SENTINEL is a once-a-month oral tablet that controls flea infestations in dogs, prevents heartworm disease caused by Dirofilaria immitis, and treats and controls parasitic infections due to adult hookworm (Ancylostoma caninum), adult roundworms (Toxocara canis, Toxascaris leonina) and adult whipworm (Trichuris vulpis) in dogs over two (2) weeks of age and greater than one (1) kilogram of body weight.

Introduction

Novartis Animal Health encourages you to take the time to read this package insert which describes the use of SENTINEL (Lufenuron / milbemycin oxime) Tablets as a convenient monthly flea control, heartworm preventive and intestinal parasite control product.

SENTINEL is only available through veterinarians.

Description

The active ingredients in SENTINEL are:

1) Lufenuron : N-[2-dichloro-4-(1,1,2,3,3,3,-hexafluoropropoxy)- phenylamino-carbonyl]-2, 6-difluorobenzamide); and

2) Milbemycin Oxime: which consists of the oxime derivatives of 5-didehydromilbemycins in the ratio of approximately 80% A4 (C32H45N07, MW 555.71) and 20% A3 (C31H43N07).

Indications

SENTINEL Tablets are indicated for the control of flea infestations on dogs by interrupting the flea life cycle at the egg and larval stage, for the prevention of heartworm disease caused by Dirofilaria immitis and for the treatment and control of parasitic infections due to adult hookworm (Ancylostoma caninum), adult roundworms (Toxocara canis, Toxascaris leonina) and adult whipworm (Trichuris vulpis) in dogs over two (2) weeks of age and greater than one (1) kilogram of body weight.

SENTINEL works by interrupting the flea life cycle, thereby preventing the build up of flea infestations in dogs and in their surroundings.

SENTINEL is also indicated for control of active mid-season flea infestations. However, in this situation, flea adulticides should be used concurrently at labeled rates for the first 6-8 weeks. This provides time for SENTINEL to impact flea population dynamics by interrupting the life cycle.

Dosage

SENTINEL (Lufenuron / Milbemycin Oxime) Tablets are available in four tablet sizes in colour-coded packages for oral administration to dogs.

SENTINEL Tablets are given orally, once a month, at the recommended minimum dosage of 10 mg/kg of body weight of Lufenuron and 0.5 mg/kg of body weight of milbemycin oxime.

Dogs over 45 kg should receive the appropriate combination of tablets.

For heartworm prevention , administer SENTINEL Tablets once per month on the same day. Reminder stickers are provided for use on a calendar. The initial dose must be given within a month after the first indication of mosquito activity and regular dosing should continue until at least one month after the end of the mosquito season. If the interval between doses exceeds 30 days, the efficacy of SENTINEL may be reduced. If regular monthly treatment is delayed, it is essential to immediately recommence treatment at the recommended dosage rate. If treatment has been delayed beyond two months, the advice of a veterinarian should be sought. When replacing an existing diethylcarbamazine citrate (DEC) or ivermectin based product, the initial dose of SENTINEL may be given at any time within 30 days of the last treatment with that product.

For hookworm , roundworms and whipworm, control may be obtained in conjunction with heartworm prevention and flea control or by separate administration of a SENTINEL Tablet.

For flea control , administer SENTINEL Tablets orally, once a month, to dogs at the recommended minimum dosage rate of 10 mg/kg of body weight of Lufenuron.

Administration

SENTINEL Tablets must be administered monthly, preferably on the same date each month. Treatment with SENTINEL Tablets may begin at any time of year. In geographic areas where fleas and mosquitoes are seasonal, the treatment schedule should begin one month prior to the expected onset. Treatments should continue until the end of "flea and mosquito season". In areas with year-round infestations, treatment should continue through the entire year without interruption.

Discontinuation of the SENTINEL regimen may result in flea reinfestation from sources outside the pets' immediate environment.

When using SENTINEL for control of active mid-season flea infestations, flea adulticidal products should be used concurrently for the first 6-8 weeks.

SENTINEL TABLETS SHOULD BE ADMINISTERED ON A FULL STOMACH. TO ENSURE ADEQUATE DRUG ABSORPTION, A FULL MEAL SHOULD BE INGESTED IMMEDIATELY PRIOR TO ADMINISTRATION OF TABLETS.

As an alternative to direct dosing, the tablets can be hidden in food or a treat. Watch the dog closely following dosing to be sure the entire dose has been consumed. In case of doubt, it is safe to readminister the entire dose.

To ensure the greatest FLEA control from the use of SENTINEL Tablets, IT IS IMPORTANT TO TREAT ALL DOGS AND CATS WITHIN A HOUSEHOLD. ALL CATS WITHIN THE HOUSEHOLD SHOULD BE TREATED WITH LUFENURON SUSPENSION OR TABLETS. FAILURE TO TREAT ALL PETS IN THE HOUSEHOLD MAY RESULT IN SUBOPTIMAL FLEA CONTROL CAUSED BY REINFESTATION FROM UNTREATED ANIMALS.

SENTINEL should be used as part of a comprehensive flea control plan under the direction of a veterinarian.

