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Drug Monograph

Penicillin-G

Penicillin G

Natural penicillin (β-lactam)

Narrow-spectrumStreptococciSyphilisMeningitisEndocarditis

Indication

Streptococcal infections (confirmed) • Neurosyphilis / syphilis • Meningococcal infection • Clostridial infections • Severe streptococcal SSTI

At a glance

INDICATIONS (CORE USE)

Streptococcal infections (confirmed) • Neurosyphilis / syphilis • Meningococcal infection • Clostridial infections • Severe streptococcal SSTI

ADULT DOSE (STANDARD)

Severe: 2–4 million units IV q4–6h High-dose: up to 24 million units/day (e.g., meningitis/endocarditis)

MAX DOSE

Max: 24 million units/day IV (reduce/extend interval in renal impairment)

Route

IV, IM (formulation-dependent)

PEDIATRIC DOSE

100,000–300,000 units/kg/day divided (per pediatric reference)

Do not miss

Must-not-miss safety points

Major warning

- Hypersensitivity (anaphylaxis risk) - Neurotoxicity (high dose or renal failure) - Electrolyte load (Na⁺ or K⁺ salts → hypernatremia or hyperkalemia) - Jarisch–Herxheimer reaction - Wrong formulation: NEVER use benzathine IM for systemic infection when aqueous IV therapy is required; NEVER benzathine IV - Resistance risk in prolonged therapy

Indications

USE IF: Streptococcal infections when confirmed or strongly suspected and susceptible; neurosyphilis and syphilis (stage-appropriate regimens); meningococcal infection; clostridial infections when penicillin G is guideline-directed. AVOID IF: Penicillin anaphylaxis; wrong formulation (benzathine vs aqueous IV) for the clinical scenario; severe renal failure without dose adjustment and close monitoring. Natural penicillin with narrow reliable spectrum—match salt formulation (sodium vs potassium) to electrolyte risk and route to indication.

  • Primary: Syphilis (all stages); streptococcal infections; meningococcal infections; severe SSTI (streptococcal)
  • Secondary: Endocarditis (streptococci); meningitis (susceptible organisms); actinomycosis; clostridial infections
  • Other: Leptospirosis; rat-bite fever

Dosing

ADULT DOSE

Standard: 2–4 million units IV q4–6h. Adult PO: not available. Adult IV: dose varies by indication/severity — severe infection up to 24 million units/day in divided doses per guideline.

PEDIATRIC DOSE

100,000–300,000 units/kg/day divided (per pediatric reference).

MAX DOSE

Max: 24 million units/day IV (reduce/extend interval in renal impairment)

Practical Note

- Renal: severe impairment — reduce dose or extend interval; monitor especially with potassium salt - Hepatic: no routine adjustment - Choose correct formulation: aqueous IV for systemic infection, benzathine IM only for syphilis

Warnings

Clinical warnings

  • Anaphylaxis
  • Hyperkalemia (K⁺ formulation)
  • Seizures (high dose / renal failure)
  • Jarisch–Herxheimer reaction
  • Hemolytic anemia
  • Interstitial nephritis
  • SJS/TEN (rare)

Adverse effects

  • Hypersensitivity including anaphylaxis
  • Jarisch–Herxheimer reaction (syphilis treatment)
  • Hyperkalemia with potassium salt formulation
  • Neurotoxicity / seizures with very high doses or renal failure
  • Hemolytic anemia
  • Acute interstitial nephritis
  • SJS/TEN (rare)
  • IV site phlebitis or irritation

Contraindications / caution

  • Do not use: Penicillin anaphylaxis when β-lactam therapy is contraindicated
  • Use caution: Renal impairment
  • Use caution: heart failure (Na⁺/K⁺ load depending on formulation)
  • Use caution: Hyperkalemia risk
  • Use caution: CNS disease (seizures)
  • Use caution: Elderly

Drug interactions

  • Probenecid → ↑ penicillin levels (reduced renal clearance)
  • Methotrexate → ↑ toxicity
  • ACEI / ARB / K-sparing diuretics → ↑ hyperkalemia risk
  • Warfarin → ↑ INR

Special populations

Pediatrics

100,000–300,000 units/kg/day divided (per pediatric reference)

Pregnancy

Safe when clinically indicated; first-line therapy for syphilis in pregnancy per standard guidelines. Breastfeeding generally compatible — routine infant monitoring. Pregnancy: Safe when indicated; first-line for syphilis per standard guidance.

Lactation

Compatible with breastfeeding.

Renal impairment

Dose adjust; monitor K⁺ with potassium formulations and high infusion rates.

