Fenbendazole was first patented in the United States in the 1970s for the treatment of helminth infections in various animals. The granular formulation developed for dogs has been one of the most successful benzimidazoles. For dogs six weeks of age and older, the Panacur(r) Granules 22.2% product is labeled for the control and removal of ascarids.
Fenbendazole was first patented in the United States in the 1970s for the treatment of helminth infections in various animals. The granular formulation developed for dogs has been one of the most successful benzimidazoles. For dogs six weeks of age and older, the Panacur(r) Granules 22.2% product is labeled for the control and removal of ascarids.
Fenbendazole was first patented in the United States in the 1970s for the treatment of helminth infections in various animals. The granular formulation developed for dogs has been one of the most successful benzimidazoles. For dogs six weeks of age and older, the Panacur(r) Granules 22.2% product is labeled for the control and removal of ascarids.
In: Recent Advances in Anesthetic Management of Large Domestic Animals, Steffey E.P. (Ed.).
International Veterinary Information Service, Ithaca NY (www.ivis.org), Last updated: 12-Nov-2007;
A0317.1107 Panacur Granules (22.2% Fenbendazole) - A Time-Tested Broad-Spectrum Antiparasitic A. Lucio-Forster 1 , D. D. Bowman 2 and S. C. Barr 3
1,2 Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. 3 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. Introduction Fenbendazole was first patented in the United States in the 1970s for the treatment of helminth infections in various animals. Since then, the granular formulation of fenbendazole in the Panacur product also received its own patents. The benzimidazoles, of which fenbendazole is a member, interact with invertebrate tubulin, lead to the depletion of energy reserves and inhibit the excretion of waste products from the cells of parasites. Due to its poor solubility, this class of compounds is not easily formulated to be given parenterally, and thus, most benzimidazoles are formulated for oral administration. The granular formulation developed for dogs has been one of the most successful benzimidazoles and one of the few that persists in the world of small animal pharmaceuticals. The only other benzimidazole used routinely in small animal medicine is the pro-benzimidazole febantel in Drontal Plus. There are currently no other benzimidazoles specifically registered in the United States for treating the parasites of small animals. For dogs six weeks of age and older (including pregnant bitches), the Panacur Granules 22.2% product administered at a dosage of 50 mg/kg PO for three consecutive days, is labeled for the control and removal of ascarids (Toxocara canis and Toxascaris leonina), hookworms (Ancylostoma caninum and Uncinaria stenocephala), whipworms (Trichuris vulpis), and tapeworms (Taenia pisiformis). This same formulation is labeled for the treatment of helminths in various zoo animals as well (lions, tigers, cheetahs, pumas, jaguars, leopards, panthers, grizzly bears, polar bears, and black bears), but it is not labeled for use in the domestic cat in the United States. Other formulations showing a wide range of safety in many different animals have been developed for many species including: horses, ruminants, swine, and turkeys. To date there are few reports of fenbendazole sensitivity in dogs. One such report involved a 1.5 year old Doberman pinscher undergoing fenbendazole treatment for suspected lungworm infection. The dog developed a bone marrow hypoplasia after 11 days of a 14 day treatment with fenbendazole (50 mg/kg PO, q 12 hrs, with food) [34]. Discontinuation of fenbendazole treatment and addition of bactericidal antibiotics and fluid therapy led to complete resolution of clinical and hematological abnormalities. In addition, an unusual case of thrombo-ischaemic pinnal necrosis associated with fenbendazole treatment was reported in 2005 by Nuttall et al., [55]: an 11-week old West Highland female terrier receiving three consecutive 100 mg daily doses of fenbendazole at three weeks of age developed inflammation, exudation and crusting of both ear tips. The dog developed complete coagulative necrosis of the distal third of both pinnae; the necrotic tips required surgical removal. The diagnosis of fenbendazole-induced thrombo-ischemic necrosis was based on the dog's clinical history, clinical findings and histopathology. The granular product has been approved for Over the Counter (OTC) sales in the form of packets containing measured volumes of granules (tradename: Panacur-C). The Center for Veterinary Medicine of the FDA approved