Naxcel

NAXCEL Sterile Powder is indicated for treatment of bovine respiratory disease (shipping fever, pneumonia) associated with Mannheimia haemolytica, Pasteurella multocida and Histophilus somni. NAXCEL Sterile Powder is also indicated for treatment of acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus.

NAXCEL Sterile Powder is indicated for treatment/control of swine bacterial respiratory disease (swine bacterial pneumonia) associated with Actinobacillus (Haemophilus) pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis and Streptococcus suis.

NAXCEL Sterile Powder is indicated for treatment of sheep respiratory disease (sheep pneumonia) associated with Mannheimia haemolytica and Pasteurella multocida.

NAXCEL Sterile Powder is indicated for treatment of caprine respiratory disease (goat pneumonia) associated with Mannheimia haemolytica and Pasteurella multocida.

NAXCEL Sterile Powder is indicated for treatment of respiratory infections in horses associated with Streptococcus zooepidemicus.

NAXCEL Sterile Powder is indicated for the treatment of canine urinary tract infections associated with Escherichia coli and Proteus mirabilis.

NAXCEL Sterile Powder is indicated for the control of early mortality, associated with E. coli organisms susceptible to ceftiofur, in day-old chicks.

NAXCEL Sterile Powder is indicated for the control of early mortality, associated with E. coli organisms susceptible to ceftiofur, in day-old turkey poults.

Administer to cattle by intramuscular or subcutaneous injection at the dosage of 0.5 to 1.0 mg ceftiofur per pound (1.1 to 2.2 mg/kg) of body weight (1-2 mL reconstituted sterile solution per 100 lbs body weight). Treatment should be repeated at 24-hour intervals for a total of three consecutive days. Additional treatments may be given on days four and five for animals which do not show a satisfactory response (not recovered) after the initial three treatments. Selection of dosage (0.5 to 1.0 mg/lb) should be based on the practitioner's judgement of severity of disease (i.e., for respiratory disease, extent of elevated body temperature, depressed physical appearance, increased respiratory rate, coughing and/or loss of appetite; and for foot rot, extent of swelling, lesion and severity of lameness).

Administer to swine by intramuscular injection at the dosage of 1.36 to 2.27 mg ceftiofur per pound (3.0 to 5.0 mg/kg) of body weight (1 mL of reconstituted sterile solution per 22 to 37 lbs body weight). Treatment should be repeated at 24-hour intervals for a total of three consecutive days.

Administer to sheep by intramuscular injection at the dosage of 0.5 to 1.0 mg ceftiofur per pound (1.1 to 2.2 mg/kg) of body weight (1-2 mL reconstituted sterile solution per 100 lbs body weight). Treatment should be repeated at 24-hour intervals for a total of three consecutive days. Additional treatments may be given on days four and five for animals which do not show a satisfactory response (not recovered) after the initial three treatments. Selection of dosage (0.5 to 1.0 mg/lb) should be based on the practitioner's judgement of severity of disease (i.e., extent of elevated body temperature, depressed physical appearance, increased respiratory rate, coughing and/or loss of appetite).

Administer to goats by intramuscular injection at the dosage of 0.5 to 1.0 mg ceftiofur per pound (1.1 to 2.2 mg/kg) of body weight (1-2 mL reconstituted sterile solution per 100 lbs body weight). Treatment should be repeated at 24‑hour intervals for a total of three consecutive days. Additional treatments may be given on days four and five for animals which do not show a satisfactory response (not recovered) after the initial three treatments. Selection of dosage (0.5 to 1.0 mg/lb) should be based on the practitioner's judgement of severity of disease (i.e., extent of elevated body temperature, depressed physical appearance, increased respiratory rate, coughing and/or loss of appetite). Pharmacokinetic data indicate that elimination of the drug is more rapid in lactating does. For lactating does, the high end of the dose range is recommended.

Administer to horses by intramuscular injection at the dosage of 1.0 to 2.0 mg ceftiofur per pound (2.2 to 4.4 mg/kg) of body weight (2-4 mL reconstituted sterile solution per 100 lbs body weight). A maximum of 10 mL may be administered per injection site. Treatment should be repeated at 24-hour intervals, continued for 48 hours after clinical signs have disappeared and should not exceed 10 days.

