Sentinel Flavor Tabs (11.5 mg/230 mg) (Canada)

Company: Elanco

lufenuron, milbemycin oxime

DIN 02238150 (2.3 mg/46 mg), 02238149 (5.75 mg/115 mg), 02238148 (11.5 mg/230 mg), 02238147 (23 mg/460 mg)

SENTINEL Flavor Tabs are once-a-month oral tablets that control flea infestations in dogs, prevent heartworm disease caused by Dirofilaria immitis, and treat and control 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: Elanco Canada Limited encourages you to take the time to read the package insert which describes the use of SENTINEL Flavor Tabs (lufenuron/milbemycin oxime) as a convenient monthly flea control, heartworm preventive and intestinal parasite control product.

SENTINEL Flavor Tabs are only available through veterinarians.

Description

The active ingredients in SENTINEL Flavor Tabs are:

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

2) Milbemycin Oxime which consists of the oxime derivatives of 5-didehydromilbemycins in the ratio of approximately 80% A₄ (C₃₂H₄₅NO₇, MW 555.71) and 20% A₃ (C₃₁H₄₃NO₇).

Sentinel Flavor Tabs (11.5 mg/230 mg) Indications

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

SENTINEL Flavor Tabs are 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 Flavor Tabs to impact flea population dynamics by interrupting the life cycle.

DOSAGE: SENTINEL Flavor Tabs are available in four tablet sizes in colour-coded packages for oral administration to dogs.

SENTINEL Flavor Tabs 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.

RECOMMENDED DOSAGE SCHEDULE

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

For heartworm prevention, administer SENTINEL Flavor Tabs 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 Flavor Tabs 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 Flavor Tabs 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 SENTINEL Flavor Tabs.

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

ADMINISTRATION: SENTINEL Flavor Tabs must be administered monthly, preferably on the same day each month. Treatment with SENTINEL Flavor Tabs 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. Treatment 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 Flavor Tabs regimen may result in flea reinfestation from sources outside the pets’ immediate environment. When using SENTINEL Flavor Tabs for control of active mid-season flea infestations, flea adulticidal products should be used concurrently for the first 6-8 weeks.

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

SENTINEL Flavor Tabs are highly palatable and may be given by hand.

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 Flavor Tabs, IT IS IMPORTANT TO TREAT ALL DOGS AND CATS WITHIN A HOUSEHOLD. ALL CATS WITHIN THE HOUSEHOLD SHOULD BE TREATED WITH A FLEA CONTROL PRODUCT SUCH AS LUFENURON SUSPENSION OR INJECTABLE. FAILURE TO TREAT ALL PETS IN THE HOUSEHOLD MAY RESULT IN SUBOPTIMAL FLEA CONTROL CAUSED BY REINFESTATION FROM UNTREATED ANIMALS.

SENTINEL Flavor Tabs 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 Flavor Tabs immediately and resume the monthly dosing schedule.

CAUTIONS: Prior to initiation of SENTINEL Flavor Tab treatment for the first time, dogs six (6) months of age or older should be tested for existing heartworm infections. Dogs on preventive medication should be retested at the start of the following season. Thereafter, testing is performed at the veterinarian’s discretion. If positive, dogs should be converted to negative status by the use of appropriate heartworm adulticides prior to SENTINEL Flavor Tab use.

Mild, transient hypersensitivity reactions manifested as laboured respiration, lethargy, vomiting, and salivation have been noted in some dogs treated with milbemycin oxime carrying a high number of circulating microfilariae. These reactions are presumably caused by release of protein from dead or dying microfilariae. In some cases, death has been reported as an outcome of the adverse events.

Warnings

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

Adverse Reactions

Although all adverse events are not reported, the following information is based on voluntary post-approval drug experience reporting. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using this data.

The post marketing adverse event reports for SENTINEL have shown suspected lack of efficacy*, emesis, lethargy and diarrhea are rarely reported.¹ Pruritus, anorexia, convulsion, ataxia, muscle tremor and dermatitis were all very rare.²

*Product efficacy requires that testing, dosing and administration instructions be carefully followed. Failure to follow label directions could result in a real or perceived lack of efficacy. Several factors, including local parasite prevalence, coprophagia, consistent and compliant administration, as well as timing and frequency of testing, can contribute to a perceived inefficacy. The majority of reports received related to suspected heartworm inefficacy originate from areas of high heartworm prevalence outside Canada.

Some Collies and other P-glycoprotein-deficient dogs (e.g. with MDR or ABCB1-1-delta gene mutation) are known to be more sensitive to the macrocyclic lactone class of medications. Such dogs may be susceptible to macrocyclic lactone toxicity with over-dosing or when used in combination with other macrocyclic lactone drugs. Signs of depression, hypersalivation, tremor and ataxia have been seen associated with macrocyclic lactone toxicity.

Signs most frequently reported following overdose of SENTINEL include lethargy, ataxia, muscle tremor and emesis.

¹Reported in at least 1 but not more than 10 animal in 10,000 animals.

²Reported in less than 1 in 10,000 animals.

Pharmacology

Lufenuron, one active ingredient of SENTINEL Flavor Tabs, 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 Flavor Tabs is exerting its life-cycle disrupting effect.

Milbemycin Oxime, the other active ingredient in SENTINEL Flavor Tabs, 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 (Ancylostoma caninum), roundworms (Toxocara canis, Toxascaris leonina) and whipworm (Trichuris vulpis) infections when administered orally according to the recommended dosage schedule.

SAFETY STUDIES: SENTINEL Flavor Tabs have a wide margin of safety in dogs.

Lufenuron / Milbemycin Oxime: Three pivotal studies provide evidence that SENTINEL Flavor Tabs 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.

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 or histo-pathological 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.

PRESENTATION: SENTINEL Flavor Tabs 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 Flavor Tabs should be stored at room temperature, between 15-25°C.

Elanco Canada Limited, 150 Research Lane, Suite 120, Guelph, Ontario N1G 4T2

Date: May 2016

Elanco, Sentinel, Flavor Tabs and the diagonal bar are trademarks owned or licensed by Eli Lilly and Company, its subsidiaries or affiliates.

27May2016

CPN: 1231063.5