AMOXICILLIN
Clinical safety rating: safe
Probenecid decreases renal tubular secretion of amoxicillin May reduce efficacy of oral contraceptives Serious and occasionally fatal hypersensitivity reactions have been reported.
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.
| Metabolism | 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. |
| Excretion | Renal: 60-80% unchanged via glomerular filtration and tubular secretion. Biliary: up to 20% excreted in bile. Fecal: minimal. |
| Half-life | Terminal elimination half-life: 1-1.5 hours in normal renal function. Prolonged to 7-20 hours in end-stage renal disease. |
| Protein binding | 17-20% bound to serum albumin. |
| Volume of Distribution | 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. |
| Bioavailability | Oral: 74-92% (absorption is not food-dependent). IM: approximately 100%. |
| Onset of Action | Oral: 1-2 hours. IV: immediate. |
| Duration of Action | 6-8 hours. For susceptible bacteria, bactericidal levels persist for 4-6 hours after oral dose. |
| Molecular Weight | 365.4 |
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.
| Dosage form | TABLET, CHEWABLE |
| Renal impairment | CrCl 30-50 mL/min: 250-500 mg every 8-12 hours. CrCl 10-29 mL/min: 250-500 mg every 12 hours. CrCl <10 mL/min: 250-500 mg every 24 hours. Hemodialysis: 250-500 mg every 24 hours, supplemented during and after dialysis. |
| Liver impairment | 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. |
| Pediatric use | 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. |
| Geriatric use | No specific dose adjustment; monitor renal function and adjust based on CrCl. Caution with concurrent nephrotoxic agents. |
| 1st trimester | Generally considered safe; no evidence of teratogenicity in human studies. |
| 2nd trimester | Safe for use; commonly prescribed for infections during pregnancy. |
| 3rd trimester | Safe for use; no known risks, but consider theoretical risk of diarrhea in neonates. |
Clinical note
Probenecid decreases renal tubular secretion of amoxicillin May reduce efficacy of oral contraceptives Serious and occasionally fatal hypersensitivity reactions have been reported.
| FDA category | Human |
| Placental transfer | Crosses placenta; achieves therapeutic levels in fetal circulation. |
| Breastfeeding | Excreted into breast milk in low amounts; generally considered compatible with breastfeeding. Monitor infant for potential rash or diarrhea. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Diarrhea |
| Serious Effects |
Hypersensitivity to penicillinsHistory of severe immediate allergic reaction (e.g., anaphylaxis) to beta-lactams
| Precautions | 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. |
| Food/Dietary |
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| Lactation Rating | L1 (Safe) |
| Teratogenic Risk | 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. |
| Fetal Monitoring | Monitor for maternal allergic reactions, diarrhea, and superinfection. No specific fetal monitoring required; assess for adverse drug effects in newborn if exposed near term. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment of fertility. |
| 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. |
| Clinical Pearls | 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 mL/min. |
| Patient Advice | 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). |