this usage because prior use of the product as a prescription-only treatment had not disclosed any concerns relative to hepatotoxicity at the labeled dosage of 50 mg/kg. Although the product has routinely been used at higher dosages and for longer periods in the treatment of some of the infections discussed below, it must be emphasized that these are off-label uses of the product which warrant careful monitoring of animals. The main focus of this paper is to summarize information available on the use of Panacur granules for the treatment of canine parasitic infections not listed on the label. As mentioned above, some of these treatment regimens require that the product be administered at higher dosages or for longer periods of time than those specified on the canine product label for the control of ascarids, hookworms, whipworms and tapeworms. Also, in some cases, e.g., in the treatment of infections in puppies, the product has been administered as a suspension rather than as granules, typically using one of the equine or ruminant formulations. Finally, the authors would like to acknowledge that alternate drug treatments may also exist, and may have been used, for some of the infections discussed below; a full review and discussion of such treatments is outside the scope of this paper. Fenbendazole Efficacy Nematodes Fenbendazole has efficacy against a number of nematodes and nematode stages in addition to those that appear on the label, some of which are discussed below. Prior to the use of injectable ivermectin, fenbendazole was the typical mainstay in the United States for treating parasitic infections that were out of the ordinary. This is not to say that ivermectin is a better therapeutic agent than fenbendazole in many of these situations; only that ivermectin is now often chosen as a means of treating these more unusual parasites or conditions. Trematodes Fenbendazole is a deworming agent that has activity against all the major groups of parasitic helminths, while avermectins have activity only against nematodes and arthropods. Thus, besides nematode infections, fenbendazole has activity against trematodes and some cestodes. More recently, praziquantel has been employed for treating trematode and cestode infections, but although this compound has excellent efficacy against most flatworms, it has no activity against nematodes or arthropods. Cestodes Fenbendazole is also cestocidal and a recent survey of intestinal parasites of stray dogs in Madrid, Spain, found it to have the greatest effect (90 - 100%) against Taenia tapeworm infections (Panacur at a dose of 50 mg/kg q 24 h for 3 days) when compared to mebendazole (Telmn, Esteve; 22 mg/kg q 24 h for 3 days), and the mixture of febantel-pyrantel- praziquantel at a dose of 15 - 5 - 5 mg/kg once (Drontal Plus, Bayer) [54]. The Panacur product is labeled specifically for the treatment of Taenia pisiformis in dogs, because at the labeled use rate of 50 mg/kg, this product does not clear all dogs of their Dipylidium caninum infections. Fenbendazole is also known to be relatively ineffective against the adults of Echinococcus granulosus. Protozoa Fenbendazole is unique amongst the anthelmintics in that it has activity against protozoa. Benzimidazoles have some of their effects through the binding of tubulin [41], and since tubulin is a major component of some protozoa, it is not surprising that benzimidazoles have been shown to be highly active against these pathogens [43]. In fact, tubulin is a major component of the attachment disk of Giardia, and thus, this protozoan appears to be one of the most susceptible to treatment with benzimidazoles. Use of Fenbendazole for the Treatment of Nematode Infections in Dogs Ascaridida Treatment for Prevention of Prenatal Infection of Puppies with in utero Acquired Larvae of Toxocara canis This large common roundworm of the small intestine of dogs and foxes is generally asymptomatic in older dogs with low worm burdens, but can be characterized unthriftiness, diarrhea and abdominal distension in young pups. Intrauterine infection of puppies is one way through which dogs become infected with this parasite, and while treatment of adult stages of this parasite is specified on the label, the treatment of infective-stage larvae is not. The ability of fenbendazole to prevent intrauterine infection of puppies, however, has been evaluated through the treatment of the bitch before, during, or right after pregnancy. Studies show that although worm burdens in pups born to treated bitches may be reduced, in some cases quite significantly, it is probably unwise to use this product for extended periods of time and in high doses in such situations due