Administer to dogs by subcutaneous injection at the dosage of 1.0 mg ceftiofur per pound (2.2 mg/kg) of body weight (0.1 mL reconstituted sterile solution per 5 lbs body weight). Treatment should be repeated at 24-hour intervals for 5-14 days.

Reconstituted NAXCEL Sterile Powder is to be administered to dogs by subcutaneous injection. No vial closure should be entered more than 20 times. Therefore, only the 1 gram vial is approved for use in dogs.

Administer by subcutaneous injection in the neck region of day-old chicks at the dosage of 0.08 to 0.20 mg ceftiofur/chick. One mL of the 50 mg/mL reconstituted solution will treat approximately 250 to 625 day-old chicks.

Reconstituted NAXCEL Sterile Powder is to be administered by subcutaneous injection only. A sterile 26 gauge needle and syringe or properly cleaned automatic injection machine should be used.

Administer by subcutaneous injection in the neck region of day-old turkey poults at the dosage of 0.17 to 0.5 mg ceftiofur/poult. One mL of the 50 mg/mL reconstituted solution will treat approximately 100 to 294 day-old turkey poults.

Reconstituted NAXCEL Sterile Powder is to be administered by subcutaneous injection only.

Cattle: When used according to label indications, dosage and routes of administration, treated cattle must not be slaughtered for 4 days following the last treatment. When used according to label indications, dosage and routes of administration, a milk discard time is not required. Use of dosages in excess of those indicated or by unapproved routes of administration, such as intramammary, may result in illegal residues in edible tissues and/or in milk.

Swine: When used according to label indications, dosage and route of administration, treated pigs must not be slaughtered for 4 days following the last treatment. Use of dosages in excess of those indicated or by unapproved routes of administration may result in illegal residues in edible tissues.

Sheep: Neither a pre-slaughter drug withdrawal interval nor a milk discard time is required when this product is used according to label indications, dosage, and route of administration. Use of dosages in excess of those indicated or by unapproved routes of administration, such as intramammary, may result in illegal residues in edible tissues and/or in milk.

Goats: Neither a pre-slaughter drug withdrawal interval nor a milk discard time is required when this product is used according to label indications, dosage, and route of administration. Use of dosages in excess of those indicated or by unapproved routes of administration, such as intramammary, may result in illegal residues in edible tissues and/or in milk.

Horses: Do not use in horses intended for human consumption.

Following subcutaneous administration of ceftiofur sodium in the neck, small areas of discoloration at the site may persist beyond five days, potentially resulting in trim loss of edible tissues at slaughter.

As with any parenteral injection, localized post-injection bacterial infections may result in abscess formation. Attention to hygienic procedures can minimize their occurrence.

The safety of ceftiofur has not been determined for swine intended for breeding.

The safety of ceftiofur has not been determined for horses intended for breeding. The administration of antimicrobials to horses under conditions of stress may be associated with acute diarrhea that could be fatal. If acute diarrhea is observed, discontinue use of this antimicrobial and initiate appropriate therapy.

The safety of ceftiofur has not been determined for dogs intended for breeding, or pregnant dogs.

Results from a five-day tolerance study in normal feeder calves indicated that formulated ceftiofur was well tolerated at 25 times (25 mg/lb/day) the highest recommended dose of 1.0 mg/lb/day for five consecutive days. Ceftiofur administered intramuscularly had no adverse systemic effects.

In a 15-day safety/toxicity study, five steer and five heifer calves per group were intramuscularly administered formulated ceftiofur at 0 (vehicle control), 1, 3, 5 and 10 times the highest recommended dose of 1.0 mg/lb/day to determine the safety factor. There were no adverse systemic effects indicating that the formulated ceftiofur has a wide margin of safety when injected intramuscularly into the feeder calves at 10 times (10 mg/lb/day) the recommended dose for three times (15 days) the recommended three to five days of therapy. The formulation was shown to be a slight muscle irritant based on results of histopathological evaluation of the injection sites at 1 and 3 times the highest recommended dose of 1.0 mg/lb/day. The histopathological evaluations were conducted at posttreatment days 1, 3, 7 and 14.

