Milbeguard Duo 12.5 mg / 125 mg Chewable Tablets for Dogs

Composition

Each tablet contains:

Active substances:

Milbemycin oxime 12.5 mg

Praziquantel 125 mg

For the full list of excipients, see section 6.1

6.1 List of excipients

Povidone

Croscarmellose sodium

Lactose monohydrate

Artificial Chicken flavour

Yeast

Cellulose microcrystalline

Silica, colloidal anhydrous

Magnesium stearate

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Pharmaceutical form

Chewable tablet.

Flavoured round tablet, beige to light brown, scored on one side. The tablet can be divided into equal halves.

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Pharmacological properties

Pharmacotherapeutic group: milbemycin oxime combinations

ATC Vet Code: QP54AB51

5.1 Pharmacodynamic properties

Milbemycin oxime belongs to the group of macrocyclic lactones, isolated from the fermentation of Streptomyces hygroscopicus var. aureolacrimosus. It is active against larval and adult stages of nematodes as well as against larvae of Dirofilaria immitis. The activity of milbemycin is related to its action on invertebrate neurotransmission: Milbemycin oxime, like avermectins and other milbemycins, increases nematode and insect membrane permeability to chloride ions via glutamate-gated chloride ion channels (related to vertebrate GABAA and glycine receptors). This leads to hyperpolarisation of the neuromuscular membrane and flaccid paralysis and death of the parasite.

Praziquantel is an acylated pyrazino-isoquinoline derivative. Praziquantel is active against cestodes. It modifies the permeability for calcium (influx of Ca2+) in the membranes of the parasite inducing an imbalance in the membrane structures, leading to membrane depolarization and almost instantaneous contraction of the musculature (tetany), rapid vacuolization of the syncytial tegument and subsequent tegumental disintegration (blebbing), resulting in easier expulsion from the gastrointestinal tract or death of the parasite.

5.2 Pharmacokinetic particulars

After oral administration of praziquantel in the dog, peak plasma levels of parent are rapidly reached 1918 µg/L. Tmax is about 30 min and ranged between 15 min and 10 hours. Plasma concentrations decline quickly (t1/2 around 1.72 hours). There is a substantial hepatic first-pass effect, with very rapid and almost complete hepatic biotransformation, principally to monohydroxylated (also some di- and tri-hydroxylated) derivatives, which are mostly glucuronide and/or sulfate conjugated before excretion. Plasma binding is about 80%. Excretion is fast and complete (about 90% in 2 days); the principal route of elimination is renal.

After oral administration of milbemycin oxime in dogs, peak plasma levels reach 773 µg/L and occur at about 1.25 hours. Tmax ranged between 45 min and 10 hours, plasma concentrations decline with a half-life of the unmetabolised milbemycin oxime of 1-5 days. Bioavailability is about 80%. In addition to relatively high liver concentrations, there is some concentration in fat, reflecting its lipophilicity.

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Target species

Dogs (dogs weighing at least 2.5 kg)

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Indications

In dogs: treatment of mixed infections by adult cestodes and nematodes of the following species:

- Cestodes:

Dipylidium caninum

Taenia spp.

Echinococcus spp.

Mesocestoides spp.

- Nematodes:

Ancylostoma caninum

Toxocara canis

Toxascaris leonina

Trichuris vulpis

Crenosoma vulpis (Reduction of the level of infection)

Angiostrongylus vasorum (Reduction of the level of infection by immature adult (L5) and adult parasite stages; see specific treatment and prevention disease schedules under section 4.9 “Administration routes and dosage”)

Thelazia callipaeda (see specific treatment schedule under section 4.9 “Administration routes and dosage”)

The product can also be used in the prevention of heartworm disease (Dirofilaria immitis) if concomitant treatment against cestodes is indicated.

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Dosage

Oral use.

Minimum recommended dose rate: 0.5 mg of milbemycin oxime and 5 mg of praziquantel per kg are given once orally.

Animals should be weighed to ensure accurate dosing. Depending on the bodyweight of the dog, the practical dosing is as follows:

Tablets are palatable. They should be administered with or after some food.

In cases when heartworm disease prevention is used and at the same time treatment against tapeworm is required, the product can replace the monovalent product for the prevention of heartworm disease.

For treatment of Angiostrongylus vasorum infections, milbemycin oxime should be given four times at weekly intervals. It is recommended, where concomitant treatment against cestodes is indicated, to treat once with the product and continue with the monovalent product containing milbemycin oxime alone, for the remaining three weekly treatments.

In endemic areas administration of the product every four weeks will prevent angiostrongylosis by reducing immature adult (L5) and adult parasite burden, where concomitant treatment against cestodes is indicated.

For the treatment of Thelazia callipaeda, milbemycin oxime should be given in 2 treatments, seven days apart. Where concomitant treatment against cestodes is indicated, the product can replace the monovalent product containing milbemycin oxime alone.

Underdosing could result in ineffective use and may favour resistance development. The need for and frequency of re-treatment(s) should be based on professional advice and should take into account the local epidemiological situation and the animal’s lifestyle.

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Contraindications

Do not use in dogs weighing less than 2.5 kg

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

See also section 4.5 "Special precautions for use".

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Adverse reactions

Dogs:

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 the national competent authority via the national reporting system. See also the last section of the package leaflet for respective contact details.