to concerns over direct effects of the chemical on puppies. The use of fenbendazole at 25 mg/kg PO, q 24 h from the 40th day of gestation through 2 days after whelping, was shown to reduce overall worm burdens in puppies born to treated bitches by 98.4% [26]. Fifteen of the 28 puppies born under such treatment in this study were found to be completely free of intestinal worms. In a similar study, puppies born to bitches treated with fenbendazole only during pregnancy (at 50 mg/kg PO, q 24 h from day 40 until parturition), showed only a 64% reduction in the number of Toxocara canis recovered [16]. However, when such treatment was extended for 2 weeks after parturition, the reduction in the number of worms recovered from the puppies could be increased to 89% [16]. Elevated dosages of fenbendazole for prevention of intrauterine transmission of toxocariasis have also been examined [68]. When high doses of fenbendazole are used (100 mg/kg PO, q 24 h from day 20 to 38 of gestation), the overall reduction of worm burdens in pups was 92%. Yet, if still a higher dose is used (150 mg/kg), some puppies will die as a result of central nervous system degeneration attributed to the high dose of the drug [68]. Thus, this product is probably not appropriate for trying to obtain worm-free puppies by treating them in utero; it is likely wiser to treat puppies after birth as described below. Treatment of Neonatal Puppies for the Prevention of Patent Toxocara canis Infections and to Decrease of Worm Burdens Treating puppies with fenbendazole early in life can have a marked effect on the number of ascarid eggs shed in the feces of, and the number of adult worms present in, treated dogs. In fact, the treatment of newborn puppies with fenbendazole (100 mg/kg PO, q 12 h, for 2 - 3 days) was shown to reduce the development of worms acquired from the mother by 91% to 99% [50]. In a study by Fisher et al., [31], greyhound pups treated on days 5, 6 and 7 of life showed a 94% reduction in worm burdens. Pups treated with two 3-day fenbendazole treatments with a 3-week interval using a fenbendazole suspension (50 mg/kg PO) beginning 14 days after whelping were found not to excrete eggs in their feces for two months after birth [1]. Furthermore, the same study determined that pups (along with bitches) treated at 2 weeks and 5 weeks of age (50 mg/kg, PO, q 24 h for 3 days) did not shed eggs during the first two months of life [1]. Lloyd and Soulsby [50], were also able to reduce worm burdens by about 90% by administering a single dose of fenbendazole (40 mg/kg PO) to 4- to 5- week-old puppies. Treatment of Neonatal Toxascariasis The developmental stages of Toxascaris leonina all occur within the mucosa of the canine host and there is neither in utero nor lactational transmission of larvae of this parasite from the bitch to her puppies. While the Panacur granules product is labeled only for the treatment of adult Toxascaris leonina in dogs, and has been shown to be 100% efficacious in this regard, it has also been shown to have high efficacy against the larval stages developing in the mucosae of dogs that have ingested infective eggs [31]. In this report, treatment of puppies with 50 mg/kg of fenbendazole for 3 consecutive days after exposure to such eggs led to an 82% reduction in the number of larvae present in the mucosae. Thus, fenbendazole in addition to being an effective adulticide also seems to have marked activity against newly hatched and developing Toxascaris leonina larvae. Enoplida Treatment of Eucoleus aerophilus The capillarid of the bronchi of dogs is Eucoleus aerophilus. Infections with this parasite have been treated with a number of compounds that are benzimidazoles related to fenbendazole for which there are no canine approved formulations in the United States. Infections have been treated with flubendazole, tetramisole, and albendazole [20,51,58,75]. Although there have apparently not been any reported attempts to treat these infections with either fenbendazole or with ivermectin, based on the success of these other benzimidazoles in treating these infections, fenbendazole may be a good candidate for treating infected animals. Treatment of Eucoleus boehmi Nasal capillariosis in dogs is caused by Eucoleus boehmi. This parasite lives in mucosa of the nasal sinuses of dogs and has been the cause of chronic nasal discharge. Infections have been successfully treated with fenbendazole (50 mg/kg PO, 24 h for 10 days), so that there were no eggs detected in the feces a month after treatment (King et al., 1990). However, the infection did recur on examination four months later, and at this time the dog, a female blue tick hound, was treated with