The injection of NAXCEL Sterile Powder at the recommended dose administered SC in the neck of cattle was well tolerated. However, a several square centimeter area of yellow-red discoloration resulting from a single SC injection persisted in many of the cattle beyond 4.5 days post-injection. Also, one of the animals developed an abscess at the injection site.

Results from a five-day tolerance study in normal feeder pigs indicated that formulated ceftiofur was well tolerated when administered at 57 mg/lb (more than 25 times the highest recommended daily dosage of 2.27 mg/lb of body weight) for five consecutive days. Ceftiofur administered intramuscularly to pigs produced no overt adverse signs of toxicity.

To determine the safety factor and to measure the muscle irritancy potential in swine, a safety/toxicity study was conducted. Five barrows and five gilts per group were intramuscularly administered formulated ceftiofur at 0, 2.27, 6.81 and 11.36 mg/lb of body weight for 15 days which is 0, 1, 3 and 5 times the highest recommended dose of 2.27 mg/lb of body weight/day and 5 times the recommended treatment length of 3 days. There were no adverse systemic effects indicating that formulated ceftiofur has a wide margin of safety when injected intramuscularly into feeder pigs at the highest recommended dose of 2.27 mg/lb/day for 3 days or at levels up to 5 times the highest recommended dose for 5 times the recommended length of treatment. The formulation was shown to be a slight muscle irritant based on results of histopathological evaluation of the injection sites at posttreatment days 1, 2, 3 and 4. By day 10 post injection the muscle reaction was subsiding and at day 15 post injection there was little evidence of muscle damage in any of the pigs in any of the treatment groups.

In a 15-day safety/toxicity study in sheep, three wether and three ewe lambs per group were given formulated ceftiofur sodium by the intramuscular route 0 (sterile water vehicle), 1, 3 or 5 times the recommended dose of 1.0 mg/lb/day for 3 times the recommended maximum duration of 5 days of treatment. There were no adverse systemic effects indicating that formulated ceftiofur is well tolerated and has a wide margin of safety in sheep. Based on examination of injection sites from study days 9, 11, 13 and 15, a low incidence of visual changes and histopathologic findings of mild, reversible inflammation from all groups including the controls indicated that the formulation is a slight muscle irritant.

In a 15-day safety/toxicity study 5 lactating does, 5 dry does, and 5 wethers were given formulated ceftiofur by the intramuscular route with 11 mg/kg/day for 15 days. This constitutes 5 times the recommended dose for 3 times the recommended maximum duration of 5 days of treatment. There were no adverse systemic effects indicating that formulated ceftiofur is well tolerated and has a wide margin of safety in goats.

In a safety study, horses received a daily intramuscular injection of either 0 mg/lb/day (saline control), 1.0 mg/lb/day (50 mg/mL), 3.0 mg/lb/day (100 mg/mL), or 5.0 mg/lb/day (200 mg/mL) of an aqueous solution of ceftiofur sodium for 30 or 31 days. Ceftiofur sodium was well tolerated when administered intramuscularly to male and female horses at doses up to 5.0 mg/lb/day for 30 or 31 days. No clinical evidence of irritation was noted at any dose. The drug-related changes detected in this study were limited to a transient decrease in food consumption in horses receiving 3.0 or 5.0 mg/lb/day ceftiofur, and general mild skeletal muscle irritation at the injection sites which resolved by regeneration of muscle fibers.

In a tolerance study, horses received a single daily intravenous infusion of either 0 (saline), 10.0 or 25.0 mg/lb/day of an aqueous solution (50 mg/mL) of ceftiofur for 10 days. The results indicated that ceftiofur administered intravenously at a dose of 10.0 or 25.0 mg/lb/day apparently can change the bacterial flora of the large intestine thereby leading to inflammation of the large intestine with subsequent diarrhea and other clinical signs (loose feces, eating bedding straw, dehydration, rolling or colic and a dull, inactive demeanor). Decreased food consumption, a loss of body weight, hematologic changes related to acute inflammation and stress, and serum chemistry changes related to decreased food consumption and diarrhea were also associated with treatment at these doses. The adverse effects were most severe a few days after dosing was initiated and tended to become less severe toward the end of the 10-day dosing period.