Hepatic impairment

No routine dose adjustment.

Elderly

Adjust for renal function; higher risk of hyperkalemia and neurotoxicity with accumulation.

Administration

Route: IV (aqueous preparations); IM (benzathine or procaine formulations per indication). IV infusion typically over ~30 minutes per institutional policy. NEVER give benzathine penicillin IV (fatal cardiopulmonary events) — IM only.

Monitoring

  • Labs: renal function; electrolytes (K⁺); CBC with prolonged therapy
  • Clinical: neurologic status; anaphylaxis; Jarisch–Herxheimer reaction during syphilis therapy
  • No clinical improvement at 48–72h → reassess diagnosis, resistance, source control, and drug interactions (DO NOT continue blindly)
  • If targets not met after reassessment of dose, organ function, and interactions → escalate per protocol (DO NOT continue blindly)

Overdose / toxicity

Clinical Picture

Toxic threshold not sharply defined; higher risk in renal failure. Features: neurotoxicity (seizures) ± electrolyte abnormalities (Na⁺/K⁺).

Immediate Actions

- Stop drug - Supportive care

Antidote

No specific antidote — supportive care

Decontamination

Not applicable to typical IV use — contact poison center for massive dosing error.

Escalation

Benzodiazepines for seizures; treat hyperkalemia; monitor labs; hemodialysis may enhance clearance per nephrology.

Clinical pearls

Common mistakes, resistance logic, and bedside traps

At a glance

FIRST LINE: Narrow-spectrum IV β-lactam for streptococci, meningococcus, syphilis. DOSE — Severe: 2–4 million units IV q4–6h; high-dose: up to 24 million units/day (e.g., meningitis/endocarditis). MAX — 24 million units/day IV (reduce/extend interval in renal impairment). AVOID — Wrong formulation for indication; renal failure without adjustment. ANTIDOTE — None.

Do not miss

- Formulation errors cause harm — always verify IV vs IM product - Potassium load → hyperkalemia risk - MUST distinguish benzathine vs aqueous - Seizures in renal failure - Jarisch–Herxheimer reaction (syphilis) - No oral formulation

Clinical pearls

Always confirm formulation (benzathine vs aqueous vs procaine). First-line for syphilis in pregnancy (no alternatives for fetal protection). Requires frequent dosing (q4–6h). Monitor potassium in high-dose therapy. Under-dosing risks treatment failure in endocarditis/meningitis. Jarisch–Herxheimer reaction is expected during syphilis therapy, not allergy.

Formulation & safety box

  • Aqueous IV for serious systemic infection — not interchangeable with benzathine IM schedules
  • NEVER administer benzathine penicillin IV (fatal cardiopulmonary events) — IM only
  • Electrolyte load varies: sodium vs potassium salts → monitor accordingly
  • Potassium salt → monitor K⁺ in ICU and renal impairment
  • Procaine penicillin IM — verify indication and allergy history
  • Document penicillin allergy before first dose

Pharmacokinetics

- Bioavailability: IV only (for aqueous systemic therapy) - Distribution: wide; CSF penetration when meninges inflamed - Protein binding: moderate - Elimination: renal - Short half-life → frequent dosing (q4–6h required)

Mechanism of action

Binds penicillin-binding proteins (PBPs), inhibiting bacterial cell wall synthesis — bactericidal in susceptible organisms.

Common brand names

Saudi Arabia

Penicillin G sodium/potassium (generic), Benzathine penicillin G

Global

Pfizerpen, Generic penicillin G, Penicillin G sodium (generic), Penicillin G potassium (generic)

Common trade names are curated examples only — formulations and availability vary. Verify the exact product name with your local pharmacy and national regulator before prescribing or dispensing.

Country practice notes

  • First-line for syphilis across Gulf guidelines
  • Common use: benzathine IM for rheumatic fever prophylaxis (long-acting) — monthly dosing
  • IV Penicillin G used in tertiary centers for meningitis/endocarditis
  • Common error: wrong formulation selection
  • Monitor potassium load in ICU patients

References

Saudi Arabia

  • SFDA (Saudi Food & Drug Authority)
  • Saudi National Formulary / MOH (where available)

International

  • WHO Model List of Essential Medicines (verify current edition)
  • US FDA or EU EMA product information (when national SmPC is unavailable)
  • SFDA
  • Saudi MOH
  • FDA
  • BNF
  • WHO
  • StatPearls
  • SFDA
  • Saudi MOH
  • FDA
  • BNF
  • WHO
  • StatPearls