SUMMARY OF PRODUCT CHARACTERISTICS

Frontline Tri-Act spot-on solution for dogs 20-40 kg [BG, HR, CY, CZ, FR, GR, HU, IT, MT, PL, PT, RO, ES, SI, SK]

Frontect spot-on solution for dogs 20-40 kg [AT, BE, DK, FI, DE, IE, LU, NL, NO, SE, UK]

Each 4 ml pipette contains:

Active substance(s)

Fipronil………………………………………….. 270.4mg

Permethrin……………………………………… 2019.2 mg

Excipient(s)

Butylhydroxytoluene (E321)………………….. 4.500 mg

For the full list of excipients, see section 6.1.

3.PHARMACEUTICAL FORM

Spot-on solution

Clear colorless to yellow-brown solution

4. CLINICAL PARTICULARS

4.1. Target species

Dogs

4.2.Indications for use, specifying the target species

For the treatment and prevention of flea and/or tick infestations whererepellent (anti-feeding) activity is necessary against sandflies, biting flies and/or mosquitoes.

Treatment and prevention of Ctenocephalides felisflea infestations and prevention of Ctenocephalides canisflea infestations. One treatment prevents new flea infestations for 4 weeks.

The product can be used as part of a treatment strategy for flea allergy dermatitis where this has been previously diagnosed by a veterinarian.

Treatment and prevention of tick infestations (Dermacentor reticulatus, Ixodes ricinus, Rhipicephalus sanguineus). One treatment kills (Dermacentor reticulatus, Ixodes ricinus, Rhipicephalus sanguineus) and repels (Ixodes ricinus, Rhipicephalus sanguineus)ticksfor 4 weeks after treatment, and repels Dermacentorreticulatus from 7 days up to 4 weeks after treatment.

Repels (anti-feeding activity) sandflies (Phlebotomus perniciosus) for 3 weeks and mosquitoes (Culex pipiens, Aedes albopictus)for 4 weeks.

Kills sandflies (Phlebotomus perniciosus) and mosquitoes(Aedes albopictus) for 3 weeks.

Repels (anti-feeding activity) and kills stable flies (Stomoxys calcitrans) for 5 weeks.

4.3. Contraindications

Do not use on sick or convalescent animals.

This product is for use on dogs only. Donotuseincats andrabbits, as adverse reactions and even death could occur.

Donotuseincaseofknownhypersensitivitytotheactivesubstancesortoanyoftheexcipients. (see also section 4.5(i)).

4.4.Special warnings for each target species

There may be an attachment of single ticks or bites by single mosquitoes or sandflies. For this reason, transmission of pathogens by these arthropods cannot be completely excluded if conditions are unfavorable. Single ticks may attach and detach within the first 24 hours after infestationand if ticks are present when the product is applied not all ticks may be killed within 48 hours after treatment.

Theproductremainseffectiveagainst fleas whentreatedanimalsareimmersed inwater occasionally(e.g.,swimming,bathing).However,dogsshouldnotbeallowedtoswimorbe shampooedwithin48hoursaftertreatment.Avoidfrequentswimming or shampooing of treated dogs as this may adversely affect maintenance of product effectiveness.

To reduce re-infestation from emergence of new fleas, it is recommended that all dogs in a household be treated. Other animals living in the same household should also be treated with a suitable product. To aid further in reducing environmental challenge, the additional use of a suitable environmental treatment against adult fleas and their developmental stages could be recommended.

4.5.Special precautions for use

Specialprecautionsforuseinanimals

In the absence of specific studies, the use of the product is not recommended in dogs younger than 8 weeks of age, or in dogs weighing less than 2 kg.

Careshouldbetakentoavoidcontactoftheveterinarymedicinalproductwiththedog’seyes.

Itisimportanttomakesurethattheproductisappliedtoanareawherethe animal cannotlickitoffandtomake sure that other animals do not lick the treatment sites following application.

Duetotheunique physiologyofcatswhichprevents them frommetabolizingcertaincompounds, includingpermethrin, the product can induce potentially fatal convulsions in this species. In caseofaccidentaldermal exposure, washthecatwithshampoo orsoap,andseek veterinaryadvicerapidly.Topreventcats frombeingaccidentallyexposedtothe product,keeptreated dogsawayfromcatsuntiltheapplicationsiteisdry.Itisimportanttoensurethatcatsdonotgroom thesiteofapplication onadogwhichhasbeentreatedwiththisproduct.Incaseofexposureofthis typeseekveterinaryadviceimmediately.

