# Cloxacillin: veterinary dose and monograph

> Cloxacillin is a veterinary antibiotic. Beta-lactamase-stable (isoxazolyl) penicillin — its niche is anti-staphylococcal activity, especially penicillinase-producing Staphylococcus aureus mastitis. Indications include bovine mastitis from penicillinase-producing Staphylococcus aureus (intramammary); dry-cow therapy and prevention of new dry-period infections (benzathine); susceptible staphylococcal skin / soft-tissue infection (with amoxicillin). This monograph lists 4 reference doses for dogs, cats and cattle, each with route, frequency and source, plus meat and milk withdrawal periods for food animals.

Source: https://vetmasterji.com/drugs/cloxacillin · Last reviewed: 2026-10-01

## At a glance

- **Drug class:** Antibiotic
- **Also known as:** Orbenin, Cloxa, Sodium cloxacillin, Benzathine cloxacillin
- **Species with doses:** Dogs, Cats and Cattle
- **General dose range:** 10–15 mg/kg PO q6–8h — check the species tables for the indication
- **Routes:** Intramammary, PO
- **Last reviewed:** 1 October 2026

## Indications

- Bovine mastitis from penicillinase-producing Staphylococcus aureus (intramammary)
- Dry-cow therapy and prevention of new dry-period infections (benzathine)
- Susceptible staphylococcal skin / soft-tissue infection (with amoxicillin)
- Surgical staphylococcal prophylaxis (combination products)

## Cloxacillin dose by species

Doses are per administration unless stated. mg/kg doses scale with body weight; per-animal, per-quarter and infusion-rate doses are shown as the reference writes them.

### Dogs

*Cloxacillin doses for dogs*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Susceptible staphylococcal infection (oral) | 20–40 mg/kg | PO | q8h | — |

- Susceptible staphylococcal infection (oral): Papich 5e and Plumb’s p.311 (Vaden & Papich 1995): 20–40 mg/kg PO q8h. Plumb’s also lists 10–15 mg/kg PO q6h for staphylococcal pyoderma or discospondylitis (14–84 days) and 10–40 mg/kg q6–8h for systemic infections. Give on an empty stomach. Oral forms are no longer marketed in the USA (use dicloxacillin).

### Cats

*Cloxacillin doses for cats*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Susceptible staphylococcal infection | 20–40 mg/kg | PO | q8h | — |

- Susceptible staphylococcal infection: Papich 5e: 20–40 mg/kg q8h PO. Plumb’s p.311: 20–40 mg/kg PO or IM q6–8h (Papich 1988); 10–15 mg/kg PO q6h for staphylococcal skin infections.

### Cattle

*Cloxacillin doses for cattle*

| Indication | Dose | Route | Frequency | Duration | Withdrawal |
| --- | --- | --- | --- | --- | --- |
| Clinical mastitis (lactating cow) | ~200 mg per affected quarter (1 syringe) after milking | Intramammary | per label q12h × 3 | — | 10d slaughter / 48h milk |
| Dry-cow therapy (benzathine cloxacillin) | 1 long-acting syringe per quarter at drying-off | Intramammary | once at drying-off | — | 28d slaughter |

- Clinical mastitis (lactating cow): Papich 5e and Plumb’s p.311 (Dariclox, cloxacillin sodium 200 mg): one 10 mL syringe per infected quarter after milking, q12h for 3 treatments. Label withdrawal: milk 48 h, slaughter 10 days.
- Dry-cow therapy (benzathine cloxacillin): Plumb’s p.311: cloxacillin benzathine 500 mg per quarter at drying-off. Slaughter withdrawal Orbenin-DC 28 days (Dry-Clox 30 days); do not use within 28–30 days of calving. Follow the product label.

### Goats

*Cloxacillin doses for goats*

| Indication | Dose | Route | Frequency | Duration | Withdrawal |
| --- | --- | --- | --- | --- | --- |
| No reference dose for this species | Not established in Papich 5e or Plumb’s 10e — do not extrapolate from another species | — | — | — | — |

- No reference dose for this species: The previous oral 10–15 mg/kg goat row had no source — oral penicillins are not a practical route in ruminants. Papich 5e: the only food-animal formulation is the bovine intramammary infusion; no goat dose is given in either reference.

