Penicillin G
Benzylpenicillin
Also known as: Bicillin C-R · Masti-Clear · Permapen · Pfizerpen · Go-Dry · crystalline penicillin G · APPG · aqueous penicillin · procaine benzylpenicillin
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Audited v13 dosing evidence
Structured calculator evidenceSusceptible infections (extra-label): Penicillin G procaine
Verified clinician required
- q12-24h
NA
Governing clinical context (4)
- NOTE: Label dosages of penicillin have been unchanged for decades and may result in marked underdosing based on current understanding of antibiotic therapy. Although consideration of the label recommendations is required, present-day recommended dosing regimens should be used.
- ■ Because penicillins usually have minimal toxicity associated with their use, monitoring for efficacy is usually all that is required unless toxic signs develop. Serum concentrations and therapeutic drug monitoring are not routinely done with these agents.
- Penicillin G procaine should be stored at 2°C to 8°C (36°F-46°F); avoid freezing. Penicillin G benzathine should be stored at 2°C to 8°C (36°F-46°F).
- Penicillin G sodium and potassium powder for injection can be stored at room temperature (15°C-30°C [59°F-86°F]). After reconstituting, the injectable solution is stable for 7 days when kept refrigerated (2°C-8°C [36°F-46°F]) and for 24 hours at room temperature.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Penicillin G (benzylpenicillin) is a narrow-spectrum, natural beta-lactam antibiotic derived from Penicillium chrysogenum. It is highly effective against most Gram-positive aerobes (e.g., Streptococcus spp., non-penicillinase-producing Staphylococcus), some Gram-negative bacteria (e.g., Pasteurella), and many anaerobes (e.g., Clostridium spp.).
Clinical Pearl: The salt form of Penicillin G dictates its route of administration and pharmacokinetic profile:
- Aqueous salts (Sodium or Potassium): Formulated for IV or IM use. They provide rapid, high peak serum concentrations but have a very short half-life, requiring frequent dosing (e.g., q4-6h).
- Repository salts (Procaine and Benzathine): Formulated as suspensions for IM or SC use ONLY (never IV). Procaine provides a depot effect lasting 12-24 hours, while Benzathine provides very low, prolonged concentrations lasting several days.
Penicillin G is susceptible to degradation by beta-lactamase (penicillinase) enzymes produced by many Staphylococci and Gram-negative enteric bacteria.
Mechanism of action
Penicillin G is a time-dependent bactericidal antibiotic.
- It covalently binds to Penicillin-Binding Proteins (PBPs) located on the inner membrane of the bacterial cell wall.
- This binding → inhibits the transpeptidation enzyme responsible for cross-linking peptidoglycan strands.
- Failure of cell wall synthesis → activation of autolytic enzymes within the cell wall → osmotic lysis and bacterial death.
Because it targets cell wall synthesis, it is most effective against actively dividing bacteria.
Safety & warnings
Contraindications
- Known hypersensitivity to penicillins or cephalosporins
- Intravenous administration of Procaine or Benzathine suspension formulations
- Oral administration in horses and hindgut fermenters (rabbits, guinea pigs) due to risk of fatal dysbiosis (unless specifically indicated, e.g., calves with clostridial enteritis)
Adverse effects
- Hypersensitivity reactions (anaphylaxis, urticaria, rash)
- Gastrointestinal upset (anorexia, vomiting, diarrhea) with oral use
- Procaine toxicity (CNS excitement, seizures) in small birds and horses if inadvertently given IV
- Pain or tissue reaction at IM injection sites
Precautions
Use cautiously in small birds as procaine penicillin may cause procaine toxicity. Do not use oral penicillin therapy in horses for systemic infections (e.g., botulism). Ensure repository forms (procaine/benzathine) are never administered intravenously. Monitor for hypersensitivity reactions. High doses of Penicillin G Potassium given rapidly IV can cause hyperkalemia and cardiac arrhythmias.
Drug interactions
May antagonize the bactericidal activity of penicillins, which require actively dividing cells to be effective.
In vivo synergy against certain bacteria; however, physically incompatible if mixed in the same syringe or IV line (inactivation of the aminoglycoside).
Competitively inhibits renal tubular secretion of penicillins, significantly prolonging their half-life and increasing serum concentrations.
Monitoring
- Clinical efficacy (resolution of infection signs)
- Signs of toxicity or hypersensitivity (anaphylaxis, rash)
- Electrolytes (if using high doses of Na or K salts IV)
Pharmacokinetics
Half-life
Absorption
Oral absorption is generally poor and variable due to degradation by gastric acid. Aqueous salts (Na/K) are rapidly absorbed after IM/SC injection. Procaine and benzathine salts are slowly absorbed from IM injection sites, providing prolonged but lower serum concentrations.
Distribution
Widely distributed to most tissues (lungs, kidneys, muscle, bone). Poor penetration into the central nervous system (CNS), eye, and prostate unless severe inflammation is present. Crosses the placenta.
Metabolism
Minimal hepatic metabolism.
Elimination
Rapidly excreted primarily unchanged in the urine via active renal tubular secretion and glomerular filtration.
Overdose
Because penicillins usually have minimal toxicity associated with their use, monitoring for efficacy is usually all that is required unless toxic signs develop.
Clinical Pearl: Massive overdoses, particularly of aqueous salts given rapidly IV, can lead to neuromuscular hypersensitivity, seizures, or electrolyte imbalances (hyperkalemia with potassium salt, hypernatremia with sodium salt). Treatment is supportive.
Available products
Formulations
- Powder for injection (Potassium or Sodium salts)
- Suspension for injection (Procaine or Benzathine salts)
- Oral tablets and powder for solution
- Intramammary infusion syringes
Veterinary
- Penicillin G Procaine Injection 300,000 Units/mL
- Penicillin G Procaine Mastitis Syringes 100,000 Units/mL (Go-Dry, Masti-Clear)
- Penicillin G Benzathine 150,000 Units/mL with Penicillin G Procaine 150,000 Units/mL Injection
Human-labeled
- Penicillin G (Aqueous) Sodium Powder for Injection: 5,000,000 Units & 20,000,000 Units
- Penicillin G (Aqueous) Potassium Injection: 1,000,000 Units, 2,000,000 Units & 3,000,000 Units
- Penicillin G Procaine Injection: 600,000 Units/vial & 1,200,000 Units/vial
- Penicillin G Benzathine Injection: 600,000, 1,200,000, & 2,400,000 Units/dose
- Penicillin G Benzathine/Penicillin G Procaine IM Injection (Bicillin C-R)
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Penicillin G sodium and potassium powders should be protected from moisture. Oral powder for solution: store at room temperature before mixing; after reconstituting, refrigerate (2-8°C) and discard after 14 days. Injectable Na/K solutions: stable for 7 days refrigerated (2-8°C) and 24 hours at room temperature. Procaine and Benzathine suspensions should be stored at 2-8°C; avoid freezing.
Client information
- Administration: Give oral penicillins on an empty stomach (1 hour before or 2 hours after a meal) to maximize absorption. If your pet experiences stomach upset (vomiting, loss of appetite), you may give it with a small amount of food.
- Compliance: It is critical to complete the entire prescription exactly as directed, even if your pet seems completely better. Stopping early can lead to resistant infections.
- Allergic Reactions: Watch for signs of an allergic reaction, such as facial swelling, hives, rash, or difficulty breathing. Contact your veterinarian immediately if these occur.
- Injection Sites: If your pet is receiving injectable forms, the injection site may become sore or swollen.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.