Deramaxx Link	Rimadyl, Miracle Drug or Silent Serial Killer?
Senior Dogs Project

Experience with Rimadyl Over view: This is an anecdotal history of 40 days following administration of Rimadyl. There is a spreadsheet document associated with this report which attempts to provide some quantification to several parameters.It must be noted that some of these parameters may be deemed subjective, and the others are "close guesses" which do not include specific weighing of intake or elimination of either food or water However, having said that, I am a scientist with many years of background experience in research and development related to the medical field, and have been in and around medicine for over 20 years. I am relatively competent to estimate volumes and weights and to judge most health related factors. Subject: Bo, an adult male Basset hound, 11 years old Bo has been fed a consistent diet of steamed rice, cooked hamburger and green beans for most of his life. He has never shown any indications of digestive problems or kidney problems. He has developed a limp in the right rear leg, with associated muscle atrophy. He, like many Bassets, has some fatty tumors, one of which is in the groin near the right rear leg. This growth has existed for several years, the vet has examined it several times and we are quite certain it is benign, as it is not attached to the muscle mass. On 8/22/03 Dr. M. saw him and Rimadyl was prescribed for the limp. We were told he would be taking 50mg of Rimadyl daily, which was provided in the form of scored 100mg tablets to be broken and fed half daily. 14 tablets were provided. He received his first dose that same day, and 19 doses in total before we discontinued it (the first time.. we subsequently resumed the drug for two doses and immediately discontinued it again. His reaction to the drug was initially unremarkable. While it did little to help with his limp, I assumed that it was helping with the pain and the limp, which remained, was due to muscle atrophy and might eventually reduce if he began to use the leg again due to pain reduction. Time Line Friday,22-Aug Rimadyl prescribed, no warnings or cautions received, gave 2 doses as recommended Saturday,23-Aug through Tuesday,26-Aug 2 doses 50mg Rimadyl Wednesday,27-Aug 1 dose 50mg Rimadyl Bo left half of his dinner uneaten. Even though we had not received any cautions, because this particular dog has never had any appetite problems I thought perhaps the Rimadyl was upsetting his stomach so I opted to reduce the dosage of Rimadyl Thursday,28-Aug 1 dose 50mg Rimadyl Friday,29-Aug 1 dose 50mg Rimadyl Obvious severe abdominal distension Saturday,30-Aug 1 dose 50mg Rimadyl Monitored for signs of bloat Sunday,31-Aug 1 dose 50mg Rimadyl Gas w noxious odor, gave simethicone Monday,1-Sep 1 dose 50mg Rimadyl Concerned about water intake, obvious lethargy encouraged drinking Tuesday,2-Sep 1 dose 50mg Rimadyl Extremely lethargic Tried to spoon feed water, managed to get about 100-150 ml of water into him Wednesday,3-Sep 1 dose 50mg Rimadyl Abdominal distension still obvious, symptoms did not match food poisoning or bloat. Began to suspect the Rimadyl, as it was the only recent change. Searched net for Rimadyl COMPLICATION, no reports indicating problems with it. (should have searched for Rimadyl REACTION) Thursday,4-Sep 1 dose 50mg Rimadyl Carried out of house, tried to walk ~ 100 ft, small bm w blood, extremely vile odor with the bm. Still unsure what was causing his problems, very suspicious of Rimadyl but unable to prove it. Decided to discontinue it entirely even without proof. Friday,5-Sep No Rimadyl given Diarrheic BM in house, 5 blood clot masses ~ 5c.c. each accompanied by about 30 ml of brownish fluid of watery consistency. It was too late in the evening to make it to the vet. Bo was essentially comatose by 8pm, skin very cold, body rigid, obvious tenting of skin indicated severe dehydration in spite of my effort to monitor and maintain fluid intake. Spent the night monitoring him and trying to get fluids into him. 1st Crisis Intervention Saturday,6-Sep, No Rimadyl given Bo was limp and totally unresponsive. With help I managed to get him into the van with a makeshift litter. Arrived at vet shortly after they opened. Asked the vet to come outside for a preliminary check, partly because his condition was so bad and partly because I was concerned about the possibility of an infectious agent being spread to the other animals in the office. We discussed the possibility of E-Coli infection, I gave the vet a quick synopsis of the history, and a fecal sample was taken to check for Parvo before transporting him into the clinic. When the parvo test was negative, we moved him inside and weighed him, found that he had lost over six pounds since the last visit (which was a long time ago). Temperature was normal. Blood was drawn for a CBC. Clotting was significantly slower than normal. At this time there were four people in the room, Terry and Anita Wright, a senior Vet who works in that clinic on Saturdays only, and a young lady in scrubs with no ID tag. I (Terry) told the senior vet