NexGard Spectra Chewable 3 Tablets for Dogs prevention of heartworm disease / Antiparassitario / vermifugo per cani 3 compresse EUROPEAN VERSION

CLINICAL PARTICULARS

Target species:  Dogs

Indications for use, specifying the target species

For the treatment of flea and tick infestations in dogs when the prevention of cardiac dirofilariasis and/or the treatment against infestations with gastrointestinal nematodes is also indicated.

Treatment of flea infestations ( Ctenocephalides felis and C. canis ) in dogs for 5 weeks. Treatment of tick infestations ( Dermacentor reticulatus, Ixodes ricinus, Rhipicephalus sanguineus ) in dogs for 4 weeks

Fleas and ticks must be attached to the host and begin the feeding process to be exposed to the active substance.

Treatment of infestations with adult gastrointestinal nematodes of the following species: roundworms ( Toxocara canis and Toxocara leonina ), hookworms ( Ancyclostoma caninum and Ancyclostoma braziliense ) and whipworms ( Trichuris vulpis ).

Prevention of cardiac heartworm disease ( Dirofilaria immitis larval stage) if administered monthly.

Contraindications:  Do not use in case of hypersensitivity to the active substances or to any of the excipients.

 Special precautions for each target species

Parasites must begin feeding on the host to be exposed to afoxolaner; therefore, the risk of transmitting infectious diseases cannot be excluded.

 Parasite resistance to a certain class of antiparasitic drugs can develop as a result of frequent use of a compound of that class. Therefore, the use of this product must be based on a case-by-case assessment and local epidemiological information on the current susceptibility of the target species to limit the possibility of future selection of resistance.

 Maintaining the effectiveness of macrocyclic lactones is essential in the control of Dirofilaria immitis . In order to minimize the risk of resistance selection, it is recommended to test dogs for both circulating antigens and blood microfilariae at the beginning of each preventive treatment period.

Only negative animals should be treated

Special precautions for use

Special precautions for use in animals

In the absence of available data, the treatment of puppies less than 8 weeks old and/or dogs weighing less than 2 kg should only be carried out based on the assessment of the risk/benefit ratio by the veterinarian.

Dogs living in areas endemic for cardiovascular heartworm disease should be tested for adult heartworm infestation prior to administration of NEXGARD SPECTRA. Infested dogs must be treated with an adulticide at the veterinarian's choice to eliminate adult heartworms. NEXGARD SPECTRA is not indicated for the elimination of microfilariae.

The recommended dosage must be strictly followed in the case of dogs of the Collie breed or other breeds related to it.

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

•  This product may cause gastrointestinal disturbances if ingested.
• Keep the tablets in blisters and the blister in the box until use.
• In case of accidental ingestion, especially by children, seek medical advice immediately and show the product label.
• Wash hands after use.

Adverse reactions (frequency and severity)

In clinical trials, there were no serious adverse reactions attributed to the combination of afoxolaner with milbemycin oxime. Uncommon reactions such as: vomiting, diarrhea, lethargy, anorexia and pruritus have been observed. These reactions generally resolved on their own and were of short duration.

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

- Very common (more than 1 in 10 animals showing adverse reactions during treatment)

- Frequent (more than 1 but less than 10 animals out of 100 animals)

- Uncommon (more than 1 but less than 10 animals in 1000 animals)

- Rare (more than 1 but less than 10 animals in 10,000 animals)

- Very rare (less than 1 animal in 10,000 animals, including isolated reports).

Use during pregnancy, lactation or during the laying period

Laboratory studies in rats and rabbits have not shown teratogenic effects or any adverse effect on male or female reproductive capacity. The safety of the veterinary medicinal product has not been established during pregnancy and lactation or for breeding dogs. To be used in accordance with the benefit-risk assessment of the veterinarian.

Interactions with other medicinal products or other forms of interaction

Milbemycin oxime is a p-glycoprotein (P-gp) substrate, so it may interact with other P-gp substrates (eg, digoxin, doxorubicin) or other macrocyclic lactones. Therefore, concomitant treatment with other P-gp substrates may lead to increased toxicity.

Quantities to be administered and route of administration

For oral administration.

Dosage:

The product should be administered at a dose of 2.50-5.36 mg/kg of afoxolaner and 0.50-1.07 mg/kg of milbemycin oxime body weight according to the following table:

Dog weight (kg)	The concentration and number of chewable tablets to be administered
	NEXGARD SPECTRA 9 mg/ 2 mg	NEXGARD SPECTRA 19 mg/ 4 mg	NEXGARD SPECTRA 38 mg/ 8 mg	NEXGARD SPECTRA 75 mg/ 15 mg	NEXGARD SPECTRA 150 mg/ 30 mg
2-3.5	1
>3.5-7.5		1
>7.5-15			1
>15-30				1
>30-60					1

 For dogs over 60 kg of body weight, the necessary combination of chewable tablets will be used

Method of administration:

The tablets are chewable and pleasant to the taste for most dogs. If the dog does not accept the tablets directly, they can be administered together with food.

Treatment scheme:

The treatment plan must be based on the veterinary diagnosis and the local epidemiological situation.

