Micotil (Canada)

Company: Elanco

Tilmicosin Injection USP

AH0230

DIN 00857602

VETERINARY USE ONLY

Sterile

Each mL contains 300 mg of tilmicosin. For subcutaneous use in cattle and lambs only. Do not use in automatically powered syringes. See pull-out label for important safety information.

Medicinal Ingredient: tilmicosin

Description

Micotil injection is a preconstituted solution of the antibiotic tilmicosin. Each mL contains 300 mg of tilmicosin activity; 25% propylene glycol; phosphoric acid as needed to adjust pH; water for injection, q.s. Tilmicosin is produced semi-synthetically and is a member of the macrolide class of antibiotics.

Micotil Indications

For the treatment of bovine respiratory disease (BRD) associated with Mannheimia (Pasteurella) haemolytica and Pasteurella multocida.

For the reduction of morbidity associated with bovine respiratory disease (BRD) in feedlot calves, caused by Mannheimia (Pasteurella) haemolytica and Pasteurella multocida, during the first 30 days in the feedlot, when administered at the time of arrival.

For the treatment of pneumonic pasteurellosis in lambs associated with Mannheimia (Pasteurella) haemolytica.

Dosage and Administration

FOR SUBCUTANEOUS USE IN CATTLE. FOR SUBCUTANEOUS USE IN LAMBS GREATER THAN 15 KG BODY WEIGHT ONLY. Administer a single subcutaneous injection of 10 mg tilmicosin per kg of body weight (1 mL per 30 kg/1.5 mL per 100 lbs.). Do not inject more than 10 mL per injection site.

For cattle and sheep, injection under the skin in the neck is suggested. If not accessible, inject under the skin behind the shoulders and over the ribs.

If no improvement is noted within 48 hours, the diagnosis should be reconfirmed.

NOTE: Swelling at the subcutaneous site of injection may be observed but is transient and usually mild.

CONTRAINDICATIONS: DO NOT USE IN AUTOMATICALLY POWERED SYRINGES. DO NOT ADMINISTER INTRAVENOUSLY. INTRAVENOUS INJECTION IN CATTLE AND LAMBS HAS BEEN FATAL.

DO NOT ADMINISTER TO ANIMALS OTHER THAN CATTLE OR SHEEP. INJECTION OF TILMICOSIN IN SWINE, GOATS AND NON-HUMAN PRIMATES HAS BEEN FATAL. TILMICOSIN MAY BE FATAL IN HORSES AND OTHER EQUIDS.

Warnings

Treated cattle must not be slaughtered for use in food for at least 28 days after latest treatment with this drug. Do not use in lactating dairy cattle.

Treated sheep must not be slaughtered for use in food for at least 36 days after latest treatment with this drug.

KEEP OUT OF REACH OF CHILDREN. AVOID CONTACT WITH EYES.

Adverse Reactions

The following adverse reactions have been reported post-approval: In cattle: injection site swelling and inflammation, lameness, collapse, anaphylaxis/anaphylactoid reactions, decreased food and water consumption, and death. In sheep: dyspnea and death.

For technical assistance or to report suspected adverse drug reactions, contact Elanco Canada Limited at 1-800-265-5475.

ACTIVITY: Micotil has an in vitro antibacterial spectrum that is predominantly Gram positive with activity against certain Gram negative microorganisms. Activity against several mycoplasma species has also been detected.

In addition to its direct antibacterial action, tilmicosin may exert an anti-inflammatory effect in the lung by increasing neutrophil apoptosis and reducing the release of pro-inflammatory mediators. However, the clinical significance of this effect is unknown.

In clinical trials, BRD treatment success with Micotil was usually characterized by rapid reduction in body temperatures, less severity of clinical signs, better weight gains and reduced mortality.

TOXICOLOGY: The cardiovascular system appears to be the target of toxicity in laboratory animals and domestic livestock administered Micotil by oral or parenteral routes. The primary cardiac effects are increased heart rate (tachycardia) and decreased contractility (negative inotropy). Cardiovascular toxicity may be due to calcium channel blockade.