that all of these symptoms had started after taking Rimadyl and asked her if there was ANY possibility of a reaction to the meds being involved. The younger woman looked at the older Vet and said "There is a known reaction to...." at which point the older vet clearly and obviously shut her up, gave her a dirty look and shook her head. She then turned to us and said that there was no drug reaction involved, she had seen this many times before and it was definitely a fast onset of a Hematic or Hepatic Carcinoma, possibly originating from a pre-existing tumor on the liver or the spleen. She assured us that there was no doubt in her mind about the diagnosis, and the CBC would prove it out. She gave us the phone numbers of two vets who do "farm visits" and suggested we call them the next day and have him put to sleep. 250 ml ringers lactate Subcutaneous, SubC Antibiotic, SubC Morphine were administered. Endosorb #10 was prescribed. We left the Vet and tried to contact the people who had been recommended for euthanasia. Fortunately, they did not answer the phone. If they had, he would have been put down that evening or the next day. NOTE: I believe that the vet who diagnosed cancer had adequate reason to do so, especially considering the odor Bo had which was similar to but slightly different from the odor associated with many cancer processes. It should be pointed out that it is entirely possible that she was not trying to conceal any information about Rimadyl reactions, but was instead just trying to prevent the assistant from raising false hopes in what she expected to be an emotionally trying experience. Sunday,7-Sep, No Rimadyl given When Bo came out of the morphine effects, he showed a phenomenal improvement. Given that the timeline for this improvement was only 14 hours, I attributed it to the ringers lactate. Re-hydration and a boost in blood sugar would account for the improvement in that time frame, but the odd part is that the vile odor coming from his mouth and any gas was completely gone. I could not see any way that the type of cancer process the vet had diagnosed could possibly be involved, simply because there was no way that the odor from that type of process would go completely away due to a ringers infusion and antibiotics I decided that, although it was still possible there was a cancerous process involved, it did not look likely. I made the decision to not have him put down until I understood exactly what had happened. The Vet who had diagnosed him called at 10am as she had promised, to tell us the results of the CBC. He had elevated liver enzymes, but not elevated enough to indicated hepatic cancer. He also had elevated white blood cell count. I was still partly asleep, so I don't recall the exact figures for the CBC. Monday,8-Sep No Rimadyl given Called vet for the rest of the CBC panel, which had not been completed on Sunday. Vet asked about his condition, I outlined his remarkably improved condition and made note of the fact that the odor had disappeared. At my request, vet provided Clavamox #14 on the premise that there was an infectious agent involved in the bowels. 14 tablets of Clavamox were given over the next 14 days. Tuesday,9-Sep through Friday,12-Sep No Rimadyl given Continued improvement, still urinating in house Saturday,13-Sep No Rimadyl given Regained bladder control Sunday,14-Sep through Friday,19-Sep No Rimadyl given Excellent appetite, regaining lost weight Note: At this time we were confident that the diagnosis of rapid onset terminal cancer was not correct, as his condition was remarkably good considering what he had been through. We did not have a viable explanation for what had happened, especially since the vet had assured us that there was no drug reaction involved. We tentatively decided that perhaps he had some form of food poisoning which had gone undetected (I understand that e-coli infections do not culture if it is too far into the progress of the disease). Even though we had no proof of what had happened, we took the vet at her word that the Rimadyl could not be at fault, so we decided to resume the Rimadyl on a reduced dose while watching carefully for any symptoms of gastric distress Saturday,20-Sep 1 dose 50mg Rimadyl Resumed Rimadyl Sunday,21-Sep 1 dose 50mg Rimadyl did not finish his meal Monday,22-Sep No Rimadyl given Obvious distress, discontinued Rimadyl because even though the vet denied any possible connection, it seemed obvious that his illness followed administration of Rimadyl Tuesday,23-Sep No Rimadyl given Abdominal distension Wednesday,24-Sep No Rimadyl given Found information on Rimadyl REACTION on net. Bo seemed viable and I hoped that since he had a much smaller dose this time he would recover unassisted, except for watching his water intake. Thursday,25-Sep No Rimadyl given Substantial vomiting undigested food 6pm, too late to go to the vet, essentially comatose 8pm Second Emergency Intervention Friday,26-Sep No Rimadyl given Coma deepened, administered activated carbon 3am, seen by vet when they opened at 9am Bo was barely conscious when we went in, he staggered over to the scales