Summary of Product Characteristics s1

Revised: May 2008 AN: 00346/2008

Summary of Product Characteristics

1 Name of the Veterinary Medicinal Product

SENTINEL® Spectrum

Tablets for small Dogs

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One tablet contains

Milbemycin oxime (INN) 5.75 mg Lufenuron (INN) 115 mg Praziquantel (INN) 57 mg

3. PHARMACEUTICAL FORM Tablets. Brown and white, round, biconvex, palatable bi-layer tablets with a meat extract odour. One side bears the imprint “ADA”, the other side “NA”.

4. Pharmacological properties

Active substances: Pharmacotherapeutic group: Milbemycin oxime Anthelmintic Lufenuron Insect Growth Regulator Praziquantel Anthelmintic

ATC vet Code

QP53BC51 Lufenuron combinations

4.1. Pharmacodynamic properties

Milbemycin oxime belongs to the group of macrocyclic lactones, isolated from the fermentation of Streptomyces hygroscopicus var. aureolacrimosus. It is active against mites, against larval and adult stages of nematodes as well as against larvae of Dirofilaria immitis. The activity of milbemycin is related to its action on invertebrate neurotransmission: Milbemycin oxime, like avermectins and other milbemycins, increases nematode and insect membrane permeability to chloride ions via glutamate-gated chloride ion channels (related to vertebrate GABAA and glycine receptors). This leads to hyperpolarisation of the neuromuscular membrane and flaccid paralysis and death of the parasite.

Lufenuron belongs to the chemical group of benzoylureas, and is an IGR (Insect Growth Regulator) or IDI (Insect Development Inhibitor). It inhibits the development of fleas by interfering with the normal synthesis, polymerisation and deposition of chitin, the principal component of the arthropod exoskeleton. The adult flea absorbs lufenuron Revised: May 2008 AN: 00346/2008 via its bloodmeal. At therapeutic levels, lufenuron has no effect on adult fleas, but passes transovarially to act on eggs and larvae, thus interrupting the insect life cycle.

Praziquantel is an acylated pyrazino-isoquinoline derivative. Praziquantel is active against cestodes and trematodes. It modifies the permeability for calcium (influx of Ca2+) in the membranes of the parasite inducing an imbalance in the membrane structures, leading to membrane depolarisation and almost instantaneous contraction of the musculature (tetany), rapid vacuolization of the syncytial tegument and subsequent tegumental disintegration (blebbing), resulting in easier expulsion from the gastrointestinal tract or death of the parasite.

4.2. Pharmacokinetic properties

Milbemycin oxime is well absorbed and reaches peak plasma concentrations within a median of 1 hour (½ – 24 h) after oral administration at the recommended dose. Thereafter, milbemycin oxime concentrations decrease in plasma with a half-life of about 1 to 3 days.

Following oral administration, lufenuron is distributed via the blood within a median of 2 hours (2 – 48 h) to the adipose tissue, from which, metabolically unmodified, it is constantly released above the minimum effective concentration for at least one month (half life between 15 and 50 days).

Praziquantel is well absorbed and reaches peak plasma concentrations between ½ and 1 hour after oral administration at the recommended dose. There is rapid and extensive first pass metabolism by the liver; parent praziquantel concentrations decrease in plasma with a half-life of between 1 and 2.5 hours. Metabolites are largely excreted in the urine within 2 days.

5. Clinical Particulars

5.1. Target species Dog Revised: May 2008 AN: 00346/2008

5.2. Indications for Use, Specifying the Target Species For dogs harbouring, or at risk from, mixed parasitic infections: For the prevention of flea infestation (Ct. felis, Ct. canis, preadult stages) in dogs where concomitant treatment of mixed infections by adult cestodes and nematodes is indicated. SENTINEL® Spectrum is effective against adult stages of the following nematode and cestode species; Cestodes: Dipylidium caninum, Taenia spp., Echinococcus spp., Mesocestoides spp..

Nematodes: Ancylostoma caninum, Toxocara canis, Toxascaris leonina, Trichuris vulpis.

This product can be used in the prevention of heartworm disease (Dirofilaria immitis) and may be used as part of a treatment strategy for flea allergy dermatitis (FAD).

5.3. Contra-indications None.

5.4. Undesirable effects (Frequency and Seriousness) Slight paleness of the visible mucous membranes and a slight increase in intestinal peristalsis were observed in some dogs. The signs disappeared spontaneously.

5.5. Special precautions for use The treatment of dogs with a high number of circulating microfilariae can sometimes lead to the appearance of hypersensitivity reactions, such as pale mucous membranes, vomiting, trembling, laboured breathing or excessive salivation. These reactions are associated with the release of toxic proteins from dead or dying microfilariae and are not a direct toxic effect of the product. The use in dogs suffering from microfilaremia should be based on a risk benefit assessment. If microfilaremic dogs are treated, animals should be observed closely, and, if needed, treated symptomatically.

As with any other heartworm disease preventative, when non-protected exposure to Dirofilaria immitis is suspected a veterinary consultation is advised to exclude the presence of any concurrent infection before commencing SENTINEL® Spectrum Tablets. In the case of a positive diagnosis, adulticidal therapy is indicated before administering SENTINEL® Spectrum Tablets.

The product should not be used in severely debilitated dogs or individuals with seriously compromised kidney or liver function.

In dogs less than 4 weeks old, tapeworm infection is unusual. Treatment of animals less than 4 weeks old with a combination product may therefore not be necessary. Revised: May 2008 AN: 00346/2008

Parasite resistance to any particular class of anthelmintic may develop following frequent, repeated use of an anthelmintic of that class.