Ceftiofur sodium was well tolerated at the therapeutic dose and is safe for the treatment of urinary tract infections in dogs. In the acute safety study, ceftiofur was well tolerated by dogs at the recommended level (1.0 mg/lb) for 5-14 days. When administered subcutaneously for 42 consecutive days, one of four females developed thrombocytopenia (15 days) and anemia (36 days). Thrombocytopenia and anemia also occurred at the 3× and 5× dose levels.

In the reversibility phase of the study (5× dose), the thrombocytopenia reversed within 8 days, and of the two anemic animals the male recovered within 6 weeks and the female was sacrificed due to the severity of the anemia. In the 15-day tolerance study in dogs, high subcutaneous doses (25 and 125 times the recommended therapeutic dose) produced a progressive and dose-related thrombocytopenia, with some dogs also exhibiting anemia and bone marrow changes. The hematopoietic changes noted in dogs treated with ceftiofur were similar to those associated with long-term cephalosporin administration in dogs and also man. The hematopoietic effects are not expected to occur as a result of recommended therapy.

In an acute toxicity study of ceftiofur in day-old chicks, a total of 60 male and 60 female chicks were each given single subcutaneous injections of 10, 100 or 1,000 mg/kg of body weight. Treatment on day 1 was followed by 6 days of observation; body weight was determined on days 1, 4 and 7; and selected hematology parameters were evaluated on day 4. No meaningful differences were noted among the treated and control groups of chicks for the parameters evaluated. Histopathologic evaluation of all deaths and chicks surviving to termination did not reveal a target organ or tissue of potential toxicity of ceftiofur when administered at up to 20 times (100 mg/kg) the intended highest use dosage.

In an acute toxicity study of ceftiofur in day-old turkey poults, a total of 30 male and 30 female poults were each administered single subcutaneous injections of 100, 400 or 800 mg/kg body weight. Injection on day 1 was followed by 6 days of observation; body weight on days 1, 4, and 7; and selected hematology parameters on day 4. No meaningful differences were noted between the treated groups at 100 or 400 mg ceftiofur/kg and a negative control group for the parameters evaluated. Histopathologic evaluation of all deaths and poults surviving to termination did not reveal a target organ or tissue of potential toxicity of ceftiofur when administered at up to 50 times (400 mg/kg) the highest use dosage. A dose of 800 mg/kg (100 times the intended highest use dosage) was toxic, resulting in clinical signs and deaths accompanied by gross and microscopic morphologic tissue alterations.

A radiolabeled residue metabolism study established tolerances for ceftiofur residues in cattle kidney, liver and muscle. These tolerances of ceftiofur residues are 0.4 ppm in kidney, 2.0 ppm in liver, 1.0 ppm in muscle, and 0.1 ppm in milk.

A pivotal tissue residue decline study was conducted in cattle. In this study, cattle received an intramuscular injection of 1.0 mg of ceftiofur per lb body weight (2.2 mg of ceftiofur per kg body weight) for five consecutive days. Ceftiofur residues in tissues were less than the tolerances for ceftiofur residues in tissues such as kidney, liver and muscle by 4 days after dosing. These data collectively support a 4-day pre-slaughter withdrawal period in cattle when used according to label directions.

Radiolabeled residue metabolism studies established tolerances for ceftiofur residues in swine kidney, liver, and muscle. These tolerances of ceftiofur residues are 0.25 ppm in kidney, 3.0 ppm in liver and 2.0 ppm in muscle.

A pivotal tissue residue decline study was conducted in swine. In this study, pigs received 2.27 mg of ceftiofur per lb body weight (5 mg of ceftiofur per kg body weight) per day for three consecutive days. Ceftiofur residues in tissues were less than the tolerances for ceftiofur residues in tissues such as kidney, liver and muscle by 4 days after dosing. These data collectively support a 4-day pre-slaughter withdrawal period in swine when used according to label directions.

At the end of the 7-day refrigeration or 12-hour room temperature storage period following reconstitution, any remaining reconstituted product may be frozen for up to 8 weeks without loss in potency or other chemical properties. This is a one-time only salvage procedure for the remaining product. To use this salvaged product at any time during the 8-week storage period, hold the vial under warm running water, gently swirling the container to accelerate thawing, or allow the frozen material to thaw at room temperature. Rapid freezing or thawing may result in vial breakage. Any product not used immediately upon thawing should be discarded.