CESTODEX

COMPOSITION Each biconvex, midline scored, light yellow coloured circular tablet contains 50 mg of praziquantel, 150 mg of fenbendazole and 144 mg of pyrantel pamoate (embonate) PHARMACOLOGICAL PROPERTIES Pharmacodynamics This product is an antihelmintic that contains tetrahydropyrimidine derivative pyrantel (as embonate salt), benzimidazole derivative fenbendazole and partially hydrogenised pyrazinoisoquinolone derivative praziquantel. It is effective against specific roundworms and worms. This particular combination of pyrantel and fenbendazole works synergistically against the roundworms (ascarides, hookworms, whipworms) in cats and dogs. The spectrum of effect includes particularly Toxocara canis, Toxascaris leonina, Uncinaria stenocephala, Ancylostoma caninum and Trichuris vulpis. The spectrum of praziquantel includes intestine worms in dogs. It includes all Taenia species, as with Multiceps multiceps, Dipylidium caninum, Echinococcus granulosus and Echinococcus multilocularis. Praziquantel is effective aganist all intestinal stages of these parasites. Pyrantel acts as a cholinergic agonist like nicotine, causing spastic paralysis by depolarization in the neuromuscular blocks of roundworms. Fenbendazole acts by blocking the effectiveness of fumarate reductase in parasites. The pharmacological activities of benzimidazoles and pro[1]benzimidazoles are disruption of tubulus-microtubules dynamic balance by binding to the parasites’ tubulus. Praziquantel is a pyrazinoisoquinolone derivative. It induces rapid and prolonged muscle contraction and tegumental disruption in the parasite. Developing contraction in the parasites’ muscular system is its primary effect and it is followed by rapid vacuolisation of syncytial tegument. The muscular contraction and tegumental disruption causes the parasitic antigens to come out, and is followed by the binding and penetration of the hosts immune cells to the parasite. Praziquantel is absorbed rapidly through the parasites’ surfaces and distributed evenly throughout its body. It causes serious damage to integuments, which causes impairment of the metabolism thus death. Pyrantel is a tetrahydropyrimidine compound and it shows a selective agonist effect on the synaptic and extrasynaptic nicotinic acetylcholin reseptors in the muscle cells of nematodes and causes contraction and spastic paralysis. Pharmacokinetics Following oral administration of praziquantel in cats and dogs almost all of it is absorbed in the small intestines. The absorbance is very rapid and it reaches maximum serum concentrations in 0.5 -2 hours. It shows wide distribution throughout the body after absorption. The rate of binding to the plasma proteins are high. Praziquantel forms inactive metabolites by metabolizing rapidly in the liver. In dogs the metabolites are eliminated through urine (66% of oral dosage) and by bile (15%). Elimination half-life in dogs are approximately 3 hours. Pyrantel (as embonate salt), as a compound which has low soluability in water, is absorbed slightly in gastrointestinal tract and reaches to the final parts of the intestine. The absorbed drug is extensively metabolized and main compounds/metabolites are excreted through urine.

 INDICATIONS FOR USE CESTODEX

 Oral Tablet is used in cats and dogs in the treatment and control of the parasitic infections caused by the following worms and roundworms. Roundworms Ascarides (adult and late-stage immature forms): Toxocara canis, Toxascaris leonina Hookworms (adult): Uncinaria stenocephala, Ancylostoma caninum Whipworms (adult): Trichuris vulpis Worms (adult and immature forms): Echinococcus granulosus, Echinococcus multilocularis, Dipylidium caninum, Taenia spp. (Taenia hydatigena, Taenia pisiformis, Taenia taeniaeformis) Multiceps multiceps (adult and immature forms) ADMINISTRATION ROUTES AND AMOUNTS

For oral administration only. CESTODEX Oral Tablet’s practical dosage in cats and dogs 1 tablet for each 10 kilograms of body weight. Tablets should be given as single administration. The practical dosages to be applied are as follows; Body Weight Amounts to apply 3-5 kg ½ tablets 6 - 10 kg 1 tablets 11 - 15 kg 1.5 tablets 16 - 20 kg 2 tablet 21 - 25 kg 2,5 tablet Administration and duration of treatment Tablets can be given with or without cats dog food, by putting inside sausage (or by wrapping with sausage) by breaking and mixing with other foods or directly swallowed. Restriction of the access to normal diet prior or after the treatment is not mandatory. The tablets should be given as single administration. The veterinarian’s advice should be sought regarding the frequency of treatment and whether it should be repeated or not. It is not used in dogs that has less weight than 3 kg. The body weight must be determined as precisely as possible to ensure the right dosage to be applied.

