Round biconvex tablets of white to beige color with brown spots and beveled edges, embossed on one side of the tablet with the letter "I".

Composition

1 g of the drug contains active substances:

• lotilaner — 351.6 mg
• milbemycin oxime — 13.2 mg.

Credelio PLUS is produced with the appropriate amount of active substances (lotilaner and milbemycin oxime) in one tablet for dogs of different body weights.

One tablet contains active ingredients:

Excipients: powdered cellulose, lactose monohydrate, silicified microcrystalline cellulose, dry meat flavoring, crospovidone, povidone K30, sodium lauryl sulfate, colloidal anhydrous silicon dioxide, magnesium stearate.

Pharmacological properties

ATC-vet classification code: QP54AB51, antiparasitic drugs, ectoparasiticides, endectocides for systemic use (milbemycin combinations).

Lotilaner belongs to the group of isoxazolines, has acaricidal and insecticidal effects. Lothilaner — pure enantiomer, active against adult ticks such as Dermacentor reticulatus, Ixodes hexagonus, I. ricinus and Rhipicephalus sanguineus, adult fleas such as Ctenocephalides felis and C. Canis, as well as ticks (Demodex canis).

Lotilaner is a potent inhibitor of GABA (γ-aminobutyric acid)-gated chloride channels and at least glutamate-gated chloride ion channels of insects and ticks, resulting in the rapid death of ticks and fleas. Parasite resistance to organochlorines (cyclodienes, e.g. dieldrin), phenylpyrazoles (e.g. fipronil), neonicotinoids (e.g. imidacloprid), formamidines (e.g. amitraz) and pyrethroids (e.g. cypermethrin) has not been found to affect the activity of lotilaner.

On ticks, the drug begins to act within 48 hours after attachment to the host and is effective within one month after application. I. ricinus ticks present on the dog before the use of the drug die within 8 hours.

On fleas, the drug begins to act within 4 hours after exposure and continues to act for one month after application. Fleas that were on the dog before using the drug die within 6 hours.

The drug destroys existing and new flea infestations in dogs before the female flea has time to lay eggs. Thus, the drug disrupts the life cycle of fleas and prevents the risk of contamination of the animal's habitat.

Milbemycin oxime belongs to the group of systemically active macrocyclic lactones, which are released as a result of the enzymatic activity of Streptomyces hygroscopicus var. aureolacrimosus. It contains two main factors — A3 and A4 (20:80 aspect ratio). Milbemycin oxime — antiparasitic endectocide, active against ticks, larval and adult stages of nematodes, as well as larvae (L3/L4) of Dirofilaria immitis.

The activity of milbemycin oxime’is related to its effect on the transmission of nerve impulses in invertebrates.

Milbemycin oxime, like avermectins and other milbemycins, increases the permeability of cell membranes of nematodes and insects to chloride ions through glutamate-gated chloride ion channels. This leads to hyperpolarization of cell membranes of nerve and muscle tissues, peripheral paralysis and death of parasites.

Lotilaner is easily absorbed after oral administration, the maximum concentration in plasma is reached within 3-5 hours. Milbemycin A3 5-oxime and Milbemycin A4 5-oxime are also rapidly absorbed after oral administration, with peak blood concentrations approximately 2-4 hours (Tmax) for each active ingredient. Food improves the absorption of both lotilaner and milbemycin oxime. The bioavailability of lotilaner is 75%, milbemycin (5-oxime A3 and A4) is about 60%.

Lotilaner and milbemycin A3 and A4 5-oximes are widely distributed in the body of dogs, the volume of distribution after intravenous administration is 3-4 l/kg. Plasma protein binding is high for both lotilaner and milbemycin oxime (> 95%).

Lotilaner is metabolized to a minor extent to more hydrophilic compounds that are observed in feces and urine.

Lotilaner is excreted from the body mainly with bile, and renal excretion is a secondary route of elimination (less than 10% of the dose). The final half-life is about 24 days, which ensures the appropriate concentration in the blood and the effectiveness of the drug during the entire period between doses. With repeated monthly doses, slight accumulation is observed, the steady state is reached after the fourth monthly dose.

Primary metabolites milbemicin oxime in dog feces and urine were identified as glucuronide conjugates of milbemycin A3 or A4 5-oxime, dealkylated milbemycin A3 or A4 5-oxime, and hydroxylated milbemycin A4 5-oxime. Hydroxymilbemycin A4 5-oxime was detected only in plasma, but not in urine or feces, indicating preferential excretion of conjugated metabolites in dogs.

