Medications - Side Effects, Reactions and Intolerance

by
,

United States Pharmacopeia's Veterinary Practitioner's Reporting Program

When an adverse reaction to a medication occurs it is best to report it to the drug manufacturer and the FDA (medications) or USDA (vaccines). To make reporting easier, the United States Pharmacopeia has established a central reporting service. If a veterinary practitioner reports a drug reaction, the USP-VPRP reports to the drug manufacturer, the FDA or USDA and the American Veterinary Medical Association with one phone call to 800-487-7776. The web site for this organization is www.usp.org.

Warning: Rimadyl will cause liver damage in some dogs. There have been some deaths in dogs with this reaction. This effects 0.02% of dogs and 70% of those are geriatric. More information can be found by consulting the Small Animal Clinics of Pharmacology's latest edition.. This is a remarkable drug for many dogs. Blood work however should be done prior to beginning treatment and one or two weeks into treatment to monitor liver values.

When Good Medications Do Bad Things

There are a number of medications which are very helpful for most pets but which make a few pets ill or even cause death in extreme instances. Using these medications is often necessary in spite of the possible side effects, especially when there are no other medications for a condition. In other cases, the beneficial effects may justify some risk taking even with serious potential consequences. Being aware of the potential for danger can help to prevent problems or to allow a pet owner or veterinarian to catch them early enough to reverse problems induced by the medications.

The ultimate example of a medication that has harmful side effects but is essential for life, at least in diabetic pets, is insulin. Even a small overdosage can have serious consequences and strict monitoring of the medication is essential. Despite that, there are few calls for it to be removed from the market. Why? Because the benefit clearly outweighs the risk. Where there is no other choice a huge risk is worth taking. For most other medications the risk to benefit picture isn't quite so clear.

Antibiotics are often harmful to patients. Sulfa/trimethoprim (Bactrim Rx, Tribrissen Rx, Ditrim Rx, Sulfatrim Rx, SMZ-TMP, other generic names) is an antibiotic that can cause joint inflammation in Dobermans and is implicated in immune mediated thrombocytopenia (ITP) in many dog breeds. Thrombocytes are the platelets in the blood, responsible for blood clotting. Thrombocytopenia is a decrease in the number of platelets. Obviously, if they get low enough there is a great risk to the pet. This antibiotic is still widely prescribed, though. It has a broad spectrum of action, it is inexpensive and most of the time it doesn't cause problems. The ITP is almost always reversible if the medication is withdrawn. Remembering that this antibiotic can cause this problem may help to save your pet's life, though. Penicillins can cause severe allergic reactions, even causing sudden death in a few patients. Many antibiotics cause diarrhea. Chloramphenicol has been associated with aplastic anemia in several species. Enrofloxacin (Baytril Rx) and tetracycline antibiotics should not be given to growing pets unless absolutely necessary due to the potential for problems with absorption of the medications into bone and/or teeth, causing defects. Amikacin and gentamicin are aminoglycoside antibiotics. This group of antibiotics can cause deafness and kidney failure. Use of antibiotics should be restricted to conditions which are likely to respond to appropriate antibiotic therapy since these are not harmless medications. When they are necessary it is obvious that some risk of use is justified.

Heartworm preventatives often come under scrutiny by pet owners when a pet suddenly dies or develops an illness that may be associated with drug reactions and the only medication the dog is taking is the heartworm prevention medication. Filaribits Plus (Rx) can cause an idiosyncratic (we don't know why it happens) liver reaction in a small number of dogs. Dobermans seem to react more commonly to this medication than other breeds, too. There are alternative heartworm preventatives, so it is possible to use another medication if reactions occur. The newer monthly heartworm preventatives are often suspected of being the cause of the problem when immune mediated hemolytic anemia occurs in dogs but there is no proven connection that I am aware of. About half the cases of immune mediated hemolytic anemia (IMHA) occur for no apparent reason but the most commonly identified reason is probably reaction to an administered medication. Therefore, people are suspicious of the monthly heartworm preventatives when IMHA develops in their pet. Heartworm is a devastating disease and if you live in an area in which it occurs it is essential to use the best medications to prevent it. For most people this is one of the monthly pills (Heartgard Rx, Interceptor Rx and ProHeart Rx). Don't risk heartworm disease in your pet because you run across suggestions of danger on newslists or from other sources.