Specialprecautionstobetakenbythepersonadministeringtheveterinary medicinalproducttoanimals

Thisproductcancauseskinandeyeirritation,therefore, avoid contactoftheproductwithskinandeyes.Do not open the pipette near or towards the face. In case of ocular exposure or if eyes become irritated during administration, immediately flush the eyes with plenty of water. If ocular irritation persists, seek medical attention. In case of dermal exposure or if skin becomes irritated during administration, immediately wash the skin with plenty of soap and water. If skin irritation persists or recurs, seek medical attention.

Peoplewithknownhypersensitivitytofipronil and/or permethrinshould avoid contact with the product.

The product is harmful if swallowed. Avoid hand-to-mouth contact. Donotsmoke,drinkoreatduringapplication. Washhandsafteruse. If swallowed rinse mouth and seek medical attention if you feel unwell.

Since the excipient N-methylpyrrolidone may induce foetotoxicity and teratogenicity after significant exposure, pregnant women should wear gloves to avoid contact with the product.Treatedanimalsshouldnotbehandleduntiltheapplicationsiteisdry,and childrenshould not be allowed toplay withtreated animalsuntilthe application siteis dry.It istherefore recommended that animals are not treatedduringtheday,butshouldbetreatedduringtheearlyevening, and thatrecentlytreatedanimalsarenotallowedtosleepwithowners,especially children.

Keep the stored pipettes in the original blister and once used, the empty pipette should immediately be disposed of appropriately, preventing further access.

Other precaution

The product may adversely affect aquatic organisms. Treated dogs should not be allowed to enter surface water for 2 days after treatment.

4.6.Adverse reactions (frequency and seriousness)

Amongtheveryraresuspectedadversereactions,transientskinreactionsatthe applicationsite(skindiscolouration,local hairloss,itching,redness)andgeneral itchingorhairlosshavebeenreportedafteruse.Excessivesalivation,reversible nervoussigns (increased sensitivitytostimulation, hyperactivity, muscle tremor, depression, othernervous signs) orvomitinghavealsobeenobservedafteruse.

If licking of the application siteoccurs, transient hypersalivation and emesismaybe observed.

4.7.Use during pregnancy, lactation or lay

Laboratory studies using fipronil or permethrin have not shown any evidence of teratogenic or embryotoxic effects. Studies have not been carried out with this product in pregnant and lactating animals (see 4.5(i)).

N-methylpyrrolidone, an excipient in the veterinary medicinal product, has been shown to be teratogenic in laboratory animals after repeated exposure at high doses.

Use only according to the benefit/risk assessment by the responsible veterinarian.

4.8.Interaction with other medicinal products and other forms of interaction

None known.

4.9.Amounts to be administered and administration route

Therecommendedminimumdoseis6.76mgfipronil/kgbodyweight,and50.48 mg/kgpermethrin equivalentto0.1mlspot-onsolutionperkgbodyweight.

The use of the product should be based on a confirmed infestation or risk of infestationwith fleas and/or ticks when repellent (anti-feeding) activity is also necessary against sand-flies and/or mosquitoes and/or biting flies.Depending on the ectoparasite challenge repetition of the treatment might be indicated. In such instances, the interval between two treatments should be at least 4 weeks.

Method of administration:

Select the appropriate pipette size for the weight of the dog. For dogs over 60 kg, use the appropriate combination of two pipette sizes that most closely matches the bodyweight.

The product should be applied in two out-of-reach spots so that the dog cannot lick the application site. These sites are at the base of the neck in front of the shoulder blades and the middle of the neck between the base of the skull and the shoulder blades.

Remove the blister card from the package and separate one blister. Remove the pipette by cutting along the dotted line with a pair of scissors or tearing open after folding the marked corner. Holding the pipette upright away from face and body, cut the pipette tip with scissors to open. Part the coat on the back of the dog until the skin is visible. Place the tip of the pipette on the skin. Squeeze the pipette, applying about half of the contents half way down the neck between the base of the skull and the shoulder blades. Repeat the application at the base of the neck in front of the shoulder blades to empty the pipette. For best results, ensure that the product is applied directly to the skin rather than on the hair.

4.10.Overdose (symptoms, emergency procedures, antidotes), if necessary

Safety has been assessed with up to 5 times the maximum dose in healthy adult dogs (treated up to 3 times at monthly intervals) and in puppies (aged 8 weeks treated once). Known side-effects may consist of mild neurological signs, emesis and diarrhea. These are transitory and generally resolve without treatment within 1-2 days.

The risk of experiencing adverse reactions (see section 4.6) may increase with overdosing, so animals should always be treated with the correct pipette size according to bodyweight.

4.11 Withdrawal period

Not applicable

5.PHARMACOLOGICAL PROPERTIES

Pharmacotherapeuticgroup:Ectoparasiticidesfortopicaluse,ATCvetcode:QP53AX65 (fipronil, combination).

