Excede (Ceftiofur Crystalline Free Acid) — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Cattle (beef and dairy)	Subcutaneous (SC) in the ear (beef cattle) or SC in the neck (dairy cattle)	1.5 mg/kg (1.5 mL per 100 kg body weight)	Single dose	Duration: Single administration; may be repeated once after 72 hours if needed (for BRD control) Notes: For BRD treatment: single dose. For control of BRD in high-risk cattle: single dose. For foot rot: single dose. Do not inject more than 10 mL per injection site. For dairy cattle, administer SC in the neck.
Swine	Intramuscular (IM) in the neck	5 mg/kg (1 mL per 20 kg body weight)	Single dose	Duration: Single administration Notes: For treatment of swine respiratory disease associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, and Streptococcus suis. Do not inject more than 5 mL per site.

Clinical Indications & Species Uses

General Indications

Treatment and control of bovine respiratory disease (BRD) in cattle.
Treatment of foot rot in cattle.

Cattle (Bovine)

Treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni.
Treatment of acute interdigital necrobacillosis (foot rot) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus.
Control of BRD in cattle at high risk of developing the disease.

Pharmacology & Mechanism of Action

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

Mechanism of Action: Ceftiofur crystalline free acid (CCFA) is a broad-spectrum cephalosporin antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). This binding disrupts the cross-linking of peptidoglycan chains, leading to cell lysis and death. It is bactericidal against many Gram-positive and Gram-negative bacteria, including those producing beta-lactamases.

Pharmacodynamics: Ceftiofur exhibits time-dependent killing. Its efficacy is related to the duration of time that the plasma concentration exceeds the minimum inhibitory concentration (MIC) of the pathogen. The crystalline free acid formulation provides sustained release, maintaining therapeutic concentrations for extended periods (up to 7-8 days in cattle). It has a post-antibiotic effect against some organisms.

⚡ Pharmacokinetics Summary

Absorption: After subcutaneous injection, ceftiofur crystalline free acid is slowly absorbed from the injection site due to its crystalline nature, providing prolonged release. Peak plasma concentrations are reached within 24-48 hours in cattle.

Distribution: Ceftiofur is widely distributed in body tissues and fluids. It crosses the blood-brain barrier poorly but achieves therapeutic concentrations in pleural, peritoneal, and synovial fluids. Protein binding is moderate (approximately 60-70% in cattle).

Metabolism: Ceftiofur is rapidly metabolized to desfuroylceftiofur, which retains antimicrobial activity. Further metabolism occurs to inactive metabolites.

Excretion: The primary route of excretion is renal, with metabolites eliminated in urine. Some excretion occurs via feces. In cattle, the elimination half-life is approximately 60-70 hours due to the slow-release formulation.

Half-Life: Cattle: ~60-70 hours; Swine: ~48-60 hours (after IM injection)

Bioavailability: High (nearly 100%) after subcutaneous or intramuscular injection

Protein Binding: Approximately 60-70% in cattle

Available Formulations & Strengths

Injectable suspension 100 mg/mL ceftiofur equivalents (Subcutaneous (cattle) or Intramuscular (swine))

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to ceftiofur or other beta-lactam antibiotics (penicillins, cephalosporins).
Do not use in animals with known allergy to ceftiofur.
Do not use in horses, dogs, cats, or other non-target species.
Do not use in poultry or other food animals not specified on the label.

Warnings & Clinical Precautions:

Use with caution in animals with a history of allergic reactions to penicillins or cephalosporins.
Do not administer intravenously; for subcutaneous or intramuscular use only.
Avoid contact with skin and eyes; wash hands after handling.
Do not use in calves less than 2 months of age unless directed by a veterinarian.
Injection site reactions may occur; rotate injection sites.
Use in lactating dairy cattle is not recommended unless specifically prescribed by a veterinarian; withdrawal times must be observed.
Federal law restricts this drug to use by or on the order of a licensed veterinarian (in the USA).

Adverse Effects & Reactions

Common:

Injection site swelling or pain
Local tissue reaction at injection site

Serious / Severe:

Anaphylaxis (rare but possible)
Clostridium difficile-associated diarrhea (rare)
Blood dyscrasias (rare)

Rare:

Allergic reactions
Neurological signs (if accidental IV administration)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Bacteriostatic antibiotics (e.g., tetracyclines, macrolides)	May antagonize the bactericidal effect of ceftiofur; avoid concurrent use.	Moderate
Aminoglycosides	Potential additive nephrotoxicity; use with caution.	Moderate
Probenecid	May increase ceftiofur concentrations by decreasing renal excretion; not commonly used in veterinary medicine.	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Injection site reactions
Gastrointestinal upset (if oral)
Neurological signs (if IV administration)
Allergic reactions

Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. Monitor for anaphylaxis and treat with epinephrine and antihistamines if necessary. In case of accidental IV administration, discontinue use and provide supportive care.

Food Animal Withdrawal Times

🥩 Meat: 13 days🥛 Milk: 4 days

For cattle: meat withdrawal is 13 days; milk withdrawal is 4 days. For swine: meat withdrawal is 7 days. No egg withdrawal is applicable as not used in poultry.

Storage, Handling & Regulatory Information

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

Handling & Special Conditions: Protect from freezing. Shake well before use. Do not use if the suspension is discolored or contains particulate matter.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved by FDA for use in cattle and swine for specific indications.

Extra-Label (Off-Label) Use: In the USA, extra-label use of ceftiofur in food animals is prohibited by the FDA (prohibited in extra-label use in food-producing animals). Use must strictly follow label directions. In other countries, regulations may vary; consult local veterinary authorities.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Excede (ceftiofur crystalline free acid) is a long-acting cephalosporin designed for single-dose therapy in cattle and swine. Its sustained-release formulation allows for prolonged therapeutic concentrations, reducing handling stress and improving compliance. It is primarily used for bovine respiratory disease (BRD) and foot rot in cattle, and for swine respiratory disease. Due to its importance in human medicine, ceftiofur is classified as a medically important antimicrobial; prudent use is essential to minimize antimicrobial resistance. Always adhere to withdrawal times and follow label instructions. In cattle, the subcutaneous injection in the ear is recommended for beef cattle to minimize injection site lesions in valuable cuts of meat; for dairy cattle, the neck is the recommended site. Monitor for injection site reactions and adverse effects. Do not use in animals with known hypersensitivity to beta-lactams. As with all antibiotics, use only when indicated and based on culture and sensitivity when possible.

References & Literature

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