Aivlosin (Tylvalosin Tartrate) Water Soluble

Aivlosin For treatment of PPE/ ileitis associated with Lawsonia intracellularis in pigs. Also as an aid in reducing the severity of swine respiratory disease associated with Haemophilus parasuis, Pasteurella multocida and Streptococcus suis in pigs.

Aivlosin Water Soluble Granules is a water soluble granular powder containing 62.5% w/w tylvalosin (as tylvalosin tartrate) for oral use by administration in the drinking water.

Key Benefits:

• Dual efficacy against both respiratory (SRD) and enteric (PPE) pathogens
• Quickly absorbed, potent novel macrolide antibiotic that is not used in human health.
• Supports judicious, responsible antibiotic use.
• Wide safety margin; compatible when treating pigs with ionophores.
• Accumulates rapidly in lung and small intestinal tissue after treatment.
• Enters into white blood cells within two hours (in vitro).
• 24-hour withdrawal
• Easy, reliable dosing in drinking water for rapid control of new outbreaks.
• Palatable, non-clogging formulation.

Indications

For the treatment of Porcine Proliferative Enteropathy (PPE) associated with Lawsonia intracellularis in pigs. As an aid in reducing the severity of swine respiratory disease (SRD) associated with Haemophilus parasuis, Pasteurella multocida and Streptococcus suis in groups of pigs experiencing an outbreak of SRD.

To reduce the development of antimicrobial resistance and maintain effectiveness, use this antibiotic prudently.

For use in drinking water of swine only.

Aivlosin® Water Soluble Granules sachet size	40 g	160 g	400 g
Tylvalosin content of sachet (g)	25	100	250
Volume of drinking water (L)	500	2000	5000
Volume of drinking water (US gallons)	132	528	1320
Tylvalosin inclusion rate in water	50 parts per million (ppm)

Note: Based on theoretical daily water consumption rate of 10% body weight, 50 ppm tylvalosin in drinking water will provide a dose rate of5 mg tylvalosin/kg body weight per day.

Administer continuously in drinking water. Medicated water should be the only source of drinking water during the treatment period. If improvement is not observed within 5 days, the diagnosis should be reconfirmed.

Mixing

Keep water supply equipment clean and in good operating condition. Clean water medication equipment before and after each use. Only a sufficient amount of medicated drinking water should be prepared to cover daily requirements. Do not mix or administer medicated water using equipment made of galvanized metal. Galvanized metal adversely affects the stability of tylvalosin in water any may reduce the effectiveness of the product. Prepare a fresh batch of medicated stock solution or medicated drinking water daily. Aivlosin® Water Soluble Granules may be mixed directly into the drinking water system or first mixed as a stock solution in a smaller amount of water, which is then added to the drinking water system, for example, using an automatic water proportioner.

Direct Mixing:

Prepare a fresh batch of medicated drinking water daily. When mixing the product directly into the drinking water system, the contents of the sachet should be sprinkled onto the surface of the water and mixed slowly and thoroughly until a clear solution is produced ( usually within 3 minutes).

Stock Solution:

Prepare a fresh batch of medicated stock solution daily. When preparing a stock solution for an automatic water proportioner, the recommended maximum concentration is one-40 g sachet per 4 L (-1 US gallon), one 160 g sachet per 16 L (-4 US gallons) or one 400 g sachet per 40 L (-10 US gallons).

Sprinkle contents onto the surface of the water and mix slowly and thoroughly for 10 minutes. After this time, any remaining cloudiness will not affect tylvalosin concentration. Use the stock solution for dilution into the drinking water system as soon as it is prepared. Add 32 mL of this stock solution per 4 L drinking water to provide a final concentration of 50 ppm. Prepare drinking water medicated with 50 parts per million tylvalosin.

Administer continuously in drinking water for five (5) consecutive days. Based on a theoretical daily water consumption rate of 10% body weight, 50 ppm tylvalosin in drinking water will provide a dose rate of 5 mg tylvalosin/kg body weight per day.

Caution:

Not for use in breeding animals the effects of tylvalosin on swine reproductive performance, pregnancy and lactation have not been determined.

Note: Good management and hygiene practices should be followed to reduce the risk of re-infection.

Warnings:

Treated swine must not be slaughtered for use in food for at least 24 hours after the latest treatment with this drug. Tylvalosin has been shown to cause hypersensitivity reactions in laboratory animals; therefore, people with known hypersensitivity to tylvalosin tartrate should avoid contact with this product. When mixing Aivlosin® Water Soluble Granules and handling the medicated water, direct avoid inhalation, oral exposure and direct contact with skin or eyes.

Keep out of reach of children.

Adverse Reactions:

No adverse reactions related to the drug were observed during clinical or target animal safety trials.

Effectiveness:

Swine:

Control of Porcine Proliferative Enteropathy (PPE):

A multi-location challenge model study was conducted to confirm the effectiveness of Aivlosin® Water Soluble Granules for the control of PPE associated with Lawsonia intracellularis. Pigs were challenged by intragastric gavage with a mucosal homogenate containing a North American isolate of Lawsonia intracellularis isolated in 2005 that induces representative disease in challenged pigs. When at least 15% of the study pigs were showing signs of infection based on abnormal fecal scores, pigs were provided water containing tylvalosin at an inclusion rate of 50 ppm for five consecutive days, or were provided non-medicated water. Effectiveness was evaluated using clinical scores (pig demeanor score, abdominal appearance score, and fecal score) and clinically-validated gross PPE lesion scores. A conclusion of the effectiveness of 50 ppm tylvalosin for the control of PPE was determined based on a statistically significant (p=0.0103) improvement in the clinically-validated gross PPE lesion scores in the 50 ppm tylvalosin-treated group compared to the non-medicated group.

Control of Swine Respiratory Disease (SRD):

The effectiveness of Aivlosin® Water Soluble Granules for the control of Swine Respiratory Disease (SRD) associated with Bordetella bronchiseptica, Haemophilus parasuis, Pasteurella multocida and Streptococcus suis was investigated in a natural field infection study conducted in the United States (three study sites) and Canada (one study site). Day 0 was defined when at least 15% of the candidate pigs were deemed clinically affected with SRD (moderate or severe respiratory scores, moderate or severe depression score, and rectal temperature greater than or equal to 104.0 °F). On Day 0 a total of 980 pigs were enrolled and randomly assigned to a tylvalosin-treated group (50 ppm tylvalosin in drinking water for 5 consecutive days) or a non-medicated control group. Treatment success was evaluated on Day 7 and was defined as a pig with normal or mild respiratory score, normal or mild depression score, and rectal temperature less than 104.0 °F. The proportion of pigs meeting the definition of treatment success was numerically higher in the tylvalosin-treated group (48.5%) compared to the proportion of pigs meeting the definition of treatment success in the non-medicated control group (41.6%), and the observed difference was statistically significant (p=0.0353).

Animal Safety:

Swine:

Margin of safety: Aivlosin® Water Soluble Granules given orally in drinking water at 0, 50, 150, and 250 ppm tylvalosin (0, 1X, 3X, and 5X the labeled dose, respectively) to 8 healthy pigs per treatment group over 15 days (3X the labeled duration) did not result in drug-induced clinical signs, gross pathologic lesions, histopathologic lesions or clinically-relevant clinical pathology abnormalities.

Storage:

Store at or below 25°C.