Savavet Kiwof Plus Broad-Spectrum Dog Dewormer Tablets | Praziquantel, Pyrantel Pamoate & Febantel | Roundworms, Hookworms, Whipworms & Tapeworms | Pack of 10 Tablets

FOR VETERINARY USE — Administer as directed by a licensed veterinarian. Savavet Kiwof Plus is a veterinary anthelmintic medicine — a scheduled drug combination requiring appropriate veterinary guidance. Do not self-dose without a veterinarian’s weight-based recommendation. Do not use in cats or any species other than dogs. Do not use in severely debilitated, febrile, or severely ill dogs without veterinary supervision. Pregnant or lactating bitches should only be dewormed under veterinary direction. In heavy worm burden infestations, a die-off reaction (release of worm antigens from mass parasite death) may temporarily cause GI signs — veterinary monitoring is advisable. Keep out of reach of children.

Savavet Kiwof Plus Broad-Spectrum Dog Dewormer Tablets | Praziquantel, Pyrantel Pamoate & Febantel | Roundworms, Hookworms, Whipworms & Tapeworms | Pack of 10 Tablets

Savavet Kiwof Plus is a broad-spectrum veterinary anthelmintic tablet for dogs, manufactured by Savavet (India), combining three complementary antiparasitic actives in a single palatable chewable tablet: praziquantel (50mg per tablet — for cestodes/tapeworms), pyrantel pamoate (144mg per tablet — for nematodes: roundworms and hookworms), and febantel (150mg per tablet — a prodrug benzimidazole for nematodes: roundworms, hookworms, and whipworms). The three-drug combination provides the broadest possible coverage of the four major canine intestinal helminth groups (nematodes: ascarids [Toxocara canis, Toxascaris leonina], hookworms [Ancylostoma caninum, Uncinaria stenocephala], whipworms [Trichuris vulpis]; cestodes: tapeworms [Dipylidium caninum, Taenia spp., Echinococcus granulosus — important zoonotic risk]) in a single dose. Pack of 10 chewable tablets, suitable for adult dogs and puppies (weight-based dosing as directed by a veterinarian).

