Nexgard spectra 38/8 mg for dogs between 7.5 and 15 kg 3 chewable tablets
Treatment of flea and tick infestations and infestations with adult gastrointestinal nematodes in dogs
NEXGARD SPECTRA 38 mg / 8 mg chewable tablets for dogs >7.5–15 kg
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each chewable tablet contains:
NEXGARD SPECTRA: Afoxolaner (mg); Milbemycin oxime (mg)
chewable tablets for dogs >7.5–15 kg: 37.50; 7.50
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Mottled red to reddish brown, circular shaped (tablets for dogs 2–3.5 kg) or rectangular shaped (tablets for dogs >3.5–7.5 kg, tablets for dogs >7.5–15 kg, tablets for dogs >15–30 kg and tablets for dogs >30-60 kg).
4. CLINICAL PARTICULARS
4.1 Target species Dogs.
4.2 Indications for use, specifying the target species
For the treatment of flea and tick infestations in dogs when the concurrent prevention of heartworm disease and/or treatment of gastrointestinal nematode infestations is 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 attach to the host and commence feeding in order to be exposed to the active substance.
Treatment of infestations with adult gastrointestinal nematodes of the following species: roundworms (Toxocara canis and Toxascaris leonina), hookworms (Ancylostoma caninum and Ancylostoma braziliense) and whipworm (Trichuris vulpis).
Prevention of heartworm disease (Dirofilaria immitis larvae) with monthly administration.
Do not use in case of hypersensitivity to the active substances or to any of the excipients.
4.4 Special warnings for each target species
Fleas and ticks need to start feeding on the host to become exposed to afoxolaner; therefore the risk of the transmission of vector-borne diseases cannot be excluded.
Parasite resistance to any particular class of parasiticides may develop following the frequent, repeated use of a product of that class. Therefore, the use of this product should be based on the 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 a future selection for resistance.
Maintenance of the efficacy of macrocyclic lactones is critical for Dirofilaria immitis control. To minimise the risk of resistance selection, it is recommended that dogs should be checked for both circulating antigens and blood microfilariae at the beginning of each season of preventative treatment. Only negative animals should be treated.
4.5 Special precautions for use Special precautions for use in animals
In the absence of available data, treatment of puppies less than 8 weeks of age and dogs less than 2 kg bodyweight should be based on a benefit-risk assessment by the responsible veterinarian.
In heartworm endemic areas, dogs should be tested for existing heartworm infestation prior to administration of NEXGARD SPECTRA. At the discretion of the veterinarian, infested dogs should be treated with an adulticide to remove adult heartworms. NEXGARD SPECTRA is not indicated for microfilariae clearance.
The recommended dose should be strictly observed in collies or related breeds.
Special precautions to be taken by the person administering the veterinary medicinal product to animals
This product may cause gastrointestinal disturbances if ingested.
Keep tablets in the blister packs until required, and keep the blisters in the outer carton.
In case of accidental ingestion, particularly in the case of children, seek medical advice immediately and show the package leaflet or the label to the physician.
Wash hands after use.
4.6 Adverse reactions (frequency and seriousness)
In clinical studies, no serious adverse reactions were attributed to the combination of afoxolaner and milbemycin oxime. Adverse reactions such as: vomiting, diarrhoea, lethargy, anorexia, and pruritus were uncommonly observed. These occurrences were generally self-limiting and of short duration.
The frequency of adverse reactions is defined using the following convention:
very common (more than 1 in 10 animals displaying adverse reactions during the course of one treatment)
common (more than 1 but less than 10 animals in 100 animals)
uncommon (more than 1 but less than 10 animals in 1,000 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).
4.7 Use during pregnancy, lactation or lay
Laboratory studies in rats and rabbits have not produced any evidence of teratogenic effects, or any adverse effect on the reproductive capacity in males and females.
The safety of the veterinary medicinal product has not been established during pregnancy and lactation or in breeding dogs. Use only according to the benefit-risk assessment by the responsible veterinarian.
4.8 Interaction with other medicinal products and other forms of interaction
Milbemycin oxime is a substrate for P-glycoprotein (P-gp) and therefore could interact with other P-gp substrates (for example, digoxin, doxorubicin) or other macrocyclic lactones. Therefore, concomitant treatment with other P-gp substrates could lead to enhanced toxicity.
4.9 Amounts to be administered and administration route For oral use.
The veterinary medicinal 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 in accordance with the following table:
Bodyweight (kg) of dog: Number and strength of tablet to be administered
2–3.5: 1 NEXGARD SPECTRA 9 mg/ 2 mg
>3.5–7.5: 1 NEXGARD SPECTRA 19 mg/ 4 mg
>7.5–15: 1 NEXGARD SPECTRA 38 mg/ 8 mg
>15–30: 1 NEXGARD SPECTRA 75 mg/ 15 mg
>30–60: 1 NEXGARD SPECTRA 150 mg/ 30 mg
For dogs above 60 kg appropriate combinations of chewable tablets are used.