NEXGARD SPECTRA can be used as a seasonal preventive treatment against fleas and ticks (replacing the treatment with a monovalent product with action only against fleas and ticks) in dogs co-infested with gastrointestinal nematodes. A single treatment is effective against gastrointestinal nematodes. After treating nematode infestations, treatment against flea and tick infestations can be continued by applying the monovalent product.

Disease: Cardiac heartworm disease:

NEXGARD SPECTRA kills Dirofilaria immitis larvae within one month of transmission by mosquitoes, therefore the product should be administered at regular monthly intervals throughout the vector-prone periods, beginning one month after the first exposure to mosquitoes. Treatment should be continued until the month following the last exposure to mosquitoes. In order to establish a treatment routine, it is recommended to administer the treatment on the same day of the month.

If replacing another cardiac heartworm prevention product, the first treatment with NEXGARD SPECTRA should begin on the day the previous medication was due.

Dogs that live in or have traveled to an area with cardiac heartworm disease can be infested with adult heartworms. No therapeutic effect has been established against adult Dirofilaria immitis . It is therefore recommended that all dogs 8 months of age or older living in heartworm endemic areas be tested for adult heartworm infestation before being treated with a heartworm prevention product.

 Overdose (symptoms, emergency procedures, antidotes), as appropriate

No adverse reactions were observed in healthy puppies over 8 weeks of age after 6 treatments with 5 times the maximum dose.

 Waiting time:  Not applicable.

PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: antiparasitic products, endectocides, milbemycin combinations.

ATC veterinary code: QP54AB51

 

Pharmacodynamic properties

Afoxolaner :

Afoxolaner is an insecticide and acaricide belonging to the isoxazoline family.

 Afoxolaner acts by interacting with chloride ion channels, mainly those with a binding site for the neurotransmitter gamma-aminobutyric acid (GABA), thus blocking the pre- and post-synaptic transfers of chloride ions across the cell membrane. This results in an uncontrolled activity of the central nervous system and the death of insects and mites. The selective toxicity of afoxolaner between insects/mites and mammals is a consequence of the characteristic sensitivity of insect/mite versus mammalian GABA receptors.

 Afoxolaner is active against adult fleas as well as tick species such as Rhipicephalus sanguineus, Dermacentor reticulatus and D. variabilis, Ixodes ricinus and I. scapularis, Amblyomma americanum and Haemaphysalis longicornis.

The product kills fleas before laying eggs and thus prevents contamination of the house. It can be used as part of the treatment strategy for the control of allergic flea dermatitis (FAD). 

Milbemycin oxime:

Milbemycin oxime is an antiparasitic endectocide that belongs to the group of macrocyclic lactones. Milbemycin oxime is the mixture of milbemycin A ₄ and milbemycin A ₃ (in a ratio of 20:80 for A ₃ :A ₄ ). It is isolated from the fermentation of Streptomyces milbemycinicus .

Milbemycin oxime acts by disrupting glutamate-activated neurotransmission in invertebrates. Milbemycin oxime increases membrane permeability of nematodes and insects to chloride ions through glutamate-gated chloride ion channels (linked to GABA and glycine receptors in vertebrates).

This leads to hyperpolarization of the neuromuscular membrane and paralysis and death of the parasites.

 

Pharmacokinetic peculiarities

Afoxolaner is very rapidly absorbed systemically. The absolute bioavailability obtained was 88%. The mean value of the maximum plasma concentration (C _max ) was 1822 ± 165 ng/ml, 2-4 hours (T _max ) after a dose of 2.5 mg/kg afoxolaner.

The distribution volume of Afoxolaner at the tissue level is 2.6 ± 0.6 l/kg and the clearance value is 5.0 ± 1.2 ml/h/kg. The half-life is approximately 2 weeks in dogs.

Plasma concentrations of Milbemycin oxime increase rapidly in the first 1-2 hours (T _max ), indicating rapid absorption from the tablet. The absolute bioavailability obtained was 81% for factor A ₃ and respectively 65% ​​for A _4. The average value of the maximum plasma concentration (C _max ), following oral administration, was 1.6 ± 0.4 days and 42 ± 11 ng/ml for A ₃ , 3.3 ± 1.4 days and 246 ± 71 ng/ml for A ₄ .

The distribution volume of Milbemycin oxime at the tissue level is 2.7 ± 0.4 and 2.6 ± 0.6 l/kg for form A _{3 and A 4} respectively . Both forms have a low clearance value of 75 ± 22 ml/h/kg for A ₃ and 41 ± 12 ml/h/kg for A ₄ .

 

PHARMACEUTICAL PARTICULARS

List of excipients

• Corn starch
• Soy protein
• Stewed beef flavoring
• Povidone (E1201)
• Macrogol 400
• Macrogol 4000
• Macrogol 15 hydroxystearate
• Glycerol (E422)
• Medium chain triglycerides
• Citric acid monohydrate (E330)
• Butyl hydroxytoluene (E321)

Incompatibilities:  Not applicable.

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

 Special precautions for storage:  Keep the blister in the secondary packaging in order to protect from light.