Penicillin G

Antibiotic Beta-lactam antibiotic (natural penicillin)

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog IM or SC 20,000-40,000 IU/kg (or 10-20 mg/kg) of aqueous penicillin G q12h to q24h Duration: 5-7 days or as directed by clinical response
Notes: For severe infections, use IV route. Procaine penicillin G: 20,000-40,000 IU/kg IM q24h. Benzathine penicillin G: 40,000 IU/kg IM q48-72h.
Cat IM or SC 20,000-40,000 IU/kg (or 10-20 mg/kg) of aqueous penicillin G q12h to q24h Duration: 5-7 days or as directed by clinical response
Notes: Procaine penicillin G: 20,000-40,000 IU/kg IM q24h. Benzathine penicillin G: 40,000 IU/kg IM q48-72h.
Horse IV or IM 22,000-44,000 IU/kg (or 10-20 mg/kg) of aqueous penicillin G q6h to q12h Duration: 5-7 days or as directed by clinical response
Notes: For severe infections, use IV route. Procaine penicillin G: 20,000-40,000 IU/kg IM q12-24h. Benzathine penicillin G: 40,000 IU/kg IM q48-72h.
Cattle IM or SC 20,000-40,000 IU/kg (or 10-20 mg/kg) of aqueous penicillin G q12h to q24h Duration: 5-7 days or as directed by clinical response
Notes: Procaine penicillin G: 20,000-40,000 IU/kg IM q24h. Benzathine penicillin G: 40,000 IU/kg IM q48-72h. Observe withdrawal times.
Small Ruminants (sheep, goats) IM or SC 20,000-40,000 IU/kg (or 10-20 mg/kg) of aqueous penicillin G q12h to q24h Duration: 5-7 days or as directed by clinical response
Notes: Procaine penicillin G: 20,000-40,000 IU/kg IM q24h. Benzathine penicillin G: 40,000 IU/kg IM q48-72h. Observe withdrawal times.
Rabbit IM or SC 40,000 IU/kg of procaine penicillin G q24h Duration: 5-7 days
Notes: Use with caution in rabbits due to risk of enterotoxemia; ensure adequate gut motility.
Bird/Poultry IM 20,000-40,000 IU/kg of aqueous penicillin G q12h Duration: 5-7 days
Notes: For poultry, use only if approved and observe withdrawal times for eggs and meat.
Exotic/Other IM or SC Dose varies by species; consult exotic animal formulary Varies Duration: Varies
Notes: For reptiles, lower doses may be needed; for small mammals, adjust based on metabolic rate.

Clinical Indications & Species Uses

General Indications
  • Treatment of infections caused by penicillin-susceptible organisms, including gram-positive bacteria, some anaerobes, and spirochetes
  • Prophylaxis for surgical procedures in some species
Dog (Canine)
  • Treatment of infections caused by susceptible gram-positive bacteria, including streptococcal infections, clostridial infections, and actinomycosis
  • Leptospirosis
  • Anaerobic infections (e.g., tetanus, gas gangrene)
  • Abscesses and wound infections
Cat (Feline)
  • Treatment of streptococcal infections
  • Leptospirosis
  • Anaerobic infections (e.g., tetanus)
  • Abscesses and wound infections
Horse (Equine)
  • Treatment of Streptococcus equi infections (strangles)
  • Clostridial infections (e.g., tetanus, gas gangrene)
  • Leptospirosis
  • Anaerobic infections
  • Pneumonia caused by susceptible organisms
Cattle (Bovine)
  • Treatment of bovine respiratory disease complex (e.g., Pasteurella multocida, Mannheimia haemolytica - though not first-line)
  • Actinomycosis (lumpy jaw)
  • Leptospirosis
  • Clostridial infections (e.g., blackleg, malignant edema)
  • Foot rot (interdigital necrobacillosis)
Small Ruminants (Sheep / Goat)
  • Treatment of clostridial infections (e.g., tetanus, enterotoxemia)
  • Leptospirosis
  • Abscesses and wound infections
  • Pneumonia caused by susceptible organisms
Rabbit & Small Mammals
  • Treatment of abscesses and wound infections caused by susceptible organisms
  • Tularemia (in combination with other antibiotics)
Avian & Poultry
  • Treatment of erysipelas (Erysipelothrix rhusiopathiae)
  • Clostridial infections
  • Streptococcal infections
Exotic & Other Species
  • Treatment of susceptible bacterial infections in reptiles, small mammals, and other exotic species (dose based on species-specific guidelines)