### Sheep

*Cloxacillin doses for sheep*

| Indication | Dose | Route | Frequency | Duration | Withdrawal |
| --- | --- | --- | --- | --- | --- |
| No reference dose for this species | Not established in Papich 5e or Plumb’s 10e — do not extrapolate from another species | — | — | — | — |

- No reference dose for this species: The previous oral 10–15 mg/kg sheep row had no source — oral penicillins are not a practical route in ruminants. Neither Papich 5e nor Plumb’s gives a sheep dose.

### Buffalo

No buffalo-specific doses are on file, so buffalo are dosed as cattle.

*Cloxacillin doses for buffalo*

| Indication | Dose | Route | Frequency | Duration | Withdrawal |
| --- | --- | --- | --- | --- | --- |
| Clinical mastitis (lactating cow) | ~200 mg per affected quarter (1 syringe) after milking | Intramammary | per label q12h × 3 | — | 10d slaughter / 48h milk |
| Dry-cow therapy (benzathine cloxacillin) | 1 long-acting syringe per quarter at drying-off | Intramammary | once at drying-off | — | 28d slaughter |

- Clinical mastitis (lactating cow): Papich 5e and Plumb’s p.311 (Dariclox, cloxacillin sodium 200 mg): one 10 mL syringe per infected quarter after milking, q12h for 3 treatments. Label withdrawal: milk 48 h, slaughter 10 days.
- Dry-cow therapy (benzathine cloxacillin): Plumb’s p.311: cloxacillin benzathine 500 mg per quarter at drying-off. Slaughter withdrawal Orbenin-DC 28 days (Dry-Clox 30 days); do not use within 28–30 days of calving. Follow the product label.

## Contraindications

Penicillin/cephalosporin hypersensitivity. Like all penicillins, NEVER orally in rabbits, guinea pigs, chinchillas, hamsters (fatal enterotoxaemia). Narrow Gram-negative spectrum — not for Gram-negative infections alone. Observe intramammary milk/meat withdrawal.

## Species-specific warnings

> **Caution:** Rabbits: Never give orally to rabbits — fatal enterotoxaemia (as with all penicillins).

> **Caution:** Cattle: Intramammary use carries strict milk and meat withdrawal — verify the specific product label and national limits.

## Adverse effects

- Hypersensitivity (rash, fever, anaphylaxis)
- GI upset (oral)
- Local irritation of the mammary gland (intramammary)
- Superinfection on prolonged use

## Drug interactions

- Aminoglycosides: synergy against staphylococci but physically incompatible in one syringe
- Bacteriostatic agents (tetracyclines, macrolides): possible antagonism
- Probenecid: prolongs penicillin half-life
- Highly protein-bound — minor displacement interactions

## Pregnancy and lactation

Penicillins are among the safest antibiotic classes in pregnancy and lactation; widely used in dairy cattle. Low milk transfer except intramammary use (observe withdrawal).

## Monitoring

- Hypersensitivity at first dosing
- Mastitis cure (clinical signs, repeat milk culture/SCC)
- Strict milk (≈96 h lactating) and meat withdrawal compliance
- Culture confirmation that the organism is Staph (cloxacillin is wasted on Gram-negatives)

## Toxicity and overdose

Very wide therapeutic margin — acute toxicity is essentially limited to hypersensitivity/anaphylaxis. As with all penicillins, oral dosing is fatal to rabbits and small hindgut fermenters via clostridial enterotoxaemia.

Management: No specific antidote — supportive. Treat anaphylaxis with epinephrine 0.01 mg/kg IM, antihistamine, corticosteroid, oxygen and IV fluids.

## Clinical pearls

- The right tool for penicillinase-producing Staph mastitis — but useless against MRSA and Gram-negative mastitis
- Benzathine cloxacillin dry-cow tubes both treat existing and prevent new dry-period infections
- In India, amoxy-cloxa combinations are the everyday systemic Gram-positive choice — cloxacillin supplies the anti-penicillinase component
- Always insert intramammary tubes aseptically (clean, disinfect teat end) to avoid introducing environmental mastitis
- Confirm the dry-cow product's calving interval so antibiotic does not contaminate colostrum/milk at freshening

## Mechanism of action

Beta-lactam that binds penicillin-binding proteins to inhibit cell-wall peptidoglycan cross-linking — bactericidal, time-dependent. Its bulky isoxazolyl side chain sterically protects the beta-lactam ring from staphylococcal penicillinase, preserving activity against penicillinase-producing Staph aureus (though NOT against MRSA, which alters PBP2a).