What about situations in which there is very little risk of death from a condition but there is a great deal of suffering associated with it, or when a medication is used to lessen the stress and anxiety of surgery or examination procedures?

The newest example of a medication with peculiar side effects in a small number of pets is carprofen (Rimadyl Rx). This medication is very effective at controlling pain and allowing dogs with arthritis to move comfortably again. It is safer than most medications in its class for use in dogs since it is much less likely to cause ulcers than other non-steroidal anti-inflammatory (NSAID) medications approved for use in dogs. However, it can cause toxic liver reactions in a few dogs. At the present time the majority of dogs affected in this manner have been Labrador retrievers but other breeds have been affected. There are a small number of confirmed cases of problems and a large number of dogs on this medication so the problem seems to be rare but definitely real. If your dog is on Rimadyl and you see any signs of inappetance, lethargy, vomiting or ill health in general, please contact your vet. Checking to see if there is evidence of liver damage would be a very good idea if any reaction to this medication occurs and it may not be a bad idea to just routinely run tests for liver enzymes a few days to a few weeks after starting Rimadyl. In any case, don't simply assume that whatever is wrong will get better in a few days and keep giving the medication. Stop, call your vet and inform him or her of the problem. Rimadyl is a very good medication and I have used it in one of my own dogs. Just be aware of the potential for problems.

Acepromazine is frequently used by veterinarians to lessen the stress and anxiety associated with anesthesia and for other beneficial effects in anesthetized patients. There are a few reports of serious side effects in boxers. It can also lower the seizure threshold and should not be used in pets known to have seizure disorders. Make sure that the vet or the veterinary assistant notes on the record or admission form that your pet suffers from seizures before a surgical procedure, just in case your vet uses this medication as a standard part of the anesthesia protocol.

There are other peculiar drug reactions and other medications with side effects. We are going to cover the side effects of corticosteroids later in this newsletter and hope to continue to keep you informed of potential problems with medications in future issues. Good medications must still be used carefully.

Mike Richards, DVM

Medications that are linked to kidney failure

Question: Dr Richards,

You said in an earlier post than antibiotics and non-steroidal anti-inflammatory medications used for arthiritis probably cause kidney failure. Would you have available those medications that could cause kidney failure?

Tony A.

Answer: Tony-

I don't have a complete list of medications that have been linked to kidney failure but I can give you at least a partial list.

Among antibiotics, tetracycline at high dosages, gentamicin, amikacin and most sulfonamides and sulfa-trimethoprim combination antibiotics can cause kidney failure in some patients. Of these, the two aminoglycosides (amikacin and gentamicin) are the most toxic to the kidneys but are only available as injections so are rarely dispensed, although they are used in severe infections in hospitalized animals not too infrequently.

The entire class of non-steroidal anti-inflammatory medications can cause kidney damage due to constriction of blood vessels in the kidney. This would include aspirin, carprofen (Rimadyl Rx), etodolac (Etogesic Rx), phenylbutazone (Butazolidin Rx) and others.

I don't think that any of these medications are highly likely to cause a problem in any individual patient, with the possible exception of the aminoglycosides, which must be used very carefully whenever they are used. However, when kidney failure signs occur and any of these medications are being used it is prudent to evaluate the necessity of the use and to consider adjusting the dosage or changing medications, if possible.

There are other medications that are linked to kidney damage to some degree. These include thiatarsamide (old heartworm treatment medication), chemotherapy agents such as cisplatin, amphotercin-B (antifungal agent), enalapril (Enacard, Rx; used for heart failure and sometimes to treat kidney disease because of beneficial effects it has in most patients), methoxyflurane (anesthetic) and iodinated contrast dyes used to help improve the ability to see problems on X-rays. All of these medications have uses that often make taking a small risk of kidney failure reasonable -- but again, when problems occur they have to be considered as possible causes.