Milbemycin A4 5-oxime is eliminated more slowly than milbemycin A3 5-oxime (clearance after intravenous administration was 47.0 and 106.8 mL/h/kg, respectively), resulting in an exposure (AUC) of milbemycin A4 that higher than milbemycin A3 5-oxime. The mean elimination half-life was 27 hours for A3 and 57 hours for A4. Elimination of milbemycin A3 and A4 5-oxime mainly occurs with feces, to a lesser extent with urine.

Application

For use in dogs with mixed parasitic infestations of ticks, fleas, gastrointestinal nematodes, heart and/or lung helminths or in dogs at risk of such infestation.

The drug is used when simultaneous treatment of flea and tick infestations and nematodes of the alimentary canal is necessary or treatment of flea and tick infestations and prevention of heartworm disease/angiostrongylosis.

Ectoparasites

Treatment of dogs with ticks (Dermacentor reticulatus, Ixodes ricinus, Rhipicephalus sanguineus and I. hexagonus) and fleas (Ctenocephalides felis and S. canis).

The drug has immediate and sustained activity against ticks and fleas for 1 month.

The drug is also used in complex therapy of allergic dermatitis caused by fleas.

For the treatment of demodicosis (caused by Demodex canis).

Nematodes of the alimentary canal

Treatment of nematodes of the alimentary canal: hookworms (L4 larvae, immature adults (L5) and adult forms of Ancylostoma caninum), roundworms (L4 larvae, immature adults (L5) and adult forms of Toxocara canis, adult forms of Toxascaris leonina) and roundworms ( adult forms of Trichuris vulpis).

Heartworms

Prevention of heartworm disease (Dirofilaria immitis).

Pulmonary helminths

Prevention of angiostrongylosis by reducing the level of infection with immature adult forms (L5) and adult stages of Angiostrongylus vasorum (pulmonary helminths) with monthly use.

Dosage

Credelio PLUS chewable tablets are used for dogs individually orally once in a dose of 20-41 mg of lotilaner and 0.75-1.53 ​​mg of milbemycin oxime per 1 kg of the animal's body weight according to the table below:

For dogs weighing more than 45 kg, an appropriate combination of available dosages should be used to achieve the recommended dose of 20-41 mg of lotilaner and 0.75-1.53 ​​mg of milbemycin oxime per 1 kg of animal body weight.

The treatment scheme should be based on the individual risk assessment for the dog, the local epidemiological situation and/or the epidemiological situation in other regions that the dog has visited or is going to visit. If, based on the opinion of the veterinarian, the dog needs repeated application(s), any subsequent application(s) should be carried out with an interval of 1 month.

The drug must be used in dogs with mixed parasitic infestations — ectoparasites (ticks or fleas) and endoparasites (nematodes of the alimentary canal and/or for the prevention of heart/lung helminths) or dogs at risk of such infection. Otherwise, a parasiticide with a narrow spectrum of action should be used.

Method of application

Credelio PLUS — pleasant-tasting flavored chewable tablets. Give pills to dogs during feeding or after feeding.

Dogs in non-endemic areas for heartworm disease:

The drug can be used as part of the seasonal treatment against ticks and/or fleas in dogs with an established diagnosis or those at risk of infection with associated nematodes of the alimentary canal or at risk of infection with pulmonary helminths. One-time use of the drug is effective in the treatment of nematodes of the alimentary canal.

Dogs located in areas endemic for heartworm disease:

Before treatment with a veterinary medicine, you should familiarize yourself with the recommendations.

For the prevention of heartworm disease and the simultaneous treatment of tick and flea infestations, the drug must be used monthly throughout the entire season of the presence of mosquitoes, mosquitoes, ticks and fleas. The first dose of the drug is used at the beginning of the mosquito and mosquito flight season and ends no earlier than 1 month after the end of their flight.

If the animal was treated with another drug for the prevention of heart helminthiasis, then the first use of Credelio PLUS should be started 1 month after the last treatment with the previous drug.

Dogs traveling to areas at risk for heartworm disease should begin treatment within one month of arrival in such area. The use of the drug for the prevention of heartworm disease must be continued monthly and stopped 1 month after the dog has left the dangerous region.

Pulmonary helminths:

In endemic areas, monthly use of the drug reduces the level of infection by immature adults (L5) and adult forms of Angiostrongylus vasorum in the heart and lungs. It is recommended to continue prevention of pulmonary helminths for at least 1 month after the last contact with slugs and snails.

To determine the optimal time to start treatment with the drug, you should consult a veterinarian.

