The Majority of this information was researched and provided by: Lorraine Shelton Thank you Lorraine for your research and very informative information. Use of Lufenuron (Program) for treating fungal infections of dogs and cats: 297 Cases (1997-1999) (Excerpts taken from article in JAVMA, Vol 217, No 10, November 15, 20000 ObjectiveTo evaluate use of Luferuron for treating cutaneous fungal infections in dogs and cats. Design-- Retrospective Study ProcedureMedical records were reviewed for dogs and cats that has been treated for dermatophytosis for other fungal infections by administration of lufenuron and 18 dogs and 42 cats that were not treated and served as a control group ResultsDogs were treated once by oral administration of lufenuron tablets at doses ranging from 54.2 to 68.3 mg/kg (24.6 to 31.0 mg/lb of body weight. Samples of skin, scrapings, and hair were obtained daily from 14 dogs with dermatophytosis: mean duration from time of treatment to time of negative fungal culture results and resolution of gross lesions were 14.5 and 20.75 days, respectively. In all treated dogs, gross lesions resolved within approx 21 days. Cats were treated once by oral administration of lufenuron suspension in doses ranging from 51.2 to 266 mg/kg (23.3 to 120.9 mg/lb. Samples were obtained daily from 23 cats: mean durations from time of treatment to time of negative fungal culture results and resolution of gross lesions were 8.3 and 12 days, respectively. Time to resolution of lesions in most untreated control animals was approximately 90 days. Adverse effects of treatment were not detected. Conclusions and clinical relevance. Results of this study suggests that lufenuron provided an effective, convenient and rapid method of treating fungal infections in dogs and cats. (J Am Vet Med Assoc 2000:217:1510-1513) Dermatophytes are classified on the basis of their morphologic characteristics and include morphologic characteristics and include Microsporum, Trichophyton, and Epidermophyton spp all of which are pathogenic for humans and animals. Three species, M canis, M gypseum and T mentagrophytes cause most clinical cases of dermatophytosis in dogs and cats. Microsporum canis is the most common cause of ringworm and is transmitted from cats and dogs to humans. Spontaneous remission of dermatophytosis in companion animals often occurs within1 to 3 months, whereas treatment is undertaken to reduce transmission to other animals, including human, and eradicate the infection. Dermatomycoses that affect companion animals include nondermatophytic superficial fungal infections with organisms such as Aspergillus, Candida, Malassezia and trichosporon spp. Traditionally, fungal infections have been treated with griseofulvin and ketoconazole. Lufenuron is classified as an insect development inhibitor because of its ability to inhibit citin ( a polymer of n-acetylglucosamine) synthesis, polymerization, and deposition. It is used in veterinary medicine as a flea control treatment, administered orally once per month. Results: 357 dogs and cats met study criteria, Sixty animals were untreated control and 297 animals with fungal infections had been treated with lufenuron. 71 were males, and 88 were females. 145 of these cats were mixed-breeds, 8 were Siamese, 7 were Persians, 1 was an Angora, and 1 was a Himalayan. Ages ranged from 2 to 128 months (mean, 16.2 ± 16 months) and body weight ranged from 0.55 to 5 kg (1.2 to 11 lb; mean 3.1 ± l.l kg; 6.8 ± 2.4 lbs). One hundred fifty-six cats were infected with M canis and 18 of these cats had generalized infection. Three cats were infected with T mentagrophytes. Lesions were located on the head and neck (n=136), limbs (10) trunk (7), and tail (6). In these treated cats, hair started to regrow after 5 or 6 days, and full growth was usually completed within 10 to 12 days. Mean clinical recovery time was 11.6 ± 1.4 days. Of the 18 cats with generalized M canis infection, 14 recovered within 10 days, 2 recovered within 11 days, and 1 recovered within 14 days. One 2 month old Persian kitten did not recover, even after 20 days. Of the 23 cats examined individually on a daily basis by use of fungal culture, mycologic cure was detected within 7 to 14 days (mean, 8.3 ± 1.2 days), whereas clinical recovery was complete within 10 to 15 days (mean, 12 ± 1.8 days). In one cat, positive culture results were obtained again 35 days after treatment; a second treatment was administered, and negative culture results were obtained for the next 8 weeks. Three cats again developed clinical signs of infection several weeks after initial remission of clinical signs; M canis was cultured from the lesions, and the cats responded well to a second treatment of lufenuron. Discussion: Results of the study reported here indicated that dermatophytosis persisted for 2 to 3 months in untreated animals, whereas dogs and cats that were treated with lufenuron had remission of clinical signs much more rapidly: approximately 10 to 15 days for cats and 16 to 25 days for dogs. Furthermore, mean recovery times of dogs affected by superficial dermatomycoses were quite similar. Evaluation of results of daily mycologic culture of specimens from 16 treated dogs and 23 treated cats permitted a comparison of mycologic cure and clinical recovery times in these animals. In all instances, culture results were negative before clinical signs had disappeared. Differences in duration between these 2 findings ranged from 1 to 19 days for dogs and 1 to 5 days for cats. Lufenuron appeared not to have adverse effects. Kittens that weighed as little as 