Pharmacology & Mechanism of Action

Drug Class: Antibiotic | Pharmacological Group: Beta-lactam antibiotic (natural penicillin)

Mechanism of Action: Penicillin G exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) located on the bacterial cell wall, thereby interfering with the transpeptidation reaction that cross-links peptidoglycan chains. This leads to a weakened cell wall, osmotic instability, and ultimately cell lysis. The drug is most effective against actively growing and dividing bacteria.

Pharmacodynamics: Penicillin G is a time-dependent antibiotic, meaning its efficacy is best correlated with the duration of time that the drug concentration remains above the minimum inhibitory concentration (MIC) for the pathogen. It is primarily active against gram-positive bacteria, including many Streptococcus spp., Staphylococcus spp. (non-penicillinase producing), Clostridium spp., Bacillus anthracis, and some anaerobes. It also has activity against some gram-negative cocci (e.g., Neisseria spp.) and spirochetes (e.g., Leptospira spp.). It is generally ineffective against gram-negative rods due to poor penetration of the outer membrane and production of beta-lactamases.

⚑ Pharmacokinetics Summary

Absorption: Penicillin G is poorly absorbed after oral administration due to degradation by gastric acid. Therefore, oral forms are not commonly used in veterinary medicine. Parenteral administration (IM, SC, IV) provides rapid and complete absorption. The procaine and benzathine salts are designed for slow absorption from the injection site, providing prolonged blood levels.
Distribution: Penicillin G is widely distributed in body tissues and fluids, but penetration into the central nervous system, eyes, and prostate is poor unless inflammation is present. It crosses the placenta and is distributed into milk. It is bound to plasma proteins to a moderate degree (approximately 60% in most species).
Metabolism: Penicillin G undergoes minimal hepatic metabolism. The majority of the drug is excreted unchanged by the kidneys via tubular secretion and glomerular filtration.
Excretion: Penicillin G is rapidly eliminated by the kidneys, primarily through active tubular secretion. In animals with renal impairment, the elimination half-life is prolonged, requiring dose adjustment. Biliary excretion also occurs but is a minor pathway.
Half-Life: The half-life is short, typically 30-60 minutes in dogs and cats, 1-2 hours in horses, and 30-60 minutes in cattle. The procaine and benzathine salts provide prolonged absorption and thus effective half-lives of 12-24 hours for procaine penicillin G and 2-4 days for benzathine penicillin G.
Bioavailability: Oral bioavailability is very low (<30%) due to acid instability. Intramuscular administration of aqueous penicillin G provides nearly 100% bioavailability. Procaine and benzathine salts have slower absorption, resulting in lower peak concentrations but prolonged duration.
Protein Binding: Approximately 60% bound to plasma proteins in most species, but can vary from 30% in horses to 80% in cattle.

Available Formulations & Strengths

Injectable Solution (aqueous) 1,000,000 IU/vial, 5,000,000 IU/vial, 10,000,000 IU/vial (IV, IM, SC)
Injectable Suspension (procaine penicillin G) 300,000 IU/mL (IM, SC)
Injectable Suspension (benzathine penicillin G) 300,000 IU/mL (IM, SC)
Oral Tablet (penicillin V potassium) 250 mg, 500 mg (PO)

Contraindications & Clinical Warnings

Contraindications:
  • Known hypersensitivity to penicillin or other beta-lactam antibiotics
  • Use in animals with a history of allergic reactions to penicillins
  • Oral administration of penicillin G (not acid-stable) is contraindicated due to poor absorption
  • Use in rabbits, guinea pigs, hamsters, and other small herbivores is contraindicated due to risk of fatal enterotoxemia (Clostridium difficile overgrowth) unless specifically indicated and with careful monitoring
Warnings & Clinical Precautions:
  • Use with caution in animals with renal impairment; dose adjustment may be necessary
  • Use with caution in animals with a history of gastrointestinal disease, as it may alter gut flora
  • In horses, procaine penicillin G can cause excitement and central nervous system signs if accidentally injected intravenously
  • In cattle and other ruminants, intramuscular injection may cause tissue irritation; use subcutaneous route when possible
  • Prolonged use may result in overgrowth of non-susceptible organisms, including fungi
  • In food animals, observe withdrawal times to avoid violative residues
  • Penicillin G is not effective against beta-lactamase-producing bacteria; consider alternative therapy if no response

