PRINCIPEN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PRINCIPEN (PRINCIPEN).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PRINCIPEN (PRINCIPEN).

Breastfeeding	Ampicillin is excreted into human breast milk in low concentrations (M/P ratio approximately 0.2-0.3). The American Academy of Pediatrics considers ampicillin compatible with breastfeeding. Potential for alteration of infant gut flora and interference with culture results if febrile. Use caution in infants with known penicillin allergy.
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.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to ampicillin or any other beta-lactam antibiotic (e.g., penicillins, cephalosporins)","Infectious mononucleosis (high incidence of maculopapular rash)"]

Clinical Precautions

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."]

Clinical Tips & Counseling

Drug interactions

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PRINCIPEN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PRINCIPEN (PRINCIPEN).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PRINCIPEN (PRINCIPEN).

Breastfeeding	Ampicillin is excreted into human breast milk in low concentrations (M/P ratio approximately 0.2-0.3). The American Academy of Pediatrics considers ampicillin compatible with breastfeeding. Potential for alteration of infant gut flora and interference with culture results if febrile. Use caution in infants with known penicillin allergy.
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.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to ampicillin or any other beta-lactam antibiotic (e.g., penicillins, cephalosporins)","Infectious mononucleosis (high incidence of maculopapular rash)"]