to weigh himself of his own volition and then went directly into an examination room On this visit Dr. X, the owner of the clinic, saw us. I told her the story about our first visit, and noted that the assistant had tried to warn us about Rimadyl and the older vet had silenced her and denied that it could be related. Dr. X listened to all this patiently and politely. I expressed extreme displeasure that this had been done, told her it was very wrong and that had we been told about the possible side effects when we asked, we would never have administered it again and would not be in the current crisis situation. I showed her printouts from the internet and proceeded to question her about the relationship between cox1 inhibition and the production of mucous, and queried her on the subjects of g.i. necrosis and secondary infections and g.i. stasis and whether antibiotics were an appropriate addition to the treatment. At this point Dr. Sholes said I was asking questions she did not know the answer to, and I asked her to please contact Pfizer for more information. They apparently referred her to the FDA Vet. Administered Ringers SubC, no antibiotic, endosorb #10. He reacted positively to the Ringers Lactate, but did not rally like he had on the first emergency intervention. Saturday,27-Sep No Rimadyl given Not responding like he did the first time, still very depressed in most vital indications Sunday,28-Sep No Rimadyl given By evening Bo was unresponsive, two people were propping his head up to squirt water and honey into his mouth and had to massage his throat to get him to swallow. At this time it becomes questionable as to whether Bo is going to survive the second reaction. It has been only two days since the ringers infusion and he has gone back down to the bottom, essentially comatose. When he was conscious he appeared to be virtually blind. He has reacted well to the ringers infusion, but could not hold his own once the absorption was complete. Observation: On the second intervention we did not introduce antibiotics or morphine. Also, on the first intervention I was giving him yogurt and honey to help with the GI problems with antibiotics. Because he was not on antibiotics this time I did not give him the Yogurt. Third Emergency Intervention Monday,29-Sep No Rimadyl given Did not see the vet, LVT administered 250 ml Ringers at my insistence. They insisted that I should take him to a full time emergency care facility. I asked them if they were trying to wash their hands of the problem, and they said no, they were simply saying that was what it would take to get him through. I pointed out that we knew what the problem was, he had responded to the first emergency intervention when both fluids and antibiotics were administered, and that he had not had antibiotics with the second intervention. Asked them to give him one more Ringers lactate infusion, and told them if they would not do it I would be forced to take him home, make up Ringers lactate solution and administer it myself Tried to discuss the obvious problem of G.I. stasis, which has gone untreated on each visit. I was told by the LVT that "you can't give dogs enemas, if you do the same thing to them that you do to people they will die". Decided I was pretty much on my own from here on out. Considered a 200 ml hyper molar Epsom salt enema to soften his stool as he had not had a bowel movement for 8 days, decided against it on the basis that it would draw fluids from his interstitial spaces and he was on the verge of dehydration already due to the renal dysfunction Chose to use deep abdominal massage to try to stimulate bowel motility. This was successful, bowel sounds returned after about ten minutes of massage, and he had two small bowel movements. Feeding yogurt and honey, baby rice pablum with baby formula and honey. Prior to the introduction of yogurt he had a sour smell, that disappeared within a few hours of his first feeding of yogurt. Tuesday,30-Sep No Rimadyl given Remarkable improvement. Bo is up, alert and ambulatory 38 hours after the administration of the Ringers solution. His appetite has returned and he has had a soft bowel movement, not diarrheic. Fluid intake is good, urine output is good and some bladder control is returning if he is reminded to not go in the house. He is alert and cheerful, but his sight is clearly diminished. He is not totally blind, can detect large objects of clearly different brightness levels and motion of small objects, but has difficulty seeing where he is going. Wednesday, 1-Oct Early morning, 3:20 am. Bo has been apparently stable for 42 hours since the ringers infusion, he ate very well yesterday. He was up and ambulatory for most of the day yesterday and consumed about 750ml of water throughout the day. He goes to his water bowl about every two hours and has managed to make it outside to urinate three times during the last 24 hours. Of course the ringers was absorbed at least 30 hours ago and he has not shown any decline since then, to the contrary he seems to be showing steady improvement. He took part of a tuna sandwich, his first solid food in