If a dose is missed and a 30-day interval between dosing is exceeded, administer SENTINEL Tablets immediately and resume the monthly dosing schedule.

Pharmacology

Lufenuron, one active ingredient of SENTINEL, belongs to the chemical group of benzoylphenylurea compounds. These compounds are classified as insect development inhibitors which interfere with the transport process involved in polymerization of chitin or in the deposition of chitin chains. Chitin is the principal component of the flea egg case and cuticle that forms the exoskeleton of larval stages and adult fleas. Most affected flea eggs fail to hatch and, of those that do hatch, surviving larval stages fail to develop.

The development inhibiting effect of this drug occurs when the adult flea is exposed through the bloodmeal to Lufenuron present in the animal's blood. Eggs and larvae from adult fleas exposed to Lufenuron in this manner fail to develop properly and die. Because female fleas must feed on blood before they can lay eggs, entire populations of immature life stages are eliminated, resulting in flea control.

Lufenuron has no direct effect on mature fleas since they have fully developed exoskeletons. In order to control existing adult flea infestations, adulticidal products should be used concurrently for the first 6-8 weeks while SENTINEL is exerting its life-cycle disrupting effect.

Milbemycin Oxime, the other active ingredient in SENTINEL Tablets, is a macrocyclic anthelmintic which is believed to act by interfering with invertebrate neurotransmission. Milbemycin Oxime eliminates the tissue stage of heartworm larvae and the adult stage of hookworm (Anclyostoma caninum), roundworms (Toxocara canis, Toxascaris leonina) and whipworm (Trichuris vulpis) infections when administered orally according to the recommended dosage schedule.

Safety

SENTINEL has a wide margin of safety in dogs.

Lufenuron / Milbemycin Oxime:
Three pivotal studies provide evidence that SENTINEL can be used safely in dogs.

Lufenuron:
Lufenuron has been tested safely in dogs, including pregnant females, breeding males and females and puppies. In well-controlled clinical studies, Lufenuron was used safely in dogs and cats, many of which received other commonly used veterinary products, such as vaccines, anthelmintics, antibiotics, steroids, flea collars, insecticide shampoos and dips.
Rev. October 24/96
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Breeding studies in laboratory beagles demonstrated no adverse responses in either the parental generation or in the birth and survival rate of their progeny following exposure to high doses of Lufenuron (in excess of three (3) times the recommended minimum dose of 10 mg/kg body weight) given daily from 90 days prior to mating, during gestation, whelping and through weaning.

In a ten-month chronic study, dogs dosed at 2x, 6x and 10x the labeled dose of Lufenuron for three consecutive days each month, demonstrated no adverse clinical reactions, hematological, blood chemistry of histopathological effects. In studies where Lufenuron was administered concomitantly with commonly used organophosphate, carbamate, or pyrethroid insecticide products for fleas, no demonstrated side effects could be attributed to Lufenuron. A tolerability study at 20x the label dose in eight-week old puppies demonstrated no adverse treatment related effects.

Milbemycin Oxime:
Milbemycin Oxime has been tested and found to have no adverse reactions in over 75 dog breeds, pregnant females, breeding males and females, and puppies greater than two (2) weeks of age and one (1) kilogram body weight when administered at the recommended monthly dosage.

Five pivotal target animal studies provided evidence that milbemycin oxime can be used safely in dogs. Milbemycin Oxime was administered daily to reproducing dogs, prior to mating and during gestation, without detectable adverse effects.

In a chronic study (10 months) milbemycin oxime was given to dogs at rates up to 5x the monthly use rate, on three (3) consecutive days. The only adverse effects found were transient ataxia and trembling in some eight-week old puppies. An additional study in eight-week old puppies demonstrated no adverse effects when milbemycin oxime was given for three (3) days at the proposed rate and only minor effects in a few animals at the 5x rate given daily for three (3) days.

Two specifically designed target animal safety studies in puppies two (2) weeks of age were conducted. These studies demonstrated a very adequate margin of safety for the use of milbemycin oxime in young puppies between two (2) and eight (8) weeks of age.

Seven supportive animal safety studies provided evidence that milbemycin oxime would not be expected to have adverse effects in dogs under normal use conditions and up to 3x the recommended use rate.

CAUTION

Prior to initiation of SENTINEL treatment, dogs over six (6) months of age should be tested for existing heartworm infections. If positive, dogs should be converted to negative status by the use of appropriate heartworm adulticides prior to SENTINEL use.

When milbemycin oxime was administered to heartworm infected dogs, a relatively mild shock-like reaction was observed, probably due to the microfilaricidal effect of milbemycin oxime.

WARNING

KEEP OUT OF REACH OF CHILDREN. If accidentally swallowed, call a physician.

Presentation

SENTINEL Tablets are available in four tablet sizes (see Dosage Section), formulated according to the weight of the dog. Each tablet size is available in colour-coded packages of six (6) tablets which are packaged ten (10) per display carton.

Storage Conditions

SENTINEL Tablets should be stored at room temperature, between 15-30ºC.