0.5 kg received an entire tube (133mg) of the drug equivalent to a dose of 266 mg/kg, which is considerably larger that that typically administered for flea control, with no apparent adverse effects. Nevertheless, approximately 5% of treated animals became reinfected including 1 dog and 1 cat that were monitored daily by use of fungal culture. Infections reappeared at 25 to 35 days after treatment, respectively, and were successfully treated with a second dose of lufenuron. It is not known whether these animals had become reinfected by natural exposure or were latently infected despite treatment. Nevertheless, oral administration of lufenuron appears to be effective treatment for certain cutaneous fungal infections in dogs and cats. For the complete text of this article, refer to JAVMA, Vol 217, No 10, November 15, 2000 ******************** E-mail inserts: ******************** Carol Johnson, DVM has written this excellent summary of the article on using the flea control product, Program, to treat ringworm. Science and the Breeder: Ringworm and Lufenuron by Carol W. Johnson, DVM PhD Microsporum canis, the most common cause of ringworm, is a parasitic fungus that is highly adapted to cats. Once introduced into a cattery, ringworm can rapidly spread and can infect most or all of the cats in a cattery before the breeder is aware that there even is a problem. In an infected cattery, the lesions often appear to resolve in adult cats after several months and kittens often will no longer show lesions as they approach maturity. In most cases, however, these cats still harbor low levels of fungus and serve to infect the kittens that are born into a cattery. Ringworm can also infect humans. While ringworm infections tend to be self-limiting in most adults, children and immunosuppressed individuals may develop severe infections that may take weeks or months to eradicate. One elderly woman told me of suffering for months after her children surprised her with a purebred kitten to provide companionship during her post-kidney transplant convalescence. The kitten carried ringworm and the poor woman developed huge skin sores and lost her hair. She became quite ill from the antifungal treatment, then almost lost her transplanted kidney during the effort to get rid of the fungal infection. Children, also, can get very severe lesions and ringworm infections of the head are considered to be fairly serious by pediatricians. Some of the biggest impediments to all catteries becoming ringworm-free has been the expense of treatment and the limited safety of the less expensive drugs. Griseofulvin (Fulvicin) is inexpensive and moderately effective against ringworm, but causes severe neutropenia and immunosuppression that can be fatal in up to 10% of the treated cats. Itraconazole (Sporonox) is much more effective and safer, but can cost up to $200 to treat a cat. Those of us who claim a ringworm-free cattery have often had to spend thousands of dollars to maintain that status and treatment of a large cattery is often beyond the economic ability of some breeders. However, an exciting recent article [Ben-Ziony Y, Arzi B. Use of lufenuron for treating fungal infections of dogs and cats: 297 cases (1997-1999) JAVMA 217(10) (Nov 15) 2000] describes what may prove to be an economically viable treatment and prevention for ringworm. A veterinarian in Israel noted that dogs and cats treated with lufenuron for flea prevention did not appear to develop ringworm, even though they were not being treated for ringworm. Lufenuron (sold in the US by Novartis under the brand name PROGRAM) is a chitin synthetase inhibitor used for flea control. Chitin is a structural molecule in the exoskeleton of insects and their eggs. After administration, lufenuron sequesters in the fat and is slowly released into blood where it is ingested by a female flea. The drug then interferes with the production of chitin in the eggs, which leads to the eggs drying out after they are laid. Chitin is not found in mammalian tissues, but is a structural component of the fungal cell wall. Thus, this drug does not appear to affect mammalian enzymes and as a result has had an excellent safety record when used according to its product insert. The Israeli clinic systematically tested lufenuron in ringworm-infected cats and dogs. Over the 2-year period, they treated 201 cats and followed 23 on a daily basis. Most cats treated with lufenuron doses ranging from 51.2 to 266 mg/kg (23.1 to 120.9 mg/lb) cultured negative for ringworm in 8.3 days and began growing hair in 12 days. Four cats either cultured positive for ringworm or developed lesions again but responded well after a second treatment. None of the cats showed signs of toxicity. I had some concerns regarding the safety of this treatment because the article used between 5 and 20 times the recommended dose used to treat fleas, so I called Novartis' Customer Service line and spoke with a veterinarian. He reported that Novartis had no information on the use of lufenuron for ringworm and the article took the company by surprise. Because this is off-label use, he can not recommend the drug for this indication. However, Novartis is very excited about the article and its potential. We extensively discussed the safety data Novartis had performed for registration, and then I reviewed the safety data on the FDA website made possible through the Freedom of Information Act. Safety studies in both dogs and cats showed the drug had a wide margin of safety. Reproduction studies were performed in dogs and cats and lufenuron did not to cause toxicity