AMPICILLIN TRIHYDRATE
Clinical safety rating: safe
Probenecid decreases renal tubular secretion of ampicillin Allopurinol may increase the incidence of skin rashes Serious and occasionally fatal hypersensitivity reactions have been reported.
Inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidation and autolysin activity.
| Metabolism | Partially hydrolyzed by penicillinases; not extensively metabolized in the liver. |
| Excretion | Renal: 75-90% unchanged; biliary: small amount; fecal: negligible |
| Half-life | Terminal elimination half-life 1-1.8 hours; prolonged in renal impairment (up to 10-20 hours in anuria) |
| Protein binding | 15-25% bound to serum albumin |
| Volume of Distribution | 0.3 L/kg; indicates distribution primarily into extracellular fluid |
| Bioavailability | Oral: 30-50% (variably absorbed); IM: ~100% |
| Onset of Action | IM: 15-30 minutes; IV: immediate; oral: 1-2 hours |
| Duration of Action | 4-6 hours; may be longer with higher doses or renal impairment |
250-500 mg PO q6h or 1-2 g IV/IM q4-6h; up to 12 g/day IV for severe infections.
| Dosage form | CAPSULE |
| Renal impairment | GFR 10-50 mL/min: extend interval to q6-8h; GFR <10 mL/min: extend interval to q8-12h; hemodialysis: administer after dialysis. |
| Liver impairment | No adjustment required for mild to moderate hepatic impairment; use caution in severe impairment as ampicillin is primarily renally eliminated. |
| Pediatric use | Neonates <7 days: 50 mg/kg/dose IV/IM q12h; 7-28 days: 50 mg/kg/dose q8h. Infants/children: 12.5-25 mg/kg/dose PO q6h; 25-50 mg/kg/dose IV/IM q6h; max 400 mg/kg/day IV for meningitis. |
| Geriatric use | Start at lower end of dosing range due to age-related renal decline; adjust based on renal function and monitor for Clostridium difficile diarrhea. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Probenecid decreases renal tubular secretion of ampicillin Allopurinol may increase the incidence of skin rashes Serious and occasionally fatal hypersensitivity reactions have been reported.
| FDA category | Human |
| Breastfeeding | Ampicillin is excreted into breast milk in low concentrations. The milk-to-plasma (M/P) ratio is approximately 0.2. The American Academy of Pediatrics considers ampicillin compatible with breastfeeding. Theoretical risks include alteration of infant gut flora and sensitization, but adverse effects are rare. Caution is advised in infants with known penicillin allergy. |
■ FDA Black Box Warning
No FDA boxed warning.
| Common Effects | Diarrhea |
| Serious Effects |
["History of allergic reaction to penicillins","Infections caused by penicillinase-producing organisms"]
| Precautions | ["Hypersensitivity reactions including anaphylaxis","Risk of Clostridium difficile-associated diarrhea","Superinfection with non-susceptible organisms","Seizures with high doses or renal impairment"] |
| Food/Dietary | Ampicillin absorption is reduced by food; take on an empty stomach at least 1 hour before or 2 hours after meals. Avoid alcohol during therapy as it may increase side effects. No known specific food interactions, but maintain adequate fluid intake. |
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| Teratogenic Risk |
| Ampicillin trihydrate is classified as FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, and adequate studies in pregnant women have not shown evidence of teratogenicity. However, use during pregnancy should be limited to situations where clearly needed, especially during the first trimester due to theoretical concerns. No increased risk of major congenital malformations has been observed in human studies. |
| Fetal Monitoring | Monitor for signs of hypersensitivity reactions (rash, urticaria, anaphylaxis) in the mother. For prolonged use, monitor for superinfection (e.g., Clostridioides difficile-associated diarrhea). Fetal monitoring is not routinely required, but if maternal infection is severe, fetal well-being should be assessed via ultrasound or non-stress test as clinically indicated. |
| Fertility Effects | No known adverse effects on fertility in animal studies or human data. Ampicillin does not impact ovulation, spermatogenesis, or implantation at therapeutic doses. Fertility is expected to return to normal after cessation of therapy if any transient effects occur. |
| Clinical Pearls | Ampicillin trihydrate is a broad-spectrum penicillin susceptible to beta-lactamase degradation; co-administration with sulbactam enhances coverage. Monitor for rash, which may indicate infectious mononucleosis (avoid use in EBV infection). Dose adjustment required in renal impairment (CrCl <10 mL/min: extend interval to q12-24h). Use cautiously in penicillin-allergic patients; cross-reactivity with cephalosporins ~5-10%. Intravenous administration can cause phlebitis; rotate sites. Aminoglycosides synergize but must be administered separately (inactivate in solution). |
| Patient Advice | Take this medication exactly as prescribed, even if you feel better. · Finish the full course of antibiotics; do not stop early. · Take each dose with a full glass of water, on an empty stomach (1 hour before or 2 hours after meals) for best absorption. · Notify your doctor if you develop a skin rash, diarrhea, or unusual bleeding/bruising. · Store at room temperature away from moisture and heat; oral suspension must be refrigerated and shaken well before use. |