Cephalexin — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	11-22 mg/kg	q8h to q12h	Duration: 5-7 days for uncomplicated infections; up to 28 days for deep pyoderma Notes: Administer on an empty stomach for optimal absorption. For deep pyoderma, continue treatment for at least 7 days beyond clinical resolution.
Cat	PO	11-22 mg/kg	q8h to q12h	Duration: 5-7 days for uncomplicated infections; up to 14 days for skin infections Notes: Administer on an empty stomach. Use with caution in cats with renal impairment.
Horse	IV or IM	10-20 mg/kg	q6h to q8h	Duration: 5-7 days or as clinically indicated Notes: Oral administration is not recommended due to poor absorption. Use parenteral formulations (e.g., cephalexin sodium) off-label.
Cattle	IM or IV	10-20 mg/kg	q12h	Duration: 3-5 days or as clinically indicated Notes: Extra-label use; observe withdrawal times. Not approved for food animals in many countries.
Small Ruminants (sheep, goats)	IM or IV	10-20 mg/kg	q12h	Duration: 3-5 days or as clinically indicated Notes: Extra-label use; observe withdrawal times.
Rabbit	PO	15-30 mg/kg	q8h to q12h	Duration: 7-14 days Notes: May cause gastrointestinal upset; monitor for diarrhea.
Bird/Poultry	PO (in drinking water) or IM	50-100 mg/kg	q12h	Duration: 5-7 days Notes: Limited data; use with caution. Extra-label use in food birds is restricted.
Exotic/Other (e.g., ferrets, reptiles)	PO or IM	15-30 mg/kg	q8h to q12h	Duration: 7-14 days Notes: Doses are extrapolated; adjust based on species and clinical response.

Clinical Indications & Species Uses

General Indications

Treatment of infections caused by susceptible gram-positive and gram-negative bacteria, particularly skin, soft tissue, urinary tract, and respiratory infections.

Dog (Canine)

Treatment of pyoderma (superficial and deep) caused by Staphylococcus spp.
Treatment of urinary tract infections (UTIs) caused by susceptible E. coli, Proteus mirabilis, and Klebsiella spp.
Treatment of skin and soft tissue infections (wounds, abscesses)
Treatment of respiratory tract infections (bronchitis, pneumonia) caused by susceptible organisms
Treatment of bone and joint infections (osteomyelitis) as adjunctive therapy

Cat (Feline)

Treatment of urinary tract infections (UTIs) caused by susceptible organisms
Treatment of skin and soft tissue infections (wounds, abscesses)
Treatment of respiratory tract infections (bronchitis, pneumonia) caused by susceptible organisms

Rabbit & Small Mammals

Treatment of respiratory infections (e.g., Pasteurella multocida) and skin infections (off-label use).

Exotic & Other Species

Used in some reptiles and small mammals (e.g., ferrets, guinea pigs) for susceptible bacterial infections, but dosing is based on extrapolation and should be done with caution.

Pharmacology & Mechanism of Action

Drug Class: Cephalosporin antibiotic | Pharmacological Group: Beta-lactam antibiotic (first-generation cephalosporin)

Mechanism of Action: Cephalexin is a first-generation cephalosporin that exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) on the bacterial cell wall, interfering with the transpeptidation step of peptidoglycan cross-linking. This leads to a weakened cell wall, osmotic instability, and eventual cell lysis. Cephalexin is generally bactericidal against susceptible organisms during the active growth phase.

Pharmacodynamics: Cephalexin has a broad spectrum of activity against many gram-positive and some gram-negative bacteria. It is effective against Staphylococcus spp. (including penicillinase-producing strains), Streptococcus spp., and many strains of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. It is not effective against methicillin-resistant staphylococci, Enterococcus spp., Pseudomonas aeruginosa, or anaerobes. Its activity is time-dependent, and optimal efficacy is achieved when drug concentrations exceed the minimum inhibitory concentration (MIC) for a significant portion of the dosing interval.

⚡ Pharmacokinetics Summary

Absorption: Cephalexin is well absorbed after oral administration in most species. In dogs and cats, oral bioavailability is approximately 75-90% when given on an empty stomach. Food may delay absorption but does not significantly reduce the total amount absorbed. In horses, oral absorption is variable and less reliable; therefore, oral dosing is not recommended in adult horses. In ruminants, oral absorption is poor due to ruminal degradation.

Distribution: Cephalexin is widely distributed into body tissues and fluids, including skin, soft tissues, bone, synovial fluid, pleural fluid, and bile. It crosses the blood-brain barrier poorly unless the meninges are inflamed. It crosses the placenta and is excreted in milk in low concentrations. The volume of distribution is approximately 0.2-0.3 L/kg in dogs and cats.

Metabolism: Cephalexin undergoes minimal hepatic metabolism. The majority of the drug is excreted unchanged in the urine via active tubular secretion and glomerular filtration. A small amount may be metabolized to inactive metabolites.

