PENICILLIN G SODIUM

Clinical safety rating: safe

Probenecid may decrease excretion Serious and occasionally fatal hypersensitivity reactions have been reported.

How it works

Penicillin G inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidase activity, and activating autolytic enzymes.

What the body does with it

Metabolism	Primarily eliminated unchanged by renal tubular secretion; minor hepatic metabolism to penicilloic acid (inactive).
Excretion	Primarily renal (60-90% unchanged) via glomerular filtration and tubular secretion; minor biliary/fecal (<10%).
Half-life	30-60 minutes in normal renal function; prolonged to 7-10 hours in anuria.
Protein binding	60-80% bound to serum albumin.
Volume of Distribution	0.3-0.5 L/kg; approximates extracellular fluid volume, limited CNS penetration unless inflamed meninges.
Bioavailability	IM: 60-80%; oral: <30% (not clinically used).
Onset of Action	IM: 15-30 minutes; IV: immediate; oral: not applicable (acid-labile).
Duration of Action	IM: 4-6 hours; IV: 2-4 hours depending on dose and renal function.

Classification & Brands

Dosing & administration

2-4 million units intravenously every 4 hours for moderate to severe infections; up to 24 million units/day for severe infections (e.g., meningitis, endocarditis).

Dosage form	INJECTABLE
Renal impairment	CrCl 10-50 mL/min: administer every 6-8 hours; CrCl <10 mL/min: administer every 8-12 hours. For high-dose therapy (e.g., >10 million units/day), reduce dose by 50% when CrCl <10 mL/min.
Liver impairment	No significant hepatic metabolism; dose adjustment not required for Child-Pugh Class A, B, or C. Monitor for electrolyte disturbances with high doses.
Pediatric use	Neonates: 50,000-100,000 units/kg/day divided every 12 hours (postnatal age ≤7 days, weight ≤2 kg) to every 8 hours (older neonates). Infants/children: 100,000-250,000 units/kg/day divided every 4-6 hours; maximum 24 million units/day. For meningitis: 300,000-400,000 units/kg/day divided every 4-6 hours.
Geriatric use	Initiate at lowest recommended adult dose (2 million units IV every 4 hours) with careful renal function monitoring. Adjust dose based on CrCl as per renal adjustment. Monitor for neurotoxicity (seizures) at high doses or with decreased renal function.

Use during pregnancy

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

Clinical note

Probenecid may decrease excretion Serious and occasionally fatal hypersensitivity reactions have been reported.

FDA category	Human
Breastfeeding	Penicillin G is excreted in breast milk in low concentrations (M/P ratio approximately 0.1-0.2). It is generally considered compatible with breastfeeding, but potential for neonatal sensitization or diarrhea exists. Use with caution.
Teratogenic Risk	Penicillin G is classified as FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, and no adequate controlled studies in pregnant women exist. Across all trimesters, no known teratogenic effects have been reported; risk is considered low.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning.

Side Effect Profile

Common Effects	Diarrhea
Serious Effects

Absolute Contraindications

["Hypersensitivity to penicillin or any component of the formulation.","Do not use in patients with immediate-type hypersensitivity reactions (urticaria, anaphylaxis) to cephalosporins."]

Clinical Precautions

Precautions

["Severe hypersensitivity reactions (anaphylaxis) can occur; cross-sensitivity with cephalosporins.","Use with caution in renal impairment (dose adjustment required).","Prolonged use may lead to superinfection.","Neurologic adverse effects (seizures) with high doses, especially in renal failure.","Jarisch-Herxheimer reaction when treating syphilis."]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

PENICILLIN G SODIUM

Clinical safety rating: safe

Probenecid may decrease excretion Serious and occasionally fatal hypersensitivity reactions have been reported.

How it works

Penicillin G inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidase activity, and activating autolytic enzymes.

What the body does with it

Metabolism	Primarily eliminated unchanged by renal tubular secretion; minor hepatic metabolism to penicilloic acid (inactive).
Excretion	Primarily renal (60-90% unchanged) via glomerular filtration and tubular secretion; minor biliary/fecal (<10%).
Half-life	30-60 minutes in normal renal function; prolonged to 7-10 hours in anuria.
Protein binding	60-80% bound to serum albumin.
Volume of Distribution	0.3-0.5 L/kg; approximates extracellular fluid volume, limited CNS penetration unless inflamed meninges.
Bioavailability	IM: 60-80%; oral: <30% (not clinically used).
Onset of Action	IM: 15-30 minutes; IV: immediate; oral: not applicable (acid-labile).
Duration of Action	IM: 4-6 hours; IV: 2-4 hours depending on dose and renal function.

Classification & Brands

Dosing & administration

2-4 million units intravenously every 4 hours for moderate to severe infections; up to 24 million units/day for severe infections (e.g., meningitis, endocarditis).

Dosage form	INJECTABLE
Renal impairment	CrCl 10-50 mL/min: administer every 6-8 hours; CrCl <10 mL/min: administer every 8-12 hours. For high-dose therapy (e.g., >10 million units/day), reduce dose by 50% when CrCl <10 mL/min.
Liver impairment	No significant hepatic metabolism; dose adjustment not required for Child-Pugh Class A, B, or C. Monitor for electrolyte disturbances with high doses.
Pediatric use	Neonates: 50,000-100,000 units/kg/day divided every 12 hours (postnatal age ≤7 days, weight ≤2 kg) to every 8 hours (older neonates). Infants/children: 100,000-250,000 units/kg/day divided every 4-6 hours; maximum 24 million units/day. For meningitis: 300,000-400,000 units/kg/day divided every 4-6 hours.
Geriatric use	Initiate at lowest recommended adult dose (2 million units IV every 4 hours) with careful renal function monitoring. Adjust dose based on CrCl as per renal adjustment. Monitor for neurotoxicity (seizures) at high doses or with decreased renal function.

Use during pregnancy

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

Clinical note

Probenecid may decrease excretion Serious and occasionally fatal hypersensitivity reactions have been reported.

FDA category	Human
Breastfeeding	Penicillin G is excreted in breast milk in low concentrations (M/P ratio approximately 0.1-0.2). It is generally considered compatible with breastfeeding, but potential for neonatal sensitization or diarrhea exists. Use with caution.
Teratogenic Risk	Penicillin G is classified as FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, and no adequate controlled studies in pregnant women exist. Across all trimesters, no known teratogenic effects have been reported; risk is considered low.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning.

Side Effect Profile

Common Effects	Diarrhea
Serious Effects

Absolute Contraindications

["Hypersensitivity to penicillin or any component of the formulation.","Do not use in patients with immediate-type hypersensitivity reactions (urticaria, anaphylaxis) to cephalosporins."]