ivermectin (0.2 mg/kg SQ once). Ultimately with these treatments and the concomitant treatments for a bacterial sinusitis, the animal's condition cleared, but it continued to shed E. boehmi eggs in its feces. Treatment has also been performed using only ivermectin (0.2 mg/kg SQ once) with good results [29]. With regards to this infection, there does not seem to be sufficient information to choose one therapy over another at this time. Treatment of Pearsonema plica Pearsonema plica is the nematode responsible for urinary capillariosis in dogs. Treatment has commonly utilized fenbendazole (50 mg/kg PO, q 24 h) from 3 [35] to 10 days [72]. In some cases, fenbendazole does not appear to clear the infection, and ivermectin (0.2 mg/kg SQ) has been utilized, resulting in the clearance of the parasite based on the disappearance of eggs from the urine and improvement of clinical signs [46,66]. Based on work with elevated doses of ivermectin (0.1 to 0.2 mg/kg SQ once) against Trichuris vulpis [2], it is possible that the increased levels of this avermectin may indeed have efficacy against this urinary canine capillarid, however, it would seem prudent to initiate therapy with a course of fenbendazole at the approved dose of 50 mg/kg for several days before choosing the alternative. Treatment of Trichinella spiralis There have been very few cases where dogs have been identified with acute trichinosis infection, and no reliable information is available on the current prevalence of this infection in dogs. In the treatment of humans with trichinosis, the Medical Letter recommends that the person be given steroids for severe symptoms and then be treated with a long course of mebendazole (200 - 400 mg PO q 8 h for 3 days, then 400 - 500 mg PO q 8 h for 10 days) with the alternative therapy being albendazole (400 mg PO q 12 h for 8 - 14 days). Experimentally infected dogs have been treated relatively successfully with albendazole (50 mg/kg PO, q 12 h for a week) starting about a month after the dogs had been infected [13]. The benzimidazoles all seem to have some activity against Trichinella spiralis, and the choice of one product over another would be difficult to judge. There are no commercial formulations of mebendazole available for veterinary use in the United States and albendazole is only available in large-animal formulations. Thus, it would probably be prudent to begin a dog with a newly discovered trichinosis infection on fenbendazole, and then switch to other products depending on how well clinical signs are ameliorated. Spirurida Treatment of Canine Infections caused by Members of the Genus Physaloptera Nematodes of the genus Physaloptera, Physaloptera rara and Physaloptera caninum, which persist in various canid, felid and mustelid reservoir hosts, embed their heads into the stomach and duodenal mucosa of infected dogs. The associated clinical sign is most typically vomiting. Panacur at 50 mg/kg is often used to treat this infection, but there is only a single report in the literature of the success of such treatment. Jergens and Greve [40] treated a dog with a Physaloptera infection, initially revealed by gastrointestinal endoscopy, with fenbendazole (50 mg/kg PO, q 24 h for 3 days). The treatment proved successful in clearing the infection. Strongylida Treating to Prevent the Transmammary Transmission of Ancylostoma caninum Larvae Infection with this hookworm is usually asymptomatic in adult dogs, but may be associated with severe anemia, bloody feces and sudden death in pups. Puppies primarily become infected via transmammary transmission of infective larvae. As in the case of Toxocara canis, fenbendazole treatment of bitches during pregnancy will have an effect on the presence of hookworms in the pups. It is unclear, however, how safe the product is when used for this purpose. Duwell and Strasser, 1978 [27] showed that daily treatment of the bitch with fenbendazole (50 mg/kg PO, q 24 h from day 45 of pregnancy through 2 to 2 weeks post-gestation) resulted in 100% clearing of Ancylostoma caninum in the pups. Higher doses (100 mg/kg PO, q 24 h from the 30th day of pregnancy until birth) have also proven capable of clearing the gastrointestinal tract and tissue stages of this parasite in both pups and bitches, but at these doses, some pups may develop anatomical defects such as cleft palates [9,67]. Since in the case of Ancylostoma caninum, almost all larval transmission to the puppies occurs through the milk, it is unclear why there should be a need to initiate treatment at such early stages prior to whelping. It is possible, that treatment of the bitch just a few days prior to whelping could prevent the larvae from making their