Credelio - summary of medicine characteristics

ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

NAME OF THE VETERINARY MEDICINAL PRODUCT

Credelio 56 mg chewable tablets for dogs (1.3–2.5 kg)

Credelio 112 mg chewable tablets for dogs (>2.5–5.5 kg)

Credelio 225 mg chewable tablets for dogs (>5.5–11 kg)

Credelio 450 mg chewable tablets for dogs (>11–22 kg)

Credelio 900 mg chewable tablets for dogs (>22–45 kg)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Active substance:

Each chewable tablet contains:

Credelio chewable tablets	lotilaner (mg)
for dogs (1.3–2.5 kg)	56.25
for dogs (>2.5–5.5 kg)	112.5
for dogs (>5.5–11 kg)	225
for dogs (>11–22 kg)	450
for dogs (>22–45 kg)	900

Excipients:

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Chewable tablet.

White to beige round chewable tablets with brownish spots.

4. CLINICAL PARTICULARS4.1 Target species

Dogs.

• 4.2 Indications for use, specifying the target species

For the treatment of flea and tick infestations in dogs.

This veterinary medicinal product provides immediate and persistent killing activity for 1 month for fleas (Ctenocephalides felis and C. canis ) and ticks (Rhipicephalus sanguineus, Ixodes ricinus, I. hexagonus and Dermacentor reticulatus ).

Fleas and ticks must attach to the host and commence feeding in order to be exposed to the active substance.

The veterinary medicinal product can be used as part of a treatment strategy for the control of flea allergy dermatitis (FAD).

4.3 Contraindications

Do not use in case of hypersensitivity to the active substance or to any of the excipients.

• 4.4 Special warnings for each target species

Parasites need to start feeding on the host to become exposed to lotilaner; therefore the risk of the transmission of parasite borne diseases cannot be completely excluded.

• 4.5 Special precautions for use

Special precautions for use in animals

All safety and efficacy data have been acquired from dogs and puppies 8 weeks of age and older and 1.3 kg of body weight and greater. Use of this veterinary medicinal product in puppies younger than 8 weeks of age or less than 1.3 kg of body weight should be based on a benefit-risk assessment by the responsible veterinarian.

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

Wash hands after handling the product.

In case of accidental ingestion, seek medical advice immediately and show the package leaflet or label to the physician.

• 4.6 Adverse reactions (frequency and seriousness)

Mild and transient gastrointestinal signs (vomiting; diarrhoea; anorexia) and lethargy have been reported very rarely based on post-marketing safety experience. These signs typically resolve without treatment.

Neurological disorders such as tremor, ataxia or convulsion may occur in very rare cases. In most cases these signs are transient.

The frequency of adverse reactions is defined using the following convention:

• – very common (more than 1 in 10 animals treated displaying adverse reaction(s))

• – common (more than 1 but less than 10 animals in 100 animals treated)

• – uncommon (more than 1 but less than 10 animals in 1,000 animals treated)

• – rare (more than 1 but less than 10 animals in 10,000 animals treated)

• – very rare (less than 1 animal in 10,000 animals treated, including isolated reports).

• 4.7 Use during pregnancy, lactation or lay

Laboratory studies in rats have not produced any evidence of teratogenic effects, or any adverse effect on the reproductive capacity of males and females. The safety of the veterinary medicinal product in breeding, pregnant and lactating dogs has not been established. Use only according to the benefit-risk assessment of the responsible veterinarian.

4.8 Interaction with other medicinal products and other forms of interaction

None known. During clinical testing, no interactions between Credelio chewable tablets and routinely used veterinary medicinal products were observed.

• 4.9 Amounts to be administered and administration route

For oral use.

The veterinary medicinal product should be administered in accordance with the following table to ensure a dose of 20 to 43 mg lotilaner/kg bodyweight.

Body weight of dog (kg)	Strength and number of tablets to be administered
	Credelio 56 mg	Credelio 112 mg	Credelio 225 mg	Credelio 450 mg	Credelio 900 mg
1.3–2.5	1
>2.5–5.5		1	1	1
>5.5–11.0
>11.0–22.0
>22.0–45.0					1
>45	Appropriate combination of tablets

Use an appropriate combination of available strengths to achieve the recommended dose of 20

43 mg/kg.

Credelio is a palatable chewable flavoured tablet. Administer the chewable tablet(s) monthly with or after food.

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

No adverse reactions were observed following oral administration to puppies aged 8–9 weeks and weighing 1.3–3.6 kg treated with overdoses of up to 5 times the maximum recommended dose (43 mg, 129 mg and 215 mg lotilaner/kg bodyweight) on eight occasions at monthly intervals.

• 4.11 Withdrawal period(s)

Not applicable.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: ectoparasiticides for systemic use, isoxazolines.

