Excenel

Description

EXCENEL RTU EZ Sterile Suspension is a ready-to-use formulation containing the hydrochloride salt of ceftiofur, a broad-spectrum cephalosporin antibiotic. Each milliliter of this sterile suspension provides ceftiofur hydrochloride equivalent to 50 mg of ceftiofur, along with 2.50 mg of polyoxyethylene sorbitan monooleate (polysorbate 80) and 6.5 mg of water for injection, all in a caprylic/capric triglyceride suspension. The chemical name of ceftiofur hydrochloride is 5-Thia-1-azabicyclo4,2.0oct-2-ene-2-carboxylic acid, 7-[[2-amino-4-thiazolyl2-amino-4-thiazolyl-acetyl] amino]-3-[[2-furanylcarbonylthio]methyl]-8-oxo-, hydrochloride salt [6R-6α,7β(Z)].

Uses and Indications

EXCENEL RTU EZ Sterile Suspension is indicated for the treatment and control of bacterial respiratory disease in swine, specifically swine bacterial pneumonia associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella Choleraesuis, and Streptococcus suis.

In cattle, EXCENEL RTU EZ Sterile Suspension is indicated for the treatment of several bacterial diseases, including bovine respiratory disease (BRD, shipping fever, pneumonia) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. Additionally, it is indicated for the treatment of acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus, as well as acute metritis occurring within 0 to 14 days post-partum associated with bacterial organisms susceptible to ceftiofur.

Limitations of use include the necessity for veterinary diagnosis and the consideration of local antimicrobial resistance patterns when prescribing this medication.

Dosage and Administration

Shake well before using.

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

In cattle, the administration varies based on the condition being treated:

For bovine respiratory disease (BRD) and acute bovine interdigital necrobacillosis, the dosage is 0.5 to 1 mg CE per pound (1.1 to 2.2 mg CE per kilogram) of body weight, given either intramuscularly or subcutaneously. This equates to 1 to 2 mL of sterile suspension per 100 pounds of body weight. The treatment should be administered daily at 24-hour intervals for a total of three consecutive days. If the animal does not show a satisfactory response after the initial three treatments, additional doses may be given on Days 4 and 5. For BRD specifically, an alternative regimen involves administering 1 mg CE per pound (2.2 mg CE per kilogram) of body weight every other day on Days 1 and 3, with a 48-hour interval between doses. As with swine, no more than 15 mL should be injected at any single injection site.

For acute post-partum metritis, the recommended dosage is 1 mg CE per pound (2.2 mg CE per kilogram) of body weight, administered intramuscularly or subcutaneously. This corresponds to 2 mL of sterile suspension per 100 pounds of body weight, with administration occurring at 24-hour intervals for five consecutive days. Again, it is crucial to limit the injection volume to no more than 15 mL per injection site.

Contraindications

The use of EXCENEL RTU EZ Sterile Suspension is contraindicated in animals with a known hypersensitivity to the drug. Administration in these cases may lead to severe allergic reactions.

Warnings and Precautions

The use of this drug is strictly regulated under federal law, which limits its administration to licensed veterinarians or their authorized agents. It is imperative that healthcare professionals adhere to these regulations to ensure compliance and patient safety.

Additionally, federal law explicitly prohibits the extra-label use of this drug in cattle and swine for disease prevention purposes. This includes any use that deviates from approved doses, frequencies, durations, or routes of administration. Furthermore, the drug must not be administered to unapproved major food-producing species or production classes. Healthcare professionals are advised to consult relevant guidelines and regulatory documents to ensure appropriate use and to avoid potential legal ramifications.

Side Effects

Patients receiving EXCENEL RTU EZ Sterile Suspension may experience adverse reactions related to the route of administration. Specifically, intramuscular and subcutaneous injections in cattle, as well as intramuscular injections in swine, can lead to transient local tissue reactions. These reactions may result in trim loss of edible tissue at the time of slaughter, which is a significant consideration for livestock management.

It is important to note that the use of EXCENEL RTU EZ Sterile Suspension is contraindicated in animals that have previously exhibited hypersensitivity to the drug. This precaution is critical to prevent serious allergic reactions in susceptible individuals.

Healthcare providers should monitor patients for these adverse reactions and consider the implications for animal welfare and food safety when administering this medication.

Drug Interactions

Penicillins and cephalosporins are known to elicit allergic reactions in individuals who have previously been sensitized. Therefore, it is imperative that individuals with a documented hypersensitivity to either penicillin or cephalosporins refrain from using this product to avoid potential adverse reactions.

In terms of drug and laboratory test interactions, the correlation between plasma concentrations of ceftiofur and its metabolite, desfuroylceftiofur, and the minimum inhibitory concentration (MIC) in plasma has not been established as a reliable indicator of effectiveness for treating bovine interdigital necrobacillosis (foot rot) caused by Fusobacterium necrophorum and Bacteroides melaninogenicus. Consequently, clinicians should exercise caution and consider alternative treatment strategies when managing this condition, as the efficacy of ceftiofur in this context remains uncertain.

