Ceftiofur hydrochloride

Uses and Indications

This drug is indicated for the treatment and control of bacterial diseases in swine and cattle.

Swine

EXCENEL RTU EZ Sterile Suspension and CEFENIL RTU are indicated for the treatment/control of swine bacterial respiratory disease (swine bacterial pneumonia) associated with:

• Actinobacillus pleuropneumoniae

• Pasteurella multocida

• Salmonella choleraesuis

• Streptococcus suis

Cattle

EXCENEL RTU EZ Sterile Suspension and CEFENIL RTU are indicated for the treatment of the following bacterial diseases:

• Bovine respiratory disease (BRD, shipping fever, pneumonia) associated with:

  • Mannheimia haemolytica

  • Pasteurella multocida

  • Histophilus somni

• Acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with:

  • Fusobacterium necrophorum

  • Bacteroides melaninogenicus

• Acute metritis (0 to 14 days post-partum) associated with bacterial organisms susceptible to ceftiofur.

Lactating Dairy Cattle

SPECTRAMAST® LC is indicated for use in lactating dairy cattle for the treatment of:

• Clinical mastitis associated with:

  • Coagulase-negative staphylococci

  • Streptococcus dysgalactiae

  • Escherichia coli

• Diagnosed subclinical mastitis associated with:

  • Coagulase-negative staphylococci

  • Streptococcus dysgalactiae

  • Streptococcus uberis

Usage Instructions

SPECTRAMAST® LC is indicated for treatment at the time of dry off for subclinical mastitis.

Dosage and Administration

The product is available in injection and suspension forms. Prior to administration, the suspension must be shaken well to ensure proper resuspension.

For swine, the recommended dosage is 1.36 to 2.27 mg ceftiofur equivalents (CE) per pound (3 to 5 mg CE/kg) of body weight, administered intramuscularly. This corresponds to 1 mL of sterile suspension per 22 to 37 pounds of body weight. Treatment should be repeated at 24-hour intervals for a total of three consecutive days. No more than 15 mL should be injected at any single site.

For cattle, the dosage varies based on the condition being treated:

• Bovine Respiratory Disease (BRD) and Acute Bovine Interdigital Necrobacillosis: Administer intramuscularly or subcutaneously at a dosage of 0.5 to 1 mg CE/lb (1.1 to 2.2 mg CE/kg) body weight, which equates to 1 to 2 mL of sterile suspension per 100 pounds of body weight. This treatment should be given daily at 24-hour intervals for three consecutive days. If the animal does not show satisfactory improvement after the initial treatment, additional doses may be administered on Days 4 and 5. For BRD specifically, a dosage of 1 mg CE/lb (2.2 mg CE/kg) body weight may be administered every other day on Days 1 and 3 (48-hour interval). No more than 15 mL should be injected at any single site.

• Acute Post-Partum Metritis: Administer intramuscularly or subcutaneously at a dosage of 1 mg CE/lb (2.2 mg CE/kg) body weight, corresponding to 2 mL of sterile suspension per 100 pounds of body weight. This treatment should be given at 24-hour intervals for five consecutive days, with a maximum of 15 mL per injection site.

For the treatment of mastitis in dairy cattle, one syringe should be infused into each affected quarter at the time of dry off. The infusion may be repeated in 24 hours, and for extended duration therapy, once daily treatment may be continued for up to eight consecutive days. Care should be taken during infusion to ensure proper insertion of the cannula into the teat canal, either fully or partially, as indicated in the product instructions.

Contraindications

The use of the products Excenel, Spectramast LC, Spectramast DC, and Cefenil RTU is contraindicated in animals previously found to be hypersensitive to any of the components of these drugs.

Warnings and Precautions

Federal law restricts the use of this drug to licensed veterinarians and prohibits extra-label use in cattle and swine for disease prevention purposes, including unapproved doses, frequencies, durations, or routes of administration, and in unapproved major food-producing species or production classes.

Allergic Reactions

Penicillins and cephalosporins, including ceftiofur, can cause allergic reactions in sensitized individuals. Topical exposure may elicit mild to severe allergic reactions, and repeated or prolonged exposure may lead to sensitization. Individuals with known hypersensitivity to penicillin or cephalosporins should avoid exposure to this product. Direct contact with the skin, eyes, mouth, and clothing should be avoided. Protective gloves are recommended to minimize skin sensitization.

Emergency Procedures

In the event of accidental eye exposure, it is crucial to flush the eyes with water for 15 minutes. For accidental skin exposure, wash the affected area with soap and water and remove contaminated clothing. If an allergic reaction occurs, such as skin rash, hives, or difficulty breathing, medical attention should be sought immediately.

Safety Information

This product is not for human use and should be kept out of reach of children. The Safety Data Sheet (SDS) contains detailed occupational safety information. For a copy of the SDS or to report adverse reactions, contact Zoetis Inc. at 1-888-963-8471 or Norbrook at 1-866-591-5777. For additional information regarding adverse drug experience reporting for animal drugs, contact the FDA at 1-888-FDA-VETS or visit www.fda.gov/reportanimalae.

