Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
AMOXICILLIN vs Amoxicillin-Clavulanate
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Amoxicillin is a beta-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidase activity, and activating autolytic enzymes.
Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidation and autolysin inhibitors. Clavulanate is a beta-lactamase inhibitor that binds to and inactivates beta-lactamases, protecting amoxicillin from hydrolysis.
Upper respiratory tract infections (e.g., otitis media, sinusitis, pharyngitis/tonsillitis),Lower respiratory tract infections (e.g., community-acquired pneumonia, acute exacerbation of chronic bronchitis),Genitourinary tract infections (e.g., cystitis, urethritis),Skin and skin structure infections,Helicobacter pylori eradication (in combination with clarithromycin and a proton pump inhibitor),Lyme disease (early localized),Prophylaxis of infective endocarditis (for dental procedures in high-risk patients),Off-label: Anthrax (post-exposure prophylaxis), uncomplicated gonorrhea
Acute bacterial sinusitis,Acute otitis media,Community-acquired pneumonia,Urinary tract infections,Skin and skin structure infections,Intra-abdominal infections,Lower respiratory tract infections,Diabetic foot infections,Prophylaxis of infection following surgery (off-label)
250-500 mg orally every 8 hours or 500-875 mg orally every 12 hours; for severe infections, up to 1 g orally every 8 hours.
500 mg/125 mg orally every 8 hours or 875 mg/125 mg orally every 12 hours; intravenous: 1 g/0.2 g every 8 hours.
Terminal elimination half-life: 1-1.5 hours in normal renal function. Prolonged to 7-20 hours in end-stage renal disease.
Amoxicillin: ~1-1.3 hours in adults with normal renal function; Clavulanate: ~1 hour. Both prolonged in renal impairment (amoxicillin up to 7-20 hours with Cr Cl <10 m L/min).
Amoxicillin is primarily metabolized by hydrolysis to penicilloic acid (inactive). It is not extensively metabolized by the liver; about 60% of an oral dose is excreted unchanged in urine.
Amoxicillin is partially metabolized via hydrolysis of the beta-lactam ring to inactive penicilloic acid, minor hepatic metabolism; excreted primarily unchanged renally. Clavulanate is extensively metabolized in the liver, primarily to metabolites excreted in urine and feces.
Renal: 60-80% unchanged via glomerular filtration and tubular secretion. Biliary: up to 20% excreted in bile. Fecal: minimal.
Amoxicillin: ~60% renal as unchanged drug via glomerular filtration and tubular secretion; Clavulanate: ~30-50% renal as metabolites and unchanged, remainder fecal. Approximately 50-70% of total dose excreted renally within 6 hours.
17-20% bound to serum albumin.
Amoxicillin: ~17% bound to serum protein (primarily albumin); Clavulanate: ~25% bound to albumin.
0.3-0.4 L/kg. Distributes well into most body fluids and tissues, including pleural, peritoneal, and synovial fluids; limited CNS penetration unless meninges inflamed.
Amoxicillin: Vd ~0.3-0.4 L/kg; clavulanate: Vd ~0.3 L/kg. Distributes well into interstitial fluid, tissues, and bone; limited CNS penetration (10-20% of serum levels) unless inflamed meninges.
Oral: 74-92% (absorption is not food-dependent). IM: approximately 100%.
Oral: 80-90% for both components; food does not significantly affect absorption (note: clavulanate is better absorbed with food, extended-release tab with food).
Cr Cl 30-50 m L/min: 250-500 mg every 8-12 hours. Cr Cl 10-29 m L/min: 250-500 mg every 12 hours. Cr Cl <10 m L/min: 250-500 mg every 24 hours. Hemodialysis: 250-500 mg every 24 hours, supplemented during and after dialysis.
Cr Cl 30-50 m L/min: 500 mg/125 mg orally every 12 hours; Cr Cl 10-29 m L/min: 500 mg/125 mg orally every 24 hours; Cr Cl <10 m L/min: 500 mg/125 mg orally every 24 hours, supplement after dialysis.
No dose adjustment required for mild to moderate hepatic impairment. Severe hepatic impairment (Child-Pugh class C): use with caution; specific dosing guidelines not established.
No specific adjustment recommended; use with caution in severe hepatic impairment (Child-Pugh C).
Children >3 months: 20-40 mg/kg/day divided every 8 hours for mild to moderate infections; 40-90 mg/kg/day divided every 8-12 hours for severe infections. Maximum 3 g/day.
3 months to 40 kg: 25-45 mg/kg/day of amoxicillin component in 2-3 divided doses; >40 kg: adult dosing.
