For Animal Use Only
PİZERO
Suspension for Injection
Veterinary Systemic Antibacterial
COMPOSITION
Pizero Suspension for Injection is a sterile suspension of white to pale yellow color containing ceftiofur hydrochloride equivalent to 50 mg of ceftiofur base per 1 ml.
PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties
Ceftiofur is a 3rd generation cephalosporin and is active against most Gram-positive and Gram-negative bacteria. Ceftiofur acts by inhibiting bacterial cell wall synthesis.
Betalactams act by interfering with bacterial cell wall synthesis. Cell wall synthesis is dependent on enzymes called penicillin linker proteins. Bacteria develop resistance to cephalosporins by 4 basic mechanisms; 1) By desensitizing penicillin-binding proteins, 2) By changing the permeability of the cell wall to betalactam, 3) By producing betalactamase, which enables the cleavage of the betalactam ring, 4) Active efflux.
Some beta-lactamases found in Gram-negative enteric organisms can increase the MIC values of first- and second-generation cephalosporins, beta-lactam-inhibiting combinations, penicillins, ampicillins, and third- and fourth-generation cephalosporins.
The MIC values of target bacteria obtained from infected animals in Europe are as follows:
| Bacteria (number of isolates) | MIC range (µg/mL) | MIC90 (µg/mL) |
| Mannheimia haemolytica (149) | ≤ 0.002 – 0.12 | 0.015 |
| Pasteurella.multocida (134) | ≤ 0.002 – 0.015 | 0.004 |
| Histophilus somni (66) | ≤ 0.002 – 0.008 | 0.004 |
| Truperella pyogenes (35) | 0.25 – 4 | 2 |
| Escherichia coli (209) | 0.13 – 2 | 0.5 |
| Fusobacterium necrophorum (67) (Foot rot isots) | ≤ 0.06 – 0.13 | TE |
| Fusobacterium necrophorum (2) (acute metritis isolates) | ≤ 0.03 – 0.06 | TE |
TE: not detected.
The Clinical and Laboratory Institute has recommended the following values for respiratory pathogens on the label for ceftiofur.
| Zone Diameter (mm) | MIC (μg/mL) | Evaluation |
| ≥ 21 | ≤ 2.0 | (S) Susceptible |
| 18 – 20 | 4.0 | (I) Intermediate |
| ≤ 17 | ≥ 8.0 | (R) Resistant |
Pharmacokinetic properties
After administration, ceftiofur is rapidly metabolized to its main metabolite, desfuroilceftiofur.
This metabolite has antimicrobial activity equivalent to ceftiofur. It binds reversibly to plasma proteins. Due to its binding to these proteins, the metabolite is actively involved at the site of infection and remains active in the presence of pus and nectoric tissue.
At a single dose of 1 mg/kg subcutaneous administration in cattle, the maximum plasma level (2.85 ± 1.11 µg/mL) was reached two hours after administration. In healthy cattle, the Cmax level in the enrometrium was measured as 2.25 ± 0.79 µg/mL after 5±2 hours in a single application. Maximum concentrations in the carncula and lochia were measured as 1.11 ± 0.24 µg/mL and 0.98 ± 0.25 µg/mL, respectively.
The half-life in cattle is 11.5 ± 2.57 hours. No accumulation was observed with daily treatments longer than five days. Excretion occurs mainly in the urine (more than 55%) and feces (31%).
The bioavailability of ceftiofur is complete after subcutaneous administration.
AREA OF USE / INDICATIONS
Target type
Cattle
Area of use for each target species
Pizero Suspension for Injections is used in catttle in the treatment of these susceptible to ceftiofur conditions:
– Respiratory system infections caused by strains of Mannheimia haemolytica (formerly Pasteurella haemolytica), Pasteurella multocida and Histophilus somni (formerly Haemophilus somnus)
– Acute interdigital necrobacillosis (panarisium, foot root) caused by Fusobacterium necrophorum and Bacteroides melaninogenicus (Porphyromonas asaccharolytica)
– Acute post-partum (puerperal) metritis caused by Escherichia coli, Arcanobacterium pyogenes and Fusobacterium necrophorum within 10 days after birth and treatment with other antibiotics has failed.
USAGE AND DOSAGE
Shake the bottle vigorously before use for no more than 60 seconds or until it is sufficiently suspended.
For an accurate dosing, the body weight of the animals should be measured as accurately as possible.
Respiratory system infections: 1 mg/kg body weight per day for 3-5 days subcutaneously (1 ml product per 50 kg body weight per day)
Acute interdigital necrobacillosis: 1 mg/kg body weight per day for 3 days subcutaneously (1 ml product per 50 kg body weight per day)
Acute post-partum metritis (within 10 days after birth): 1 mg/kg body weight per day subcutaneously for 5 days (1 ml product per 50 kg body weight per day). In some cases, this infection may require supportive treatment.