Excretion: Cephalexin is primarily eliminated by the kidneys via glomerular filtration and tubular secretion. In dogs, the elimination half-life is approximately 1.5-2.5 hours. In cats, the half-life is slightly longer, around 2-3 hours. In horses, the half-life is short (0.5-1 hour) after IV administration. In renal impairment, the half-life is prolonged, and dose adjustments may be necessary.

Half-Life: Dog: 1.5-2.5 hours; Cat: 2-3 hours; Horse: 0.5-1 hour (IV); Cattle: 1-2 hours (IV); Rabbit: 1-2 hours

Bioavailability: Oral: Dogs and cats ~75-90%; Horses: poor and variable (not recommended); Ruminants: poor due to rumen degradation.

Protein Binding: Cephalexin is approximately 10-15% bound to plasma proteins in dogs and cats.

Available Formulations & Strengths

Oral Capsule 250 mg, 500 mg (PO)

Oral Tablet 250 mg, 500 mg, 1 g (PO)

Oral Suspension (reconstituted) 125 mg/5 mL, 250 mg/5 mL (PO)

Injectable Solution (as cephalexin sodium) 100 mg/mL (various) (IV, IM)

Contraindications & Clinical Warnings

Contraindications:

Known hypersensitivity to cephalosporins or other beta-lactam antibiotics (e.g., penicillins)
Use in animals with a history of anaphylactic reactions to penicillins (cross-reactivity risk)
Do not use orally in adult horses due to poor absorption
Do not use in rabbits or guinea pigs orally if severe gastrointestinal disease is present (risk of dysbiosis)

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 (e.g., colitis) due to potential for antibiotic-associated diarrhea.
Prolonged use may result in overgrowth of non-susceptible organisms (e.g., Candida, Clostridium difficile).
In food-producing animals, observe withdrawal times and follow extra-label use regulations.
Administer oral doses on an empty stomach to maximize absorption; if gastrointestinal upset occurs, give with food.
Do not use in animals with known hypersensitivity to beta-lactams.

Adverse Effects & Reactions

Common:

Gastrointestinal upset (vomiting, diarrhea, anorexia) – more common in cats and rabbits
Hypersensitivity reactions (skin rash, urticaria) – rare but possible
Injection site pain or swelling (with IM administration)

Serious / Severe:

Anaphylaxis (rare but potentially fatal)
Acute interstitial nephritis (rare)
Clostridium difficile-associated diarrhea (especially with prolonged use)
Seizures (with very high doses or in renal failure)

Rare:

Blood dyscrasias (neutropenia, thrombocytopenia)
Hepatotoxicity (elevated liver enzymes)
Superinfections (e.g., candidiasis)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Probenecid	Probenecid decreases renal tubular secretion of cephalexin, increasing its plasma concentration and half-life.	Moderate
Aminoglycosides (e.g., gentamicin)	Additive nephrotoxicity; monitor renal function when used concurrently.	High
Loop diuretics (e.g., furosemide)	May increase nephrotoxicity of cephalosporins.	Moderate
Bacteriostatic antibiotics (e.g., tetracyclines, macrolides)	May antagonize the bactericidal effect of cephalexin; avoid concurrent use.	Moderate
Warfarin	Cephalexin may enhance the anticoagulant effect of warfarin; monitor coagulation parameters.	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Gastrointestinal signs (vomiting, diarrhea)
Neurological signs (seizures, tremors) – especially with very high doses or in renal impairment
Acute renal failure (rare)

Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. Induce vomiting if recent ingestion and the animal is conscious. Administer activated charcoal to reduce absorption. Provide fluid therapy to maintain hydration and promote renal excretion. Monitor renal function and neurological status. In severe cases, hemodialysis may be considered.

Food Animal Withdrawal Times

🥩 Meat: 5 days🥛 Milk: 3 days

Withdrawal times are not established for cephalexin in food animals in many countries; extra-label use requires extended withdrawal periods. Consult regulatory guidelines. For cattle, a meat withdrawal of at least 5 days and milk withdrawal of 3 days is often recommended, but verify with local regulations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (20-25°C) in a dry place.

Handling & Special Conditions: Oral suspensions should be stored in the refrigerator after reconstitution and discarded after 14 days. Injectable solutions should be stored according to manufacturer's instructions; protect from freezing.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs and cats in the US (e.g., Cephalexin tablets and capsules). Not approved for food animals.

Extra-Label (Off-Label) Use: In the US, cephalexin is not approved for use in food animals; extra-label use in food animals is prohibited under AMDUCA unless a veterinary-client-patient relationship exists and a withdrawal time is established. In companion animals, extra-label use is permitted under veterinary discretion.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Cephalexin is a first-generation cephalosporin commonly used in small animal practice for skin and urinary tract infections. It is generally well-tolerated, but gastrointestinal upset is the most common adverse effect. It is important to administer on an empty stomach for optimal absorption. For deep pyoderma, prolonged therapy (up to 4 weeks) may be required. In horses, oral use is unreliable; parenteral administration is preferred. In food animals, extra-label use is restricted, and withdrawal times must be observed. Always perform culture and sensitivity testing when possible to ensure efficacy and reduce antimicrobial resistance.

References & Literature

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