Canine Intestinal Helminths: Parasite Biology and Disease Burden

• Toxocara canis (canine roundworm) — the most prevalent canine intestinal nematode and a significant zoonosis: T. canis is an ascarid nematode (Ascaridida: Ascarididae; adults: cream-coloured, 7–15cm in length, living in the small intestinal lumen); lifecycle: (a) direct transmission — embryonated eggs ingested → larvae hatch in the small intestine → penetrate the intestinal wall → hepatoportal circulation → hepatic first pass → right heart → pulmonary circulation → lung alveoli (Loeffler’s syndrome equivalent in heavy infections: pulmonary eosinophilia → cough, dyspnoea) → tracheal migration → swallowed → small intestinal adult stage; (b) transplacental transmission: L3 larvae in the dam’s somatic tissues are mobilised during late pregnancy (rising progesterone → impaired larval somatic encystment) → cross the placenta → foetal liver and lungs; neonates are born with L3 larvae already in their lungs → tracheal migration completes to intestinal adult worms within 2–3 weeks of birth — this is why puppies can have massive roundworm burdens even at 2–3 weeks of age and why the first deworming is recommended as early as 2 weeks of life; (c) transmammary (milk) transmission: L3 larvae mobilised into mammary gland tissue → neonates ingest larvae in milk; clinical disease: heavy roundworm burdens in puppies → pot-bellied appearance (abdominal distension from intestinal mass of adult worms), failure to thrive, poor coat condition (worm competition for B vitamins, proteins, and fat-soluble vitamins at the brush border), intermittent vomiting and diarrhoea, and occasionally intestinal obstruction or intussusception (in mass infestations); zoonotic risk: human visceral larva migrans (VLM — T. canis L3 larvae ingested by humans [particularly young children via geophagy/soil ingestion] cannot complete the adult lifecycle in humans → aberrant larval migration to the liver, eyes [ocular larva migrans — OLM: retinal granuloma formation → strabismus and vision loss in children], lungs, and CNS); T. canis is the most important zoonotic helminth in India from dogs
• Ancylostoma caninum (canine hookworm) — the haematophagous nematode causing anaemia and hypoproteinaemia: A. caninum (hookworm; Strongylida: Ancylostomatidae; adults: 1–2cm, anchored to the small intestinal mucosa by their cutting plates — the ‘hook’ shape of their anterior end reflects the ventral curvature of the mouth capsule); lifecycle routes: percutaneous penetration (L3 larvae in soil penetrate intact skin − the primary route in warm, humid climates including India), oral ingestion of L3, and transmammary; blood feeding: A. caninum is a blood-feeding nematode — each adult hookworm consumes approximately 0.1–0.4 mL blood per day (via capillary rupture using their cutting plates and secretion of anticoagulant proteins [hookworm anticoagulant peptide − HAP — a reversible active site inhibitor of Factor Xa; the canine hookworm’s anticoagulant is the most potent Factor Xa inhibitor of any hookworm species]); haematophagic blood consumption → iron-deficiency anaemia (microcytic, hypochromic) + hypoproteinaemia (albumin loss into the gut − hookworm proteases cleave mucosal proteins → protein-losing enteropathy) → clinical signs: pale mucous membranes, weakness, weight loss, tarry stools (melaena from digested blood), and in severe cases, peracute death in neonatal pups (neonatal hookworm disease — the combination of transmammary larvae and the neonate’s total blood volume [approximately 100mL in a 500g puppy] means even 50 adult hookworms can exsanguinate a neonate); cutaneous larva migrans (CLM): A. caninum and A. braziliense L3 percutaneously penetrating human skin → linear, serpiginous, intensely pruritic subcutaneous tracks in humans (particularly bare feet in contact with contaminated soil — a significant zoonotic risk in India where dogs roam in areas frequented by children)
• Trichuris vulpis (canine whipworm) — the large intestinal nematode causing colitis and bloody diarrhoea: T. vulpis (whipworm; Trichurida: Trichuridae; adults: 4–7cm, with a characteristically narrow anterior end [the ‘whip handle’] embedded in the caecal and colonic mucosa and a thicker posterior end [the ‘whip lash’] free in the lumen); site of infection: the caecum and proximal colon (unlike the small intestinal nematodes above) → T. vulpis causes large bowel diarrhoea (haematochezia — bright red blood in/on stool, tenesmus [painful straining], mucoid stool); heavy T. vulpis infections mimic Addison’s disease (hypoadrenocorticism) biochemically: T. vulpis causes sodium loss and potassium retention in the colon (the worms disrupt the colonic Na+/K+ transport mechanism — the colonic epithelial Na+/K+-ATPase and ENaC sodium channel, which are aldosterone-regulated — resulting in a pseudo-hypoadrenocorticism electrolyte pattern: hyponatraemia + hyperkalaemia − Na:K ratio <27 — making Trichuris infection an important differential diagnosis for suspected Addison’s disease in dogs); T. vulpis eggs are barrel-shaped with bipolar plugs and are highly resistant in the environment (thick-walled, sticky surface → adhere to soil, concrete, and grass; remain infective for up to 5 years in temperate soil; survive standard disinfectant concentrations); eggs are not shed continuously − periodic egg shedding plus a 3-month prepatent period means a single faecal FLOTATION can miss Trichuris — requiring repeat testing or empirical treatment based on clinical signs
• Dipylidium caninum and Taenia spp. (canine tapeworms) — the cestodes requiring an intermediate host: tapeworms (Cestoda: Cyclophyllidea) are segmented flatworms living in the small intestinal lumen; D. caninum (the flea tapeworm): requires the cat flea Ctenocephalides felis or dog flea C. canis as the intermediate host (flea larvae ingest tapeworm eggs → cysticercoid develops in the flea’s abdominal cavity → dog grooms and ingests adult flea containing cysticercoid → scolex evaginates in the canine small intestine → attaches via suckers and rostellar hooks → grows into adult tapeworm up to 50cm in length; the gravid proglottids — rice-grain-sized motile segments — detach and migrate to the perianal area → the characteristic sign of tapeworm infection: the dog scoots, drags its perineum on the floor, and rice-grain segments are visible in the faeces or adhered to perianal fur; Taenia spp. — intermediate hosts: rodents [T. taeniaeformis uses rodents; T. ovis uses sheep; T. pisiformis uses rabbits]; Echinococcus granulosus [hydatid tapeworm, E. granulosus sensu lato — the most important zoonotic cestode]: intermediate hosts include sheep, cattle, goats, and humans; humans ingesting E. granulosus eggs develop hydatid cysts (cystic echinococcosis) in the liver (70%) and lungs (20%) — a potentially fatal zoonosis; E. granulosus is endemic in parts of India [particularly in sheep-farming communities]; treatment of dogs with praziquantel (in Kiwof Plus) is a critical component of Echinococcus zoonosis control

