For Animal Use Only
MACROTİL
Solution for Injection
Veterinary Systemic Antibacterial
COMPOSITION
It is a light yellow-amber coloured, clear sterile injectable solution containing Tilmicosin phosphate equivalent to 300 mg Tilmicosin base per ml.
PHARMCOLOGICAL PROPERTIES
Tilmicosin, which comes from the macrolide group, is a semi-synthetic antibiotic. It acts by binding to the 50 S ribosomal subunit in bacteria, inhibiting protein synthesis and stopping bacterial growth. Bacteria on which it is effective to include Staphylococcus aureus, Streptococcus agalactiae, Corynebacterium pyogenes, Clostridium perfringens and Mycoplasma species, and microorganisms such as Pasteurella haemolytica, Pasteurella multocida, Haemophilus somnus, and Fusobacterium necrophorum. Following a single-dose administration of 10 mg/kg body weight given subcutaneously in cattle, peak Tilmicosin concentration is achieved in the plasma within 1 hour and levels of 0.07 µg/ml are maintained in the plasma for 3 days.
Tilmicosin reaches a concentration in the lungs of approximately 60 times the serum level, and this concentration persists for more than 3 days. This feature makes it preferred in the treatment of respiratory system infections. It also reaches high concentrations in the liver, breast tissue and kidneys. In a 21-day period, 24% of the drug is excreted in the urine and 68% in the stool.
AREA OF USE/INDICATIONS
In cattle and sheep, especially with respiratory tract infections caused by Pasteurella haemolytica and other susceptible microorganisms; It is used in the treatment of mastitis caused by Staphylococcus aureus and Mycoplasma agalactiae and abortions of Chlamydia psittaci in sheep. It is also used in the treatment of interdigital necrobacillosis in cattle.
USAGE AND DOSAGE
Unless recommended otherwise by the veterinarian;
It is administered to cattle and sheep with a single dose of 10 mg / kg body weight (1 ml / 30 kg body weight) and only subcutaneously. The application site is the back of the forelimbs and the upper part of the ribs in cattle, and the shoulder area in sheep. More than 15 ml of drug should not be applied to an application area, if it is necessary to apply in larger amounts, the dose should be divided and injected into separate places.
UNDESIRED EFFECTS
Occasionally, a temporary and mild swelling may be seen at the injection site. In studies with laboratory animals and pets, Tilmicosin has shown to have a toxic effect on the heart muscle. Its main effects on the heart appeared to be tachycardia and decreased force of contraction (negative inotropic effect). In cattle, subcutaneous doses of 10, 30 and 50 mg/kg were repeated 3 times at 72 hour intervals and no mortality was observed. As expected, edema occurred at the injection site. The only group with lesions at necropsy was the 50 mg/kg dose group, and minimal myocardial necrosis was observed. Administration of 150 mg/kg subcutaneous dose with 72 hour intervals resulted in deaths. Edema occurred at the injection site. The only lesion at necropsy is minimal myocardial necrosis. Intravenous administration at a dose of 5 mg/kg resulted in deaths in cattle.
DRUG INTERACTIONS
It should not be mixed with other parenteral solutions as it may cause precipitation of the active ingredient. Tilmicosin is an antagonist with phenicols, lincosamides and other macrolide antibacterials. The toxic side effects of tilmicosin on the cardiovascular system are exacerbated by beta-adrenergic receptor antagonists such as propranolol.
RESIDUAL WARNINGS FOR FOOD PRODUCING ANIMALS
Drug Residue Elimination Period: during the treatment and after the last drug application, cattle raised for meat should not be sent to slaughter until 60 days and sheep 42 days after. Sheep milk obtained during the use of the drug and for 15 days (30 milkings) following the cessation of use should not be offered for consumption. It should not be used in cows producing milk for human consumption. It is not recommended to be applied to sheep producing milk for human consumption due to the long wash-out period in milk.
CONTRAINDICATIONS
It should not be administered intravenously. It should not be used in lambs with a body weight of less than 15 kg, as it may cause death.
Use in Pregnancy: In clinical studies on the effects of tilmicosin on reproduction in rats, no teratogenic or embryotoxic effects were observed.