way into the puppies in the milk. It seems there have been no studies that have examined beginning fenbendazole treatment only 1 or 2 days prior to parturition. It would be interesting to explore the effect of treating the bitch about 2 days before parturition and continuing treatment for a few to several days after the puppies are born to assess the transmission of larval stages to the pups. This treatment regimen might be an adequate means of preventing the puppies from being infected without putting them at risk for any teratological effects of the drug. Treatment of Angiostrongylus vasorum Infections Angiostrongylus vasorum is rarely seen in North America, only being reported in dogs from the far-eastern coastal regions of Canada. The adult worms live in the vasculature of the lung of infected dogs. Although the worms themselves cause damage to the lung vasculature, the eggs deposited by the female and the hatched larvae cause the majority of the lung pathology (similar to what occurs with Aelurostrongylus abstrusus infections in cats). A review of canine angiostrongylosis by Bolt et al., [7] suggests the best treatment for this infection may be levamisole. However, the authors noted the drug's palatability is poor, the therapeutic safety level in dogs low, and some dogs may show neurological signs after treatment. Thus, the best alternative therapy, they suggest, is fenbendazole at 20 mg/kg PO for 2 to 3 weeks or ivermectin at 0.2 mg/kg, though neither treatment may assure complete removal of adult worms and may only stop larval shedding in the feces for some period of time. Furthermore, they note that post-treatment complications such as, severe dyspnea and ascites may arise. There have been several recent case reports in which fenbendazole was the chosen treatment. Brennan et al., [15] reported on two cases that were successfully treated with fenbendazole (at doses ranging from 20 mg/kg q 24 h up to 100 mg/kg q 24 h for 7 to 21 days) [15] have been reported to be effective in the treatment of Angiostrongylus vasorum. A 17-month-old female greyhound with right-sided cardiac enlargement and verminous pneumonia was successfully treated with 50 mg/kg q 24 h for five days. A 23-month-old male Jack Russell terrier with cardiac enlargement and pulmonary changes was treated with the same dose of fenbendazole PO for 7 days. Baermann fecal examinations two months after treatment were negative for A. vasorum larvae. Estves et al., [28] reported on treatment of a one-year-old neutered female beagle with widespread pneumonitis evidenced by radiographic imaging. The animal was shedding numerous A. vasorum larvae in its feces and was placed on fenbendazole for 15 days (20 mg/kg q 24 h). After two weeks of treatment the dog's condition was markedly improved. Chapman et al., [18] treated 23 dogs presenting with A. vasorum infections to the Queen Mother Hospital for Animals North Mymms, Hertfordshire, UK. Three dogs died shortly after admission; these three dogs were severely dyspneic and two had experienced syncopal episodes. Fortunately, the remaining 20 dogs were successfully treated using fenbendazole at 50 mg/kg PO, q 24 h, for 5 to 21 days. Four of the dogs had positive fecal samples after the treatment had resolved clinical signs. In dogs treated with fenbendazole, follow-up radiographs have demonstrated resolution of the alveolar pattern and development of a mild, hazy interstitial pattern [5]. Whitley et al., [73] published a report on the treatment of a 14-month-old female golden retriever with a history of conjunctival hemorrhage and neurological signs determined to be infected with A. vasorum. The dog was placed on fenbendazole (50 mg/kg PO q 24 h) for 21 days, and two weeks later was reported to be clinically normal. Boag et al., [6] reported on three cases of hypercalcaemia associated with angiostrongylosis. Hypercalcaemia and respiratory signs both resolved with treatment of the parasite with fenbendazole at 50 mg/kg q 24h for 15 - 22 days. In 2006, Nicolle et al., [56] reported on a case of angiostrongylosis in a Yorkshire terrier presenting with dyspnea, coughing, abdominal distension, and mild exercise intolerance. The case resolved after treatment with fenbendazole (30 mg/kg PO, q 24 h) for 3 weeks. And finally, most recently, Tebb et al., [69] successfully treated a 2 year old male neutered Cocker Spaniel with a history of soft cough for its angiostrongylosis with a 10 day course of fenbendazole at 50 mg/kg q 24 h. Two weeks after treatment the dog showed much clinical improvement, and eight weeks after initial presentation was assessed to be clinically normal. Thus, these reports provide good evidence that fenbendazole