ATCvet code: QP53BE04

5.1 Pharmacodynamic properties

Lotilaner, a pure enantiomer from the isoxazoline class is active against fleas (Ctenocephalides felis and Ctenocephalides canis ) as well as the tick species Dermacentor reticulatus, Ixodes hexagonus, Ixodes ricinus and Rhipicephalus sanguineus.

Lotilaner is a potent inhibitor of gamma-aminobutyric acid (GABA)-gated chloride channels, resulting in rapid death of ticks and fleas. The activity of lotilaner was not affected by resistance to organochlorines (cyclodienes, e.g. dieldrin), phenylpyrazoles (e.g. fipronil), neonicotinoids (e.g. imidacloprid), formamidines (e.g. amitraz) and pyrethroids (e.g. cypermethrin).

For fleas, the onset of efficacy is within 4 hours of attachment for one month after product administration. Fleas on the animal prior to administration are killed within 6 hours.

For ticks, the onset of efficacy is within 48 hours of attachment for one month after product administration. Existing I. ricinus ticks on the animal prior to administration are killed within 8 hours.

The veterinary medicinal product kills existing and newly emerged fleas on dogs before they can lay eggs. Therefore, the product breaks the flea life cycle and prevents environmental flea contamination in areas to which the dog has access.

• 5.2 Pharmacoki­netic particulars

Following oral administration, lotilaner is readily absorbed and peak blood concentration is reached within 2 hours. Food enhances the absorption. The terminal half-life is approximately 4 weeks. This long terminal half-life provides effective blood concentrations for the entire duration of the interdosing interval.

The major route of elimination is biliary excretion and renal excretion is the minor route of elimination (less than 10% of the dose). Lotilaner is metabolized to a small extent into more hydrophilic compounds which are observed in faeces and urine.

6. PHARMACEUTICAL PARTICULARS6.1 List of excipients

Cellulose, powdered

Lactose monohydrate

Silicified microcrystalline cellulose

Meat dry flavour

Crospovidone Povidone

K30 Sodium

laurilsulfate

Silica, colloidal anhydrous

Magnesium stearate

6.2 Major incompatibilities

Not applicable.

6.3 Shelf life

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

6.4. Special precautions for storage

This medicinal product does not require any special storage conditions.

• 6.5 Nature and composition of immediate packaging

The tablets are packaged in aluminium/aluminium blisters packaged into an outer cardboard box.

Each tablet strength is available in pack sizes of 1, 3 or 6 tablets.

Not all pack sizes may be marketed.

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

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

7. MARKETING AUTHORISATION HOLDER

Elanco GmbH

Heinz-Lohmann-Str. 4

27472 Cuxhaven

Germany

8. MARKETING AUTHORISATION NUMBER(S)

EU/2/17/206/001–015

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 25/04/2017

10 DATE OF REVISION OF THE TEXT

<{DD/MM/YYYY}>

Detailed information on this veterinary medicinal product is available on the website of the European

Medicines Agency.

PROHIBITION OF SALE, SUPPLY AND/OR USE

Not applicable.

NAME OF THE VETERINARY MEDICINAL PRODUCT

Credelio 12 mg chewable tablets for cats (0.5–2.0 kg)

Credelio 48 mg chewable tablets for cats (>2.0–8.0 kg)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Active substance:

Each chewable tablet contains:

Credelio chewable tablets	lotilaner (mg)
for cats (0.5–2.0 kg)	12
for cats (>2.0–8.0 kg)	48

Excipients:

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Chewable tablet.

White to brownish round chewable tablets with brownish spots.

4. CLINICAL PARTICULARS4.1 Target species

Cats.

• 4.2 Indications for use, specifying the target species

For the treatment of flea and tick infestations on cats.

This veterinary medicinal product provides immediate and persistent killing activity for 1 month against fleas (Ctenocephalides felis and C. canis ) and ticks (Ixodes ricinus ).

Fleas and ticks must attach to the host and commence feeding in order to be exposed to the active substance.

The veterinary medicinal product can be used as part of a treatment strategy for the control of flea allergy dermatitis (FAD).

4.3 Contraindications

Do not use in cases of hypersensitivity to the active substance or to any of the excipients.

• 4.4 Special warnings for each target species

Parasites need to start feeding on the host to become exposed to lotilaner; therefore the risk of the transmission of parasite borne diseases cannot be completely excluded.

Acceptable levels of efficacy may not be achieved if the veterinary medicinal product is not administered with food or within 30 minutes after feeding.

Due to insufficient data to support efficacy against ticks in young cats, this product is not recommended for the treatment of ticks in kittens 5 months of age or younger.

• 4.5 Special precautions for use

Special precautions for use in animals

Safety and efficacy data has been studied in cats aged 8 weeks and older with a body weight of 0.5 kg or more. Therefore, use of this veterinary medicinal product in kittens younger than 8 weeks of age or less than 0.5 kg of body weight should be based on a benefit-risk assessment by the responsible veterinarian.

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

Wash hands after handling the product.