Active Ingredients & Mechanisms of Action

• Praziquantel (50mg per tablet) — the cestocidal agent: praziquantel (2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one; MW 312.41 g/mol) acts specifically against cestodes (tapeworms) and trematodes (flukes) via: (a) rapid increase in calcium ion permeability of the tegument (the tapeworm’s outer syncytial surface — the tegument replaces the skin in cestodes; unlike nematodes which have a cuticle, cestodes absorb nutrients through the tegument); praziquantel’s mechanism at the tegument: interaction with voltage-gated Ca2+ channels in the cestode tegument plasma membrane → massive Ca2+ influx into the tegument cytosol → spastic paralysis of the worm musculature (the tegumental Ca2+ spike triggers sustained muscle contraction via Ca2+-calmodulin activation → the worm cannot move and loses its sucker and rostellar hook grip on the intestinal mucosa); (b) tegumental disruption: the Ca2+-induced tegumental damage causes vacuolation and blebbing of the tegument surface (the tegument’s outer syncytium disintegrates into blebs − exposed to the intestinal lumen’s digestive enzymes − the host’s trypsin and chymotrypsin rapidly digest the exposed worm body); praziquantel therefore achieves cestocidal activity via two simultaneous mechanisms — paralysis (preventing escape) and tegumental dissolution (physical destruction); (c) the host’s immune response is also activated: the disrupted tegument exposes cryptic tapeworm surface antigens normally hidden from the host immune system → IgG and IgM antibody-dependent cellular cytotoxicity (ADCC) by eosinophils and macrophages against the damaged tegument; praziquantel is highly effective against all four Dipylidium, Taenia, and Echinococcus tapeworm species; it has negligible activity against nematodes (roundworms, hookworms, whipworms)
• Pyrantel pamoate (144mg per tablet) — the nematocide for roundworms and hookworms: pyrantel (1,4,5,6-tetrahydro-1-methyl-2-[trans-2-(2-thienyl)vinyl]pyrimidine) as the pamoate salt (an insoluble salt providing sustained luminal concentration with minimal systemic absorption — the pamoate anion [4,4’-methylenebis(3-hydroxy-2-naphthalenecarboxylate)] reduces GI absorption, concentrating pyrantel at the site of action in the intestinal lumen); mechanism: depolarising nicotinic acetylcholine receptor (nAChR) agonist at the nematode neuromuscular junction (NMJ): (a) pyrantel binds the nematode nAChR (specifically the L-subtype nematode nAChR — the ACR-16 homomeric receptor and the N-type ACR-26/ACR-27 heteromeric receptor in Ascaris suum; the ACR-16 L-type receptor is the primary pyrantel target; it is distinct from mammalian nicotinic receptors − providing selectivity); (b) pyrantel is a partial agonist at the nematode nAChR → sustained, non-desensitising depolarisation of the nematode muscle cell membrane (unlike ACh which causes brief depolarisation followed by rapid receptor desensitisation and repolarisation; pyrantel’s non-desensitising agonism produces sustained flaccid paralysis); (c) the paralysed nematode cannot maintain its position in the intestinal lumen against peristaltic flow → expelled in faeces; pyrantel is highly effective against Toxocara canis (ascarid roundworms — the ACR-16 nAChR is well-expressed in Toxocara) and Ancylostoma caninum (hookworms); its activity against Trichuris vulpis (whipworms) is minimal — whipworms express different nAChR subtypes (the Trichuris nAChR is primarily ACR-8/ACR-21 and is much less sensitive to pyrantel); hence febantel is added to Kiwof Plus specifically to cover Trichuris