Mike Richards, DVM 8/13/2001

Ursodiol side effects

Question: Hello Dr. Mike, I've written you in the past about my (now) 13-yr-old neutered male Min. Schnauzer, Ruckus, who has chronic liver inflammation and also experienced a near-death toxic reaction to zinc supplements last summer. We have consistently ruled out Cushing's and tumors and cancer, but he continued to have sky high Alk Phos, ALT, AST, etc levels and accompanying anemia. He has now been on Ursodiol for a bit over two months and for the first time in 16 months, his liver enzymes are all either normal or almost so. I'm hoping it's a permanent condition, and not one of the dozens of ups and downs we've had this past year. ANYHOW, the reason I'm writing is to see if you know of side effects from Ursodiol. Since shortly after starting on this drug, Ruckus exhibits his perky, upbeat personality ONLY if I've actively engaged him into interaction or activity. Otherwise, he stands with his head lowered, almost as if in a stupor or exhausted. He also has become cranky, which is definitely not part of his typical temperament. His dosage is 80MG, once/day. He weighs about 15 pounds. Are these typical side effects with this drug? Do you suggest a lower dosage? My local vet, who is a good guy, doesn't have Internet access, and neither calls to other vets nor his pharmacology book don't indicate these types of side effects, so he's somewhat at a dead end as far as researching the drug much further. Thanks for any insight you can provide to this. Liz

Answer: Liz-

I have a very new pharmacology text which lists only occasional vomiting and diarrhea as known side effects of ursodiol (Boothe, "Small Animal Clinical Pharmacology and Therapeutics", 2001) I have heard of a few cases of behavioral symptoms occurring in dogs but these have been nervousness or pacing, possibly associated with nausea or gastrointestinal discomfort or possibly an unusual direct reaction to the medication. I do think individual reactions to medications can occur that are far from the "normal" side effects in a few patients and so I would not want to rule out a reaction to ursodiol as the cause of the depressed attitude. However, since it would be an unusual reaction it would be a good idea to look for other possible problems.

The recommended dosage of ursodiol is usually 5 to 15mg/kg per day. Some vets recommend splitting this total dosage into two smaller doses and giving the medication twice a day. A 15 lb. dog weighs about 7kg, so the dosage recommendation would be 35 to 105mg per day, which puts the current dose in the middle of the range, which is usually a good place to be. It might help to split the dosage although we have always used ursodiol once daily in our practice so I don't actually have any experience to suggest that is the case.

It sounds like you have been looking for other things that might be causing these signs and doing a good job of it, but it would still be a good idea to re-evaluate when if any new symptoms appear that might help point the way to a problem. The only odd things I can think of that might cause this posture are potassium deficiency and thiamine deficiency. I can't remember seeing potassium deficiency in a dog but it happens in cats and the posture is typical, as well as apathy in affected cats. I can't remember seeing a case of thiamine deficiency except in hand raised baby birds but one of the reported symptoms is ventral flexion of the neck which is what I think you are describing. I guess that cervical disc disease might also cause this symptom but usually that is painful when the neck is moved.

Just thinking "out loud" about the possible causes of the posture. These are probably not problems that are present but they were the things I could think of.

Mike Richards, DVM 6/18/2001

Tylosin and Tylanol side effects with IBD

Question: Dear Dr. Mike

My dog appears to be suffering from ulcerative colitis...induced by a NSAID. My dog is very sensitive to any NSAID including ASA at any dose...4-5 days and stools become loose. She is presently taking Sucralfate (4 grams/day) along with Pepsid (2x/day).

Based on the fact that she is sensitve to salicylates, what treatment would you recommend for her. My vet Rx Flagyl and Tylosin. My concern is any side effects that may be related to these. She recently got over a bout of nystagmus and is not to steady on her feet. I am feeding her white rice and poached chicken at this time. At the time of this writing however, she has not eatten anything today and seems to have no appetite.

Could you also tell me the risk factor in giving a dog of her age 325mg of Tylenol/day. Thank you. Jim

Answer: Jim-

Tylosin (Tylan Rx) seems to be very safe in dogs. It causes problems in ruminants and horses sometimes, but that seems to be related to the fact that they are herbivores with a high dependence on bacterially aided digestion. Tylosin can interfere with lab testing for ALT and AST, so if there are elevations in liver enzymes after starting it there is a possibility it is a lab error produced by the antibiotic. I could not find any reports of toxicity with long term use and tylosin appears to be pretty safe even when overdosed (short term).

