5.2 Dosing Guidelines in Adult and Pediatric Populations (Weight ≥ 40 kg)

For adults and children weighing 40 kg or more, dosing is typically standardized.

• Mild-to-Moderate Infections (e.g., ENT, Skin, GU): 500 mg every 12 hours OR 250 mg every 8 hours.[21]
• Severe Infections (e.g., Lower Respiratory Tract Infection): 875 mg every 12 hours OR 500 mg every 8 hours.[21]
• For H. pylori Eradication:
• Triple Therapy: 1 gram (1000 mg) amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (every 12 hours) for 14 days.[15]
• Dual Therapy: 1 gram (1000 mg) amoxicillin and 30 mg lansoprazole, each given three times daily (every 8 hours) for 14 days.[15]
• For Extended-Release Tablets (Tonsillitis/Pharyngitis): 775 mg once daily for 10 days, taken within 1 hour of finishing a meal.[15]

5.3 Dosing Guidelines in Pediatric Populations

For pediatric patients, dosing is more nuanced and typically based on body weight to ensure safety and efficacy.

• Neonates and Infants (≤ 12 weeks / 3 months): Due to incompletely developed renal function which can delay elimination, the recommended upper dose is 30 mg/kg/day divided every 12 hours.[15]
• Children (> 3 months and < 40 kg):
• Mild-to-Moderate Infections: 20 mg/kg/day in divided doses every 8 hours OR 25 mg/kg/day in divided doses every 12 hours.[21]
• Severe Infections (e.g., LRTI) or Infections Requiring Higher Doses (e.g., Acute Otitis Media, Sinusitis): 40 mg/kg/day in divided doses every 8 hours OR 45 mg/kg/day in divided doses every 12 hours.[21]

5.4 Dose Adjustments for Renal Impairment

As amoxicillin is primarily cleared by the kidneys, dose adjustment is critical in patients with renal dysfunction to prevent drug accumulation and toxicity.

• Adults and Pediatrics ≥ 40 kg:
• Glomerular Filtration Rate (GFR) > 30 mL/min: No dose adjustment is generally required.[21]
• GFR 10 to 30 mL/min: The dose should be reduced to 500 mg or 250 mg every 12 hours, depending on infection severity. The 875 mg tablet should NOT be used in this population.[20]
• GFR < 10 mL/min: The dose should be reduced to 500 mg or 250 mg every 24 hours.[20]
• Hemodialysis Patients: Should receive a dose of 500 mg or 250 mg every 24 hours, with an additional supplemental dose administered both during and at the end of the dialysis session to account for drug removal.[20]

A significant evidence gap and clinical dilemma exists for pediatric patients, as the FDA label explicitly states, "There are currently no dosing recommendations for pediatric patients with impaired renal function".[21] While adult guidelines are precise, clinicians treating a child with both a severe infection and kidney disease are forced to extrapolate from adult data or rely on institutional protocols and expert opinion. This introduces considerable uncertainty and risk, highlighting an area of unmet need for future pediatric pharmacology research.

The following table summarizes the complex dosing information into a more accessible clinical tool.

Patient Population	Indication / Severity	Dosing Regimen	Renal Impairment Adjustment (GFR)
Adults & Peds ≥ 40 kg	Mild-to-Moderate Infection	500 mg q12h OR 250 mg q8h	10-30 mL/min: 500/250 mg q12h<10 mL/min: 500/250 mg q24h
	Severe Infection (e.g., LRTI)	875 mg q12h OR 500 mg q8h	Do NOT use 875 mg dose if GFR < 30 mL/min
	H. pylori (Triple Therapy)	1000 mg q12h for 14 days	Refer to component drug adjustments
Pediatrics > 3 mo & < 40 kg	Mild-to-Moderate Infection	25 mg/kg/day ÷ q12h OR 20 mg/kg/day ÷ q8h	No specific recommendations available
	Severe Infection / AOM / Sinusitis	45 mg/kg/day ÷ q12h OR 40 mg/kg/day ÷ q8h	No specific recommendations available
Neonates & Infants ≤ 3 mo	General Infections	Max 30 mg/kg/day ÷ q12h	No specific recommendations available