or congenital defects at the doses tested. Because this is off-label use and one article does not prove efficacy or safety, I can not recommend lufenuron for the treatment of ringworm in cats. However, for those breeders determined to try it, I have some suggestions. Lufenuron is sold under the brand name PROGRAM. SENTINEL also contains lufenuron, but in addition contains milbemycin, which may be toxic when given at the overdoses suggested by the article. So do NOT use SENTINEL for ringworm. Lufenuron comes as a tablet, a suspension, or as an injectable. The injectable lasts 6 months, but can leave a lump (granuloma) at the injection site, and this may be a consideration for show cats. Novartis found that the tablet appears to have better efficacy than the suspension. I have not used PROGRAM, but understand that some cats do not like the taste of the suspension, so this may be a consideration when treating some cats. If you are going to try it to see if it works on a few cats, try to keep them separate from other ringworm-infected cats. Ringworm, like many parasitic organisms, can become drug resistant and it will do neither the breeder nor the rest of the cat fancy any good to develop Lufenuron resistant ringworm. Similarly, once the decision to treat a cattery is made, break down, bite the bullet, and treat the whole cattery and not just a few cats. Couple treatment of cats with physically cleaning the cattery to get rid of the spores so the cats are not reinfected. Getting rid of the problem will be cheaper in the long run than living with it and will be much less likely to generate resistant forms. Plan to treat once monthly for 2 to 3 months to make sure it is really gone. Yes, the article had good success after one treatment, but a cattery situation is very different than the average pet household. I'm getting a lot of questions about the safety of Program/lufenuron. Below the asterisks is the information from Novartis on the initial safety data done to gain approval of this drug for use in cats and dogs. Beyond this, additional studies have been performed in breeding cats (as well as dogs), again at levels far exceeding that used for flea or ringworm control. This drug has been in use for years without any reports of adverse events. But the most convincing body of supporting evidence is testing performed for the accpetance of an almost identical drug (the two drugs act exactly the same) for the control of the Gypsy Moth in area of human habitation. The data required for use in human areas is much more rigorous than that required for animal studies! Again, the same results were obtained: THEY JUST COULDN'T MAKE THIS DRUG TOXIC TO MAMMALS, NO MATTER HOW HARD THEY TRIED! Traditional tests of toxicity, such as the LD50 test, could not even be performed in rodents, because no matter how much of this stuff they crammed into the little critters (100X the dose per body weight), they just couldn't get rodents (even babies and pregnant ones) to look sideways at the researchers! This is EXTREMELY rare in the world of modern pharmaceuticals. Since the sole mechanism of this drug is to interfere with the synthesis and use of chitin, this makes a lot of sense, since CHITIN DOES NOT EXIST IN THE BODY OF MAMMAL! The safety of this drug is, to the satisfaction of my mind and that of the FDA, absolutely without question. For me, the main test remaining to be done is EFFICACY in large cattery environments, particularly those with Persian cats. ************* E-mail inserts: ************* From the Novartis web site: Safety PROGRAM has undergone numerous safety trials to test its margin of safety at various doses. In addition, it has been available world wide in over 30 countries with no adverse reactions found. The reason that PROGRAM is so safe, is that Lufenuron has no reaction in mammals. Mammals do not contain chitin, so the molecule is absorbed and excreted without ever having been metabolized. As such it is safe in all mammals. PROGRAM has been tested at hundreds of times the label dose with no difficulties in mammals. Lufenuron has no effect on breeding animals, nor does it affect conception rates or litter size in breeding pets. It crosses the milk barrier and the placental barrier with no harmful effects to the unborn cats and dogs. They are, in fact, protected from continuing the flea life cycle by Lufenuron passed on from the mother's milk. PROGRAM exhibits no drug interactions, therefore it has no ill effect on older pets, or pets with liver or renal problems, regardless of any medication those pets may be on for their medical condition. It does not affect diabetics or pets on antibiotics. There is no bio-accumulation so there is no chance of lufenuron "building up" in the pet and causing a problem in the long term. Normal pesticides and other prescription drugs have to be tested for an LD50. This is the recognized dose in animals where the drug turns toxic in 50% of laboratory rats. It was not possible to establish an LD50 for PROGRAM. Program, lufenuron, the *flea* product. Almost 300 cats infected with ringworm were put on Program and the ringworm went away in about two weeks. Not only that, these cats cultured negative just as quickly. That is important, because many cats get treated until the lesions go away... but remain "assymptomatic carriers" of the fungus after treatment with other antifungal drugs. Lufenuron works by interfering with the synthesis and deposition of chitin in the growing/developing flea. Well, interestingly enough, fungus also grows by using chitin to construct a cell wall (think