Adverse Effects & Reactions

Common:

  • Pain and swelling at injection site
  • Gastrointestinal upset (nausea, vomiting, diarrhea) with oral administration
  • Allergic reactions (urticaria, rash, fever)

Serious / Severe:

  • Anaphylaxis (rare but potentially fatal)
  • Severe allergic reactions (angioedema, bronchospasm)
  • Neurotoxicity (seizures) with high doses or in renal impairment
  • Clostridial enterotoxemia in rabbits and other small herbivores

Rare:

  • Hemolytic anemia
  • Neutropenia
  • Interstitial nephritis
  • Hepatotoxicity

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Probenecid Probenecid decreases renal tubular secretion of penicillin, increasing and prolonging penicillin blood levels. Moderate
Aminoglycosides (e.g., gentamicin, amikacin) May have synergistic bactericidal effect against some organisms, but they are physically incompatible in the same syringe; administer separately. Moderate
Tetracyclines and chloramphenicol Bacteriostatic antibiotics may antagonize the bactericidal effect of penicillin; avoid concurrent use. Moderate
Nonsteroidal anti-inflammatory drugs (NSAIDs) May increase risk of gastrointestinal ulceration and bleeding; use with caution. Mild
Methotrexate Penicillin may reduce renal excretion of methotrexate, increasing its toxicity. High

Overdose & Toxicity Management

Signs of Toxicity:

  • Neurological signs including seizures, muscle twitching, and coma (especially with high IV doses)
  • Gastrointestinal signs (vomiting, diarrhea) with oral overdose
  • Allergic reactions
  • Electrolyte imbalances (with potassium penicillin G)

Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. Discontinue the drug, provide supportive care (IV fluids, anticonvulsants for seizures, antihistamines or epinephrine for allergic reactions). In severe cases, hemodialysis may be considered to remove the drug.

Food Animal Withdrawal Times

πŸ₯© Meat: 5 daysπŸ₯› Milk: 3 daysπŸ₯š Eggs: 0 days

Withdrawal times vary by formulation and country. For procaine penicillin G in cattle: meat 5 days, milk 3 days. For benzathine penicillin G: meat 30 days, milk 6 days. In poultry, withdrawal times for eggs are not established; use only if permitted and follow local regulations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (20-25Β°C) for dry powder; after reconstitution, store in refrigerator (2-8Β°C) and use within 7 days unless otherwise specified.

Light Sensitivity: Light-sensitive β€” protect from direct exposure.

Handling & Special Conditions: Protect from light and moisture. Do not freeze. Keep out of reach of children.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in veterinary medicine in various formulations (e.g., injectable solutions, suspensions).

Extra-Label (Off-Label) Use: In the US, extra-label use of penicillin G in food animals is permitted under AMDUCA, but requires a valid veterinary-client-patient relationship and must not result in violative residues. Extended withdrawal times may be necessary.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Penicillin G is a narrow-spectrum antibiotic that remains useful for treating infections caused by susceptible gram-positive organisms and anaerobes. It is a time-dependent antibiotic, so frequent dosing is necessary for aqueous forms. Procaine and benzathine salts provide prolonged activity but achieve lower peak concentrations. In veterinary practice, penicillin G is commonly used for skin infections, abscesses, respiratory infections, and clostridial diseases. It is important to confirm susceptibility before use, as many bacteria have developed resistance. In food animals, strict adherence to withdrawal times is essential. For small herbivores like rabbits, use with extreme caution due to the risk of enterotoxemia; alternative antibiotics may be preferred. Always monitor for adverse reactions, especially allergic responses.

References & Literature

  • πŸ“š Plumb's Veterinary Drug Handbook
  • πŸ“š Papich Veterinary Pharmacology and Therapeutics
  • πŸ“š Compendium of Veterinary Products (CVP)