Packaging & NDC

The table below lists each NDC Code for Excenel (ceftiofur hydrochloride) veterinary formulations. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Ceftiofur is not indicated for use in calves intended for veal production. The effects of ceftiofur on reproductive performance, pregnancy, and lactation in cattle and swine have not been established. Additionally, a withdrawal period has not been determined for pre-ruminating calves. Caution should be exercised when considering the use of ceftiofur in these populations.

Geriatric Use

Elderly patients may not require specific dosage adjustments or safety considerations when using EXCENEL RTU EZ (ceftiofur hydrochloride injection, suspension), as the provided drug insert does not indicate any unique geriatric use considerations. However, as with all medications, it is prudent for healthcare providers to monitor elderly patients closely for any potential adverse effects or changes in response to treatment, given the general physiological changes associated with aging.

Pregnancy

The effects of ceftiofur on reproductive performance, pregnancy, and lactation in cattle and swine have not been determined. As such, the safety of ceftiofur during pregnancy in these species remains unclear. Ceftiofur is contraindicated in animals that have previously exhibited hypersensitivity to the drug. There are no specific warnings or contraindications regarding the use of EXCENEL RTU EZ during pregnancy mentioned in the prescribing information. Therefore, healthcare professionals should exercise caution and consider the potential risks when administering this drug to pregnant patients.

Lactation

This product may be used in lactating dairy cattle. The effects of ceftiofur on cattle and swine reproductive performance, pregnancy, and lactation have not been determined. When used according to label indications, dosage, and route of administration, a milk discard time is not required.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to this patient population.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In the absence of specific information regarding overdosage, healthcare professionals are advised to exercise caution and consider the potential implications of excessive dosing.

It is essential to monitor patients closely for any signs or symptoms that may arise from an overdosage scenario. Symptoms may vary depending on the substance involved and the individual patient's response.

In the event of suspected overdosage, immediate medical intervention is recommended. Healthcare providers should initiate supportive care and symptomatic treatment as necessary. It is advisable to consult local poison control centers or relevant medical authorities for guidance on management protocols tailored to the specific situation.

Documentation of the incident, including the amount ingested and the time of exposure, is crucial for effective management and follow-up care. Continuous assessment of the patient's condition will aid in determining the appropriate course of action.

Nonclinical Toxicology

Evaluation of target animal safety in swine was conducted through a pharmacokinetic comparison between the reformulated EXCENEL RTU EZ Sterile Suspension and the original EXCENEL RTU Sterile Suspension. Ceftiofur, administered to swine as the reformulated EXCENEL RTU EZ Sterile Suspension at a dose of 5 mg CE/kg BW via intramuscular injection, demonstrated bioequivalence to the corresponding IM injection of EXCENEL RTU Sterile Suspension, as evidenced by comparable AUC0-LOQ and Cmax values. This bioequivalence confirms the systemic safety of the reformulated product when administered at the specified dose for three consecutive days.

Injection site tissue tolerance and resolution were assessed following intramuscular administration of EXCENEL RTU EZ Sterile Suspension to eight young pigs, with a maximum proposed volume of 5 mL per injection site once daily for three consecutive days. No test article-related health issues were reported. Mild swelling, erythema, and firmness were noted in a very small number of instances (≤ 2% of total observations). No swelling was observed from three days post-injection through the conclusion of the study. However, grossly visible discoloration of the injection site and histopathologic changes consistent with inflammation were observed in treated pigs necropsied seven and fourteen days after injection.

A second injection site tissue tolerance study involved sixteen adult commercial crossbred pigs, evaluating the administration of EXCENEL RTU EZ Sterile Suspension via intramuscular injection with a maximum dose volume of 15 mL per injection site once daily for three consecutive days. No test article-related health issues were observed, and no swelling, erythema, or firmness were noted during the study. Nevertheless, gross necropsy and histopathologic changes consistent with inflammation were documented in treated pigs necropsied up to forty-two days after injection.

In cattle, target animal safety was evaluated through two pharmacokinetic studies comparing the reformulated EXCENEL RTU EZ Sterile Suspension and the original EXCENEL RTU Sterile Suspension, one focusing on intramuscular administration and the other on subcutaneous administration. In both studies, ceftiofur, administered at a dose of 2.2 mg CE/kg BW of the reformulated EXCENEL RTU EZ Sterile Suspension, was shown to be bioequivalent to a 2.2 mg CE/kg BW dose of the original formulation. This bioequivalence confirms the systemic safety of the reformulated product when administered either intramuscularly or subcutaneously at the specified dose for five consecutive days.