SPECIAL CLINICAL INFORMATION AND SPECIAL WARNINGS FOR TARGET SPECIES

 Fleas commonly be an intermediate host for a single species of intestine worm (Dipylidium caninum). Infestations of intestinal worms is definitely repeated in cases when the control of the intermediate hosts such as flea, mice is not fully ensured. External parasite control should be done for the success of cestod infections. In cases when the control of intermediate host is not achieved, the worm treatment should be repeated. Its unlikely to see intestinal worm infestations on puppies younger than 6 weeks of age. Following practices should be avoided because of their risk to increase the resistance development thus making the treatment ineffective. Because of the development of antihelmintic drug resistance, the strategies should be avoided are as follows: - Frequently and repeatedly using the same class of antihelmintic in a broad time period. - Administrating a lesser dose than treatment dosage. Clinical cases where antihelmintic resistance is suspected should be evaluated by appropriate tests. (eg. Faecal Egg Count Reduction test) In situations where the tests are indicating resistance to the mentioned antihelmintic, another antihelmintic from a different pharmacological class that has a different mechanism of effect should be used. To minimize the risk of reinfestation and new infestation, the feces should be collected and eliminated properly following the 24 hours of the treatment. For the control of Toxocara infections, dogs giving birth should be treated every two weeks until weaning, starting two weeks after birth. It can be applied to puppies once every two weeks, starting from the fourth week from birth to 12th week of age. From then, the treatment must be applied in 3 month intervals. For adult cats and dogs, it should be administrated as a single dosage. The veterinarian’s advice should be sought regarding the frequency of treatment and whether it should be repeated or not. In severe roundworm infestations, the repeat dose should be given after 14 days. Use during pregnancy: In pregnant animals, it should be consultated to veterinarian before the treatment of roundworms. Fenbendazole’s teratogenic effect is reported on rats and sheep in high doses, when applied in the early period of pregnancy. No studies conducted for this products safety in the first and second 1/3 periods of pregnancy. Do not apply on dogs on the first and second 1/3 periods of pregnancy. The treatment that administered as a single application on the last 1/3 period of pregnancy and on lactation was shown to be safe.

ADVERSE REACTIONS

In very rare cases, digestive tract disturbances such as mild and rapid vomiting and / or diarrhea may occur. In some special occasions, non[1]specific symptoms like lethargy, anorexia and hyperactivity may accompany these symptoms. The frequency of these adverse reactions is defined by the following method: - very common (adverse effects that is seen in more than 1 of 10 animals in one period of treatment) - common (more than 1 in 100 animals but lesser than 10) - uncommon (more than 1 in 1000 animals but lesser than 10) - rare (more than 1 in 10.000 animals but lesser than 10) - very rare (lesser than 1 in 10.000 animals)

DRUG INTERACTIONS

Antihelmintic effects of this product and products that contain piperazine is antagonized when used together. Concurrent usage with other cholinergic compounds causes toxicity. This product should not be used at the same time with other drugs that has a cholinergic effect. Concurrent usage of the compounds that inhibits acetylcholinesterase activity (e.g. organophosphates) can increase the systemic effect of pyrantel. OVERDOSE (SYMPTOMS, EMERGENCY PROCEDURES, ANTIDOTES) Benzimidazoles have a wide margin of safety. Pyrantel is not absorbed systemically in anyway. Praziquantel also has a margin of safety up to five times the dosage recommended. WITHDRAWAL PERIOD(S) Not applicable. CONTRAINDICATIONS Do not use in situations when there is a hypersensitivity to the active substance or any other excipient. Do not use with piperazine compounds. Do not use in the first 1/3 and 2/3 periods of pregnancy. It is not used in the dogs that are younger than 4 weeks of age and / or weights less than 3 kilograms.

 GENERAL WARNINGS

 Do not use the product without consulting a veterinarian. Consult a veterinarian if any unexpected effect occurs. Keep out of reach of children. Any used packaging should be disposed of to trash. NECESSARY PRECAUTIONS TO TAKE DURING APPLICATION Avoid contact with eyes. In case of contact with eye, rinse the eyes with plenty of water. Avoid transition from hand to eye and hand to mouth while applying the product. In case of accidental oral intake, seek medical help urgently and show the leaflet or outer packaging of the product to the physician. In terms of hygiene, people who apply the product directly to the dog or add it to the cats and dog food should wash their hands after the procedure. SPECIAL PRECAUTIONS FOR STORAGE, AND SHELF LIFE Keep the product inside the outer carton below 25 °C, do not freeze and protect from light. Shelf life is 2 years from the date of production. DISPOSAL AFTER USE AND WARNINGS FOR NON-TARGET SPECIES Unused veterinary medicinal products and residual waste from these products should be disposed of according to local rules.

MARKETING PACKAGING

 Each tablet is sold in aluminium foil bags inside cardboard boxes that contains 50 tablets and in White polyethylene bottles inside cardboard boxes that contains 50 tablets.

 SALE LOCATIONS AND CONDITIONS Veterinary clinics and pharmacies with veterinary prescription (VHR). MINISTRY OF AGRICULTURE AND FORESTRY MARKETING AUTHORISATION DATE AND NUMBER: 01/2021-42 MARKETING AUTHORISATION OWNER NAME AND ADDRESS: VMD FARMA Sağlık ve Veteriner Ürünleri San. ve Tic. Ltd. Şti. Sadıkoğlu İş Merkezi-1 Eğitim Mah. Ahsen Çıkmazı Sok. No: 10 Kat: 3 Daire: 67 Kadıköy / İSTANBUL Tel: 0216 317 20 24 MANUFACTURER NAME AND ADDRESS: DAMLA İlaç ve Kimya San. Tic. Ltd. Şti. İDOSB Sama Cad. L3-1 Parsel No:9 Tuzla / İSTANBUL