SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Fiprotec Combo 268 mg/ 241.2 mg spot-on solution for large dogs

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 2.68 ml pipette contains:

Active substance:

Fipronil	268 mg
S-Methoprene	241.2 mg

Excipients:

Qualitative composition of excipients and other constituents	Quantitative composition if that information is essential for proper administration of the veterinary medicinal product
Butylhydroxyanisole (E320)	0.54 mg
Butylhydroxytoluene (E321)	0.27 mg
Povidone (K25)
Polysorbate 80
Ethanol 96 per cent
Diethylene glycol monoethyl ether

Clear yellow solution.

3. CLINICAL INFORMATION

3.1 Target species

Dogs >20-40 kg (dogs weighing over 20 kg and up to 40 kg)

3.2 Indications for use for each target species

To be used against infestations with fleas, alone or in association with ticks and/or biting lice.

- Treatment of flea infestations (Ctenocephalides spp.). Insecticidal efficacy against new infestations with adult fleas persists for 8 weeks. Prevention of the multiplication of fleas by inhibiting the development of eggs (ovicidal activity) and larvae and pupae (larvicidal activity) originating from eggs laid by adult fleas for eight weeks after application.

- Treatment of tick infestations (Ixodes ricinus, Dermacentor variabilis, Dermacentor reticulatus, Rhipicephalus sanguineus). The veterinary medicinal product has persistent acaricidal efficacy for up to 4 weeks against ticks.

- Treatment of infestations with biting lice (Trichodectes canis).

3.3 Contraindications

In the absence of available data, the veterinary medicinal product should not be used on puppies less than 8 weeks old and/or weighing less than 2 kg. Do not use in sick (e.g. systemic diseases, fever) or convalescent animals. Do not use in cases of hypersensitivity to the active substances or to any of the excipients.

Do not apply on wounds or damaged skin.

Do not use in cats and ferrets, as this could lead to overdosing.

Do not use in rabbits, as adverse reactions with even mortality could occur. Do not use in any other non-target species.

3.4 Special warnings

Bathing/immersion in water within 2 days after application of the veterinary medicinal product and more frequent bathing than once a week should be avoided, as no study has been performed to investigate how this affects the efficacy of the veterinary medicinal product. Emollient shampoos can be used prior to treatment, but reduce the duration of protection against fleas to approximately 5 weeks when used weekly after application of the veterinary medicinal product. Weekly bathing with a 2% chlorhexidine medicated shampoo did not affect efficacy against fleas during a 6 weeks long study.

There may be an attachment of a few ticks. For this reason, a transmission of infectious diseases cannot be completely excluded if conditions are unfavourable. When treating infestations of parasites, all in-contact animals should be treated with an appropriate veterinary medicinal product at the same time. Fleas from pets often infest the animal's basket, bedding and regular resting areas such as carpets and soft furnishings which should be treated, in case of massive infestation and at the beginning of the control measures, with a suitable insecticide and vacuumed regularly.

3.5 Special precautions for use

Special precautions for safe use in the target species:

Avoid contact with the animal's eyes.

It is important to make sure that the veterinary medicinal product is applied to an area where the animal cannot lick it off and to make sure that animals do not lick each other following treatment. Do not overdose.

Special precautions to be taken by the person administering the veterinary medicinal product to animals:

This veterinary medicinal product can cause mucous membrane, skin and eye irritation. Therefore, contact of the veterinary medicinal product with mouth, skin and eyes should be avoided.

People with a known hypersensitivity (allergy) to fipronil, S-methoprene, insecticides or alcohol should avoid contact with the veterinary medicinal product. Avoid contents coming into contact with the fingers. If this occurs, wash hands with soap and water. After accidental ocular exposure the eye should be rinsed carefully in clean water. If the veterinary medicinal product is accidentally swallowed, seek medical advice immediately and show the package leaflet to the physician.

Wash hands after use.

Do not smoke, drink or eat during application.

Treated animals should not be handled until the application site is dry, and children should not be allowed to play with treated animals until the application site is dry. It is therefore recommended that animals are not treated during the day, but should be treated during the early evening, and that recently treated animals are not allowed to sleep with owners, especially children.

Keep pipettes in original packaging until ready to use.

Special precautions for the protection of the environment:

Dogs should not be allowed to swim in watercourses for 2 days after application (see section 5.5).

3.6 Adverse events Dogs:

Very rare (<1 animal / 10,000 animals treated, including isolated reports):

Application site hair loss1, Application site itching1, Application site reddening1, Application site skin discolouration1 Generalised itching, General hair loss Hypersalivation2, Vomiting Neurological signs3, Hyperaesthesia3 Respiratory signs Depression3

¹ Transient

² May be observed briefly in the case of licking the administration site, also (mainly due to the nature of the carrier)

³ Reversible

Reporting adverse events is important. It allows continuous safety monitoring of a veterinary medicinal product. Reports should be sent, preferably via a veterinarian, to either the marketing authorisation holder or its local representative or the national competent authority via the national reporting system. See the package leaflet for respective contact details.

3.7 Use during pregnancy, lactation or lay Pregnancy and lactation:

Can be used during pregnancy and lactation.

3.8 Interaction with other medicinal products and other forms of interaction

Do not use simultaneously with other flea products which are applied directly on to the animal.

3.9 Administration routes and dosage

External use only, spot-on use.