of it as a miniature plant) and without chitin, the fungus dies. The dose used in the study appears to be a bit higher than that used for flea control. The 1-10# cat size of Program should be used to treat a 1-6# cat. The 11-20# size of Program should be used to treat a 7-11.5# cat. Cats 12# and over should be treated with 1.5 doses of the 11-20# size of Program. This cured ringworm in 95% of the cats, with 5% of the cats requiring a second dose a month later. Program is available in tablet form or as a liquid at a price (ordered on the Internet) of about $26-30 for six doses. It has been proven to be safe in pregnant queens, breeding males, and kittens over the age of six weeks. The six-month injectible form of Program is available only from vets and has NOT been proven to be safe in breeding cats (no studies performed). A wonderful summary of this prepared by one of our members, complete with the abstract of the journal article from the November 15, 2000 issue of the Journal of the American Veterinary Medical Association is available in the archives of our list. Visit http://www.yahoogroups.com to look through the list archives. It is message number 341. This is truly exciting news in the cat fancy! ******************* Because the dose amounts for dogs differ so much than for cats, using the largest dog size really doesn't save you much money. Heck, folks, this drug is only $4-6 a cat dosed ONLY once a month. Let's "splurge" and do it right, rather than playing Scrooge ;-) Here is the dosage for treating cats for fungus with Program: A cat that weighs 1-6 pounds needs to get one of the tablets in the package marked "for 1-10# cats". A cat that weighs 7-11.5 pounds needs to get one of the tablets in the package marked "for 11-20# cats". For cats weighing 11.5+ pounds, give them one and a half of the tablets marked "for 11-20# cats". DO NOT use the dog formulation or try to dose based on any dog dosage. Remove all food the night before. Give tablet, then serve large (preferably greasy and tasty) meal. The drug is only absorbed with food. For more information on using Program (lufenuron) to treat ringworm in cats, join the fanciershealth list at egroups, where this information was first presented to the cat fancy on the Internet, by sending an e-mail to: fanciershealth@yahoogroups.com. Information (including a summary of the original JAVMA article) can be found in the Messages archives and in the Files section, which can be accessed by going to: ****************** E-Mail (12-8-2000) A couple of things probably preclude the injectable form of Program/lufenuron from being used in cattery situations to treat ringworm. 1) The injectable form of this drug has not been tested in breeding animals. Although I have no reason to suspect it would cause problems in a population of breeding animals, safety in breeding populations *has* been demonstrated for the oral forms of this drug. 2) According to the information I have read from Novartis, the injectable form of this drug does not deposit in the fatty tissue of the cat as quickly as the oral form. Therefore, recovery times from infection would be expected to be much longer than with the oral drug. Could this injectible form of Program/lufenuron work as an effective every-six-months "vaccine" against ringworm in non-infected (cultured negative) cats? Possibly, although the "lead time" to protection looks like it would be about two to three weeks. This is the type of data that takes time (and financing!) to generate. ************* E-Mail 12-12-2000 Because PROGRAM is regulated and approved by the FDA*, it's held to the same high standards as human medicines. That means it's proven safe for dogs and cats. PROGRAM has no adverse effects on health, growth or reproduction. It can be used safely by pregnant and nursing animals, and puppies and kittens as young as six weeks. ****** March 5, 2001 email Here is some updated information, including a recommendation for a new dosage schedule, for using Program to treat ringworm in a cattery environment. This is from the researcher in Israel who published the study that first reported the efficacy of Program used in this way. He now recommends treating cats in catteries with 100mg/kg Program (45 mg per pound cat weight) given twice, two weeks apart and then using the normal flea control dosage once a month thereafter in high risk or ringworm endemic catteries. He again emphasizes that the dose must be given with food and that environmental control of spores is an important element of treating this disease. --Lorraine |
This information is just that, information from publications and Veterinarians. I do not necessarily use all these remedies, but feel the information is here, for responsible breeders. Fungus by: Susan Little DVM Dipolmate ABVP (Feline) Bytown Cat Hospital Ottawa, Canada The drug Lamisil verses Fulvicin The main difference is cost. Lamisil (terbinafine) is considerably more expensive. Not much is known about terbinafine in cats, but a small study was published this year (1999) in the New Journal Of Feline Medicine & Surgery. The study was done in Italy at the University of Pisa. A group of 15 cats with ringworm caused by M. Canis who had previously been cured were treated with terbinafine at 30 mg/kg once daily for 2 weeks. At the end of the two weeks, sme cats required a third week of treatment. Twelve of the 15 cats finished the trial (2 died of unrelated causes, one cat could not tolerate the drug). Of the 12 cats, 11 were cured with terbinafine. The cats were cultured on the last day of therapy (day 14) and