5.5 Administration Instructions

• Duration of Therapy: Treatment should be continued for a minimum of 48 to 72 hours beyond the time the patient becomes asymptomatic or evidence of bacterial eradication is obtained.[21] For any infection caused by Streptococcus pyogenes, a minimum treatment duration of 10 days is recommended to prevent the occurrence of acute rheumatic fever.[21]
• Oral Suspension: The bottle should be tapped to loosen the powder, then reconstituted with water as directed and shaken vigorously. It must be shaken well before each use. The suspension can be placed directly on the child's tongue or mixed with formula, milk, fruit juice, or other cold drinks and consumed immediately.[15]
• Adherence: Patients should be counseled to take all medication as directed, even if they feel better after a few days. Stopping treatment prematurely can lead to treatment failure and contribute to the development of drug-resistant bacteria.[15]

Section 6: Comprehensive Safety Profile

While amoxicillin is generally well-tolerated, it is associated with a range of potential adverse effects, from common gastrointestinal upset to rare but life-threatening hypersensitivity reactions. A thorough understanding of its safety profile is paramount for its appropriate use.

6.1 Contraindications

Amoxicillin is absolutely contraindicated in patients with a known history of a serious hypersensitivity reaction to amoxicillin or any other β-lactam antibiotic (e.g., other penicillins, cephalosporins, carbapenems).[20] Such reactions include:

• Anaphylaxis
• Severe Cutaneous Adverse Reactions (SCARs), such as Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN).

6.2 Warnings and Precautions

These represent the most significant risks associated with amoxicillin therapy and require careful consideration by the prescriber.

• Anaphylaxis and Hypersensitivity: Serious and occasionally fatal anaphylactic reactions have been reported. While more frequent with parenteral penicillin therapy, they can occur with oral administration. These reactions are more likely in individuals with a personal or family history of penicillin hypersensitivity or sensitivity to multiple allergens. Careful inquiry into a patient's allergy history is mandatory before initiating therapy. If an allergic reaction occurs, amoxicillin must be discontinued immediately, and emergency treatment with epinephrine, oxygen, intravenous steroids, and airway management must be instituted.[18]
• Severe Cutaneous Adverse Reactions (SCARs): Amoxicillin is known to cause a spectrum of SCARs, including SJS, TEN, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and Acute Generalized Exanthematous Pustulosis (AGEP). The safety profile is dominated by these hypersensitivity reactions of varying types and severity, creating a significant clinical challenge. Every rash in a patient taking amoxicillin must be carefully evaluated to distinguish a minor side effect from the onset of a medical emergency. If a patient develops a skin rash, they should be monitored closely, and amoxicillin should be discontinued if the lesions progress.[18]
• Clostridioides difficile-Associated Diarrhea (CDAD): Like nearly all antibacterial agents, amoxicillin alters the normal flora of the colon, which can lead to the overgrowth of C. difficile. This bacterium produces toxins A and B, causing CDAD, which can range in severity from mild diarrhea to life-threatening pseudomembranous colitis. CDAD must be considered in any patient who presents with diarrhea following antibiotic use, even up to two months after therapy has been completed. If CDAD is suspected or confirmed, discontinuation of amoxicillin may be necessary, and appropriate fluid, electrolyte, and protein management, along with specific antibiotic treatment for C. difficile, should be initiated.[20]
• Drug-Induced Enterocolitis Syndrome (DIES): This is a distinct, non-IgE-mediated food protein-induced enterocolitis that has been reported with amoxicillin use, presenting with delayed vomiting and diarrhea.[23]
• Use in Patients with Mononucleosis: A high percentage of patients with infectious mononucleosis who are treated with amoxicillin or ampicillin develop a characteristic, non-allergic, erythematous, maculopapular rash. The mechanism is thought to be related to the underlying immune activation from the viral infection. To avoid this confusing clinical picture, amoxicillin should not be administered to patients with mononucleosis.[20]
• Development of Drug-Resistant Bacteria: The warnings regarding CDAD and the development of drug-resistant bacteria are two sides of the same coin, representing the ecological consequences of antibiotic use. CDAD is an adverse effect on the patient's internal ecosystem (the gut microbiome), while resistance is an adverse effect on the external ecosystem (the global population of bacteria). Both stem from the same fundamental action: the selective pressure exerted by the antibiotic. Prescribing amoxicillin in the absence of a proven or strongly suspected bacterial infection is unlikely to benefit the patient and actively contributes to the public health crisis of antimicrobial resistance.[20] This understanding reframes antimicrobial stewardship not just as a tool to prevent future resistance, but also as a strategy to prevent immediate, potentially fatal harm (CDAD) to the current patient.