No more than 15 ml of ml should be injected into one injection site. Injections on different days should be given to different areas.
SPECIAL CLINICAL INFORMATION AND SPECIAL WARNINGS FOR TARGET SPECIES
Specific warnings for each target species
Not known.
Special warnings for use
(i) Special warnings for use in animals
Shake the bottle well to reconstitute into suspension before use.
If an allergic reaction is observed, treatment should be discontinued.
This product is selective for resistant strains producing extended-spectrum beta-lactamases that may pose a risk to human health (eg via food). Therefore, this product should be reserved as a reserve antibiotic for situations where initial therapy is poor or expected to result (severe acute conditions in which therapy must be initiated without a bacteriological diagnosis).
Regional and national antimicrobial policies should be considered in the use of this product. Increased use of this product, including use other than as specified in this document, may result in an increased prevalence of resistant bacteria. For this reason, the product should be used as much as possible according to the results of the susceptibility test.
It is not used for preventive purposes in case of retention of the placenta.
This product is for individual treatment. It is not used as part of disease prevention or herd health programs. Group treatment of animals should be limited to epidemics only, in accordance with approved terms of use.
Use during pregnancy, lactation and ovulation
Although studies in laboratory animals have not shown effects on teratogenicity, abortion and reproduction, the safe use of the product in pregnant cows has not been studied. It can only be used during pregnancy according to the benefit/risk assessment of the veterinarian.
UNDESIRED EFFECTS (FREQUENCY AND SEVERITY)
Dose-independent hypersensitivity reactions may occur. Allergic reactions (e.g. skin reactions, anaphylaxis) have been reported very rarely (less than 1 in 10000 animals). After subcutaneous application in cattle, swelling and stiffness were observed at the application site. Up to 42 days after injection, mild to moderate local tissue reactions (edema, discoloration, etc.) were observed. According to field reports, injection site reactions are very rare.
DRUG INTERACTIONS
Interaction with other medicinal products and other forms of interaction
The bactericidal action of beta-lactams is inhibited by bacteriostatic antibiotics such as macrolides, sulfonamides and tetracyclines. Aminoglycosides positively affect the action of cephalosporins.
Incompatibilities
It should not be mixed with other products.
SYMPTOMS OF OVERDOSE, PRECAUTIONS AND ANTIDOTE
There was no significant indication of systemic toxicity in parenteral overdose in cattle.
WITHDRAWAL WARNINGS FOR FOOD PRODUCING ANIMALS
Withdrawal period: During the treatment and after the last drug administration, cattle should not be sent to slaughter until 8 days have passed. Residue purification period for milk is “0” days.
CONTRAINDICATIONS
Do not administer to animals known to be sensitive to ceftyrofura or beta-lactams.
Do not administer intravenously.
Do not use in cases of resistance to other cephalosporins or beta-lactams.
Not for use in chickens due to the risk of danger to humans from antimicrobial resistance, including laying hens.
GENERAL PRECAUTIONS
None.
PRECAUTIONS TO BE TAKEN AND RECOMMENDATIONS FOR PHYSICIANS
Penicillin and cephalosporins may cause hypersensitivity (allergy) reactions after injection, inhalation, ingestion or skin contact. Sensitivity to penicillins causes sensitivity to cephalosporins and vice versa. Rarely, these reactions can be very serious.
If you are sensitive and have received medical advice not to work with such products, do not touch this product.
If symptoms such as skin rash develop, seek immediate medical treatment and show this warning to the healthcare professional. Take the necessary precautions not to accidentally inject yourself with the product. In such a case, immediately apply to a health institution.
Symptoms such as swelling of the face, lips, or eyes or difficulty breathing are very serious and require immediate medical attention.
Wash your hands after use.
STORAGE CONDITIONS AND SHELF LIFE
It should be stored at room temperature (between 15°C-25°C). It should not be frozen. Shelf life is 2 years from the date of manufacture. Shelf life after first use is 30 days by keeping it below 25°C.
END DISPOSAL AND WARNINGS FOR NON-TARGET SPECIES
Unused or leftover product should be disposed of in accordance with the relevant legislation.
TRADE DRESS
It is presented in 20 ml, 50, 100 ml transparent colored glass bottles and 100, 250 ml plastic bottles with cardboard boxes, and 500 ml plastic bottles without boxes.
PLACE AND CONDITIONS OF SALE
Sold in pharmacies and veterinary clinics with a veterinarian’s prescription.