• Febantel (150mg per tablet) — the benzimidazole prodrug for roundworms, hookworms, and critically, whipworms: febantel (N-[2-[(methoxycarbonyl)amino]-4-(phenylthio)phenyl]carbamic acid methyl ester; MW 446.50 g/mol) is a non-benzimidazole prodrug that is metabolised in the GI tract to its active benzimidazole metabolites — primarily fenbendazole (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl)carbamate) and oxfendazole (fenbendazole sulfoxide); mechanism of fenbendazole/oxfendazole: (a) beta-tubulin binding: benzimidazoles bind selectively to nematode beta-tubulin (the β-tubulin subunit of the αβ-tubulin heterodimer − the structural unit of microtubules); binding occurs at the colchicine-binding site (the inter-dimer interface of α-tubulin and β-tubulin, distinct from the taxane site and the vinca alkaloid site); fenbendazole binding → inhibits tubulin polymerisation → prevents microtubule assembly → disrupts the nematode’s intracellular transport system (microtubules are required for: (i) secretory vesicle transport from the Golgi to the plasma membrane [the nematode’s secretory pathway for cuticle maintenance proteins, digestive enzymes, and immunomodulatory excretory/secretory products]; (ii) mitotic spindle formation in dividing nematode intestinal cells [the nematode intestine is replaced by dividing cells]; (iii) absorptive microvillar structure in the nematode intestinal brush border [microtubules provide the structural core of the microvilli]); (b) glucose uptake inhibition: benzimidazole-induced microtubule disruption also impairs glucose transporter recycling to the nematode intestinal brush border membrane → reduced glucose uptake → glycogen depletion → nematode energy starvation; (c) selectivity: mammalian tubulin has three amino acid differences (F200Y, E198A, H197Y in the colchicine-binding site) that dramatically reduce benzimidazole affinity — fenbendazole’s Kd for nematode β-tubulin is approximately 1000-fold lower than for mammalian β-tubulin; febantel/fenbendazole is the only component with robust Trichuris vulpis activity in Kiwof Plus (Trichuris β-tubulin is highly sensitive to benzimidazoles — Trichuris lacks the pyrantel-sensitive ACR-16 nAChR expressed in ascarids and ancylostomatids)

Dosage & How to Use

• Give the tablet strictly as per your veterinarian’s dose recommendation for your dog’s body weight and age
• The tablet can be offered directly as a chew or hidden in a small portion of food that your dog finishes completely
• Routine deworming intervals: every 3 months for adult dogs in India (the tropical climate with year-round larval survival in soil warrants more frequent deworming than the standard 6-month interval recommended in temperate climates); more frequently for puppies (every 2 weeks from 2 weeks of age to 3 months, then monthly to 6 months, then quarterly — as directed by a veterinarian); consult your veterinarian for the appropriate schedule for your dog’s lifestyle and environment
• Do not exceed the recommended dose; do not repeat sooner than directed unless your veterinarian instructs you

Safety & Precautions

• For use in dogs only — do not give to cats or any other species
• Not recommended in very young puppies unless your veterinarian confirms the appropriate age and weight-based dose
• Avoid use in severely ill, debilitated, or dehydrated dogs without veterinary supervision
• If your dog vomits, develops diarrhoea, or appears unwell after dosing, contact your veterinarian
• Pregnant or lactating bitches should only be dewormed under veterinary direction
• Keep out of reach of children and other animals; store in a cool, dry place away from direct sunlight in the original blister packaging