6.3 Adverse Drug Reactions: A System-Organ Class Review

The following adverse reactions have been reported in clinical trials and post-marketing surveillance.

• Common (>1% incidence): The most frequently reported side effects are gastrointestinal in nature and include diarrhea, nausea, and vomiting. Skin rash is also common.[17]
• Gastrointestinal: In addition to the common effects, more severe or unusual reactions include hemorrhagic/pseudomembranous colitis (CDAD) and black hairy tongue, a benign discoloration of the filiform papillae.[18]
• Dermatologic / Hypersensitivity: Beyond the SCARs, other reported reactions include serum sickness-like reactions (fever, rash, arthralgia), erythema multiforme, exfoliative dermatitis, hypersensitivity vasculitis, and urticaria (hives).[18]
• Hepatic: Liver-related adverse effects can occur, typically manifesting as elevated liver enzymes (AST/ALT). More severe, though rare, reactions include cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis. While usually reversible, hepatic dysfunction can be severe, and fatalities have been reported, particularly in the context of combination products or in patients with serious underlying diseases.[26]
• Renal: Crystalluria, the formation of amoxicillin crystals in the urine, can occur, especially with high doses or in patients who are dehydrated or have pre-existing renal dysfunction. This can lead to acute kidney injury or oliguric renal failure. Acute Interstitial Nephritis (AIN), an allergic reaction in the kidney tubules, has also been reported.[19]
• Hematologic: A range of hematologic abnormalities have been observed, though they are generally reversible upon discontinuation of the drug. These include anemia (including immune-mediated hemolytic anemia), thrombocytopenia (low platelets), thrombocytopenic purpura, eosinophilia, leukopenia (low white blood cells), and, rarely, agranulocytosis (severe lack of neutrophils).[26]
• Central Nervous System (CNS): CNS effects are uncommon but can be serious. They include reversible hyperactivity, agitation, anxiety, insomnia, confusion, behavioral changes, dizziness, and convulsions (seizures). These are more likely to occur with very high doses or in patients with severe renal impairment, where drug levels can accumulate to toxic concentrations.[26]
• Other: Disruption of normal microbial flora can lead to opportunistic infections, most commonly mucocutaneous candidiasis (oral thrush or vaginal yeast infections).[18] Reversible tooth discoloration (brown, yellow, or gray staining) has also been reported, particularly in children, and is usually removed by brushing.[17]

Section 7: Clinically Significant Drug and Food Interactions

The safe administration of amoxicillin requires an awareness of its potential interactions with other drugs, foods, and laboratory tests. These interactions can alter the efficacy or safety of amoxicillin or the co-administered agent. The drug interactions of amoxicillin are primarily driven by three distinct mechanistic categories: interference with its renal excretion, alteration of the gut microbiome, and pharmacodynamic antagonism. Understanding these categories allows for better prediction and management of interactions.

7.1 Pharmacokinetic Drug Interactions

These interactions affect the absorption, distribution, metabolism, or excretion of amoxicillin or a concurrent drug.

• Probenecid: Probenecid, a uricosuric agent used for gout, competitively inhibits the renal tubular secretion of penicillins. Co-administration with amoxicillin blocks its primary route of active elimination, leading to higher and more prolonged plasma concentrations of amoxicillin.[16] While this increases the potential for dose-related side effects, this interaction has been exploited therapeutically in the past to "boost" penicillin levels for treating certain infections like gonorrhea.[28]
• Other Antibiotics (Antagonism): Bacteriostatic antibiotics, which inhibit bacterial growth but do not kill bacteria, may interfere with the action of bactericidal agents like amoxicillin. Penicillins are most effective against actively dividing bacteria that are synthesizing new cell walls. Bacteriostatic agents (e.g., tetracyclines like doxycycline and minocycline; macrolides like erythromycin; sulfonamides) can arrest this growth, potentially reducing the efficacy of amoxicillin. Therefore, concurrent use is generally avoided.[16]
• Mycophenolate Mofetil (MMF): Amoxicillin may decrease the plasma concentrations of mycophenolic acid (MPA), the active metabolite of MMF, an immunosuppressant drug. The proposed mechanism is the disruption of gut bacteria that are responsible for the enterohepatic recirculation of MPA, leading to reduced drug exposure and a potential risk of organ rejection in transplant patients. Close monitoring is warranted.[29]

7.2 Pharmacodynamic Drug Interactions

These interactions involve drugs acting on similar or opposing physiological pathways.