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Warnings

i). Special precautions for use in animals

In heartworm risk-areas, or if it is known that a dog has been travelling to and from heartworm risk regions, before using the product, a veterinary consultation is advised to exclude the presence of any concurrent infestation of Dirofilaria immitis. In the case of a positive diagnosis, adulticidal therapy is indicated before administering the product.

Treatment of dogs with a high number of circulating microfilariae can sometimes lead to the appearance of hypersensitivity reactions, such as pale mucous membranes, vomiting, trembling, laboured breathing or excessive salivation. These reactions are associated with the release of proteins from dead or dying microfilariae and are not a direct toxic effect of the product. The use in dogs suffering from microfilaremia is thus not recommended.

No studies have been performed with severely debilitated dogs or individuals with seriously compromised kidney or liver function. The product is not recommended for such animals or only according to a benefit/risk assessment by the responsible veterinarian.

Studies with milbemycin oxime indicate that the margin of safety in certain dogs of Collie or related breeds is less than in other breeds. In these dogs, the recommended dose should be strictly observed. The tolerance of the product in young puppies from these breeds has not been investigated. Clinical signs in Collies are similar to those seen in the general dog population when overdosed (see section 3.10 “Symptoms of overdose”).

In dogs less than 4 weeks old, tape worm infection is unusual. Treatment of animals less than 4 weeks old with a combination product may therefore not be necessary. The tablets are flavoured. In order to avoid any accidental ingestion, store tablets out of reach of the animals.

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

This veterinary medicinal product may be harmful when ingested, particularly for children. To avoid accidental ingestion, the product should be stored out of sight and reach of children. Any unused part of tablet should be stored in the opened blister, inside the outer packaging and always be used at the next administration.

In case of accidental ingestion of the tablets, particularly by a child, seek medical advice immediately and show the package leaflet or the label to the physician. The product may cause a weak skin sensitization. Do not handle this product in case of known hypersensitivity to the active substances or to any of the excipients. Wash hands after use.

iii). Other precautions

Echinococcosis represents a hazard for humans. As Echinococcosis is a notifiable disease to the World Organisation for Animal Health (OIE), specific guidelines on the treatment and follow up and on the safeguard of persons need to be obtained from the relevant competent authority.

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Use during pregnancy, lactation or lay

The safety of the veterinary medicinal product has been established during pregnancy and lactation.

Can be used during pregnancy and lactation.

Can be used in breeding animals.

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Interactions

The concurrent use of the product with selamectin is well tolerated. No interactions were observed when the recommended dose of the macrocyclic lactone selamectin was administered during the treatment with the product at the recommended dose. In the absence of further studies, caution should be taken in the case of concurrent use of the product and other macrocyclic lactones. Also, no such studies have been performed with reproducing animals.

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Overdose

No other signs than those observed at the recommended dose have been observed (see section 4.6 “Adverse events”).

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Special warnings

It is recommended to treat all the animals living in the same household concomitantly. When infection with the cestode D. caninum has been confirmed, concomitant treatment against intermediate hosts, such as fleas and lice, should be discussed with a veterinarian to prevent re-infection.

Unnecessary use of antiparasitics or use deviating from the instructions given in the SPC may increase the resistance selection pressure and lead to reduced efficacy. The decision to use the product should be based on confirmation of the parasitic species and burden, or of the risk of infection based on its epidemiological features, for each individual animal.

Parasite resistance to any particular class of anthelmintic may develop following frequent, repeated use of an anthelmintic of that class.

In the absence of risk of co-infection with nematodes or cestodes, a narrow spectrum product should be used when available.

The use of this product should take into account local information about susceptibility of the target parasites, where available.

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Withdrawal period

Not applicable.

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Incompatibilities

Not applicable

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Immediate packaging

Polyamide-Aluminium-Polyvinyl chloride / aluminium heat sealed blisters.

I Cardboard box with 1 blister of 2 tablets (2 tablets).

II Cardboard box with 2 blisters of 2 tablets (4 tablets).

III Cardboard box with 5 blisters of 2 tablets (10 tablets).

IV Cardboard box with 12 blisters of 2 tablets (24 tablets).

V Cardboard box with 24 blisters of 2 tablets (48 tablets).

VI Cardboard box with 50 blisters of 2 tablets (100 tablets).

Not all pack sizes may be marketed.

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Storage

This veterinary medicinal product does not require any special storage conditions. Halved tablets should be stored in the original blister and be used for the next administration.

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Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 48 months

Shelf life for halved tablet after first opening the blister: 6 months

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Disposal of unused product

Medicines should not be disposed of via wastewater or <household waste>.

The veterinary medicinal product should not enter water courses as this may be dangerous for fish and other aquatic organisms.

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.

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Additional information

Vm 14966/5010

9 DATE OF FIRST AUTHORISATION

02 November 2023

10 DATE OF REVISION OF THE TEXT

February 2026

PROHIBITION OF SALE, SUPPLY AND/OR USE

11 CLASSIFICATION OF VETERINARY MEDICINAL PRODUCTS

Veterinary medicinal product subject to prescription except for some pack sizes. Not all pack sizes may be subject to prescription. (Concerned pack-sizes to be completed nationally)

Approved: 26 March 2026

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Registration holder

Ceva Sante Animale

8 rue de Logrono

33500 Libourne

France

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