Treatment of demodicosis (caused by Demodex canis)

Monthly use of preparationsatu for 2 months in a row is effective and leads to a noticeable improvement in clinical signs. Treatment should be continued until the results of 2 consecutive monthly laboratory tests are negative (skin scrapings). In severe cases, long-term monthly treatment may be necessary.

Since demodicosis — it is a multifactorial disease, it is recommended, if possible, to carry out appropriate treatment of the main diseases.

Contraindications

Do not use in dogs with known hypersensitivity to active or auxiliary substances.

Side effect

Gastrointestinal disorders (diarrhea and vomiting), anorexia, muscle tremors, lethargy, pruritus, and behavioral changes have been reported infrequently. These phenomena, as a rule, were self-limiting and short-lived.

Nervous disorders (convulsions, muscle tremors and ataxia) were rarely recorded in the post-marketing experience of the safety of the active substance lotilaner, which is part of the monovalent drug Credelio in the same dose as in the drug Credelio PLUS. These symptoms usually disappear without treatment.

Disclaimer

All data on the safety and efficacy of the drug were obtained for dogs and puppies aged 8 weeks and older and weighing 1.4 kg or more. Use of this veterinary medicinal product in puppies less than 8 weeks of age or weighing less than 1.4 kg should be based on a benefit/risk assessment by a veterinarian.

The recommended dose should be strictly followed for dogs with a (-/-) MDR1 gene mutation with non-functional P-glycoprotein, including Collies and related breeds.

Before the first use of the drug in dogs from areas endemic for heartworm disease or those who have visited endemic areas, the dogs should be examined for heartworm disease. A veterinarian decides on the need to treat infected dogs with drugs that act on adult heartworms.

It is not recommended to use products containing milbemycin oxime (such as this product) in dogs with high numbers of circulating microfilariae to avoid hypersensitivity reactions associated with the release of proteins from the dead microfilariae.

All dogs in the household should be treated with the appropriate drug.

Ticks and fleas must start feeding after attaching to the animal, so that the active ingredients of the drug start acting on them; therefore, the risk of transmission of diseases, the causative agents of which are transmitted through parasites, cannot be completely excluded.

Parasite resistance to any particular class of parasiticides may develop after frequent or repeated use of drugs of that class. Therefore, the use of this drug should be based on an assessment of each individual case and on local epidemiological information about the current susceptibility of the target species in order to limit the possibility of selective resistance to the drug.

The necessity and frequency of repeated treatment, as well as the selection of a drug for the treatment of nematodes of the alimentary canal (monodrug or combined drug) should be evaluated by a veterinarian.

Maintaining the effectiveness of macrocyclic lactones is critical for the prevention of heartworm (Dirofilaria immitis), therefore, to minimize the risk of resistance, it is recommended that dogs be tested for the presence of circulating antigens and microfilariae in the blood at the beginning of each heartworm season before starting monthly preventive treatment. The drug is not effective against adult Dirofilaria immitis and is not intended to kill microfilariae.

Use during pregnancy, lactation

The safety of the drug has not been studied in pregnant, lactating dogs and dogs intended for breeding. Laboratory studies of the active substances on rats did not reveal any evidence of teratogenic effects or any negative effect on the reproductive capacity of males and females.

During pregnancy and lactation, use only under the conditions of assessing the benefit/risk ratio determined by a veterinarian.

Special precautions for persons and service personnel

Accidental ingestion of the drug can cause disorders of the digestive tract. Store the drug in a place inaccessible to children, packed in blisters and in the outer packaging.

In case of accidental ingestion of the drug, it is necessary to immediately consult a doctor and show him the leaflet or the label for the drug.

Hands must be washed after working with the drug.

Form of release

Credelio PLUS chewable tablets are produced in five dosages:

• Credelio PLUS 56.25 mg/2.11 mg chewable tablets for dogs weighing 1.4 - 2.8 kg
• Credelio PLUS 112.5 mg/4.22 mg chewable tablets for dogsbody weight (>2.8 - 5.5 kg)
• Credelio PLUS 225 mg/8.44 mg chewable tablets for dogs with body weight (>5.5 - 11 kg)
• Credelio PLUS 450 mg/16.88 mg chewable tablets for dogs with body weight (>11 - 22 kg)
• Credelio PLUS 900 mg/33.75 mg chewable tablets for dogs with body weight (>22 - 45 kg).

The drug is produced in aluminum foil blisters of 1, 3, 6 or 18 chewable tablets, packed in cardboard boxes.

Storage

Store the drug in the manufacturer's closed package at a temperature no higher than 30 °C.

Keep out of the reach of children.

Expiry date

3 years from the date of production, subject to storage in the original packaging.

For use in veterinary medicine!