• Allopurinol: The concurrent use of allopurinol, another medication for gout, and amoxicillin significantly increases the incidence of skin rash compared to amoxicillin given alone.[20] The mechanism is not a typical allergic cross-reactivity but is thought to be an idiosyncratic potentiation. This, combined with the warning about a similar rash in patients with mononucleosis, points to a potential shared pathophysiology related to altered immune responses or drug metabolism in certain patient subgroups. It suggests that the "amoxicillin rash" may be a final common pathway for different underlying conditions that predispose a patient to react.
• Anticoagulants (Warfarin): Amoxicillin, by altering the gut flora, can reduce the population of bacteria that synthesize vitamin K. Since warfarin exerts its anticoagulant effect by inhibiting vitamin K-dependent clotting factors, this reduction in endogenous vitamin K can potentiate the effect of warfarin, leading to an elevated International Normalized Ratio (INR) and an increased risk of bleeding. Close monitoring of prothrombin time or INR is essential when amoxicillin is added to or removed from the regimen of a patient on warfarin.[20]
• Oral Contraceptives: It has been suggested that antibiotics, including amoxicillin, may rarely reduce the efficacy of combined oral contraceptives. The proposed mechanism involves interference with the enterohepatic circulation of estrogen, leading to lower hormone levels. While the evidence for this interaction with amoxicillin is weak and controversial compared to enzyme-inducing antibiotics, as a precaution, patients are often counseled to use an additional non-hormonal method of contraception during and for a short period after a course of amoxicillin.[20]

7.3 Interactions with Vaccines and Laboratory Tests

• Live Bacterial Vaccines: Amoxicillin is an antibacterial agent and can inactivate live bacterial vaccines, rendering them ineffective. This is a clinically significant interaction for the live oral typhoid vaccine (Vivotif) and the live oral cholera vaccine (Vaxchora). It is recommended to complete the amoxicillin course at least 72 hours before receiving the typhoid vaccine and to avoid the cholera vaccine within 14 days of antibiotic use.[28]
• Urine Glucose Tests: High urinary concentrations of amoxicillin can interfere with non-enzymatic copper-reduction methods for detecting glucose in the urine (e.g., Clinitest®), leading to false-positive results. Enzymatic glucose oxidase methods (e.g., Clinistix®) are not affected and should be used for diabetic patients taking amoxicillin.[23]

7.4 Food and Supplement Interactions

• Food: For immediate-release formulations, there are no clinically significant drug-food interactions. Amoxicillin can be taken with or without food, though administration with food may improve gastrointestinal tolerability.[15] Extended-release tablets must be taken with a meal.[15]
• Supplements: Some fiber supplements, such as guar gum, may decrease the absorption of amoxicillin; administration should be separated by at least two hours.[16] The pineapple-derived enzyme bromelain may increase the absorption of amoxicillin, potentially increasing both its effects and side effects.[16]

The following table provides a quick-reference guide for clinicians to identify and manage the most significant drug interactions with amoxicillin.

Interacting Drug/Class	Mechanism of Interaction	Clinical Consequence	Recommended Management
Probenecid	Inhibition of renal tubular secretion	Increased and prolonged amoxicillin levels; increased risk of side effects	Avoid routine co-administration unless therapeutically intended to "boost" amoxicillin levels.
Warfarin	Alteration of gut flora, reducing Vitamin K synthesis	Increased anticoagulant effect; increased INR and bleeding risk	Monitor INR/prothrombin time closely, especially when starting or stopping amoxicillin. Adjust warfarin dose as needed.
Allopurinol	Unknown pharmacodynamic interaction	Significantly increased incidence of skin rash	Use with caution. Counsel patient on increased rash risk and monitor closely.
Tetracyclines, Macrolides	Pharmacodynamic antagonism (bacteriostatic vs. bactericidal)	Potential for reduced amoxicillin efficacy	Avoid concurrent use where possible.
Oral Contraceptives	Possible interference with enterohepatic circulation of estrogen	Potential for reduced contraceptive efficacy (rare)	Counsel patient on potential risk and recommend using a backup non-hormonal contraceptive method.
Live Bacterial Vaccines	Inactivation of the live bacteria in the vaccine	Vaccine failure	Separate administration. Wait at least 72 hours after last amoxicillin dose for typhoid vaccine.