again one month later (day 44). At day 44, most of the cats were still positive on culture. Those with a heavily positive culture were given an extra week of treatment at this point. By 3 months (day 104) after culture, all but one of the cats was negative, even though most had long stopped taking the drug. This is due to the high and long-lasting residual activity of the drug. Exactly how long it takes to effect a cure is hard to say, since the cultures were only done on day 44 and on day 104 and the cats cured sometime in between. My initial impression is that this drug will no necessarily give a cure quicker than itraconazole or fluconazole, but the number of treatments that need to be given might be less. Routine For Fungus Breakout I have recently found out that 50% of the time the shot "Fel-O-Vax MCK (Fort Dodge), heals the leions from the fungus, if followed with the schedule of 3 injections, 2 weeks after the first injection and 4 weeks after the second injection. |
The Majority of this information was researched and provided by: Lorraine Shelton Thank you Lorraine for your research and very informative information. Use of Lufenuron (Program) for treating fungal infections of dogs and cats: 297 Cases (1997-1999) (Excerpts taken from article in JAVMA, Vol 217, No 10, November 15, 20000 ObjectiveTo evaluate use of Luferuron for treating cutaneous fungal infections in dogs and cats. Design-- Retrospective Study ProcedureMedical records were reviewed for dogs and cats that has been treated for dermatophytosis for other fungal infections by administration of lufenuron and 18 dogs and 42 cats that were not treated and served as a control group ResultsDogs were treated once by oral administration of lufenuron tablets at doses ranging from 54.2 to 68.3 mg/kg (24.6 to 31.0 mg/lb of body weight. Samples of skin, scrapings, and hair were obtained daily from 14 dogs with dermatophytosis: mean duration from time of treatment to time of negative fungal culture results and resolution of gross lesions were 14.5 and 20.75 days, respectively. In all treated dogs, gross lesions resolved within approx 21 days. Cats were treated once by oral administration of lufenuron suspension in doses ranging from 51.2 to 266 mg/kg (23.3 to 120.9 mg/lb. Samples were obtained daily from 23 cats: mean durations from time of treatment to time of negative fungal culture results and resolution of gross lesions were 8.3 and 12 days, respectively. Time to resolution of lesions in most untreated control animals was approximately 90 days. Adverse effects of treatment were not detected. Conclusions and clinical relevance. Results of this study suggests that lufenuron provided an effective, convenient and rapid method of treating fungal infections in dogs and cats. (J Am Vet Med Assoc 2000:217:1510-1513) Dermatophytes are classified on the basis of their morphologic characteristics and include morphologic characteristics and include Microsporum, Trichophyton, and Epidermophyton spp all of which are pathogenic for humans and animals. Three species, M canis, M gypseum and T mentagrophytes cause most clinical cases of dermatophytosis in dogs and cats. Microsporum canis is the most common cause of ringworm and is transmitted from cats and dogs to humans. Spontaneous remission of dermatophytosis in companion animals often occurs within1 to 3 months, whereas treatment is undertaken to reduce transmission to other animals, including human, and eradicate the infection. Dermatomycoses that affect companion animals include nondermatophytic superficial fungal infections with organisms such as Aspergillus, Candida, Malassezia and trichosporon spp. Traditionally, fungal infections have been treated with griseofulvin and ketoconazole. Lufenuron is classified as an insect development inhibitor because of its ability to inhibit citin ( a polymer of n-acetylglucosamine) synthesis, polymerization, and deposition. It is used in veterinary medicine as a flea control treatment, administered orally once per month. Results: 357 dogs and cats met study criteria, Sixty animals were untreated control and 297 animals with fungal infections had been treated with lufenuron. 71 were males, and 88 were females. 145 of these cats were mixed-breeds, 8 were Siamese, 7 were Persians, 1 was an Angora, and 1 was a Himalayan. Ages ranged from 2 to 128 months (mean, 16.2 ± 16 months) and body weight ranged from 0.55 to 5 kg (1.2 to 11 lb; mean 3.1 ± l.l kg; 6.8 ± 2.4 lbs). One hundred fifty-six cats were infected with M canis and 18 of these cats had generalized infection. Three cats were infected with T mentagrophytes. Lesions were located on the head and neck (n=136), limbs (10) trunk (7), and tail (6). In these treated cats, hair started to regrow after 5 or 6 days, and full growth was usually completed within 10 to 12 days. Mean clinical recovery time was 11.6 ± 1.4 days. Of the 18 cats with generalized M canis infection, 14 recovered within 10 days, 2 recovered within 11 days, and 1 recovered within 14 days. One 2 month old Persian kitten did not recover, even after 20 days. Of the 23 cats examined individually on a daily basis by use of fungal culture, mycologic cure was detected within 7 to 14 days (mean, 8.3 ± 1.2 days), whereas clinical recovery was complete within 10 to 15 days (mean, 12 ± 1.8 days). In one cat, positive culture results were obtained again 35 days after treatment; a second treatment was administered, and negative culture results were obtained for the next 8 weeks. Three cats again developed clinical signs of infection several weeks after initial remission of