Cloxacillin Sodium — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	10-25 mg/kg	q8h	Duration: 5-7 days or as directed Notes: Administer on an empty stomach for optimal absorption.
Dog	IV/IM	10-20 mg/kg	q8h	Duration: 5-7 days Notes: For severe infections.
Cat	PO	10-20 mg/kg	q8h	Duration: 5-7 days Notes: Use with caution in cats due to potential GI upset.
Horse	IV/IM	10-20 mg/kg	q6-8h	Duration: 5-7 days Notes: For systemic infections.
Cattle (lactating)	Intramammary	200-500 mg per infected quarter	q12h for 2-3 milkings	Duration: 2-3 days Notes: Follow label instructions; milk withdrawal must be observed.
Cattle (dry cow)	Intramammary	500 mg per quarter	Single infusion at drying off	Duration: Once Notes: For dry cow therapy.
Sheep/Goats	Intramammary	200-500 mg per quarter	q12h for 2-3 milkings	Duration: 2-3 days Notes: Extra-label; milk withdrawal may be longer.
Rabbit	PO	15-25 mg/kg	q12h	Duration: 5-7 days Notes: May cause GI disturbances; monitor for diarrhea.
Birds	PO/IM	50-100 mg/kg	q8-12h	Duration: 5-7 days Notes: Limited data; use with caution.

Clinical Indications & Species Uses

General Indications

Treatment of infections caused by penicillinase-producing staphylococci
Prophylaxis in surgery (off-label)

Dog (Canine)

Treatment of pyoderma and skin infections caused by penicillinase-producing staphylococci
Treatment of respiratory tract infections
Treatment of urinary tract infections
Treatment of wound infections

Cat (Feline)

Treatment of skin and soft tissue infections
Treatment of respiratory tract infections
Treatment of urinary tract infections

Horse (Equine)

Treatment of respiratory infections
Treatment of skin and soft tissue infections
Treatment of joint infections (septic arthritis) caused by susceptible staphylococci

Cattle (Bovine)

Treatment of mastitis caused by penicillinase-producing staphylococci (intramammary infusion)
Treatment of respiratory infections (systemic use)

Small Ruminants (Sheep / Goat)

Treatment of mastitis (intramammary)
Treatment of skin infections

Rabbit & Small Mammals

Treatment of staphylococcal infections (e.g., abscesses, respiratory infections)

Exotic & Other Species

Treatment of staphylococcal infections in small mammals (e.g., guinea pigs, rats) and reptiles (under expert guidance)

Pharmacology & Mechanism of Action

Drug Class: Antibiotic | Pharmacological Group: Penicillinase-resistant penicillin (beta-lactam)

Mechanism of Action: Cloxacillin is a semisynthetic penicillin that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs) and interfering with peptidoglycan cross-linking. It is resistant to staphylococcal penicillinase (beta-lactamase), making it effective against beta-lactamase-producing Staphylococcus species. It is bactericidal against susceptible organisms.

Pharmacodynamics: Cloxacillin exhibits time-dependent killing. Its efficacy is best correlated with the time that plasma concentrations exceed the minimum inhibitory concentration (MIC) of the organism. It is active primarily against Gram-positive bacteria, including penicillinase-producing staphylococci, and some streptococci. It is not effective against Gram-negative organisms due to poor penetration and beta-lactamase production.

⚡ Pharmacokinetics Summary

Absorption: Cloxacillin is acid-stable and well absorbed after oral administration in monogastric animals, but absorption is variable in ruminants. Intramuscular and subcutaneous injections provide rapid absorption. In cattle, oral absorption is poor due to ruminal degradation.

Distribution: Cloxacillin is widely distributed in body fluids and tissues, but penetration into the central nervous system is poor unless meninges are inflamed. It crosses the placenta and is excreted in milk. Protein binding is high (approximately 90-95%).

Metabolism: Cloxacillin undergoes minimal hepatic metabolism. The majority of the drug is excreted unchanged in the urine via tubular secretion and glomerular filtration.

Excretion: Cloxacillin is primarily excreted via the kidneys. In lactating animals, significant amounts are excreted in milk. Biliary excretion also occurs.

Half-Life: Dog: 0.5-1 hour; Cat: 0.5-1 hour; Horse: 1-2 hours; Cattle: 1-2 hours (intramammary infusion has prolonged local half-life).

Bioavailability: Oral: 30-50% in dogs and cats (variable); IM: nearly complete; Intramammary: local absorption is minimal, with prolonged retention in the udder.