is effective alleviating the symptoms of angiostrongylosis and discontinuing larval shedding in the feces of treated dogs. A report on three dogs with intracranial hemorrhage secondary to severe coagulation defects associated with infection with A. vasorum infection was published by Garosi et al., [33]. The first case was diagnosed postmortem, but the other two dogs (a four year old male, neutered, cocker spaniel, and a 14 month old, neutered female Staffordshire bull terrier) were treated with a seven day course of 50 mg/kg fenbendazole PO q 24 h. Both dogs had normal coagulation profiles a week after treatment; repeat fecal analyses two weeks after treatment were negative for larvae in both cases. Treatment of Crenosoma vulpis Crenosoma vulpis is considered mainly a parasite of foxes that on occasion finds its way into dogs through ingestion of infective-stage larvae in slugs or snails. Infections of the lower respiratory tract with this parasite, [along with Angiostrongylus vasorum, Oslerus osleri, Filaroides hirthi, Eucoleus aerophila, and Paragonimus kellicotti (and other species of Paragonimus outside of North America)], are known to cause eosinophilic bronchitis in dogs. Dogs will typically present with either a productive or a non-productive cough, and if infections is severe, respiratory distress. Radiographs of the lungs may show bronchial patterns with some interstitial components throughout the parenchyma. As with Oslerus, Filaroides, and Angiostrongylus, diagnosis can be made through the finding of larvae in the feces. Crenosoma vulpis infection in dogs has been effectively treated with fenbendazole (50 mg/kg PO, q 24 h) for 3 days [60], 5 days [39], or 14 days [49]. It has been suggested, however, that extending the treatment beyond the 3-day standard recommendation for fenbendazole offers no benefit [4], yet lower doses of fenbendazole for longer periods of time (20 mg/kg PO, q 24 h, 14 days) have been reported to be effective [52]. In addition, febantel (with praziquantel and pyrantel) in Drontal Plus given for 7 consecutive days has been used to treat this infection in a dog [19]. It would appear that the most direct course of therapy would be to treat dogs with the approved intestinal dose of fenbendazole (50 mg/kg PO, q 24 h for three days) and several weeks later ascertain if further treatment is warranted. Treatment of Filaroides hirthi Infections Filaroides hirthi lives in the parenchyma of the lung of infected dogs and may be asymptomatic or lead to pneumonia in immunosuppressed animals. Fenbendazole has proven to be very effective in treating this infection. Pinckney et al., [61] treated a 1-year-old Yorkshire terrier with a single oral dose of 0.068 mg of ivermectin followed with fenbendazole (50 mg/kg PO, q 24 h for two weeks). After treatment this dog's feces became negative for the larvae of this parasite, and the dog improved without any recurrence of signs. Caro-Vadillo et al., [17] recently reported that treatment of a Scottish terrier with 50 mg/kg of fenbendazole, q 24 h PO for three weeks eliminated the parasite and improved the clinical condition of the dog. Rubash [64] reported on the treatment of a Chihuahua presenting with sudden weakness and rapid breathing, found to be infected with Filaroides hirthi. The dog was treated with fenbendazole (50 mg/kg PO, q 24 h) for 14 days. On Day 1 of treatment, the dog developed signs of facial swelling and urticaria, so prednisolone was also given during the course of treatment. On Day 3 of treatment, the coughing worsened and the dog became dyspneic, but treatment with furosemide and hydrocodone led to improvement over the next 24 hours. Forty days after the initiation of therapy, the dog appeared healthy, and larvae were not detected in the feces. The dog was last examined 4 months after discharge and found to be normal. In one other report, Bourdeau and Ehm [10] found that fenbendazole (50 mg/kg PO, q 24 h for 14 days) did not clear a dog of its infection, but that ivermectin (0.050 mg/kg SQ once) reduced the number of larvae in the feces. This dog apparently recovered 2 weeks after the ivermectin treatment. Treatment of Oslerus (Filaroides) osleri Infections This worm causes nodules in the mucosa of the trachea of dogs, and is usually associated with cough and respiratory distress in affected animals. Numerous authors have reported on the treatment of Oslerus osleri infections with either fenbendazole or ivermectin with mixed results [11,37,42,47,48,53,57,65]. Thus, it seems at this time, the physical removal of the nodules followed by treatment with oxfendazole (10 mg/kg PO, q 24 h, for 4 weeks) may be a better treatment option. Oxfendazole