AMOXICILLIN AND CLAVULANATE POTASSIUM
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 inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. Clavulanate potassium is a beta-lactamase inhibitor that irreversibly inactivates beta-lactamase enzymes, preventing degradation of amoxicillin.
| Metabolism | Amoxicillin undergoes partial hepatic metabolism via hydrolysis. Clavulanate is extensively metabolized in the liver, primarily by hydrolysis and conjugation. |
| Excretion | Renal: ~50-70% amoxicillin unchanged; ~25-40% clavulanate as metabolites. Fecal: minimal. Biliary: minor. |
| Half-life | Amoxicillin: ~1-1.5 hours; Clavulanate: ~1 hour. Prolonged in renal impairment. |
| Protein binding | Amoxicillin: ~20% (mainly albumin); Clavulanate: ~25% (albumin). |
| Volume of Distribution | Amoxicillin: ~0.3-0.4 L/kg; Clavulanate: ~0.3 L/kg. Distributes into tissues, not CSF unless inflamed. |
| Bioavailability | Oral: ~80-90% for amoxicillin; ~60-75% for clavulanate. Enhanced with food. |
| Onset of Action | Oral: ~1-2 hours; IV: immediate. |
| Duration of Action | 6-8 hours; dosing q8h or q12h based on infection severity. |
| Molecular Weight | Amoxicillin: 365.4 Da; Clavulanate: 199.2 Da |
500 mg amoxicillin/125 mg clavulanate orally every 8 hours or 875 mg amoxicillin/125 mg clavulanate orally every 12 hours. For severe infections: 875 mg amoxicillin/125 mg clavulanate orally every 8 hours or 1000 mg amoxicillin/62.5 mg clavulanate extended-release orally every 12 hours.
| Dosage form | TABLET |
| Renal impairment | For CrCl 10-30 mL/min: 250-500 mg amoxicillin component every 12 hours. For CrCl <10 mL/min: 250-500 mg amoxicillin component every 24 hours. Hemodialysis: 250-500 mg every 24 hours, give additional dose during and after dialysis. |
| Liver impairment | No specific dose adjustment recommended for mild to moderate hepatic impairment. Use with caution in severe hepatic impairment (Child-Pugh C); consider alternative therapy or reduced dosing, but no formal guidelines. |
| Pediatric use | For children >3 months: 25-45 mg/kg/day of amoxicillin component divided every 12 hours (based on 200 mg/28.5 mg per 5 mL suspension) or 20-40 mg/kg/day divided every 8 hours (based on 125 mg/31.25 mg per 5 mL suspension). For severe infections, up to 90 mg/kg/day of amoxicillin component divided every 12 hours (using 400 mg/57 mg per 5 mL suspension). |
| Geriatric use | Initiate at lower end of dosing range due to increased risk of renal impairment. Monitor renal function and adjust dose based on creatinine clearance as per renal adjustment guidelines. |
| 1st trimester | Use only if clearly needed; associated with a small increased risk of cleft palate in animal studies, but human data limited. |
| 2nd trimester | Generally considered safe; no known harm. |
| 3rd trimester | Considered safe; may carry theoretical risk of neonatal infection if used near term. |
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 | Amoxicillin crosses the placenta readily; clavulanate crosses to a lesser extent. |
| Breastfeeding |
■ FDA Black Box Warning
No FDA boxed warning.
| Common Effects | Diarrhea |
| Serious Effects |
Hypersensitivity to amoxicillin, clavulanate, or any componentHistory of cholestatic jaundice or hepatic dysfunction with amoxicillin/clavulanateHypersensitivity to penicillins
| Precautions | Hypersensitivity reactions (anaphylaxis, Stevens-Johnson syndrome) in patients with penicillin allergy, Clostridioides difficile-associated diarrhea, Hepatic toxicity (elevated liver enzymes, hepatitis, cholestatic jaundice) more common in elderly and with prolonged use, Renal impairment requires dose adjustment, Risk of superinfection with prolonged therapy, Skin rash can occur in patients with mononucleosis |
| Food/Dietary | May be taken with or without food; food enhances absorption; avoid ingestion with high-dose clavulanate? (no significant interaction); no specific food restrictions; milk-containing products do not interact significantly. |
Loading safety data…
| Excreted into breast milk in low concentrations; generally considered compatible with breastfeeding; monitor for potential gastrointestinal effects in the infant. |
| Lactation Rating | L1 (Safe) |
| Teratogenic Risk | Amoxicillin-clavulanate is pregnancy category B. No evidence of teratogenicity in animal studies; human data do not demonstrate increased risk of major congenital malformations. Use during first trimester is considered safe if clinically indicated. During second and third trimesters, no known fetal risks. However, avoid use near term due to potential for neonatal kernicterus (theoretical risk from high doses, but not confirmed). |
| Fetal Monitoring | No specific fetal monitoring required. Monitor maternal renal function if high doses or prolonged therapy. Observe for signs of maternal allergic reaction or Clostridioides difficile diarrhea. |
| Fertility Effects | No known adverse effects on fertility in animal or human studies. |
| Clinical Pearls | Use weight-based dosing for pediatric patients; reconstitute oral suspension with appropriate amount of water; administer at start of meal to reduce GI upset; check renal function before dosing; avoid in patients with mononucleosis due to risk of maculopapular rash; higher doses of clavulanate may cause diarrhea; intravenous infusion over 30-40 minutes; consider penicillin allergy cross-reactivity; not effective against MRSA; requires dose adjustment in CrCl <30 mL/min. |
| Patient Advice | Take this medication exactly as prescribed, usually every 12 hours. · Take with food to reduce stomach upset and improve absorption. · Complete the full course even if you feel better. · Shake the oral suspension well before each use. · Store oral suspension in refrigerator, discard after 10 days. · Report severe diarrhea, rash, or signs of allergy immediately. · May cause diarrhea; do not treat without consulting doctor. · Inform your doctor if you are pregnant, breastfeeding, or have liver disease. |