SPECIAL CLINICAL INFORMATION AND SPECIAL WARNINGS FOR TARGET SPECIES
Oral or parenteral administration of tilmicosin may cause cardiotoxic effects. The primary effects are increased heart rate (tachycardia) and decreased force of contraction of the heart (negative inotropy). Cardiovascular toxicity may result from blockade of the calcium channel. Calcium chloride treatment after administration of tilmicosin in dogs produced a positive effect on the inotropic status of the left ventricle and some improvement in vascular blood pressure and tachycardia. The negative inotropic effect of tilmicosin in dogs can be partially reversed with dobutamine. Beta adrenergic antagonists such as propanolol exacerbate the negative inotropic effect. Intramuscular administration of 10 mg/kg tilmicosin in pigs increased respiration, vomiting and convulsions; the 20 mg/kg dose killed 3 out of 4 animals and the 30 mg/kg dose killed all 4 animals. Intravenous administration of 4.5 and 5.6 mg/kg, followed by intravenous administration of 1 ml of epinephrine (1/1000) 2-6 times, resulted in the death of all 6 injected pigs. All the pigs that were administered the same dose of tilmicosin and not given epinephrine survived. These results indicate that intravenous administration of epinephrine may be contraindicated.
SYMPTOMS OF OVERDOSE, PRECAUTIONS AND ANTIDOTE
In all animals, especially puppies, the specified time and dose should not be exceeded, otherwise the mentioned side effects may occur. In case of overdose, drug administration should be stopped.
GENERAL PRECAUTIONS
Consult your veterinarian before use and in case of an unexpected effect. Keep out of reach of children. It should be kept away from foodstuff.
PRECAUTIONS TO BE TAKEN AND RECOMMENDATIONS FOR PHYSCIANS
INJECTING THIS DRUG INTO PEOPLE CAN CAUSE DEATH. BE EXTREMELY CAREFUL TO AVOID ACCIDENTAL INJECTIONS AND CAREFULLY READ THE FOLLOWING RECOMMENDATIONS FOR USE AND APPLICATION.
* This medicine should only be administered by a veterinarian.
* Never carry the Macrotil drawn syringe with its needle.
* The needle should only be attached to the syringe when drawing drugs into the syringe or during injection. At other times, keep the syringe and needle separate.
* Do not use automatic injectors during applications.
* Take the animals to be injected in good restraint. Take necessary precautions so that nearby animals do not threaten the injection safety.
* Do not work alone while applying Macrotil.
* For accidental injections in humans, CONSULT A PHYSICIAN IMMEDIATELY and take the medicine bottle, medicine box or leaflet with you. Apply a cold compress to the injection site (do not apply ice directly)
Additional security warnings:
* Avoid contact of the drug with eyes.
* Sensitization may occur in case of skin contact.
* Wash your hands with water after use.
WARNINGS FOR PHYSCIANS
INJECTING THIS DRUG INTO PEOPLE CAN CAUSE DEATH.
In the case of injection, toxicity occurs in the cardiovascular system. This toxicity is likely related to calcium channel blockade. Administering calcium chloride intravenously should only be done if it is certain that the person has been injected with tilmicosin.
In studies in dogs, injection of tilmicosin caused a negative inotropic effect resulting in tachycardia and a reduction in systemic arterial and pulse pressure.
DO NOT GIVE THE PATIENT BETA-ADRENERGIC ANTAGONISTS, SUCH AS ADRENALINE OR PROPRANOLOL.
In pigs, tilmicosine-related deaths are increased when adrenaline is used.
In dogs, intravenous administration of calcium chloride produced a positive effect on the inotropic status of the left ventricle and some improvement in vascular blood pressure and tachycardia.
Preclinical data and a clinical report suggest that calcium chloride infusion in humans may be effective in reversing tilmicosin-induced changes in vascular pressure and heart rate.
Even if it is not effective on tachycardia, the use of dobutamine should also be considered because of its positive inotropic effects. Since tilmicosin remains in the tissues for a few days, the cardiovascular system should be closely monitored and supportive treatment should be applied.
Physicians dealing with people exposed to this drug are advised to contact the National Poison Center. (National Poison Center phone number: 114; Cemal Gürsel Street, No:18 Sıhhiye – ANKARA; zehir@saglik.gov.tr )
STORAGE CONDITIONS AND SHELF LIFE
Shelf life is 2 years from the date of manufacture when kept under 25o C protected from light.
END DISPOSAL AND WARNINGS FOR NON-TARGET SPECIES
For cattle and sheep only, should not be applied to equidae, dogs and goats as it can cause death.
TRADE DRESS
It is offered for sale in amber-colored glass bottles of 20, 50, 100, 250, and 500 ml in cardboard boxes.
PLACE AND CONDITIONS OF SALE
It is sold in pharmacies, veterinary clinics, outpatient clinics, and animal hospitals with a veterinary prescription.