clinical signs; M canis was cultured from the lesions, and the cats responded well to a second treatment of lufenuron. Discussion: Results of the study reported here indicated that dermatophytosis persisted for 2 to 3 months in untreated animals, whereas dogs and cats that were treated with lufenuron had remission of clinical signs much more rapidly: approximately 10 to 15 days for cats and 16 to 25 days for dogs. Furthermore, mean recovery times of dogs affected by superficial dermatomycoses were quite similar. Evaluation of results of daily mycologic culture of specimens from 16 treated dogs and 23 treated cats permitted a comparison of mycologic cure and clinical recovery times in these animals. In all instances, culture results were negative before clinical signs had disappeared. Differences in duration between these 2 findings ranged from 1 to 19 days for dogs and 1 to 5 days for cats. Lufenuron appeared not to have adverse effects. Kittens that weighed as little as 0.5 kg received an entire tube (133mg) of the drug equivalent to a dose of 266 mg/kg, which is considerably larger that that typically administered for flea control, with no apparent adverse effects. Nevertheless, approximately 5% of treated animals became reinfected including 1 dog and 1 cat that were monitored daily by use of fungal culture. Infections reappeared at 25 to 35 days after treatment, respectively, and were successfully treated with a second dose of lufenuron. It is not known whether these animals had become reinfected by natural exposure or were latently infected despite treatment. Nevertheless, oral administration of lufenuron appears to be effective treatment for certain cutaneous fungal infections in dogs and cats. For the complete text of this article, refer to JAVMA, Vol 217, No 10, November 15, 2000 ******************** E-mail inserts: ******************** Carol Johnson, DVM has written this excellent summary of the article on using the flea control product, Program, to treat ringworm. Science and the Breeder: Ringworm and Lufenuron by Carol W. Johnson, DVM PhD Microsporum canis, the most common cause of ringworm, is a parasitic fungus that is highly adapted to cats. Once introduced into a cattery, ringworm can rapidly spread and can infect most or all of the cats in a cattery before the breeder is aware that there even is a problem. In an infected cattery, the lesions often appear to resolve in adult cats after several months and kittens often will no longer show lesions as they approach maturity. In most cases, however, these cats still harbor low levels of fungus and serve to infect the kittens that are born into a cattery. Ringworm can also infect humans. While ringworm infections tend to be self-limiting in most adults, children and immunosuppressed individuals may develop severe infections that may take weeks or months to eradicate. One elderly woman told me of suffering for months after her children surprised her with a purebred kitten to provide companionship during her post-kidney transplant convalescence. The kitten carried ringworm and the poor woman developed huge skin sores and lost her hair. She became quite ill from the antifungal treatment, then almost lost her transplanted kidney during the effort to get rid of the fungal infection. Children, also, can get very severe lesions and ringworm infections of the head are considered to be fairly serious by pediatricians. Some of the biggest impediments to all catteries becoming ringworm-free has been the expense of treatment and the limited safety of the less expensive drugs. Griseofulvin (Fulvicin) is inexpensive and moderately effective against ringworm, but causes severe neutropenia and immunosuppression that can be fatal in up to 10% of the treated cats. Itraconazole (Sporonox) is much more effective and safer, but can cost up to $200 to treat a cat. Those of us who claim a ringworm-free cattery have often had to spend thousands of dollars to maintain that status and treatment of a large cattery is often beyond the economic ability of some breeders. However, an exciting recent article [Ben-Ziony Y, Arzi B. Use of lufenuron for treating fungal infections of dogs and cats: 297 cases (1997-1999) JAVMA 217(10) (Nov 15) 2000] describes what may prove to be an economically viable treatment and prevention for ringworm. A veterinarian in Israel noted that dogs and cats treated with lufenuron for flea prevention did not appear to develop ringworm, even though they were not being treated for ringworm. Lufenuron (sold in the US by Novartis under the brand name PROGRAM) is a chitin synthetase inhibitor used for flea control. Chitin is a structural molecule in the exoskeleton of insects and their eggs. After administration, lufenuron sequesters in the fat and is slowly released into blood where it is ingested by a female flea. The drug then interferes with the production of chitin in the eggs, which leads to the eggs drying out after they are laid. Chitin is not found in mammalian tissues, but is a structural component of the fungal cell wall. Thus, this drug does not appear to affect mammalian enzymes and as a result has had an excellent safety record when used according to its product insert. The Israeli clinic systematically tested lufenuron in ringworm-infected cats and dogs. Over the 2-year period, they treated 201 cats and followed 23 on a daily basis. Most cats treated with lufenuron doses ranging from 51.2 to 266 mg/kg (23.1 to 120.9 mg/lb) cultured negative for ringworm in 8.3 days and began growing hair in 12 days. Four cats either cultured positive for ringworm