Cefenil Rtu

Description

CEFENIL® RTU (ceftiofur hydrochloride 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 contains 50 mg of ceftiofur hydrochloride, along with 5.73 mg of aluminum monostearate, 1.03 mg of sorbitan monooleate, and medium chain triglycerides.

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

CEFENIL RTU is indicated for the treatment and control of bacterial diseases in swine and cattle.

In swine, CEFENIL RTU is indicated for the treatment and control of bacterial respiratory disease (swine bacterial pneumonia) associated with the following pathogens: Actinobacillus (Haemophilus) pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis, and Streptococcus suis.

In cattle, CEFENIL RTU 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.

• Acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus.

• Acute metritis occurring within 0 to 14 days post-partum, associated with bacterial organisms susceptible to ceftiofur.

Limitations of use have not been established for CEFENIL RTU in specific populations outside of the indicated conditions.

Dosage and Administration

Before administration, the suspension must be shaken for 90 seconds to ensure complete resuspension.

For swine, the recommended dosage is 1.36 to 2.27 mg ceftiofur equivalents per pound of body weight (3.0 to 5.0 mg/kg). This corresponds to administering 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.

In cattle, the following dosing regimens apply:

Bovine Respiratory Disease (BRD) and Acute Bovine Interdigital Necrobacillosis:

• Administer either intramuscularly or subcutaneously at a dosage of 0.5 to 1.0 mg ceftiofur equivalents per pound of body weight (1.1 to 2.2 mg/kg), 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 a satisfactory response after the initial three treatments, additional doses may be administered on Days 4 and 5.

• For BRD specifically, administer 1.0 mg ceftiofur equivalents per pound of body weight (2.2 mg/kg) intramuscularly or subcutaneously every other day on Days 1 and 3, maintaining a 48-hour interval.

• It is important not to exceed 15 mL per injection site.

Acute Post-Partum Metritis:

• Administer intramuscularly or subcutaneously at a dosage of 1.0 mg ceftiofur equivalents per pound of body weight (2.2 mg/kg), which is 2 mL of sterile suspension per 100 pounds of body weight.

• This treatment should be given at 24-hour intervals for five consecutive days.

• As with other treatments, do not inject more than 15 mL per injection site.

Contraindications

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

Warnings and Precautions

NOT FOR HUMAN USE. This product must be kept out of reach of children to prevent accidental ingestion or exposure.

Allergic Reactions Penicillins and cephalosporins, including ceftiofur, have the potential to cause allergic reactions in individuals who are sensitized. Topical exposure to these antimicrobials may result in mild to severe allergic reactions. Repeated or prolonged exposure can lead to sensitization. It is imperative to avoid direct contact with the skin, eyes, mouth, and clothing. Individuals with a known hypersensitivity to penicillin or cephalosporins should strictly avoid exposure to this product.

Accidental Exposure Management In the event of accidental eye exposure, it is crucial to flush the eyes with water for at least 15 minutes. For accidental skin exposure, wash the affected area thoroughly with soap and water and remove any contaminated clothing.

Medical Attention Should an allergic reaction occur, characterized by symptoms such as skin rash, hives, or difficulty breathing, immediate medical attention is required.

Occupational Safety Information For more detailed information regarding occupational safety, refer to the safety data sheet (SDS). To report suspected adverse drug events or for technical assistance, contact Norbrook at 1-866-591-5777. For additional information on adverse drug experience reporting for animal drugs, contact the FDA at 1-888-FDA-VETS or visit www.fda.gov/reportanimalae.

Side Effects

Patients may experience allergic reactions to ceftiofur, particularly those who are sensitized to penicillins and cephalosporins. These reactions can range from mild to severe and may occur following topical exposure to the antimicrobial. It is important to note that repeated or prolonged exposure to ceftiofur may lead to sensitization. Individuals with a known hypersensitivity to penicillin or cephalosporins should avoid contact with this product entirely.

In the event of accidental exposure, specific measures should be taken. For eye exposure, it is recommended to flush the eyes with water for 15 minutes. In cases of skin exposure, the affected area should be washed with soap and water, and any contaminated clothing should be removed. Should an allergic reaction manifest—such as skin rash, hives, or difficulty breathing—immediate medical attention is advised.

The effects of ceftiofur on reproductive performance, pregnancy, and lactation in cattle and swine have not been established. In swine, discoloration at the injection site may occur and can lead to trim-out of edible tissues at slaughter if it persists for 11 days or less. Additionally, the safety of ceftiofur has not been demonstrated for pregnant swine or those intended for breeding.

In cattle, discoloration at the injection site following intramuscular or subcutaneous administration in the neck may last beyond 11 days, resulting in trim loss of edible tissues at slaughter. If administered intramuscularly in the rear leg, discoloration may persist for more than 28 days, also leading to trim loss.