No specific dose adjustment; monitor renal function and adjust based on Cr Cl. Caution with concurrent nephrotoxic agents.
Adjust based on renal function; initiate with lower end of dosing due to age-related renal decline.
No FDA black box warning.
None
Hypersensitivity reactions including anaphylaxis have been reported; contraindicated in patients with known penicillin allergy.,Clostridium difficile-associated diarrhea (CDAD) may occur and must be considered in patients presenting with diarrhea after antibiotic use.,Serious skin reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis) can occur; discontinue if rash or other allergic signs appear.,Use caution in patients with renal impairment; dosage adjustment may be necessary.,Prolonged use may result in superinfection with non-susceptible organisms.
Serious hypersensitivity reactions (anaphylaxis) can occur,Clostridium difficile-associated diarrhea (CDAD) risk,Hepatic dysfunction, including hepatitis and cholestatic jaundice, especially in elderly and patients with prior therapy,Renal impairment requires dose adjustment,Potential for superinfection with prolonged therapy
History of hypersensitivity reaction to any penicillin or beta-lactam antibiotic.,Infectious mononucleosis (increases risk of maculopapular rash).,Phenylketonuria (some formulations contain aspartame).
History of hypersensitivity reaction to any penicillin,History of cholestatic jaundice or hepatic dysfunction associated with amoxicillin-clavulanate,Infectious mononucleosis (risk of erythematous rash)
No significant food interactions. Absorption is not affected by food; may be taken with meals to reduce gastrointestinal upset. Avoid concurrent alcohol consumption as it may increase risk of side effects like nausea and vomiting.
May be taken with food to reduce GI irritation. No significant food interactions. Avoid high-fat meals if taking extended-release formulation (fat increases absorption variability).
FDA Pregnancy Category B. No evidence of teratogenicity in animal studies. First trimester: no increased risk of major malformations observed in large cohort studies. Second and third trimesters: use only if clearly needed; no known fetal harm, but caution due to maternal physiological changes.
FDA Category B. No evidence of teratogenicity in animal studies; human data do not indicate increased risk of major birth defects. However, use only when clearly needed in pregnancy, especially during first trimester. Theoretical risk of neonatal kernicterus if used near term due to bilirubin displacement from albumin.
Amoxicillin is excreted into breast milk in small amounts (M/P ratio approximately 0.014-0.015). Considered compatible with breastfeeding; potential for diarrhea or allergic sensitization in infant, but generally safe.
Compatible with breastfeeding. Excreted into breast milk in low amounts (M/P ratio not established; amoxicillin milk concentration ~ 0.5-1% of maternal serum). No adverse effects reported in nursing infants. Consider monitoring for diarrhea or rash.
No dose adjustment required for amoxicillin in pregnancy; however, increased renal clearance and expanded plasma volume may lower serum concentrations. For severe infections, consider standard dosing with monitoring of clinical response.
No routine dose adjustment in pregnancy despite increased renal clearance and expanded plasma volume. Standard adult dosing is appropriate unless GFR <30 m L/min. Monitor for therapeutic efficacy in pregnancy-related infections (e.g., UTIs, chorioamnionitis).
For streptococcal pharyngitis, amoxicillin 50 mg/kg once daily (max 1 g) is as effective as multiple daily doses and improves adherence. In penicillin-allergic patients, the cross-reactivity risk with cephalosporins is low; a cephalosporin can be used if no history of immediate-type hypersensitivity. Amoxicillin is not effective against penicillinase-producing staphylococci or most Gram-negative organisms due to beta-lactamase production. Monitor for rash in patients with infectious mononucleosis (ampicillin rash occurs more frequently, but amoxicillin also has increased risk). Dose adjustment needed for creatinine clearance <30 m L/min.
Administer with food to reduce GI upset. Monitor for rash, especially in patients with mononucleosis (EBV). Dose adjustment required for Cr Cl <30 m L/min. High dose (2000 mg amoxicillin) provides adequate coverage for penicillin-resistant S. pneumoniae. Avoid in penicillin allergy; cross-reactivity with cephalosporins is low but possible.
Take exactly as prescribed; complete the full course even if you feel better.,Can be taken with or without food; if stomach upset occurs, take with a meal.,Swallow capsules whole; do not crush or chew; oral suspension shake well before each dose.,Skip missed dose if almost time for next; do not double dose.,Seek immediate medical help for signs of allergic reaction: hives, difficulty breathing, swelling of face/lips/tongue.,May cause diarrhea; contact doctor if watery or bloody stools.,Inform doctor if you are pregnant, planning to become pregnant, or breastfeeding.,Avoid large amounts of grapefruit juice as it may affect absorption (limited clinical significance).