Section 8: Antimicrobial Resistance and Stewardship

The long-term utility of amoxicillin, like all antibiotics, is critically threatened by the global rise of antimicrobial resistance. Understanding the mechanisms of resistance and adhering to the principles of antimicrobial stewardship are essential to preserve its effectiveness.

8.1 Mechanisms of Resistance

Bacteria have evolved several mechanisms to defend themselves against β-lactam antibiotics like amoxicillin.

• β-Lactamase Production: This is the most common and clinically significant mechanism of resistance. Bacteria acquire genes that code for β-lactamase enzymes, which hydrolytically cleave the amide bond in the β-lactam ring of the antibiotic. This destroys the molecule's structural integrity and renders it inactive before it can reach its PBP target. The development of the combination drug amoxicillin/clavulanate was a direct response to the spread of β-lactamase-producing organisms, representing a successful strategy of "rescuing" an effective antibiotic by co-administering a "shield".[1]
• Alteration of Target Site: Bacteria can develop mutations in the genes encoding for Penicillin-Binding Proteins (e.g., pbp genes). These mutations alter the structure of the PBP's active site, reducing its binding affinity for amoxicillin. The antibiotic can no longer bind effectively, and cell wall synthesis continues. This is the primary mechanism of resistance in Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA).
• Reduced Permeability and Efflux: In Gram-negative bacteria, the outer membrane acts as a barrier. Resistance can arise from mutations that decrease the number or size of porin channels, through which amoxicillin must pass to reach the PBPs in the periplasmic space. Additionally, bacteria can acquire or upregulate efflux pumps, which actively transport the antibiotic out of the cell before it can reach its target.

The emergence and global spread of pathogens carrying these resistance mechanisms represent a steep incline in antimicrobial resistance and a severe threat to public health, necessitating the urgent development of new antimicrobials and strategies to preserve existing ones.[9]

8.2 Antimicrobial Stewardship

Antimicrobial stewardship refers to a coordinated set of strategies to improve the appropriate use of antimicrobial medications. The goal is to enhance patient health outcomes, reduce antimicrobial resistance, and decrease the spread of infections caused by multidrug-resistant organisms. The FDA labels for amoxicillin contain a prominent, repeated warning that functions as a public health mandate embedded within a clinical document: "To reduce the development of drug-resistant bacteria and maintain the effectiveness of AMOXIL and other antibacterial drugs, AMOXIL should be used only to treat infections that are proven or strongly suspected to be caused by bacteria".[14] This reflects a shift in regulatory thinking, where the responsibility for preserving an antibiotic's efficacy is placed on every prescriber. Every prescription becomes a public health decision, not just a clinical one.

Key principles of stewardship for amoxicillin include:

• Appropriate Diagnosis: Avoiding the use of amoxicillin for viral infections, such as the common cold or influenza, where it provides no benefit and only contributes to resistance and potential side effects.[25]
• Appropriate Dosing and Duration: Using the correct dose and treating for the recommended duration is critical. Patients must be counseled to complete the full course of therapy, even if they begin to feel better, to ensure the complete eradication of the pathogen and prevent the selection and survival of a more resistant subpopulation.[15]
• Narrowing Spectrum: When culture and susceptibility results are available, therapy should be tailored to the narrowest-spectrum agent that is effective against the identified pathogen.

Section 9: Synthesis and Expert Recommendations

9.1 Overall Profile Summary

Amoxicillin is a cornerstone β-lactam antibiotic whose nearly 50-year history of clinical use is a testament to its robust profile. It possesses a well-defined bactericidal mechanism of action, a favorable pharmacokinetic profile that makes it ideal for oral outpatient therapy, and a broad range of established indications. Its primary clinical strengths lie in its efficacy against common susceptible pathogens like Streptococcus pyogenes, its formulation flexibility that makes it a workhorse in pediatric medicine, and its critical role as a reliable anchor component in combination therapies designed to combat resistant organisms (with clavulanate) and complex infections (like H. pylori).

This utility is balanced by a significant and clinically challenging safety profile dominated by the risk of hypersensitivity reactions, which range from benign rashes to life-threatening anaphylaxis and SCARs. Furthermore, its use carries the ecological risks of C. difficile-associated diarrhea and the promotion of antimicrobial resistance. The safety and efficacy of amoxicillin are critically dependent on patient renal function, necessitating careful dose adjustments in neonates, the elderly, and individuals with kidney disease. The story of amoxicillin is a microcosm of the antibiotic era: a "wonder drug" that became a ubiquitous tool, faced the challenge of resistance, was partially rescued by chemical innovation, and now requires deliberate and careful stewardship to preserve its utility for future generations.

