PRINCIPEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PRINCIPEN (PRINCIPEN).
Ampicillin, a beta-lactam antibiotic, inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs) and interfering with transpeptidation, leading to cell lysis.
| Metabolism | Ampicillin is partially metabolized by hepatic hydrolysis to penicilloic acid; approximately 90% of an oral dose is excreted unchanged in urine via tubular secretion and glomerular filtration. |
| Excretion | Primarily renal (90–100% unchanged) via tubular secretion and glomerular filtration. Minor biliary excretion (<1%). |
| Half-life | 0.5–1 hour; prolonged to 7–10 hours in renal impairment (creatinine clearance <10 mL/min). |
| Protein binding | 60–80% bound to albumin. |
| Volume of Distribution | 0.3–0.5 L/kg; indicates limited extravascular distribution. |
| Bioavailability | Oral: 30–50% (variable due to gastric acid lability); IM: 70–85%. |
| Onset of Action | IM: 15–30 min; IV: immediate; Oral: 30–60 min. |
| Duration of Action | 2–4 hours; extended with probenecid coadministration or renal impairment. |
| Molecular Weight | 349.4 |
250-500 mg orally every 6 hours or 500 mg intravenously every 6 hours for moderate infections; severe infections: 500 mg-1 g every 4-6 hours.
| Dosage form | CAPSULE |
| Renal impairment | CrCl >50 mL/min: no adjustment; CrCl 10-50 mL/min: 250-500 mg every 6-8 hours; CrCl <10 mL/min: 250-500 mg every 12 hours; hemodialysis: 250-500 mg every 12 hours, give dose after dialysis. |
| Liver impairment | No adjustment required for mild to moderate hepatic impairment; caution in severe hepatic disease due to potential for accumulation, but specific Child-Pugh adjustments not established. |
| Pediatric use | Neonates 0-7 days: 50-100 mg/kg/day IV divided every 12 hours; Infants 1-4 weeks: 75-150 mg/kg/day IV divided every 8 hours; Children >1 month: 25-50 mg/kg/day orally divided every 6 hours, or 100-200 mg/kg/day IV divided every 4-6 hours; maximum 12 g/day. |
| Geriatric use | No specific dose adjustment required; consider age-related renal impairment and adjust based on renal function; monitor for electrolyte disturbances and neurotoxicity. |
| 1st trimester | Ampicillin is generally considered safe in the first trimester, but use only if clearly needed. Animal studies have not shown fetal harm, but adequate human studies are lacking. |
| 2nd trimester | Safe in the second trimester when indicated. No known teratogenic effects. |
| 3rd trimester | Safe in the third trimester. Considered compatible with pregnancy. |
Clinical note
Comprehensive clinical and safety monograph for PRINCIPEN (PRINCIPEN).
| Placental transfer | Ampicillin crosses the placenta readily, achieving therapeutic concentrations in fetal tissues and amniotic fluid. Approximately 20-30% of maternal serum levels are reached in fetal circulation. |
| Breastfeeding | Ampicillin is excreted into breast milk in small amounts. It is generally considered compatible with breastfeeding, but may cause diarrhea or allergic sensitization in the infant. Monitor for potential adverse effects. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to ampicillin, penicillins, or any component of the formulationInfections caused by penicillinase-producing organisms
| Precautions | Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported; discontinue therapy if reaction occurs., Clostridium difficile-associated diarrhea (CDAD) may occur, ranging in severity from mild diarrhea to fatal colitis., Prolonged use may result in overgrowth of nonsusceptible organisms (e.g., Candida)., Use with caution in patients with renal impairment; dose adjustment may be necessary., Use with caution in patients with history of allergies (e.g., asthma, hay fever, urticaria) due to increased risk of hypersensitivity. |
| Food/Dietary | Food decreases absorption; take on an empty stomach. Avoid acidic beverages (e.g., citrus juices) which may degrade the drug. No specific dietary restrictions. |
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| Lactation Rating | L1 (Safe) |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies have not revealed evidence of fetal harm. No adequate, well-controlled studies in pregnant women. However, penicillin-class antibiotics are generally considered low risk. First trimester: No documented teratogenicity. Second and third trimesters: No documented fetal adverse effects. Use only if clearly needed. |
| Fetal Monitoring | No specific routine monitoring required. Observe mother for hypersensitivity reactions (rash, anaphylaxis). Monitor for signs of superinfection (e.g., diarrhea, candidiasis). In prolonged use, monitor renal and hematological parameters. |
| Fertility Effects | No evidence of impaired fertility in animal studies. No known adverse effects on human fertility. |
| Clinical Pearls | Principen (ampicillin) is a penicillinase-sensitive penicillin. For empiric coverage, consider local resistance patterns; many E. coli and H. influenzae isolates are resistant. Administer on an empty stomach (1 hour before or 2 hours after meals) for optimal absorption. Monitor for hypersensitivity reactions, especially in patients with penicillin allergy. Use with caution in mononucleosis due to high rash incidence. |
| Patient Advice | Take on an empty stomach, at least 1 hour before or 2 hours after meals. · Complete the full course even if you feel better. · Notify your doctor if you develop a rash, diarrhea, or difficulty breathing. · Do not take if you are allergic to penicillins or cephalosporins. · Store capsules and oral suspension at room temperature; discard unused suspension after 14 days. |