or developed lesions again but responded well after a second treatment. None of the cats showed signs of toxicity. I had some concerns regarding the safety of this treatment because the article used between 5 and 20 times the recommended dose used to treat fleas, so I called Novartis' Customer Service line and spoke with a veterinarian. He reported that Novartis had no information on the use of lufenuron for ringworm and the article took the company by surprise. Because this is off-label use, he can not recommend the drug for this indication. However, Novartis is very excited about the article and its potential. We extensively discussed the safety data Novartis had performed for registration, and then I reviewed the safety data on the FDA website made possible through the Freedom of Information Act. Safety studies in both dogs and cats showed the drug had a wide margin of safety. Reproduction studies were performed in dogs and cats and lufenuron did not to cause toxicity or congenital defects at the doses tested. Because this is off-label use and one article does not prove efficacy or safety, I can not recommend lufenuron for the treatment of ringworm in cats. However, for those breeders determined to try it, I have some suggestions. Lufenuron is sold under the brand name PROGRAM. SENTINEL also contains lufenuron, but in addition contains milbemycin, which may be toxic when given at the overdoses suggested by the article. So do NOT use SENTINEL for ringworm. Lufenuron comes as a tablet, a suspension, or as an injectable. The injectable lasts 6 months, but can leave a lump (granuloma) at the injection site, and this may be a consideration for show cats. Novartis found that the tablet appears to have better efficacy than the suspension. I have not used PROGRAM, but understand that some cats do not like the taste of the suspension, so this may be a consideration when treating some cats. If you are going to try it to see if it works on a few cats, try to keep them separate from other ringworm-infected cats. Ringworm, like many parasitic organisms, can become drug resistant and it will do neither the breeder nor the rest of the cat fancy any good to develop Lufenuron resistant ringworm. Similarly, once the decision to treat a cattery is made, break down, bite the bullet, and treat the whole cattery and not just a few cats. Couple treatment of cats with physically cleaning the cattery to get rid of the spores so the cats are not reinfected. Getting rid of the problem will be cheaper in the long run than living with it and will be much less likely to generate resistant forms. Plan to treat once monthly for 2 to 3 months to make sure it is really gone. Yes, the article had good success after one treatment, but a cattery situation is very different than the average pet household. I'm getting a lot of questions about the safety of Program/lufenuron. Below the asterisks is the information from Novartis on the initial safety data done to gain approval of this drug for use in cats and dogs. Beyond this, additional studies have been performed in breeding cats (as well as dogs), again at levels far exceeding that used for flea or ringworm control. This drug has been in use for years without any reports of adverse events. But the most convincing body of supporting evidence is testing performed for the accpetance of an almost identical drug (the two drugs act exactly the same) for the control of the Gypsy Moth in area of human habitation. The data required for use in human areas is much more rigorous than that required for animal studies! Again, the same results were obtained: THEY JUST COULDN'T MAKE THIS DRUG TOXIC TO MAMMALS, NO MATTER HOW HARD THEY TRIED! Traditional tests of toxicity, such as the LD50 test, could not even be performed in rodents, because no matter how much of this stuff they crammed into the little critters (100X the dose per body weight), they just couldn't get rodents (even babies and pregnant ones) to look sideways at the researchers! This is EXTREMELY rare in the world of modern pharmaceuticals. Since the sole mechanism of this drug is to interfere with the synthesis and use of chitin, this makes a lot of sense, since CHITIN DOES NOT EXIST IN THE BODY OF MAMMAL! The safety of this drug is, to the satisfaction of my mind and that of the FDA, absolutely without question. For me, the main test remaining to be done is EFFICACY in large cattery environments, particularly those with Persian cats. ************* E-mail inserts: ************* From the Novartis web site: Safety PROGRAM has undergone numerous safety trials to test its margin of safety at various doses. In addition, it has been available world wide in over 30 countries with no adverse reactions found. The reason that PROGRAM is so safe, is that Lufenuron has no reaction in mammals. Mammals do not contain chitin, so the molecule is absorbed and excreted without ever having been metabolized. As such it is safe in all mammals. PROGRAM has been tested at hundreds of times the label dose with no difficulties in mammals. Lufenuron has no effect on breeding animals, nor does it affect conception rates or litter size in breeding pets. It crosses the milk barrier and the placental barrier with no harmful effects to the unborn cats and dogs. They are, in fact, protected from continuing the flea life cycle by Lufenuron passed on from the mother's milk. PROGRAM exhibits no drug interactions, therefore it has no ill effect on older pets, or pets with liver or renal problems, regardless of any medication those pets may be on for their medical condition. It