5.1.Pharmacodynamic properties

Fipronil is an insecticide and acaricide belonging to the phenylpyrazole family. Fipronil and its metabolite fipronil sulfone act at ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA) as well as desensitising (D) and non-desensitising (N) channels gated by glutamate (Glu, unique invertebrate ligand-gated chloride channels), thereby blocking pre- and post-synaptic transfer of chloride ions across cell membranes. This results in uncontrolled activity of the central nervous system and death of arthropods.

PermethrinbelongstotheTypeIclassofpyrethroids, whichareacaricidesandinsecticides with repellentactivity.Pyrethroidsaffectthevoltage-gated sodiumchannelsinvertebratesandnon-vertebrates. Pyrethroids areso-called“openchannelblockers” affectingthe sodium channelby slowingboththe activationand the inactivationproperties,thusleadingtohyper-excitabilityanddeath oftheparasite. Permethrin in the product provides repellent activity (anti-feeding activity)against sandflies (> 80% for 4 weeks), mosquitoes and ticks.

In one experimental study, the product had a faster onset on flea adulticidal activity than fipronil alone at 7 and 14 days after treatment administration.

Speed of kill

The product kills new infesting fleas (C. canis, C. felis) within 6 hours from 2 days after treatment and for a full month. C. felisfleas already present on dogs when the treatment is applied are killed in 24 hours. Speed of kill against pre-existing C. canishas not been evaluated.

The product kills new infesting ticks (R. sanguineusand I. ricinus) within 6 hours from 2 days after treatment and for a full month. Ticks (R. sanguineus, I. ricinus, D. reticulatus) already present on dogs when the treatment is applied are killed in 48 hours.

In one experimentalstudy, the product was shown to indirectly reduce the risk of transmission of Babesia canisfrom infected Dermacentor reticulatusticks from 7 days after application up to 4 weeks, thereby reducing the risk of canine babesiosis in treated dogs in this study.

In one experimentalstudy, the product was shown to indirectly reduce the risk of transmission of Ehrlichia canisfrom infected Rhipicephalus sanguineusticks, from 7 days after application up to 4 weeks, thereby reducing the risk of ehrlichiosis in treated dogs in this study.

However, the effectiveness of the product at reducing the transmission of infectious agents following natural exposure under field conditions has not been investigated.

5.2.Pharmacokinetic particulars

The pharmacokineticprofiles of fipronil andpermethrin incombination werestudiedaftertopical applicationindogs by measuring plasma and hair concentrations for 58 days following treatment. Both permethrin and fipronil,togetherwithitsmajormetabolite,fipronil sulfone, arewell­ distributedon thehaircoatofadogduring the first dayafterapplication.The concentrationsof fipronil, fipronil sulfone and permethrin inthe hair coat decreasewithtimeandaredetectableforatleast58daysafterdosing.

Fipronil and permethrin act topically upon contact with external parasitesand thelowsystemic absorptionoffiproniland permethrin isnotrelevantfortheclinicalefficacy.

The spot-on application resulted in negligible systemic absorption of permethrin with sporadic measureable concentrations of cis-permethrin between 11.4 ng/mL and 33.9 ng/mL observed 5 to 48 hours following treatment.

Mean maximum plasma concentrations (Cmax) of 30.1 ± 10.3 ng/ml fipronil and 58.5 ± 20.7 ng/ml of fipronil sulfone were observed between Day 2 and 5 (Tmax) following application. Fipronil plasma concentrations then decline with a mean terminal half-life of 4.8 ± 1.4 days.

6. PHARMACEUTICAL PARTICULARS

6.1. List of excipients

N-methylpyrrolidone

Butylhydroxytoluene (E321)

Medium-chain triglycerides

6.2.Incompatibilities

None known

6.3.Shelf life

Shelflifeoftheproductaspackagedforsale:30months.

6.4.Special precautions for storage

Store in the original blister.

Do not store above 25°C.

6.5.Nature and composition of immediate packaging

The primary packaging is a heat-formed film of polyethylene-ethylvinyl alcohol-polyethylene/polypropylene.

The secondary packaging consists of a plastic/aluminium blister with a plastic/aluminium backing.

Plastic card of 1 pipette containing 4 ml.

Carton box of 3 or 6 pipettes containing 4 ml each.

One size only per box.

Notallpacksizesmaybemarketed.

6.6.Special precautions for the disposal of unused veterinary medicinal products or waste materials derived from the use of such products

Any unused veterinary medicinal product or waste material derived from such veterinary medicinal product should be disposed of in accordance with local requirements.

The product may adversely affect aquatic organisms. Do not contaminate ponds, waterways or ditches with the product or empty container.

Merial Animal Health Ltd

PO Box 327

Sandringham House

Harlow Business Park

Harlow

Essex

CM19 5TG

Vm 08327/4261

16 October 2014

September 2016

16 September 2016