One pipette of 2.68 ml (268 mg fipronil + 241.2 mg (S)-methoprene) per dog weighing over 20 kg and up to 40 kg corresponding to a minimum recommended dose of 6.7 mg/kg for fipronil and 6 mg/kg for (S)-methoprene, by topical application to the skin.

In the absence of safety studies, the minimum treatment interval is 4 weeks.

Method of administration:

1. Remove the pipette from its packaging. Hold the pipette in an upright position, twist and pull the cap off.

2. Turn the cap around and place the other end of the cap back on the pipette.

Push and twist the cap to break the seal, then remove the cap from the pipette.

3. Part the coat on the back of the animal at the base of the neck in front of the shoulder blades until the skin is visible. Place the tip of the pipette onto the skin and squeeze the pipette several times to empty its contents completely and directly onto the skin in one spot.

Temporary changes to the coat (clumped/greasy hair) may be noted at the application site.

3.10 Symptoms of overdose (and where applicable, emergency procedures and antidotes)

No adverse effects were observed in target animal safety studies in 8 week-old puppies, growing dogs and dogs weighing about 2 kg treated once at five times the recommended dose. The risk of experiencing adverse effects (see section 3.6) may however increase when overdosing, so animals should always be treated with the correct pipette size according to bodyweight.

3.11 Special restrictions for use and special conditions for use, including restrictions on the use of antimicrobial and antiparasitic veterinary medicinal products in order to limit the risk of development of resistance

Not applicable.

3.12 Withdrawal periods Not applicable.

4. PHARMACOLOGICAL INFORMATION

4.1 ATCvet code: QP53AX65

4.2 Pharmacodynamics

Fipronil is an insecticide and acaricide belonging to the phenylpyrazole family. It acts by interacting with ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA), thereby blocking pre- and postsynaptic transfer of chloride ions across cell membranes. This results in uncontrolled activity of the central nervous system and death of insects or acarines. Fipronil kills fleas within 24 hours and ticks (Dermacentor reticulatus, Dermacentor variabilis, Rhipicephalus sanguineus, and Ixodes ricinus) and lice within 48 hours postexposure.

(S)-Methoprene is an insect growth regulator (IGR) of the class of compounds known as juvenile hormone analogues that inhibit the development of immature stages of insects. This compound mimics the action of juvenile hormone and causes impaired development and death of the developing stages of fleas. The on-animal ovicidal activity of (S)-methoprene results from either direct penetration of the eggshell of newly laid eggs or from absorption through the cuticle of the adult fleas. (S)-methoprene is also effective in preventing flea larvae and pupae from developing, which prevents contamination of the environment of the treated animals with the immature stages of fleas.

4.3 Pharmacokinetics

Studies of metabolism of fipronil have demonstrated that the major metabolite is the sulfone derivative of fipronil.

(S)-methoprene is extensively degraded into carbon dioxide and acetate that are subsequently incorporated into endogenous materials.

The pharmacokinetic profiles after topical application of fipronil and (S)-methoprene in combination were studied in dogs in comparison to intravenous dosing of fipronil or (S)-methoprene alone. This established absorption and other pharmacokinetic parameters. The topical application resulted in low systemic absorption of fipronil (11%) with a mean maximum concentration (C_max) of approximately 35 ng/ml fipronil and 55 ng/ml of fipronil sulfone in plasma.

Peak fipronil plasma concentrations are slowly attained (mean t_max approximately 101 h), and decline slowly (mean terminal half-life approximately 154 h, highest values are observed for males).

Fipronil is extensively metabolised to fipronil sulfone after topical administration.

Plasma concentrations of (S)-methoprene were below the limit of quantitation (20 ng/ml) in dogs after topical application.

Both (S)-methoprene and fipronil, together with its major metabolite, are welldistributed in the haircoat of a dog within one day after application. The concentrations of fipronil, fipronil sulfone and (S)-methoprene in the hair coat decrease with time and are detectable for at least 60 days after dosing. Parasites are killed through contact rather than systemic exposure.

No pharmacological interaction between fipronil and (S)-methoprene was noted.

5. PHARMACEUTICAL PARTICULARS

5.1 Major incompatibilities

None known.

5.2 Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 2 years

5.3 Special precautions for storage

Store below 30 °C.

Store in the original package in order to protect from light and moisture.

5.4 Nature and composition of immediate packaging

White polypropylene single-dose pipette packaged in aluminium foil sachets.

Pack sizes:

Cardboard box containing 1, 3 or 6 pipettes. Not all pack sizes may be marketed.

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

Medicines should not be disposed of via wastewater.

The veterinary medicinal product should not enter water courses as Fipronil and (S) methoprene may be dangerous for fish and other aquatic organisms. Do not contaminate ponds, waterways or ditches with the product or empty container.

Use take-back schemes for the disposal of any unused veterinary medicinal product or waste materials derived thereof in accordance with local requirements and with any national collection systems applicable to the veterinary medicinal product concerned.

6. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto

7. MARKETING AUTHORISATION NUMBER

Vm 01656/4120

8. DATE OF FIRST AUTHORISATION

12 October 2015

9. DATE OF THE LAST REVISION OF THE SUMMARY OF THE PRODUCT CHARACTERISTICS

April 2025

10. CLASSIFICATION OF VETERINARY MEDICINAL PRODUCTS

Veterinary medicinal product not subject to prescription.

Find more product information by searching for the ‘Product Information Database’ on www.gov.uk.

Gavin Hall Approved: 14 October 2025