Injection site tissue tolerance and lesion resolution were evaluated after administration of the reformulated EXCENEL RTU EZ Sterile Suspension via intramuscular and subcutaneous injections to sixteen growing cattle (eight for each route) at a maximum volume of 15 mL per injection site, once daily for five consecutive days. No test article-related health issues were reported. Injection site reactions included firmness and swelling at the injection sites, with swelling observed in 4 out of 1030 (0.4%) of IM injection site observations and in 606 out of 1029 (58.9%) of SC injection site observations. Swelling progressively decreased over time, although it was still present in both animals injected subcutaneously that were necropsied on Day 42. Grossly visible discoloration of the injection site and/or histopathologic changes consistent with inflammation were noted through Day 42 in both SC and IM injection sites.

Postmarketing Experience

The postmarketing experience includes reports of adverse events received voluntarily or through surveillance programs. Detailed occupational safety information is available in the safety data sheet, which can be obtained by contacting Zoetis Inc. at 1-888-963-8471. Additionally, for information regarding adverse drug experience reporting for animal drugs, individuals may reach out to the FDA at 1-888-FDA-VETS or visit the FDA's website at http://www.fda.gov/AnimalVeterinary/SafetyHealth.

Patient Counseling

Healthcare providers should inform patients that federal law restricts the use of this drug to administration by or on the order of a licensed veterinarian. It is important to emphasize that federal law prohibits extra-label use of this drug in cattle and swine for disease prevention purposes, as well as at unapproved doses, frequencies, durations, or routes of administration, and in unapproved major food-producing species or production classes.

Patients must be made aware that this product is not for human use and should be kept out of reach of children. Healthcare providers should discuss the potential for allergic reactions, particularly in individuals sensitized to penicillins and cephalosporins. They should advise patients that topical exposure to antimicrobials, including ceftiofur, may lead to mild to severe allergic reactions, and that repeated or prolonged exposure could result in sensitization. Direct contact with the skin, eyes, mouth, and clothing should be avoided.

Individuals with a known hypersensitivity to penicillin or cephalosporins should be cautioned to avoid exposure to this product. In the event of accidental eye exposure, patients should be instructed to flush the eyes with water for 15 minutes. For accidental skin exposure, washing with soap and water is recommended, and contaminated clothing should be removed. If an allergic reaction occurs, such as skin rash, hives, or difficulty breathing, patients should seek medical attention immediately.

Healthcare providers should inform patients that the safety data sheet contains more detailed occupational safety information. To obtain a safety data sheet (SDS) or to report any adverse events, patients can call 1-888-963-8471. For additional information regarding adverse drug experience reporting for animal drugs, patients should be directed to contact the FDA at 1-888-FDA-VETS or visit http://www.fda.gov/AnimalVeterinary/SafetyHealth.

It is crucial to discuss the implications of injection site volume on the withdrawal period in swine. When used according to label indications, dosage, and route of administration, treated swine must not be slaughtered for 6 days following the last treatment if injection site volumes exceed 5 mL, up to a maximum of 15 mL. Conversely, if injection site volumes are less than or equal to 5 mL, the withdrawal period is 4 days. Providers should stress that no more than 15 mL should be injected per injection site, as exceeding indicated dosages or injection volumes may lead to illegal residues in edible tissues.

For cattle, when used according to label indications, dosage, and route of administration, treated animals must not be slaughtered for 4 days following the last treatment, and no milk discard time is required. Providers should caution against using dosages in excess of those indicated or by unapproved routes of administration, such as intramammary, as this may result in illegal residues in edible tissues and/or milk. Additionally, a withdrawal period has not been established for pre-ruminating calves, and the use of this product in calves intended for veal processing is not recommended.

Lastly, healthcare providers should inform patients that the effects of ceftiofur on reproductive performance, pregnancy, and lactation in cattle and swine have not been determined. They should also note that intramuscular and subcutaneous injections in cattle, as well as intramuscular injections in swine, may cause transient local tissue reactions, potentially resulting in trim loss of edible tissue at slaughter.

Storage and Handling

The product is supplied in a configuration that allows for effective use and storage. 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). It is essential to protect the product from freezing to maintain its integrity.

Prior to administration, the product must be shaken well to ensure proper mixing. Once the first dose is removed, the contents should be utilized within 42 days to ensure optimal efficacy.

Additional Clinical Information

Injection site volume significantly influences the withdrawal period for swine. Specifically, swine treated with injection volumes greater than 5 mL, up to a maximum of 15 mL, must not be slaughtered for 6 days following the last treatment. Conversely, if the injection volume is 5 mL or less, the withdrawal period is reduced to 4 days. It is important to note that no more than 15 mL should be administered at a single injection site.

For cattle, the withdrawal period is 4 days post-treatment, and there is no requirement for a milk discard time. However, a withdrawal period has not been established for pre-ruminating calves, and the product should not be used in calves intended for veal processing.

Drug Information (PDF)

This document includes the full labeling information for Excenel, as submitted by Zoetis Inc. for veterinary use. It may include dosage by species, withdrawal periods, and administration instructions.

View veterinary label (PDF)