Protein Binding: Approximately 90-95% in most species.

Available Formulations & Strengths

Oral Capsule 250 mg, 500 mg (PO)

Oral Solution (reconstituted) 50 mg/mL (PO)

Injectable Solution 250 mg/mL (IV/IM)

Intramammary Infusion (syringe) 200 mg, 500 mg per syringe (Intramammary)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to penicillins or cephalosporins
Use in animals with a history of allergic reactions to beta-lactam antibiotics
Oral administration in ruminants (due to poor absorption and disruption of rumen flora)
Systemic use in rabbits and guinea pigs (risk of enterotoxemia) - use with extreme caution

Warnings & Clinical Precautions:

Use with caution in animals with renal impairment (dosage adjustment may be necessary)
In horses, use with caution as penicillins may cause diarrhea and Clostridioides difficile-associated colitis
In cattle, observe milk withdrawal times and meat withdrawal times
Intramammary infusion should be performed with strict aseptic technique
Prolonged use may result in overgrowth of non-susceptible organisms (superinfection)
Use in food animals must comply with regulatory guidelines (e.g., AMDUCA in the US)

Adverse Effects & Reactions

Common:

Gastrointestinal upset (vomiting, diarrhea)
Injection site pain or swelling
Allergic reactions (rash, urticaria)

Serious / Severe:

Anaphylaxis (rare but potentially fatal)
Clostridioides difficile-associated diarrhea in horses
Enterotoxemia in rabbits and guinea pigs
Acute interstitial nephritis (rare)

Rare:

Bone marrow suppression
Hepatotoxicity
Neurotoxicity (with high doses in renal failure)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Probenecid	Decreases renal tubular secretion of cloxacillin, increasing its plasma concentration and half-life.	Moderate
Bacteriostatic antibiotics (e.g., tetracyclines, macrolides)	May antagonize the bactericidal effect of cloxacillin; avoid concurrent use.	Moderate
Aminoglycosides	Synergistic effect against some Gram-positive bacteria; but do not mix in same syringe due to inactivation.	Mild
Methotrexate	Penicillins may reduce methotrexate clearance, increasing toxicity risk.	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Gastrointestinal signs (vomiting, diarrhea)
Neurological signs (tremors, seizures) with very high doses
Allergic reactions

Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. Induce emesis if recent oral ingestion and animal is stable. Administer activated charcoal to reduce absorption. Provide IV fluids for dehydration and electrolyte imbalances. Monitor for signs of anaphylaxis and treat with epinephrine and corticosteroids if needed. In severe cases, consider hemodialysis (though not commonly performed in veterinary patients).

Food Animal Withdrawal Times

🥩 Meat: 4 days🥛 Milk: 3 days

Withdrawal times vary by formulation and country. For intramammary use in lactating cows, milk withdrawal is typically 3-4 days (72-96 hours) and meat withdrawal is 4-7 days. For dry cow therapy, meat withdrawal may be longer (e.g., 30 days). Always follow label instructions and local regulations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F), with excursions permitted between 15-30°C (59-86°F).

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from moisture. Reconstituted oral solutions should be refrigerated and used within 14 days. Intramammary syringes should be stored at room temperature and protected from freezing.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in veterinary medicine; specific products are FDA-approved for intramammary infusion in cattle and oral/injectable formulations for dogs and cats (some are approved for horses).

Extra-Label (Off-Label) Use: In the US, extra-label use of cloxacillin in food animals is permitted under AMDUCA (Animal Medicinal Drug Use Clarification Act) only with a valid veterinary-client-patient relationship, and must follow established withdrawal times. Use in minor species may be extra-label. In the EU, similar regulations apply under Regulation (EU) 2019/6.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Cloxacillin is a valuable antibiotic for treating infections caused by penicillinase-producing staphylococci, particularly in cases of pyoderma, mastitis, and wound infections. It is often used in combination with other antibiotics for broader coverage. In dairy cattle, intramammary infusion is a common treatment for mastitis, but strict adherence to withdrawal times is essential. In small animals, oral administration is convenient, but GI upset may occur. In horses, systemic use requires careful monitoring for diarrhea. For rabbits and other small herbivores, oral administration is risky due to disruption of gut flora; parenteral administration is preferred. Always perform culture and sensitivity testing when possible to ensure efficacy. Cloxacillin is generally well-tolerated, but allergic reactions can occur, especially in animals with a history of beta-lactam hypersensitivity.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)