Take with food or milk to minimize stomach upset.,Complete the full course even if you feel better.,Shake oral suspension well before each use.,Use backup contraception if on oral contraceptives.,Contact doctor if rash, watery diarrhea, or signs of liver problems (yellowing skin, dark urine).,Do not take if allergic to penicillin or cephalosporins.
"Amoxicillin may reduce the metabolism of Indinavir via inhibition of CYP3A4, leading to increased plasma concentrations of Indinavir. This can elevate the risk of Indinavir-related toxicities such as nephrolithiasis, hepatotoxicity, and gastrointestinal intolerance. Patients may experience exacerbated adverse effects without a corresponding increase in antiviral efficacy."
"Amoxicillin may inhibit the CYP3A4-mediated metabolism of nicardipine, a calcium channel blocker, leading to increased plasma concentrations of nicardipine. This can potentiate vasodilation and negative chronotropic effects, resulting in an increased risk of hypotension, bradycardia, and peripheral edema. Patients, especially those with pre-existing cardiovascular conditions, should be monitored for enhanced antihypertensive effects and adverse reactions when these drugs are coadministered."
"Amoxicillin may inhibit the metabolism of bortezomib through competitive inhibition of cytochrome P450 enzymes, particularly CYP3A4 and CYP2C19, potentially leading to increased bortezomib exposure. This interaction could result in enhanced toxicity of bortezomib, including peripheral neuropathy, myelosuppression, and gastrointestinal adverse effects. Clinicians should monitor for signs of bortezomib toxicity when amoxicillin is coadministered, especially in patients with pre-existing hepatic impairment or other risk factors."
"Amoxicillin may reduce the metabolism of Indinavir via inhibition of CYP3A4, leading to increased plasma concentrations of Indinavir. This can elevate the risk of Indinavir-related toxicities such as nephrolithiasis, hepatotoxicity, and gastrointestinal intolerance. Patients may experience exacerbated adverse effects without a corresponding increase in antiviral efficacy."
"Amoxicillin may inhibit the CYP3A4-mediated metabolism of nicardipine, a calcium channel blocker, leading to increased plasma concentrations of nicardipine. This can potentiate vasodilation and negative chronotropic effects, resulting in an increased risk of hypotension, bradycardia, and peripheral edema. Patients, especially those with pre-existing cardiovascular conditions, should be monitored for enhanced antihypertensive effects and adverse reactions when these drugs are coadministered."
"Amoxicillin may inhibit the metabolism of bortezomib through competitive inhibition of cytochrome P450 enzymes, particularly CYP3A4 and CYP2C19, potentially leading to increased bortezomib exposure. This interaction could result in enhanced toxicity of bortezomib, including peripheral neuropathy, myelosuppression, and gastrointestinal adverse effects. Clinicians should monitor for signs of bortezomib toxicity when amoxicillin is coadministered, especially in patients with pre-existing hepatic impairment or other risk factors."
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about AMOXICILLIN vs Amoxicillin-Clavulanate, answered by our medical review team.
AMOXICILLIN is a Penicillin Antibiotic that works by Amoxicillin is a beta-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidase activity, and activating autolytic enzymes.. Amoxicillin-Clavulanate is a Penicillin Antibiotic + Beta-Lactamase Inhibitor that works by Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidation and autolysin inhibitors. Clavulanate is a beta-lactamase inhibitor that binds to and inactivates beta-lactamases, protecting amoxicillin from hydrolysis.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between AMOXICILLIN and Amoxicillin-Clavulanate depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of AMOXICILLIN is: 250-500 mg orally every 8 hours or 500-875 mg orally every 12 hours; for severe infections, up to 1 g orally every 8 hours.. The standard adult dose of Amoxicillin-Clavulanate is: 500 mg/125 mg orally every 8 hours or 875 mg/125 mg orally every 12 hours; intravenous: 1 g/0.2 g every 8 hours.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between AMOXICILLIN and Amoxicillin-Clavulanate in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. AMOXICILLIN is classified as Category A/B. FDA Pregnancy Category B. No evidence of teratogenicity in animal studies. First trimester: no increased risk of major malformations observed in large cohort studies. Second and th. Amoxicillin-Clavulanate is classified as Category C. FDA Category B. No evidence of teratogenicity in animal studies; human data do not indicate increased risk of major birth defects. However, use only when clearly needed in pregnanc. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.