Oops, misread you last sentence. But since I looked up tylosin, I'm sending that information, anyway!

On to acetaminophen (Tylenol Rx). The first thing to mention here is that acetaminophen is very toxic for cats and it is important to make sure that cats aren't exposed by eating a treat with the capsule in it or something like that. The dosage of acetaminophen in dogs is supposed to be around 10mg to 15mg/kg twice a day, but I am not sure how that figure was arrived at since I haven't found any references that I have access to that discuss how the dosage was arrived at. I did find one report that suggests that the toxic dosage in dogs is around 150mg/kg, which would be a pretty good safety margin as long as the proper dosage is used. It would be possible for a small dog to get acetaminophen toxicity if it got into a bottle of Tylenol, though. In overdosage situations dogs are more likely to develop liver damage than humans from acetaminophen. I am not sure how many dogs develop this problem with ordinary dosages used over a long time but we have not seen this problem, yet, and we use a lot of acetaminophen/hydrocodone (Vicodin Rx) for chronic pain in dogs.

I don't think that acetaminophen would be helpful for inflammatory bowel disease (IBD), though. It doesn't have much, if any, anti-inflammatory affect. It is primarily an analgesic and pain isn't all that big a factor in IBD.

I'd want to try a food trial with a hypoallergenic diet like Hill's z/d or Purinas HA and if that didn't help I'd probably go to prednisone or other immunosuppressive medications in a dog that I wasn't comfortable using sulfasalazine (Azulfidine Rx) or metronidazole (Flagyl Rx) for. Your vet may have better ideas and if you have pretty good control of the situation doing what you are already doing, it may be best to leave well enough alone, even if it isn't perfect.

Good luck with this.

Mike Richards, DVM 2/14/2001

Medication side effects and IBD

Question: Hello You have a wonderful site. I have found it to be very helpful. My dog has had bloody diarhea since Oct. Tried alot of different things finally got referred for endoscopy. The vet found ulerations in his stomach and esophagus. The biospy also showed severe irritable bowel disease. She presribed 10mg predizone (2 5mg tabs bid), prilosec 10 mg 1x daily, tylan 1/16 tsp. bid.

He started to respond well after a couple of days of force feeding and pedialyte. By the end of a week he was eating a can of low residue and a small can of a high calorie food a week. She wanted him to have 3 days of panacur when he was eating well so I started that on Wed. evening and on Thursday am he was back to being force fed and he was very weak, (legs go out from under him). He also ran out of the prilosec on Monday. Could the panacur have done this, I can not find anything written on this medication except that it is for certain types of worms. He finished the panacur on Friday and he is back on the prilosec today (Sunday). He continues to be extremely weak with no appetite. I feel like we are starting all over again. He is also supposed to be taking azulfadine and leukeran but I have not started them yet as they come with there own side effects. He is also taking flagyl 125mg bid.

My dog is about 11 yrs old (pound dog) and I have had him for 10 yrs. He is supposed to weigh about 24 lbs and he now weighs about 17lbs. The vet does not feel that it is just old age as everything else seems fine.

Please help. CJ

Answer: CJ-

Fenbendazole (Panacur Rx), is considered to be one of the safer medications in veterinary medicine. It is usually non-toxic even at very high doses. There is a small chance of an anaphylactic shock reaction when using Panacur in heavily parasitized animals, but not because of the Panacur itself. The death of large numbers of parasites at once, due to the medication, can lead to this problem. It is very unlikely that would have been the case for your dog, because he is old enough that natural resistance should be helping to keep parasite numbers down, even if some are present.

Metronidazole (Flagyl Rx) will cause neurologic signs in some dogs and cats and I would be more suspicious of this medication, if the symptoms are due to a medication. There is also the possibility in older patients that there is more than one problem causing symptoms, so having inflammatory bowel disease (IBD) and a neurologic disorder or neuromuscular disorder at the same time is possible.