Method of administration:
The tablets are chewable and palatable to most dogs. If the dog does not accept the tablets directly they may be administered with food.
The treatment schedule should be based on veterinary diagnosis and on the local epidemiological situation.
NEXGARD SPECTRA can be used as part of the seasonal treatment of fleas and ticks (replacing treatment with a monovalent flea and tick product) in dogs with diagnosed concurrent gastrointestinal nematode infestations. A single treatment is effective for the treatment of gastrointestinal nematodes. After treatment of the nematode infestations, further flea and tick treatment should be continued with a monovalent product.
NEXGARD SPECTRA kills Dirofilaria immitis larvae up to one month after their transmission by mosquitoes therefore the product should be administered at regular monthly intervals during the time of the year when vectors are present, starting in the month after the first expected exposure to mosquitoes. Treatment should continue until 1 month after the last exposure to mosquitoes. To establish a treatment routine, it is recommended that the same day or date be used each month.
When replacing another heartworm preventative product in a heartworm prevention programme, the first treatment with NEXGARD SPECTRA should start on the date when the former medication was due to have been administered.
Dogs living in heartworm endemic areas, or those which have travelled to endemic areas, may be infested with adult heartworms. No therapeutic effect against adult Dirofilaria immitis has been established. It is therefore recommended that all dogs 8 months of age or more, living in heartworm endemic areas, should be tested for existing adult heartworm infestation before being treated with the product for heartworm prevention.
4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary
No adverse reactions were observed in eight-week old healthy puppies after 6 treatments at up to 5 times the maximum dose.
4.11 Withdrawal period Not applicable.
5. PHARMACOLOGICAL PROPERTIES
Pharmacotherapeutic group: antiparasitic products, endectocides, milbemycin combinations.
ATCvet code: QP54AB51.
5.1 Pharmacodynamic properties
Afoxolaner is an insecticide and acaricide of the isoxazoline family.
Afoxolaner acts as an antagonist at ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA). Isoxazolines, among the chloride channel modulators, bind to a distinct and unique target site within the insect GABACls, thereby blocking pre- and post-synaptic transfer of chloride ions across cell membranes.
Prolonged afoxolaner-induced hyperexcitation results in uncontrolled activity of the central nervous system and death of insects and acarines. The selective toxicity of afoxolaner between insects, acarines and mammals may be inferred by the differential sensitivity of the insects and acarines’ GABA receptors versus mammalian GABA receptors.
It is active against adult fleas as well as against several tick species such as Rhipicephalus sanguineus, Dermacentor reticulatus and D. variabilis, Ixodes ricinus and I. scapularis, Amblyomma americanum, and Haemaphysalis longicornis.
Afoxolaner kills fleas before egg production and therefore prevents the risk of household contamination. It can be used as part of a treatment strategy for the control of flea allergy dermatitis (FAD).
Milbemycin oxime is an antiparasitic endectocide belonging to the group of macrocyclic lactones. Milbemycin oxime contains two major factors, A3 and A4 (ratio of 20:80 for A3:A4). It is a fermentation product of Streptomyces milbemycinicus. Milbemycin oxime acts by disrupting the glutamate neuro-transmission in invertebrates. Milbemycin oxime increases glutamate binding with consequent enhanced chloride ion flow into the cell. This leads to hyperpolarisation of the neuromuscular membrane resulting in paralysis and death of the parasites.
5.2 Pharmacokinetic particulars
Afoxolaner had high systemic absorption. The absolute bioavailability is 88%. The mean maximum concentration (Cmax) is 1822 ± 165 ng/ml in plasma found 2–4 hours (Tmax) after a 2.5 mg/kg afoxolaner dose.
Afoxolaner distributes into tissues with a volume of distribution of 2.6 ± 0.6 l/kg and a systemic clearance value of 5.0 ± 1.2 ml/h/kg. The terminal plasma half-life is approximately 2 weeks in dogs.
Milbemycin oxime plasma concentrations peak quickly within the first 1–2 hours (Tmax) indicating that absorption from the chewable is fast. The absolute bioavailability is 81% and 65% for the A3 and A4 forms, respectively. The terminal half-lives and maximum concentrations (Cmax) following oral administration are 1.6 ± 0.4 days and 42 ± 11 ng/ml for the A3 form, 3.3 ± 1.4 days and 246 ± 71 ng/ml the A4 form.
Milbemycin oxime distributes into tissues with a volume of distribution of 2.7 ± 0.4 and 2.6 ± 0.6 l/kg for the A3 and A4 forms respectively. Both forms have low systemic clearance (75 ± 22 ml/h/kg for the A3 form and 41 ± 12 ml/h/kg for A4 form).
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Soy protein fines
Beef braised flavouring
Macrogol 15 hydroxystearate
Triglycerides, medium-chain Citric acid monohydrate (E330)
6.2 Incompatibilities Not applicable.
6.3 Shelf life
Shelf life of the veterinary medicinal product as packaged for sale: 2 years.
6.4 Special precautions for storage
Keep the blister in the outer carton in order to protect from light.