## Formulations and products

- Intramammary lactating-cow syringe (e.g. 200 mg/quarter)
- Intramammary dry-cow syringe (benzathine, ~500 mg/quarter)
- 250 mg capsule (oral, human)
- Amoxy+Cloxa combination vial (parenteral)
- Orbenin LC / DC (Zoetis) — Cloxacillin (lactating) / Benzathine cloxacillin (dry cow), Intramammary syringe
- Cloxa-Mast / Mastilox (Various (India)) — Cloxacillin ± ampicillin intramammary, Intramammary syringe
- Moxicloxa (Assure Biotech, Jagadhri (HR)) — Cloxacillin 2 g + Amoxycillin 2 g, Dry powder vial + 20 mL WFI ampoule
- Bioclox / Cloxacillin — 250 / 500 mg capsule, Capsule (human-label)

## Storage

Intramammary syringes and oral forms: 15–25 °C, protect from light/heat. Do not freeze. Use intramammary tubes immediately once opened.

## Before you use this dose

> **Caution:** Reference doses for veterinary professionals. Confirm the dose against the product label, the patient’s condition, current guidance and local regulations before use; the attending veterinarian remains responsible for every clinical decision.

## Other antibiotics

- [Chloramphenicol](https://vetmasterji.com/drugs/chloramphenicol)
- [Ciprofloxacin](https://vetmasterji.com/drugs/ciprofloxacin)
- [Clarithromycin](https://vetmasterji.com/drugs/clarithromycin)
- [Clindamycin](https://vetmasterji.com/drugs/clindamycin)
- [Colistin (Polymyxin E)](https://vetmasterji.com/drugs/colistin)
- [Danofloxacin](https://vetmasterji.com/drugs/danofloxacin)
- [Doxycycline](https://vetmasterji.com/drugs/doxycycline)
- [Enrofloxacin](https://vetmasterji.com/drugs/enrofloxacin)

## Frequently asked questions

### What is the dose of Cloxacillin for dogs?

Reference doses for Cloxacillin in dogs: 20–40 mg/kg PO q8h (Susceptible staphylococcal infection (oral)). Confirm against the label and the patient before use.

### What is the dose of Cloxacillin for cats?

Reference doses for Cloxacillin in cats: 20–40 mg/kg PO q8h (Susceptible staphylococcal infection). Confirm against the label and the patient before use.

### What is the dose of Cloxacillin for cattle?

Reference doses for Cloxacillin in cattle: ~200 mg per affected quarter (1 syringe) after milking Intramammary per label q12h × 3 (Clinical mastitis (lactating cow)); 1 long-acting syringe per quarter at drying-off Intramammary once at drying-off (Dry-cow therapy (benzathine cloxacillin)). Confirm against the label and the patient before use.

### What is the withdrawal period for Cloxacillin?

Cattle, Intramammary (Clinical mastitis (lactating cow)): 10d slaughter / 48h milk; Cattle, Intramammary (Dry-cow therapy (benzathine cloxacillin)): 28d slaughter. Follow the product label and national regulations where they differ.

### When should Cloxacillin not be used?

Penicillin/cephalosporin hypersensitivity. Like all penicillins, NEVER orally in rabbits, guinea pigs, chinchillas, hamsters (fatal enterotoxaemia). Narrow Gram-negative spectrum — not for Gram-negative infections alone. Observe intramammary milk/meat withdrawal.

### What are the side effects of Cloxacillin in animals?

Hypersensitivity (rash, fever, anaphylaxis); GI upset (oral); Local irritation of the mammary gland (intramammary); Superinfection on prolonged use.

## Sources

- Plumb's Veterinary Drug Handbook
- Merck Veterinary Manual, 11th edition
- Papich, Papich Handbook of Veterinary Drugs, 5th edition

---

VetMasterJi is a clinical decision-support and education platform for veterinary professionals and students. It does not provide veterinary advice, diagnosis or treatment for specific animals. All drug doses, calculators and differentials are references that must be independently verified before clinical use; the attending registered veterinarian remains solely responsible for every clinical decision.