Side Effects

Patients receiving ceftiofur products, including Excenel, Spectramast, and Cefenil RTU, may experience a range of adverse reactions primarily related to hypersensitivity and local tissue reactions.

Serious Reactions

• Allergic Reactions: Penicillins and cephalosporins, including ceftiofur, can cause allergic reactions in sensitized individuals. Reactions may range from mild (skin rash, hives) to severe (difficulty breathing). Individuals with a known hypersensitivity to these classes of antibiotics should avoid exposure to these products. In the event of an allergic reaction, immediate medical attention is advised.

Local Reactions

• Injection Site Reactions: Intramuscular and subcutaneous injections in cattle and swine may lead to transient local tissue reactions. This can result in discoloration at the injection site, which may persist for varying durations:

  • In swine, discoloration may lead to trim loss of edible tissues at slaughter if it occurs within 11 days post-injection.

  • In cattle, discoloration at the injection site may persist beyond 11 days, particularly following intramuscular or subcutaneous administration in the neck, and beyond 28 days when administered in the rear leg, also resulting in trim loss of edible tissues at slaughter.

Precautions

• Skin and Eye Exposure: Direct contact with the skin, eyes, mouth, or clothing should be avoided to prevent sensitization. In case of accidental exposure:

  • Eye exposure should be flushed with water for 15 minutes.

  • Skin exposure should be washed with soap and water, and contaminated clothing should be removed.

Contraindications

• The use of Excenel, Spectramast, and Cefenil RTU is contraindicated in animals previously found to be hypersensitive to ceftiofur or related compounds.

These adverse reactions highlight the importance of monitoring for signs of hypersensitivity and managing injection site care to minimize local tissue reactions.

Drug Interactions

Penicillins and cephalosporins are known to cause allergic reactions in sensitized individuals. Therefore, individuals with a known hypersensitivity to these classes of antibiotics should avoid exposure to products containing ceftiofur, such as Excenel and Spectramast.

Drug & Laboratory Test Interactions

The relationship between plasma concentrations of ceftiofur and its desfuroyl metabolites above the minimum inhibitory concentration (MIC) in plasma and their effectiveness for treating bovine interdigital necrobacillosis (foot rot) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus has not been established. Additionally, the effects of ceftiofur on reproductive performance, pregnancy, and lactation in cattle and swine remain undetermined.

Following intramammary infusion with antibiotics in lactating cows, it is essential that milk obtained during treatment and the subsequent milk discard period is properly discarded and not fed to calves. Furthermore, standardized procedures necessitate the use of laboratory control organisms for both standardized diffusion and dilution techniques to ensure accurate testing results. The 30 μg ceftiofur sodium disk should yield specific zone diameters, and the ceftiofur sodium standard reference powder or disk should provide defined MIC values for the reference strain.

Pediatric Use

The safety and efficacy of ceftiofur in pediatric patients have not been established. The available data do not provide specific information regarding recommended ages, dosing differences, or safety concerns for children.

Ceftiofur has been evaluated in calves, with studies indicating that it is well tolerated at doses significantly higher than the recommended dose. In a five-day tolerance study, ceftiofur sodium was well tolerated at 25 times the highest recommended dose (25 mg ceftiofur equivalents/lb or 55 mg/kg body weight). Additionally, intramuscular administration of ceftiofur produced no overt adverse signs of toxicity in pigs and calves, and local tissue tolerance studies showed no systemic toxicity when administered at recommended doses.

However, caution is advised as the effects of ceftiofur on reproductive performance, pregnancy, and lactation in cattle and swine have not been determined. The labeling includes a general warning to keep the product out of reach of children, but no specific pediatric use information is provided.

Milk obtained during treatment and the milk discard period should not be fed to calves, emphasizing the need for careful management in pediatric settings.

Geriatric Use

Elderly patients may require special consideration when using ceftiofur products, as the safety of ceftiofur has not been established for this population. Dosage adjustments may be necessary due to potential reduced kidney function commonly observed in geriatric patients. Additionally, elderly patients may exhibit increased sensitivity to side effects, necessitating careful monitoring for adverse reactions. Special precautions should be taken when administering ceftiofur, considering the overall health status of elderly patients and any concurrent medications they may be taking. No specific geriatric use considerations, dosage adjustments, or safety concerns have been explicitly mentioned for other ceftiofur formulations.

Pregnancy

The use of ceftiofur in pregnant patients is associated with significant considerations. For SPECTRAMAST LC and SPECTRAMAST DC, the use of these products is contraindicated during pregnancy due to the absence of specific safety studies, which raises concerns regarding potential risks to fetal outcomes. Caution is advised when considering the use of these products in pregnant animals, as the effects of ceftiofur on reproductive performance, pregnancy, and lactation have not been determined.

Additionally, while EXCENEL RTU EZ does not have specific warnings or contraindications regarding its use during pregnancy, the lack of data on the safety of ceftiofur in pregnant animals suggests that its use should be approached with caution. The safety of ceftiofur has not been demonstrated for pregnant swine or those intended for breeding, further emphasizing the need for careful consideration in this population.