9.2 Expert Recommendations for Clinicians

Based on a comprehensive analysis of its pharmacology, efficacy, and safety, the following recommendations are provided for the optimal clinical use of amoxicillin:

• Patient Screening and Contraindication Assessment:
• Prior to prescribing, a thorough allergy history must be obtained. Specifically inquire about any previous reactions to penicillins, cephalosporins, or other β-lactam antibiotics. A history of a serious hypersensitivity reaction (e.g., anaphylaxis, SJS) is an absolute contraindication.
• Be particularly vigilant for the signs and symptoms of infectious mononucleosis (fever, pharyngitis, lymphadenopathy) in adolescents and young adults presenting with a sore throat, as amoxicillin should be avoided in this population to prevent the characteristic non-allergic rash.
• Assess renal function, especially in elderly patients, and be prepared to adjust dosing based on estimated GFR.
• Prescribing and Antimicrobial Stewardship:
• Adhere strictly to the principles of antimicrobial stewardship. Reserve amoxicillin for infections with a proven or strongly suspected bacterial etiology. Utilize local antibiograms to guide empirical therapy.
• Select the narrowest spectrum agent appropriate for the clinical syndrome. For example, use penicillin VK for streptococcal pharyngitis if local guidelines support it, reserving amoxicillin for situations where its broader spectrum or dosing convenience is required.
• When prescribing amoxicillin/clavulanate, ensure the indication warrants the broader spectrum to avoid unnecessary pressure on resistance.
• Patient Counseling:
• Educate all patients on the signs and symptoms of a severe allergic reaction (e.g., hives, swelling of the lips/tongue/throat, difficulty breathing, severe blistering rash) and instruct them to discontinue the drug and seek immediate emergency medical care if they occur.
• Warn patients about the risk of severe diarrhea (CDAD) and advise them to contact their healthcare provider immediately if it develops, even if it occurs weeks after therapy is completed. Advise against the use of anti-diarrheal medications without medical consultation.
• Emphasize the critical importance of completing the full prescribed course of treatment to maximize the chance of cure and minimize the risk of developing resistance.
• For patients taking oral contraceptives, discuss the potential for reduced efficacy and recommend using a backup non-hormonal contraceptive method during the course of therapy.
• Clinical Monitoring:
• For patients receiving concurrent warfarin therapy, monitor INR/prothrombin time closely, particularly at the initiation and cessation of amoxicillin treatment.
• In patients with known renal impairment, calculate the GFR and adjust the dose according to established guidelines. Remember that the 875 mg strength is contraindicated in patients with a GFR < 30 mL/min.
• Approach any rash that develops during therapy with a high index of suspicion. Carefully evaluate the morphology of the rash and the presence of systemic symptoms to differentiate between a benign eruption and a potentially life-threatening SCAR.