does not affect diabetics or pets on antibiotics. There is no bio-accumulation so there is no chance of lufenuron "building up" in the pet and causing a problem in the long term. Normal pesticides and other prescription drugs have to be tested for an LD50. This is the recognized dose in animals where the drug turns toxic in 50% of laboratory rats. It was not possible to establish an LD50 for PROGRAM. Program, lufenuron, the *flea* product. Almost 300 cats infected with ringworm were put on Program and the ringworm went away in about two weeks. Not only that, these cats cultured negative just as quickly. That is important, because many cats get treated until the lesions go away... but remain "assymptomatic carriers" of the fungus after treatment with other antifungal drugs. Lufenuron works by interfering with the synthesis and deposition of chitin in the growing/developing flea. Well, interestingly enough, fungus also grows by using chitin to construct a cell wall (think of it as a miniature plant) and without chitin, the fungus dies. The dose used in the study appears to be a bit higher than that used for flea control. The 1-10# cat size of Program should be used to treat a 1-6# cat. The 11-20# size of Program should be used to treat a 7-11.5# cat. Cats 12# and over should be treated with 1.5 doses of the 11-20# size of Program. This cured ringworm in 95% of the cats, with 5% of the cats requiring a second dose a month later. Program is available in tablet form or as a liquid at a price (ordered on the Internet) of about $26-30 for six doses. It has been proven to be safe in pregnant queens, breeding males, and kittens over the age of six weeks. The six-month injectible form of Program is available only from vets and has NOT been proven to be safe in breeding cats (no studies performed). A wonderful summary of this prepared by one of our members, complete with the abstract of the journal article from the November 15, 2000 issue of the Journal of the American Veterinary Medical Association is available in the archives of our list. Visit http://www.yahoogroups.com to look through the list archives. It is message number 341. This is truly exciting news in the cat fancy! ******************* Because the dose amounts for dogs differ so much than for cats, using the largest dog size really doesn't save you much money. Heck, folks, this drug is only $4-6 a cat dosed ONLY once a month. Let's "splurge" and do it right, rather than playing Scrooge ;-) Here is the dosage for treating cats for fungus with Program: A cat that weighs 1-6 pounds needs to get one of the tablets in the package marked "for 1-10# cats". A cat that weighs 7-11.5 pounds needs to get one of the tablets in the package marked "for 11-20# cats". For cats weighing 11.5+ pounds, give them one and a half of the tablets marked "for 11-20# cats". DO NOT use the dog formulation or try to dose based on any dog dosage. Remove all food the night before. Give tablet, then serve large (preferably greasy and tasty) meal. The drug is only absorbed with food. For more information on using Program (lufenuron) to treat ringworm in cats, join the fanciershealth list at egroups, where this information was first presented to the cat fancy on the Internet, by sending an e-mail to: fanciershealth@yahoogroups.com. Information (including a summary of the original JAVMA article) can be found in the Messages archives and in the Files section, which can be accessed by going to: ****************** E-Mail (12-8-2000) A couple of things probably preclude the injectable form of Program/lufenuron from being used in cattery situations to treat ringworm. 1) The injectable form of this drug has not been tested in breeding animals. Although I have no reason to suspect it would cause problems in a population of breeding animals, safety in breeding populations *has* been demonstrated for the oral forms of this drug. 2) According to the information I have read from Novartis, the injectable form of this drug does not deposit in the fatty tissue of the cat as quickly as the oral form. Therefore, recovery times from infection would be expected to be much longer than with the oral drug. Could this injectible form of Program/lufenuron work as an effective every-six-months "vaccine" against ringworm in non-infected (cultured negative) cats? Possibly, although the "lead time" to protection looks like it would be about two to three weeks. This is the type of data that takes time (and financing!) to generate. ************* E-Mail 12-12-2000 Because PROGRAM is regulated and approved by the FDA*, it's held to the same high standards as human medicines. That means it's proven safe for dogs and cats. PROGRAM has no adverse effects on health, growth or reproduction. It can be used safely by pregnant and nursing animals, and puppies and kittens as young as six weeks. ****** March 5, 2001 email Here is some updated information, including a recommendation for a new dosage schedule, for using Program to treat ringworm in a cattery environment. This is from the researcher in Israel who published the study that first reported the efficacy of Program used in this way. He now recommends treating cats in catteries with 100mg/kg Program (45 mg per pound cat weight) given twice, two weeks apart and then using the normal flea control dosage once a month thereafter in high risk or ringworm endemic catteries. He again emphasizes that the dose must be given with food and that environmental control of spores is an important element of treating this disease. --Lorraine |
This page was last updated on: May 12, 2002