In summary, due to the lack of safety data and potential risks to the fetus, the use of ceftiofur products in pregnant patients should be undertaken with caution, and alternative treatments should be considered when possible.

Lactation

Ceftiofur has the potential for excretion in breast milk, and the safety and effectiveness of this drug in nursing mothers have not been established. Caution should be exercised when administering ceftiofur to lactating mothers due to the potential for adverse effects on breastfed infants.

For lactating dairy cattle, ceftiofur may be used without a required milk discard time when administered according to label indications, dosage, and route of administration. However, for products like Spectramast, milk obtained during treatment and for 72 hours after the last treatment must not be used for human consumption. Proper disposal of milk during the treatment period is essential to prevent exposure to calves.

Overall, while ceftiofur can be used in lactating dairy cattle, its implications for nursing mothers and breastfed infants warrant careful consideration.

Renal Impairment

Patients with renal impairment may not have specific dosage adjustments, monitoring requirements, or safety considerations outlined for the following medications: Excenel (Injection, Suspension), Spectramast (Suspension), and Cefenil Rtu (Suspension). The available data does not provide guidance on the use of these products in individuals with reduced kidney function. Therefore, healthcare professionals should exercise caution and consider individual patient circumstances when prescribing these medications to patients with renal impairment.

Hepatic Impairment

Patients with hepatic impairment have no specific dosage adjustments, special monitoring requirements, or precautions outlined for the following medications: Excenel (injection, suspension), Spectramast (suspension), and Cefenil Rtu (suspension). The available information does not provide guidance on the use of these medications in individuals with liver problems. Therefore, healthcare providers should exercise caution and consider individual patient factors when prescribing these treatments to patients with hepatic impairment.

Overdosage

In the event of an overdose, specific information regarding the management and symptoms associated with overdose for Excenel, Spectramast, and Cefenil Rtu is not provided in the available data. Therefore, it is recommended that healthcare professionals monitor patients closely for any unusual symptoms or adverse reactions following administration of these medications.

In the absence of detailed overdose information, standard supportive care should be initiated. This may include monitoring vital signs, providing symptomatic treatment, and ensuring the patient is stable. If an overdose is suspected, it is advisable to contact a poison control center or seek immediate medical attention for further guidance on management strategies.

Healthcare providers should remain vigilant and consider the potential for individual variability in response to these medications, even in the absence of specific overdose data.

Nonclinical Toxicology

Teratogenic Effects

No data regarding teratogenic effects are available from the reviewed sources.

Non-Teratogenic Effects

Ceftiofur has been evaluated for non-teratogenic effects in various animal studies. In swine, ceftiofur sodium was well tolerated at a dose of 57 mg ceftiofur equivalents/lb (125 mg/kg), with no overt adverse signs of toxicity observed following intramuscular administration. Similarly, in feeder calves, ceftiofur sodium was well tolerated at 25 times the highest recommended dose, with no adverse systemic effects noted. Injection site reactions were infrequent, with mild local swelling observed in a small percentage of sites, which resolved within 7 to 28 days.

In a pivotal GLP udder irritation study involving 40 cows, daily intramammary infusion of an oil-based suspension containing 125 mg of ceftiofur for up to 8 consecutive days resulted in a transient and clinically insignificant rise in somatic cell count (SCC) to levels below 200,000 cells/mL. No clinical signs of udder irritation, changes in body temperature, or alterations in milk production were reported. Additional clinical field efficacy studies involving 971 lactating dairy cows corroborated these findings, with no reports of udder irritation or adverse events.

Animal Toxicology

The safety and tolerance of ceftiofur have been extensively evaluated in various animal species. In swine, studies demonstrated that ceftiofur administered intramuscularly produced no adverse systemic effects, indicating a wide margin of safety. Injection site tissue tolerance studies revealed that ceftiofur hydrochloride was well tolerated, with no systemic toxicity observed. Local tissue reactions were generally mild and transient, characterized by localized swelling and discoloration, which resolved within a few weeks.

In cattle, both intramuscular and subcutaneous administrations of ceftiofur were shown to be safe, with no significant adverse effects reported. Injection site reactions were noted but were minimal and resolved over time. The systemic safety of the reformulated EXCENEL RTU EZ Sterile Suspension was confirmed through pharmacokinetic studies, demonstrating bioequivalence to the original formulation.

Overall, the data indicate that ceftiofur is well tolerated across multiple species and administration routes, with a favorable safety profile and minimal adverse effects.

Storage and Handling

Excenel is supplied as an injection and suspension. It should be stored at a controlled room temperature of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 40°C (59° to 104°F). The product must be protected from freezing and shaken well before use. Once the first dose is removed, the contents should be used within 42 days.

Spectramast is available as a suspension and should also be stored at a controlled room temperature of 20° to 25°C (68° to 77°F). It is important to protect the product from light. Syringes should be stored in their carton or pail until they are ready to be used. Additionally, plastets should be kept in their carton until needed.

Cefenil Rtu is provided as a suspension and must not be stored above 30°C (86°F). Similar to the other products, it should be shaken well before use and protected from freezing. The contents should be utilized within 42 days after the first dose is removed.