The palatable once-a-month prescription tablet that prevents heartworm disease and flea populations in dogs and

puppies. SENTINEL

®

FLAVOR TABS

®

(milbemycin oxime/lufenuron) also control flea populations and adult

hookworms, and remove and control adult roundworm and whipworm infections in dogs and puppies.

Caution

Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.

Warnings

0.23 mg/pound (0.5 mg/kg) of milbemycin oxime and 4.55 mg/pound (10 mg/kg) body weight of lufenuron.

Milbemycin oxime consists of the oxime derivatives of 5-didehydromilbemycins in the ratio of approximately

80% A

4

(C

45

(C

31

H

43

NO

7

, MW 541.68). Milbemycin oxime is classified as a

macrocyclic anthelmintic.

Lufenuron is a benzoylphenylurea derivative with the following chemical composition: N-[2,5-dichloro-4-

(1,1,2,3,3,3,-hexafluoropropoxy)-phenylaminocarbonyl]-2,6-difluoro-benzamide (C

H

O

, MW 511.15).

of heartworm larvae and the adult stage of hookworm (Ancylostoma caninum), roundworm (Toxocara canis and

Toxascaris leonina) and whipworm (Trichuris vulpis) infestations when administered orally according to the

recommended dosage schedule.

Lufenuron, the other active ingredient in SENTINEL FLAVOR TABS, is an insect development inhibitor which

breaks the flea life cycle by inhibiting egg development. Lufenuron’s mode of action is interference with chitin

synthesis, polymerization and deposition. Lufenuron has no effect on the adult flea. After biting a lufenuron-

treated dog, the female flea ingests a blood meal containing lufenuron which is subsequently deposited in her

eggs. Lufenuron prevents most flea eggs from hatching or maturing into adults and thus prevents and controls

flea populations by breaking the life cycle. (See Efficacy).

and Trichuris vulpis (whipworm) infections.

Lufenuron controls flea populations by preventing the development of flea eggs and does not kill adult fleas.

Concurrent use of an adulticide product may be necessary for adequate control of adult fleas.

Without concurrent use of an adulticide, adequate flea control may not be achieved in dogs that

have repeated exposure to flea infested animals or environments.

Precautions

Do not use in puppies less than four weeks of age and less than two pounds of body weight. Prior to

administration of SENTINEL FLAVOR TABS, dogs should be tested for existing heartworm infections. Infected

dogs should be treated to remove adult heartworms and microfilariae prior to initiating treatment with SENTINEL

Therefore, noticeable control may not be observed until several weeks after dosing when a preexisting infestation

is present. Cooler geographic areas may have longer lag periods due to a prolonged flea life cycle. The concurrent

use of an approved adulticide may be employed depending on the severity of the infestation.

If a SENTINEL FLAVOR TABS-treated dog comes in contact with a flea-infested environment, adult fleas may infest

the treated animal. These adult fleas are unable to produce viable offspring. The temporary use of an adulticide

product may be necessary to kill these adult fleas.

Efficacy: Milbemycin Oxime

Milbemycin oxime provided complete protection against heartworm infection in both controlled laboratory

and clinical trials.

10 mg/kg in studies using experimental flea infestations. In well-controlled clinical trials, when treatment with

lufenuron tablets was initiated prior to the flea season, mean flea counts were lower on lufenuron-treated dogs

versus placebo-treated dogs. After 6 monthly treatments, the mean number of fleas on lufenuron-treated dogs

was approximately 4 compared to 230 on placebo-treated dogs.

When treatment was initiated during the flea season, lufenuron tablets were effective in controlling flea infestations

on dogs that completed the study. The mean flea count per lufenuron-treated dog was approximately 74 prior to

treatment but had decreased to 4 after six monthly doses of lufenuron. A topical adulticide was used in the first

eight weeks of the study to kill the pre-existing adult fleas.

Safety: Milbemycin Oxime

reactions in treated dogs with high microfilaremia counts (see Precautions for reactions observed). Safety studies

in pregnant dogs demonstrated that high doses (1.5 mg/kg = 3X) of milbemycin oxime given in an exaggerated

dosing regimen (daily from mating through weaning), resulted in measurable concentrations of the drug in milk.

Puppies nursing these females which received exaggerated dosing regimens demonstrated milbemycin-related

effects. These effects were directly attributable to the exaggerated experimental dosing regimen. The product is

normally intended for once-a-month administration only. Subsequent studies included using 3X daily from

mating to one week before weaning and demonstrated no effects on the pregnant females or their litters. A second

study where pregnant females were dosed once at 3X the monthly use rate either before, on the day of or shortly

after whelping resulted in no effects on the puppies.