is available in several preparations from Fort Dodge Animal Health as Benzelmin Equine Paste in a 12 gram syringe, Bovine Dewormer Suspension 22.5%, and Synantic Bovine Dewormer 18.5%. Typically, treatment with the Synantic Bovine Dewormer at 90 mg/ml is used (approximately 1 ml per 10 kg). Use of Fenbendazole for Treatment of Trematode Infections in Dogs Digenea Treatment of Heterobilharzia americana Dogs in the southeastern United States that come in contact with water containing cercariae can become infected with the blood fluke Heterobilharzia americana. The infection can cause chronic hepatitis and thickened bowel walls due to the host's reaction to eggs shed by the female into the blood stream that become lodged in the tissues. The preferred treatment for this infection is most likely praziquantel at dosages similar to those used in human schistosomiasis, i.e., around 20 mg/kg q 8 h for 1 day. However, fenbendazole treatment (40 mg/kg PO q 24 h for 10 days) of a dog with a 2-year-old experimental infection resulted in the dog having no worms present when euthanatized 17 days after treatment [63]. Troy et al., [71] also reported that fenbendazole will cause clinical improvement in treated animals. Treatment of Paragonimus kellicotti The lung fluke, Paragonimus kellicotti, is an uncommon but occasional parasite of dogs in the Eastern and Central United States. Dogs with Paragonimus kellicotti infections have been successfully treated with fenbendazole (50 mg/kg PO, 24 h for 14 days; or at 100 mg/kg PO q 24 h for 10 days) [25]. Dogs have also been treated using albendazole (30 mg PO, q 24 h for 12 days) with good success [70]. Praziquantel (23 mg/kg, q 8 h, for three days) also clears dogs of their infections [14]. It would appear that either therapy is efficacious in clearing dogs of their lung fluke infections. Thus, the choice of either Panacur or Droncit for therapy may depend on factors such as which product is available at the time of diagnosis. Treatment of Opisthorchis caninus Dogs experimentally infected with an intestinal fluke (Opisthorchis caninus) after being fed infected fish were cleared of their infections by fenbendazole treatment (200 mg/kg PO, q 24 h for three days) [62]. Although treating intestinal flukes with praziquantel (6 to 40 mg/kg PO once), such as is done with Nanophyetus salmincola [32], would probably be the preferred method today, fenbendazole would be an alternative therapy. Use of Fenbendazole for the Treatment of Cestode Infections in Dogs Cyclophyllidea Treating Larval Mesocestoides Infections It is not known how dogs become infected with the larval stage of Mesocestoides. It is thought that a cysticercoid stage must precede the tetrathyridium stage infectious to the final host, and that perhaps this cysticercoid develops in a coprophilic insect [12] which may then be ingested by the dog and lead to infection. The larval stage, the tetrathyridium, which develops in the abdominal cavities of infected dogs, causes severe and significant disease. Treatment often requires a laparotomy and the washing of the abdominal cavity. The liver and other organs can also become involved. In fact, the washing of the abdomen may have to be repeated several times. It has been found in these cases the infections with the larval forms do not respond to praziquantel or albendazole, but repeated treatment with fenbendazole, (100 mg/kg, PO, q 12 h for 28 days), may clear infections [23]. In a case report from Italy, a mixed-breed dog presenting with anorexia, depression, and pain upon abdominal palpation, was found to have a peritoneal infection caused by an unidentified Mesocestoides species [8]. The dog was initially treated with fenbendazole at a dose of 50 mg/kg PO, q 24 h for 10 days, and with a single dose of praziquantel at 5 mg/kg. There was initial improvement, but almost a week after the end of treatment the dog developed abdominal distension and fever. Bacterial contamination in addition to a few calcarious corpuscles were evident in recovered peritoneal fluid. Antibiotics were given and a laparotomy and peritoneal lavage was performed with further evidence of peritoneal cestodiasis. During the following 8 months the dog experienced recurring episodes of bacterial peritonitis and peritoneal cestodiasis that were treated with fenbendazole at 100 mg/kg q 24 h continuously along with antibiotics. The dog was reportedly alive a year after presentation and still on continuous fenbendazole. Thus, it is evident that although fenbendazole is the treatment of choice for peritoneal cestodiasis caused by the larval forms of this parasite, treatment may ameliorate clinical signs and bring a marked reduction to