The use of CEFENIL RTU is contraindicated in animals that have previously exhibited hypersensitivity to the drug.

Drug Interactions

Penicillins and cephalosporins are known to potentially induce allergic reactions in individuals who have previously been sensitized to these classes of antibiotics. Clinicians should exercise caution when prescribing these medications to patients with a history of allergies to beta-lactam antibiotics.

Regarding ceftiofur, there is currently insufficient data to assess its effects on reproductive performance, pregnancy, and lactation in cattle and swine. Therefore, it is advisable to monitor these parameters closely when administering ceftiofur to these animal populations, as the implications of its use in these contexts remain undetermined.

Packaging & NDC

The table below lists each NDC Code for Cefenil Rtu (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 safety of ceftiofur has not been established in pregnant swine or swine intended for breeding, and its effects on reproductive performance, pregnancy, and lactation in cattle and swine remain undetermined.

In studies involving pigs, ceftiofur administered intramuscularly did not produce overt adverse signs of toxicity. A five-day tolerance study in feeder calves demonstrated that ceftiofur sodium was well tolerated at doses up to 25 times the highest recommended dose (25 mg ceftiofur equivalents/lb or 55 mg/kg body weight) without any adverse systemic effects.

Local tissue tolerance assessments for intramuscular injection of ceftiofur hydrochloride in cattle indicated that it was well tolerated, with no systemic toxicity observed at a dose of 1.0 mg ceftiofur equivalents/lb (2.2 mg/kg body weight). Injection sites exhibited discoloration of subcutaneous tissues and muscle, which resolved within approximately 7 to 15 days in the neck and 19 to 28 days in the rear leg. Additionally, a separate tissue tolerance study showed that ceftiofur hydrochloride was well tolerated when administered subcutaneously at doses of 0.5 or 1.0 mg ceftiofur equivalents/lb (1.1 or 2.2 mg/kg body weight) at 24-hour intervals for five days, with no systemic toxicity reported.

Geriatric Use

Elderly patients may exhibit increased sensitivity to side effects when administered ceftiofur. The safety of ceftiofur has not been established for this population, necessitating careful consideration before prescribing.

Dosage adjustments may be necessary for elderly patients due to the potential for reduced kidney function, which can affect drug metabolism and excretion. It is essential to monitor these patients closely, taking into account their overall health status and any concurrent medications that may influence treatment outcomes. Special precautions should be implemented to ensure the safe and effective use of ceftiofur in geriatric patients.

Pregnancy

The effects of ceftiofur on reproductive performance, pregnancy, and lactation in cattle and swine have not been determined. Additionally, the safety of ceftiofur has not been established for pregnant swine or those intended for breeding. Therefore, healthcare professionals should exercise caution when considering the use of ceftiofur in pregnant patients or in animals that may become pregnant. Further studies are needed to clarify the potential risks and fetal outcomes associated with ceftiofur administration during pregnancy.

Lactation

This product may be used in lactating mothers. When administered according to label indications, dosage, and route of administration, a milk discard time is not required. However, the effects of ceftiofur on lactation have not been determined. Therefore, healthcare professionals should exercise caution and consider the lack of data regarding its impact on breastfed infants.

Renal Impairment

There is no information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution and consider the lack of specific guidance when prescribing to patients with reduced kidney function.

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 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 when administering the medication. It is essential to monitor patients closely for any signs of adverse effects or unexpected reactions, particularly in cases of suspected overdose.

Should an overdosage occur, the management approach should include supportive care tailored to the patient's clinical presentation. Healthcare providers are encouraged to assess the patient's vital signs and overall condition, and to implement appropriate interventions as necessary.

In the event of an overdose, it is recommended that healthcare professionals consult local poison control centers or relevant toxicology resources for guidance on management strategies. Continuous monitoring and supportive measures are critical to ensure patient safety and mitigate potential complications associated with overdosage.

Nonclinical Toxicology

Ceftiofur sodium has demonstrated a favorable safety profile in nonclinical studies. It was well tolerated in swine at a dose of 57 mg ceftiofur equivalents/lb (125 mg/kg), with no overt adverse signs of toxicity observed following intramuscular administration. In feeder calves, ceftiofur sodium was also well tolerated at 25 times the highest recommended dose, with no adverse systemic effects noted, indicating a wide margin of safety.

Ceftiofur hydrochloride exhibited similar tolerability in cattle, producing no systemic toxicity when administered intramuscularly. Clinically noted changes at injection sites were infrequent, with local swelling occurring in only 2 out of 48 sites in the neck. Changes at rear leg sites were more common, occurring in 21 out of 48 sites, typically evident the day after injection. These injection site reactions were characterized by discoloration of subcutaneous tissues and muscle, which resolved within approximately 7 to 15 days in the neck and 19 to 28 days in the rear leg.

