Section 15 · Monograph
Penicillin G
Reviewed Nov 2026FDA label
Pfizerpen (IV potassium)Penicillin (beta-lactam)
- Forms
- IV: potassium 5, 20 million units | premixed bags
- Dose
- Neurosyphilis: 18-24 million units/day IV (3-4 million units every 4h or continuous) x10-14 days | Meningitis (Listeria, susceptible pneumococcus): 24 million units/day divided every 4h
- MOA
- Binds penicillin-binding proteins, inhibits cell-wall synthesis
Indications
- Neurosyphilis and other syphilisFDA-labeled
- Bacterial meningitis due to susceptible organisms (pneumococcus, Listeria, meningococcus)FDA-labeled
- Other serious infections caused by penicillin-susceptible organismsFDA-labeled
Mechanism of Action
- Beta-lactam that binds penicillin-binding proteins and inhibits peptidoglycan cross-linking; achieves CSF concentrations adequate for treponemal killing at high IV doses
Full Dosing
Adult / usual
- Neurosyphilis: 18-24 million units/day IV, given as 3-4 million units every 4 hours or by continuous infusion, for 10-14 days; some experts add benzathine penicillin 2.4 million units IM weekly for up to 3 weeks afterward
- Bacterial meningitis: 24 million units/day divided every 4 hours, tailored to susceptibility
Renal
- Adjust for renal impairment; patients with penicillin allergy and neurosyphilis should be desensitized
Contraindications
- Hypersensitivity to penicillins
- Not for IV use: benzathine penicillin (Bicillin L-A) must never be given intravenously and does not achieve treponemicidal CSF levels
Drug Interactions
- Probenecid raises levels
- Methotrexate toxicity may increase
- Bacteriostatic antibiotics may antagonize bactericidal effect
Adverse Effects
- Hypersensitivity including anaphylaxis
- Jarisch-Herxheimer reaction in the first 24 hours of syphilis treatment
- Seizures with very high doses, especially in renal failure
- Hyperkalemia with potassium salt (about 1.7mEq K per million units)
- Hemolytic anemia, neutropenia, interstitial nephritis with prolonged use
Monitoring Parameters
- Renal function and potassium
- Clinical and CSF response (repeat CSF at about 6 months for neurosyphilis)
- Serologic follow-up (RPR/VDRL)
Pregnancy & Lactation
- Penicillin is the only recommended treatment for syphilis in pregnancy; desensitize if allergic
- Compatible with breastfeeding