their number, but it may not clear the infection or prevent recurrence [8]. Use of Fenbendazole for the Treatment of Protozoal Infections in Dogs Diplomonadida Treating Canine Giardia Infections Giardia spp. are flagellates of the small intestine of many animals including dogs. The infection may be asymptomatic or may lead to chronic diarrhea (especially in young animals). Fenbendazole has been shown to be one of the benzimidazoles that functions very well as an agent against intestinal giardiasis. It has been shown have high potency in vitro against G. duodenalis [54]. Furthermore, the treatment of dogs with 50 mg/kg PO, q 24 h fenbendazole for 3 days has been shown to be highly efficacious in clearing dogs of their Giardia infections both in experimental and clinical cases [3,38,74]. Fenbendazole at 50 mg/kg PO, sid, 7 days, was also able to eliminate cyst shedding in treated dogs [44]. Dryden et al., [24] recommend the use of fenbendazole (50 mg/kg) or the combination of praziquantel, pyrantel pamoate, and febantel (5, 5, and 25 mg/kg, respectively) for 3 to 5 days [59] for the treatment of giardiasis in dogs. Concluding Remarks Fenbendazole is a broad-spectrum anti-parasiticide that provides significant ability to control various helminth parasites in dogs and also has the ability to clear dogs of their Giardia infections. This is a product that has been time-tested and found to be very safe for dogs even when given to sick animals daily at double the usual therapeutic dosage for periods of up to a month. Few reports of adverse reactions have been published, but careful monitoring of animals is warranted. Out of all the dogs given fenbendazole since it entered the market, there have been only 230 Adverse Drug Experiences (ADEs) reported to the FDA. Of these, the top two are vomiting and depression/lethargy (Table 1). It is noteworthy that death is reported in some 24 dogs (10%), however, it is important to bear in mind FDA cautions relative to ADEs. Most importantly (Table 1): "For any given (ADE) report, there is no certainty that the reported drug caused the adverse event. The adverse event may have been related to an underlying disease, using other drugs at the same time, or other non-drug related causes." and "Accumulated ADE reports should not be used to calculate incidence rates or estimates of drug risk, because there is no accurate way to determine how many animals were given the drug." Thus, this product in its granular form (Panacur) still seems to have a place in the veterinarian's pharmacopoeia even though for specific parasites better therapies may be currently available. From http://www.fda.gov/cvm/ade_description.htm 1. For any given Adverse Drug Experiences (ADE) report, there is no certainty that the reported drug caused the adverse event. The adverse event may have been related to an underlying disease, using other drugs at the same time, or other non-drug related causes. And, this listing does not include information about underlying diseases, other drugs used at the same time, other non-drug related causes, or the final outcome of the reaction. 2. The accuracy of information regarding the ADE is dependent on the quality of information received from the veterinarian or animal owner. 3. Accumulated ADE reports should not be used to calculate incidence rates or estimates of drug risk, because there is no accurate way to determine how many animals were given the drug. For example, if a drug is widely used to treat Table 1. Top 15 adverse drug experiences in dogs reported to the FDA from 1987 to 2007 using oral fenbendazole; a total of 230 canine reports were evaluated by the agency [30]. Sign Reacted Vomiting 122 Depression/lethargy 116 Anorexia 84 Diarrhea, mild 58 Diarrhea 30 Death 24 Dehydration 24 Pain, abdomen 19 Ineffect, ascarids 15 Hyperactivity 12 Weight loss 11 Fever, body 10 Birth defect(s) 9 Convulsion(s) 9 Trembling 8 certain conditions, there may be more ADEs for that drug than another product that is not used as often. This would not mean that the first drug was more unsafe than the second. The number of reports simply represents the numbers of ADEs received for a particular drug, by species, and route of administration. References 1. Abbott EM, Dent CN. Comparison of two different treatment regimens for the control of Toxocara canis infections in commercial breeding kennels. Canine Pract 1998; 23:6-7. 2. Anderson DL, Roberson EL. Actvity of ivermectin against canine intestinal helminths. Am J Vet Res 1982; 43:1681- 1683. 3. Barr SC, Bowman DD, Heller RL. Efficacy of fenbendazole against giardiasis in dogs. Am J Vet Res 1994; 55:988-990. 4. 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