Further evaluations of ceftiofur hydrochloride indicated that it was well tolerated and produced no systemic toxicity when administered subcutaneously at doses of 0.5 or 1.0 mg ceftiofur equivalents/lb (1.1 or 2.2 mg/kg). Mild and transient local swelling reactions were observed at the injection site, characterized by edema and limited increases in thickness and color changes of the subcutaneous tissue and/or fascial surface of the underlying muscle.

Overall, the results from various tolerance and safety studies in both swine and cattle support the conclusion that ceftiofur has a wide margin of safety and is well tolerated across different administration routes and dosages.

Postmarketing Experience

Postmarketing experience has revealed several observations related to the administration of the product. Areas of discoloration associated with the injection site have been reported, with persistence noted beyond 11 days following intramuscular or subcutaneous administration in the neck, and beyond 28 days in the rear leg. Such discoloration may result in trim loss of edible tissues at slaughter.

Clinical evaluations conducted at necropsy indicated no apparent changes, such as swelling or inflammation, within 12 hours post-injection. However, areas of discoloration were observed at injection sites within 11 days after the last injection. Local swelling at injection sites in the neck was infrequent, occurring in 2 out of 48 sites, while changes in rear leg sites were more common, noted in 21 out of 48 sites. These changes in the rear leg were typically evident the day following injection and lasted from 1 to 11 days.

At necropsy, injection sites were characterized by discoloration of subcutaneous tissues and muscle, with resolution occurring approximately 7 to 15 days in the neck and 19 to 28 days in the rear leg. Mild and usually transient reactions, such as local swelling, were localized at the injection site. Routine necropsy findings included edema, a limited increase in thickness, and color changes of the subcutaneous tissue and/or fascial surface of the underlying muscle.

For reporting suspected adverse drug events or for technical assistance, Norbrook can be contacted at 1-866-591-5777. Additional information regarding adverse drug experience reporting for animal drugs is available through the FDA at 1-888-FDA-VETS or online at www.fda.gov/reportanimalae.

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, including unapproved doses, frequencies, durations, or routes of administration, as well as in unapproved major food-producing species or production classes.

Patients must be made aware that this product is not intended 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 result in mild to severe allergic reactions, and that repeated or prolonged exposure could lead to sensitization.

It is crucial to instruct patients to avoid direct contact with the product on the skin, eyes, mouth, and clothing. 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 advised to flush the eye with water for 15 minutes. For accidental skin exposure, they should wash the area with soap and water and remove any contaminated clothing. If an allergic reaction occurs, such as skin rash, hives, or difficulty breathing, patients should seek medical attention immediately.

Healthcare providers should also inform patients that the safety data sheet contains more detailed occupational safety information. For reporting suspected adverse drug events, obtaining technical assistance, or acquiring a copy of the safety data sheet, patients can contact Norbrook at 1-866-591-5777. 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 www.fda.gov/reportanimalae.

When used according to label indications, dosage, and route of administration, treated swine must not be slaughtered for 4 days following the last treatment, and treated cattle must not be slaughtered for 3 days following the last treatment. It should be noted that a milk discard time is not required when used as directed, and a withdrawal period has not been established for pre-ruminating calves. Additionally, patients should be advised not to use this product in calves intended for veal processing.

Storage and Handling

The product is supplied in a configuration that includes specific NDC numbers, which should be referenced for accurate identification. It is essential to store the product at temperatures not exceeding 30ºC (86ºF) to maintain its efficacy. Care should be taken to protect the product from freezing, as exposure to low temperatures may compromise its integrity.

Prior to use, the product must be shaken well to ensure proper mixing of its components. Once the first dose is removed, the contents should be utilized within 42 days to ensure optimal effectiveness.

Additional Clinical Information

A summary of the minimum inhibitory concentration (MIC) values for SRD pathogens isolated from clinical field effectiveness studies is available in Table 3, while historic diagnostic laboratory MIC values from the US and Canada can be found in Table 4. These summaries adhere to the Clinical and Laboratory Standards Institute (CLSI) Guidelines. Pharmacokinetic studies indicate that for swine, a single intramuscular injection of 1.36 to 2.27 mg ceftiofur equivalents/lb (3.0 to 5.0 mg/kg) body weight, and for cattle, 0.5 to 1.0 mg ceftiofur equivalents/lb (1.1 to 2.2 mg/kg) body weight, are recommended. CLSI also provides breakpoints based on MIC and disk diffusion data, emphasizing the necessity of using laboratory control organisms in standardized procedures.

For treated swine, it is essential that they are not slaughtered for 4 days following the last treatment when used according to label indications, dosage, and route of administration. Similarly, treated cattle must not be slaughtered for 3 days after the last treatment, although a milk discard time is not required.

Drug Information (PDF)

This document includes the full labeling information for Cefenil Rtu, as submitted by Norbrook Laboratories Limited for veterinary use. It may include dosage by species, withdrawal periods, and administration instructions.

View veterinary label (PDF)