Echinococcosis represents a hazard for humans. In case of Echinococcosis, specific guidelines on the treatment and follow up and on the safeguard of persons have to be followed. Experts or institutes of parasitology should be consulted

5.6. Use During Pregnancy and Lactation The safety of SENTINEL® Spectrum Tablets has not been tested in pregnant or lactating dogs. Therefore, use in such animals is not recommended. Studies with milbemycin oxime, lufenuron or praziquantel performed separately in dogs and laboratory animals did not reveal any alteration on reproductive function. Neither foetal nor neonatal toxicity were observed.

5.7. Interaction with other Medicaments and other Forms of Interaction During treatment with SENTINEL® Spectrum Tablets, no other antiparasitic macrocyclic lactones should be administered.

5.8. Posology and Method of Administration Oral administration with or after a full meal. SENTINEL Spectrum tablets, available in four sizes, are given according to the weight of the dog, consistent with the administration of a minimum recommended dose rate of 0.5 mg milbemycin oxime, 10 mg lufenuron and 5 mg of praziquantel per kg bodyweight. The practical dosing is as follows:

Dog Weight Posology Milbemycin Lufenuron Praziquantel si oxime z e Small > 4.5 – 11 kg: 1 tablet 5.75 mg 115 mg 57 mg

Flea control and prevention To prevent flea infestations, lufenuron (either as a monovalent product or, in cases where treatment for concurrent mixed gastrointestinal nematode and cestode infection is required, as the combination product, SENTINEL® Spectrum) should be administered at monthly intervals and, where there is a flea season, starting two months before the fleas become active. If the dog is already infested with fleas, no viable flea eggs are produced from 24 hours after the first administration. The speed at which a pre-existing infestation is eliminated is dependent on the number of flea larvae and pupae in the environment when treatment starts and the climatic conditions. If dogs have a high level of flea infestation at the start of the treatment, it may be necessary to administer a flea adulticide at that time. It is important to treat all dogs and cats in the household for fleas. Cats in the same household should be treated with an appropriate product for use in that species.

Lufenuron (either as a monovalent product or, in cases where treatment for concurrent mixed gastrointestinal nematode and cestode infection is required, as the combination Revised: May 2008 AN: 00346/2008 product, SENTINEL® Spectrum) should be administered at monthly intervals when used as part of a treatment strategy for flea allergy dermatitis.

Heartworm disease prevention For prevention of heartworm disease, milbemycin oxime (either as a monovalent product or, in cases where prevention of flea infestation and treatment of concurrent cestode infection is required, as the combination product, SENTINEL® Spectrum) must be administered at regular monthly intervals during the time of the year when mosquitoes are present. The appropriate treatment should be administered within at least one month after the first expected exposure to mosquitoes. Treatment should continue at regular monthly intervals until one month after the last exposure to mosquitoes. To establish a treatment routine, it is recommended that the same day or date be used each month. When replacing another heartworm preventative product in a heartworm prevention program, SENTINEL® Spectrum must be given within one month of the last dose of the former medication. If the interval between treatments is greater than six weeks, treatment should be resumed immediately and be continued at monthly intervals and a veterinarian should be consulted.

Echinococcus infections As with other praziquantel formulations SENTINEL Spectrum can be used as part of a treatment strategy against Echinococcosis.

Roundworm infections In ascarid infections, especially in puppies, complete elimination of worm burden cannot be expected, resulting in a continued risk of infection for people coming into contact with the young animals. Repeated monthly treatments should, therefore, be carried out in puppies up to three months with milbemycin oxime (either as a monovalent product or, in cases where prevention of flea infestation and treatment of concurrent cestode infection is required, as the combination, SENTINEL® Spectrum).

Whipworm infections It has been demonstrated under kennel conditions that monthly administration of milbemycin oxime (either as a monovalent product or, as the combination product, SENTINEL® Spectrum) significantly reduces egg shedding of Trichuris vulpis.

5.9. Overdose (Symptoms, emergency procedures, antidotes) (if necessary) In case of overdosing, transient ataxia, trembling, depression, salivation and mydriasis may be observed. The signs will disappear spontaneously within a day. There is no specific antidote.

5.10. Special Warnings for each target species Studies with milbemycin oxime indicate that the margin of safety in certain dogs of Collie or related breeds is less than in other breeds. In these dogs, the recommended dose should be strictly observed. The tolerance of SENTINEL® Spectrum in young puppies from these breeds has not been investigated and it is important that they are accurately weighed prior to dosing. Clinical signs in Collies are similar to those seen in the general dog population when overdosed.

5.11. Withdrawal period Revised: May 2008 AN: 00346/2008

Not applicable.

11.12. Special Precautions to be taken by the Person Administering the Medicinal Product to Animals In the case of accidental ingestion, seek medical advice immediately and show the package insert or the label to the physician. Wash hands after use.

6. Pharmaceutical Particulars

6.1. Major Incompatibilities Not applicable.

6.2. Shelf - life Shelf-life of the veterinary medicinal product as packaged for sale: 3 years

6.3. Special Precautions for Storage This medicinal product does not require any special storage conditions.

6.4. Nature and Contents of Container

Alu/Alu blisters containing 6 tablets/blister. Cardboard box with one blister.

Sales units: A blister card of 6 tablets

6.5 Special Precautions for the Disposal of Unused Medicinal Product or Waste Materials, if any Any unused product or waste material should be disposed of in accordance with national requirements.

7. Name or Corporate Name and Address or Registered Place of Business of the Authorisation Holder

Novartis Animal Health UK Ltd. Frimley Business Park Frimley Camberley Surrey GU16 7SR

Marketing Authorisation number

Vm 12501/4157

Date of first Authorisation/Renewal of the Authorisation

23 June 2005

Date of Revision the Text Revised: May 2008 AN: 00346/2008

May 2008