many days. He just went past me on his way to the back porch and managed to wag his tail slightly as he went by. Although there is obvious reduced renal capacity and visual problems, it now looks as though he has hopes of an eventual recovery, or at least partial recovery ADDENDUM: Bo died on the 29th of October. I believe that if we had known about the reaction before the second dosing, he would have recovered from the first reaction. AUTOIMMUNE mediated secondary disorders are known to occur in some Rimadyl reactions. In this scenario the dog is basically allergic to everything, including food and even their own body. Auto-immune mediated hemolytic anemia causes the body to destroy it's own blood cells. Look into the possibility of auto-immunity if your pet has had a reaction. It can be treated with prednisone and antibiotics. Observations a) Although it is my understanding that the FDA has required Pfizer to include warnings in their distribution of Rimadyl, it appears by anecdotal evidence on the internet and is certainly the case in my personal experience that Rimadyl is typically delivered to the end consumer in bottles with no cautionary information provided in writing or in person b) The vets who I had personal contact with seem to feel the only way to diagnose an adverse reaction is elevated liver enzymes, even though the Pfizer documentation states that the first indicator in the majority of cases is the loss of appetite. Otherwise well informed vets still seem to believe that only Labs have reactions to this drug. c) Most vets try to treat an adverse reaction by focusing on renal or hepatic failure. While this is immediately life threatening, there seems to be another factor which is being ignored. I refer to G.I. stasis and the resulting septic bowel condition which followed. (I distinguish sepsis in the bowel contents from the common usage of septic i.e. blood related) d) Due to possible necrosis or ulceration of the bowel, differentiating between G.I. stasis due to COX1 inhibition and the resultant reduction of mucous production as opposed to peritoneal sepsis resulting from a bowel perforation may be difficult e) The decision of whether or how to treat G.I. stasis is difficult. In the case of Bo, the fact that he had not had a bowel movement for 8 days was in my mind enough evidence to indicate that some intervention was required, if for no other reason than to reduce stress on the liver which is associated with G.I. stasis. However, due to the repeated severe dehydration there was also reason to assume that he might have a hard dried mass of feces located in the bowels, in which case the administration of Propulsid would probably be ineffectual and might exacerbate bowel ulceration and create perforations. I chose abdominal massage to stimulate bowel motility in spite of possible hemorrhage complications. f) When intervention was just Ringers Lactate he did not respond well. When the intervention included antibiotics and a course of Yogurt and honey he responded much better. Obviously it could be argued that a high lactose content feed would not be correct in his situation, and a better course of action might have been the introduction of Lactobacillus Acidophilus. g) I personally believe that the incidence of death related to Rimadyl is severely under reported. Among a small group of my wife's friends, one of 13 had a dog who had died after taking Rimadyl, and the vet wrote it off to old age even though the symptoms were identical to the warning symptoms of a Rimadyl reaction. Coincidence? Perhaps. h) If the primary function of Rimadyl is to provide comfort, and the side effects deadly, I question whether it's place on the market is justified, or whether it should be withdrawn and eventually replaced with a COX2 selective inhibitor. Pfizer argues that it in fact is filling a life saving function, because many dogs would have been put down if they had not recieved Rimadyl. I) The cautionary information that is being delivered is inadequate. It is the responsibility of Pfizer to package the medication in a form which ensures that the warnings are received by the pet owner, without the onus of delivery of warnings being placed on the Vet, to make them clear and obvious, not in fine print at the bottom of a package insert that nobody will ever read. This information is provided in the hope that it may contribute in some small way to the body of information re: current practices in the distribution of Rimadyl or the diagnosis and treatment of Rimadyl related adverse reactions. It is in no way to be construed as a criticism of the animal health practitioners involved. I wish to make it clear that the Veterinary practice involved has served us and our pets faithfully for many years and I do believe they hold themselves to very high standards of performance and do their very best to provide excellent service at all times I can not overstate or over emphasize the fact that all of the people in this particular practice have always been, in my personal experience, excellent care providers and have always functioned at a high level of competence