Works cited

1. Amoxicillin: Uses, Interactions, Mechanism of Action | DrugBank ..., accessed July 15, 2025, https://go.drugbank.com/drugs/DB01060
2. Amoxicillin | C16H19N3O5S | CID 33613 - PubChem, accessed July 15, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/33613
3. 6-{[Amino(4-hydroxyphenyl)acetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid | C16H19N3O5S | CID 2171 - PubChem, accessed July 15, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/2171
4. CAS RN 26787-78-0 - Fisher Scientific, accessed July 15, 2025, https://www.fishersci.com/us/en/browse/cas/26787-78-0
5. PRESCRIBING INFORMATION Amoxicillin Capsules, USP 500 mg Rx only - DailyMed, accessed July 15, 2025, https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=2b59175e-42f0-0ebc-e054-00144ff8d46c
6. Amoxicillin, L- | C16H19N3O5S | CID 32324 - PubChem, accessed July 15, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/Amoxicillin_-L
7. 26787-78-0 (Unlabeled) | C16H19N3O5S | CID 6426609 - PubChem, accessed July 15, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/26787-78-0-_Unlabeled
8. Amoxicillin sodium [USAN] - PubChem, accessed July 15, 2025, https://pubchem.ncbi.nlm.nih.gov/substance/135049168
9. Structure of user compound (Amoxicillin) (Drug Bank ID: DB01060). - ResearchGate, accessed July 15, 2025, https://www.researchgate.net/figure/Structure-of-user-compound-Amoxicillin-Drug-Bank-ID-DB01060_fig2_374417778
10. Infections, Bacterial Withdrawn Phase 2 Trials for Amoxicillin (DB01060) | DrugBank Online, accessed July 15, 2025, https://go.drugbank.com/indications/DBCOND0036507/clinical_trials/DB01060?phase=2&status=withdrawn
11. Bacterial Infections Completed Phase Trials for Amoxicillin (DB01060) | DrugBank Online, accessed July 15, 2025, https://go.drugbank.com/indications/DBCOND0027917/clinical_trials/DB01060?status=completed
12. Bacterial Infections Completed Phase 4 Trials for Amoxicillin (DB01060) | DrugBank Online, accessed July 15, 2025, https://go.drugbank.com/indications/DBCOND0027917/clinical_trials/DB01060?phase=4&status=completed
13. Amoxicillin Completed Phase 1 Trials for Respiratory Tract Infections (RTI) Other - DrugBank, accessed July 15, 2025, https://go.drugbank.com/drugs/DB01060/clinical_trials?conditions=DBCOND0070409&phase=1&purpose=other&status=completed
14. AMOXIL - accessdata.fda.gov, accessed July 15, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050542s24,050754s11,050760s10,050761s10lbl.pdf
15. Amoxicillin (oral route) - Mayo Clinic, accessed July 15, 2025, https://www.mayoclinic.org/drugs-supplements/amoxicillin-oral-route/description/drg-20075356
16. Amoxicillin interactions to avoid - SingleCare, accessed July 15, 2025, https://www.singlecare.com/blog/amoxicillin-interactions/
17. Amoxicillin: MedlinePlus Drug Information, accessed July 15, 2025, https://medlineplus.gov/druginfo/meds/a685001.html
18. MOXATAG® (amoxicillin extended-release) Tablets - accessdata.fda.gov, accessed July 15, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050813s003lbl.pdf
19. This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda, accessed July 15, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/065056s017lbl.pdf
20. AMOXICILLIN tablet, film coated - DailyMed, accessed July 15, 2025, https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=7c34c955-aa27-486b-bd23-13e6fbce7a6c
21. This label may not be the latest approved by FDA. For current ..., accessed July 15, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/050542s032,050754s022,050760s023,050761s019lbl.pdf
22. AMOXIL (amoxicillin) capsules, tablets, or powder for oral suspension) - accessdata.fda.gov, accessed July 15, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/50542s02950754s01950760s01950761s016lbl.pdf
23. MOXATAG® (amoxicillin extended-release tablets) - This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda, accessed July 15, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/050813s010lbl.pdf
24. Amoxicillin Dosage Guide + Max Dose, Adjustments - Drugs.com, accessed July 15, 2025, https://www.drugs.com/dosage/amoxicillin.html
25. Amoxicillin: Uses, Dosage, Side Effects, Warnings - Drugs.com, accessed July 15, 2025, https://www.drugs.com/amoxicillin.html
26. Amoxicillin: Side Effects, Uses, Dosage, Interactions, Warnings - RxList, accessed July 15, 2025, https://www.rxlist.com/amoxicillin/generic-drug.htm
27. Prevpac (lansoprazole/amoxicillin/clarithromycin) dosing, indications, interactions, adverse effects, and more. - Medscape Reference, accessed July 15, 2025, https://reference.medscape.com/drug/prevpac-lansoprazole-amoxicillin-clarithromycin-999477
28. Everything You Should Know About Amoxicillin Interactions - GoodRx, accessed July 15, 2025, https://www.goodrx.com/amoxicillin/interactions
29. amoxicillin/clavulanate (Rx) - Medscape Reference, accessed July 15, 2025, https://reference.medscape.com/drug/augmentin-amoxicillin-clavulanate-342474
30. Amoxil (amoxicillin) dosing, indications, interactions, adverse effects, and more, accessed July 15, 2025, https://reference.medscape.com/drug/amoxil-amoxicillin-342473
31. Amoxicillin oral tablet interactions: Alcohol, medications, and other factors, accessed July 15, 2025, https://www.medicalnewstoday.com/articles/drugs-amoxicillin-tablet-interactions