In case of accidental ingestion, seek medical advice immediately and show the package leaflet or label to the physician.

• 4.6 Adverse reactions (frequency and seriousness)

Vomiting has been reported very rarely based on post marketing safety experience and typically resolves without treatment.

The frequency of adverse reactions is defined using the following convention:

• – very common (more than 1 in 10 animals treated displaying adverse reaction(s))

• – common (more than 1 but less than 10 animals in 100 animals treated)

• – uncommon (more than 1 but less than 10 animals in 1,000 animals treated)

• – rare (more than 1 but less than 10 animals in 10,000 animals treated)

• – very rare (less than 1 animal in 10,000 animals treated, including isolated reports).

• 4.7 Use during pregnancy, lactation or lay

Laboratory studies in rats have not produced any evidence of teratogenic effects, or any adverse effect on the reproductive capacity of males and females. The safety of the veterinary medicinal product in cats has not been established during pregnancy and lactation. 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.

During clinical testing, no interactions between Credelio chewable tablets and routinely used veterinary medicinal products were observed.

• 4.9 Amounts to be administered and administration route

For oral use.

The flavoured veterinary medicinal product should be administered in accordance with the following table to ensure a single dose of 6 to 24 mg lotilaner/kg bodyweight.

Body weight of cat (kg)	Strength and number of tablets to be administered
	Credelio 12 mg	Credelio 48 mg
0.5–2.0	1
>2.0–8.0		1

>8.0	Appropriate combination of tablets

For cats of more than 8 kg body weight, use an appropriate combination of available strengths to achieve the recommended dose of 6–24 mg/kg.

Administer the veterinary medicinal product with food or within 30 minutes after feeding.

For optimal control of tick and flea infestations, the veterinary medicinal product should be administered at monthly intervals and continued throughout the flea and/or tick season based on local epidemiological situations.

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

No adverse reactions were observed following oral administration to kittens aged 8 weeks, weighing 0.5 kg, which were treated with more than 5 times the maximum recommended dose (130 mg lotilaner/kg bodyweight) on eight occasions at monthly intervals.

• 4.11 Withdrawal period(s)

Not applicable.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: ectoparasiticides for systemic use, isoxazolines.

ATCvet code: QP53BE04

5.1 Pharmacodynamic properties

Lotilaner, a pure enantiomer from the isoxazoline class, is active against fleas (Ctenocephalides felis and Ctenocephalides canis ) and ticks (Ixodes ricinus ).

Lotilaner is a potent inhibitor of gamma-aminobutyric acid (GABA)-gated chloride channels, resulting in rapid death of ticks and fleas. In in vitro studies, the activity of lotilaner against some arthropod species was not affected by resistance to organochlorines (cyclodienes, e.g. dieldrin), phenylpyrazoles (e.g. fipronil), neonicotinoids (e.g. imidacloprid), formamidines (e.g. amitraz) and pyrethroids (e.g. cypermethrin).

For fleas, the onset of efficacy is within 12 hours of attachment for one month after product administration. Fleas on the animal prior to administration are killed within 8 hours.

For ticks, the onset of efficacy is within 24 hours of attachment for one month after product administration. Existing ticks on the animal prior to administration are killed within 18 hours.

The-veterinary medicinal product kills existing and newly emerged fleas on cats before they can lay eggs. Therefore, the product breaks the flea life cycle and prevents environmental flea contamination in areas to which the cat has access.

• 5.2 Pharmacoki­netic particulars

Following oral administration, lotilaner is readily absorbed and peak blood concentration is reached at 4 hours. Lotilaner is approximately 10 times more bioavailable when administered with food. The terminal half-life is approximately 4 weeks (harmonic mean). This terminal half-life provides effective blood concentrations for the entire duration of the inter-dosing interval.

The major route of elimination is biliary excretion, and renal excretion is the minor route of elimination (less than 10 % of the dose). Lotilaner is metabolized to a small extent into more hydrophilic compounds, which are observed in faeces and urine.

6.1 List of excipients

Yeast powder (flavour)

Silicified microcrystalline cellulose

Cellulose, powdered

Lactose monohydrate

Povidone K30

Crospovidone

Sodium laurilsulfate

Vanillin (flavour)

Silica, colloidal anhydrous

Magnesium stearate

6.2 Major incompatibilities

Not applicable.

6.3 Shelf life

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

6.4. Special precautions for storage

This medicinal product does not require any special storage conditions.

• 6.5 Nature and composition of immediate packaging

The tablets are packaged in aluminium/ aluminium blisters packaged into an outer cardboard box.

Each tablet strength is available in pack sizes of 1, 3 or 6 tablets.

Not all pack sizes may be marketed.

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

7. MARKETING AUTHORISATION HOLDER

Elanco GmbH

Heinz-Lohmann-Str. 4

27472 Cuxhaven

Germany

8. MARKETING AUTHORISATION NUMBER(S)

EU/2/17/206/016–21

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 25/04/2017