Upon injection subcutaneously, the acute median lethal dose (MLD) of tilmicosin in mice is 97 mg of activity per kg and in rats is 185 mg/kg of body weight. Given orally, the MLD of tilmicosin is 800 mg/kg and 2250 mg/kg in fasted and nonfasted rats respectively. No compound-related lesions were found at necropsy.

In dogs, intravenous calcium offset Micotil-induced tachycardia and negative inotropy, restoring arterial pulse pressure within approximately 20 minutes. Dobutamine dose-dependently partially offset the negative inotropic effects induced by Micotil in dogs, but did not have an effect on the increased heart rate caused by Micotil. β-adrenergic antagonists, such as propranolol, exacerbated the negative inotropy of Micotil in dogs.

In monkeys, a single intramuscular dose of Micotil at 10 mg/kg caused no signs of toxicity. A single dose of Micotil at 20 mg/kg caused vomiting and 30 mg/kg caused the death of the only monkey tested.

In swine, intramuscular injection of Micotil at 10 mg/kg caused increased respiration, emesis and a convulsion, 20 mg/kg resulted in mortality in 3 of 4 pigs and 30 mg/kg caused the death of all 4 pigs tested. Injection of Micotil at 4.5 and 5.6 mg/kg intravenously followed by epinephrine, 1 mL (1:1000) intravenously 2 to 6 times, resulted in death of all pigs injected. All pigs given 4.5 mg/kg and 5.6 mg/kg Micotil intravenously with no epinephrine survived. These results suggest intravenous epinephrine may be contraindicated.

Results of genetic toxicology studies were all negative. Results of teratology and reproduction studies in rats were negative. The no effect level in dogs after daily oral doses of tilmicosin for up to one year is 4 mg/kg of body weight.

In cattle, subcutaneous doses of Micotil at 10, 30 and 50 mg/kg of body weight, each injected at 72 hour intervals for three times, did not cause any deaths. As expected, edema at the site of injection was noted. In cattle, the only lesion observed at necropsy was minimal myocardial necrosis in the 50 mg/kg Micotil group. Subcutaneous doses of Micotil at 150 mg/kg injected at 72-hour intervals resulted in deaths. Edema was marked at the site of injection. Minimal myocardial necrosis was the only lesion observed at necropsy. Deaths of cattle have been observed with a single intravenous dose of Micotil at 5 mg/kg of body weight.

In lambs, single subcutaneous doses of Micotil up to 150 mg/kg of body weight did not cause death. Deaths of lambs have been observed with a single intravenous dose of Micotil at 7.5 mg/kg body weight.

PHARMACOKINETICS: A single subcutaneous injection of Micotil at 10 mg/kg of body weight in cattle resulted in peak tilmicosin levels within one hour and detectable levels (0.07 µg/mL) in serum beyond 3 days. However, lung concentrations of tilmicosin remained above the tilmicosin MIC (95% of 3.12 µg/mL) for Mannheimia (Pasteurella) haemolytica for at least three days following the single injection. Serum tilmicosin levels are a poor indicator of total body tilmicosin. The lung/serum tilmicosin ratio in favour of lung tissue appeared to equilibrate by three days post injection at approximately 60. In a study with radioactive tilmicosin, 24% and 68% of the dose was recovered from urine and feces respectively over 21 days.

Storage

Store at room temperature, below 30°C. Protect from direct sunlight. Use within 84 days of first puncture.

How Supplied

Micotil is supplied in multidose amber bottles containing 300 mg of tilmicosin activity per mL.

MANUFACTURED BY: Elanco Canada Limited, 1919 Minnesota Court, Suite 401, Mississauga, Ontario L5N 0C9

Micotil, Elanco and the diagonal bar logo are trademarks of Elanco or its affiliates.

© 2023 Elanco or its affiliates.

Net 100 mL, 250 mL

14Feb2023

CPN: 1231127.3