VetSheet

Cloxacillin

Cloxacillin sodium; Cloxacillin benzathine

Antibiotic - Anti-staphylococcal PenicillinIntramammary (IMM)POIMTopical (Ophthalmic)DogsCatsCattle

Also known as: Orbenin-DC · Dry-Clox · Dariclox · Boviclox · Opticlox · BRL-1621 · sodium cloxacillin · chlorphenylmethyl isoxazolyl penicillin sodium · methylchlorophenyl isoxazolyl penicillin sodium · cloxacilina sodica · cloxacillinum natricum · P25 · Cloxacillin benzathine

Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference

WHO highly important antibioticresponsible use recommended
20-40 mg/kg PO q8hPO· q8h
🐕

Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.

Dosing by species

🌎 NA — North America🌍 EU — Europe

Dogs

IndicationDoseRouteFrequencyDurationRegion
Susceptible infections20-40 mg/kg PO q8hPOq8h🌎 NA
Staph. pyoderma, diskospondylitis, osteoarthritis or skin infections10-15 mg/kg PO q6h for 14-84 daysPOq6h14-84 days🌎 NA
Systemic infections, bacteremia10-40 mg/kg PO q6-8h for 7-14 daysPOq6-8h7-14 days🌎 NA
Ocular infectionsApply 1/10 of a tube (0.3 g)topicalq24h🌍 EU
  • Susceptible infections: Oral dosage forms are no longer available commercially in the USA
  • Ocular infections: Specifically for beta-lactamase-producing Staphylococcus

Cats

IndicationDoseRouteFrequencyDurationRegion
Susceptible infections20-40 mg/kg PO or IM q6-8hPO/IMq6-8h🌎 NA
Staph. pyoderma, diskospondylitis, osteoarthritis or skin infections10-15 mg/kg PO q6h for 14-84 daysPOq6h14-84 days🌎 NA
Systemic infections, bacteremia10-40 mg/kg PO q6-8h for 7-14 daysPOq6-8h7-14 days🌎 NA
Ocular infectionsApply 1/10 of a tube (0.3 g)topicalq24h🌍 EU
  • Ocular infections: Specifically for beta-lactamase-producing Staphylococcus

Cattle

IndicationDoseRouteFrequencyDurationRegion
Mastitis (treatment or prophylaxis) caused by susceptible organisms - Lactating cowAfter milking out and disinfecting teat, instill contents of syringe; massage.Intramammaryq12h3 total doses🌎 NA
Mastitis (treatment or prophylaxis) caused by susceptible organisms - Dry (non-lactating) cowsAfter last milking (or early in the dry period), instill contents of syringe and massage into each quarter.IntramammaryOnce🌎 NA
  • Mastitis (treatment or prophylaxis) caused by susceptible organisms - Lactating cow: Using lactating cow formula (Dari-Clox)
  • Mastitis (treatment or prophylaxis) caused by susceptible organisms - Dry (non-lactating) cows: Using dry cow formula (benzathine)

Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.

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Overview

  • ​Class:​ Narrow-spectrum, penicillinase-resistant penicillin (isoxazolyl-penicillin).
  • ​Spectrum:​ Highly effective against penicillinase-producing gram-positive cocci, particularly Staphylococcus species.
  • ​Limitations:​ Inactive against Rickettsia, mycobacteria, fungi, Mycoplasma, and viruses. Methicillin-resistant staphylococci (MRSA/MRSP) are inherently resistant.
  • ​Availability:​ In the USA, only intramammary infusion products are currently marketed for veterinary use (dairy cattle). Oral formulations are no longer commercially available in the US, though they may be compounded or available internationally.

Mechanism of action

Cloxacillin is a bactericidal beta-lactam antibiotic.

Binds to ​Penicillin-Binding Proteins (PBPs)​ → inhibits peptidoglycan cross-linking → disrupts bacterial cell wall synthesis → cell lysis and death.

​Mechanistic Pearl:​ The bulky isoxazolyl side chain sterically hinders staphylococcal beta-lactamases, preventing the enzymatic hydrolysis of the beta-lactam ring that normally inactivates natural penicillins.

Safety & warnings

Contraindications

  • Known hypersensitivity to penicillins or cephalosporins

Adverse effects

  • Hypersensitivity reactions (rashes, fever, anaphylaxis)
  • Eosinophilia
  • Neutropenia
  • Agranulocytosis
  • Thrombocytopenia
  • Leukopenia
  • Anemias
  • Lymphadenopathy
  • Local irritation (ophthalmic)

Precautions

​Warning:​ Contraindicated in patients with a history of hypersensitivity to penicillins.

  • ​Cross-Reactivity:​ Use cautiously in patients with documented hypersensitivity to other beta-lactam antibiotics (e.g., cephalosporins, cefamycins, carbapenems). In humans, 1-15% of cephalosporin-allergic patients cross-react with penicillins.
  • ​Pregnancy:​ FDA Category B (human); Papich Class A (veterinary). Generally considered safe, but use only when potential benefits outweigh risks. Crosses the placenta but no documented teratogenic problems.

Monitoring

  • Clinical efficacy (resolution of infection/mastitis)
  • Signs of hypersensitivity or toxicity
  • Resolution of clinical signs of ocular infection
  • Signs of local irritation or hypersensitivity

Pharmacokinetics

Absorption

Minimal systemic absorption expected from topical ophthalmic application.

Distribution

Distributes well into local ocular tissues.

Metabolism

Hepatic (for systemically absorbed fraction).

Elimination

Renal (for systemically absorbed fraction).

Overdose

Overdosage of intramammary infusions is unlikely to pose much systemic risk to the patient.

​Note:​ Excessive dosing may prolong required withdrawal times for milk and meat in food-producing animals.

Available products

Formulations

  • Intramammary infusion (peanut-oil gel or vegetable oils)
  • Oral capsules/suspension (historically/internationally)
  • Ophthalmic suspension 16.7%

Veterinary

  • Cloxacillin Benzathine 500 mg intramammary syringe (Orbenin-DC, Dry-Clox, Boviclox)
  • Cloxacillin Sodium 200 mg intramammary syringe (Dariclox)
  • Opticlox ophthalmic suspension
  • Orbenin ophthalmic suspension

Human-labeled

  • None (Oral dosage forms no longer marketed in USA)

Regulatory status

European Union✓ ApprovedPrescription onlyEMA
🐕 Dogs🐈 Cats

POM-V

United Kingdom✓ ApprovedPrescription onlyVMD
🐕 Dogs🐈 Cats

POM-V

No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU

Storage & stability

Unless otherwise instructed by the manufacturer, cloxacillin benzathine or cloxacillin sodium mastitis syringes should be stored at temperatures less than 25°C in tight containers.

Client information

​Important:​ If using oral compounded formulations for pets, complete the entire prescription even if the pet feels better.

  • ​Food Animals:​ Adhere strictly to withdrawal times. Dry cow products (benzathine) require a 28-30 day slaughter withdrawal. Lactating cow products (sodium) require a 48-hour milk withdrawal and 10-day slaughter withdrawal.
  • ​Allergic Reactions:​ Watch for signs of allergy such as hives, facial swelling, or difficulty breathing. Contact your veterinarian immediately if these occur.

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.