PRINCIPEN W/ PROBENECID
Clinical safety rating: safe
Increases levels of many drugs by inhibiting their renal secretion (eg penicillins methotrexate) Can cause GI upset and nephrotic syndrome.
Ampicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs) and inhibiting transpeptidase activity. Probenecid competitively inhibits renal tubular secretion of ampicillin, increasing its plasma concentration and duration.
| Metabolism | Ampicillin is metabolized by hydrolysis to penicilloic acid; probenecid undergoes hepatic metabolism via glucuronidation and oxidation. |
| Excretion | Renal: ~60-80% of ampicillin excreted unchanged in urine via tubular secretion and glomerular filtration; probenecid reduces this to ~20-30%. Biliary/fecal: minor, <10%. |
| Half-life | Ampicillin: 1-1.8 hours (prolonged to 4-6 hours with probenecid due to reduced renal clearance). Probenecid: 6-12 hours. Clinical context: extended half-life allows less frequent dosing. |
| Protein binding | Ampicillin: 15-25% bound to albumin. Probenecid: 85-95% bound to albumin. |
| Volume of Distribution | Ampicillin: 0.3-0.4 L/kg (distributes well into extracellular fluid, low CNS penetration unless inflamed meninges). |
| Bioavailability | Oral: 30-50% for ampicillin (enhanced by probenecid? probenecid does not significantly alter ampicillin absorption). Probenecid: nearly 100% oral. |
| Onset of Action | Oral: 1-2 hours (peak serum levels). IM: 30-60 minutes. IV: immediate. |
| Duration of Action | 6-8 hours (due to probenecid prolonging ampicillin serum levels). Clinical notes: allows every-6-hour dosing for susceptible infections. |
1.5-3 g IM q6h (20 mg/kg/day probenecid component).
| Dosage form | CAPSULE |
| Renal impairment | CrCl 30-50 mL/min: 1.5 g IM q8h; CrCl 10-29 mL/min: 1.5 g IM q12h; CrCl <10 mL/min: 1.5 g IM q24h. |
| Liver impairment | No adjustment required for mild to moderate impairment. Severe impairment (Child-Pugh C): consider reducing dose by 25-50%. |
| Pediatric use | Children 2-12 years: 50 mg/kg/day IM in 4 divided doses (probenecid component 25 mg/kg/day). Maximum single dose 2 g. |
| Geriatric use | Reduce dose based on renal function; avoid if CrCl <30 mL/min due to probenecid accumulation. Monitor for CNS toxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Increases levels of many drugs by inhibiting their renal secretion (eg penicillins methotrexate) Can cause GI upset and nephrotic syndrome.
| FDA category | Animal |
| Breastfeeding | Ampicillin excreted in breast milk in low levels (M/P ratio 0.02-0.1); probenecid probably excreted but data limited. Compatible with breastfeeding; monitor infant for diarrhea, rash, or candidiasis. Theoretical risk of kernicterus in jaundiced infants if probenecid displaces bilirubin. |
| Teratogenic Risk |
■ FDA Black Box Warning
None.
| Common Effects | Hyperuricemia |
| Serious Effects |
["Hypersensitivity to penicillins or probenecid","History of cholestyramine or uricosuric agent hypersensitivity","Severe renal impairment (CrCl < 30 mL/min) for probenecid-containing products","Blood dyscrasias or uric acid calculi (probenecid)"]
| Precautions | ["Hypersensitivity reactions including anaphylaxis","Severe cutaneous adverse reactions (SCARs)","C. difficile-associated diarrhea","Renal impairment (dose adjustment for ampicillin)","Sodium overload with high doses","Allergic cross-reactivity with cephalosporins"] |
Loading safety data…
| FDA Pregnancy Category B: No evidence of risk in humans. Ampicillin crosses placenta; probenecid crosses placenta but no teratogenicity reported. First trimester: No known teratogenic effects. Second/third trimester: Use caution due to potential for altered fetal gut flora. Peripartum: Risk of kernicterus in neonates if maternal hyperbilirubinemia. |
| Fetal Monitoring | Maternal: Renal function, CBC with differential, liver enzymes, signs of hypersensitivity. Fetal: Ultrasound for growth if prolonged use; neonatal monitoring for jaundice, hypoglycemia, or infection if used near term. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment of fertility. Probenecid may affect uric acid excretion but no direct impact on reproductive function. |