Tylosin (Tylan Rx) tastes pretty bad and we have a number of patients who simply refuse to eat when this medication is being administered, whether it is mixed with their food or given separately. We still use it sometimes, because this doesn't happen in all patients and because it is nice to have a backup medication when sulfasalazine (Azulfidine Rx) doesn't work, but it wouldn't surprise me if it contributed to the poor appetite.

I am not familiar with the use of chlorambucil (Leukeran Rx) for inflammatory bowel disease but it is used for other immune mediated disorders. It has significant side effects in some patients and I would not be in a hurry to use it, especially if you are seeing some progress using other medications, but your vet may be very familiar with its use and more comfortable with it based on experience.

Your vet has done a good work up and is using standard medications for the problems that exist. Sometimes, when this is the case and there still isn't a good response to therapy it can be helpful to get an opinion from an internal medicine specialist. Your vet can refer you to a specialist in your area, if the problems continue.

I hope that there has been some improvement by now.

Mike Richards, DVM 1/23/2001

Allergic reaction to metronidazole in Dobie

Q: Hi Dr. Mike:&nbspMy 5 year old Doberman had a severe allergic reaction (generalized giant hives and swelling of his muzzle) while being treated for giardia diarrhea with metronidazole and imodium. I found no sign of an insect sting so the presumptive diagnosis was a reaction to one of the medications. He is doing fine with an antihistamine (benadryl). I am so worried now that we may forever be restricted from using these very important drugs.

Questions: -is there a reliable way of deciding which of these drugs is responsible (blood tests, skin tests)? -I found that there are other drugs that can be used in place of metronidazole but what can be used in place of imodium? Both imodium and lomotil are piperidine opioids (found it on the internet) so is cross-allergy likely? - Are all opioid pain relievers and anesthetic agents to be avoided? My dog is von Willebrands affected so I never use peptobismol.

I am driving myself noodles anticipating the bleakest of possibilities. I will be grateful for any help you can offer.

Regina

A: Regina-

The only way that I know of to test to see which medication your Doberman is sensitive to would be to administer one of them and see what happens. If there was no reaction then the other medication would be the most likely culprit or it may take the combination of medications to cause the observed effect. Personally, unless I had to use one or the other of these medications I would be reluctant to test for a reaction in this manner.

I would be most suspicious of the metronidazole with this reaction, only because we have seen some odd adverse reactions to metronidazole and I can't remember a reaction to loperamide (Immodium AD (TM)). If loperamide is the culprit then diphenoxylate (Lomotil Rx) is very likely to cause reactions as well, as you have surmised.

It would be inconvenient not to be able to use loperamide or diphenoxylate but I can't think of a situation in which not having them would be life-threatening. It is possible to manage patients with diarrhea without using medications to control the diarrhea itself. Most of the time if the underlying cause of the diarrhea is controlled, hydration is maintained and there is good nursing care diarrhea will resolve whether medications are used to stop it or not.

Metronidazole is useful and it would be inconvenient not to be able to use it but everything it does can be accomplished with other medications. Fenbendazole (Panacur Rx) is supposed to be capable of killing giardia and many vets think that is safer to use than metronidazole.

I don't see any reason to avoid most anesthetics even if the reaction is to the loperamide. It would just be a good idea to avoid opiod narcotics as pre-medications or as pain relief medications before or after surgery. There are lots of possible anesthetic combinations and pain relief formulations available that do not rely on administration of opiods.

Hope this helps some. For right now, it seems logical to treat the giardia with alternative medications and hope that it isn't necessary to use either metronidazole or loperamide in the future. If the time comes when one or the other really seems necessary, remind your vet of the reaction and makes sure that a plan is in place to deal with any severe allergic reactions that may occur.

Mike Richards, DVM

Intolerance to Lysodren in dog with hyperadrenocorticism.

Q: Dear Dr. Mike, I am a Vetinfo Digest new subscriber. My dog Sable, age 13-1/2 is a chocolate lab who was diagnosed about three months ago with Cushings Disease, the pituitary variety. I believe she has been ill for over 6 months. She was started on Lysodren 500 mg bid and 20 mg prednisone by our regular vet and did this for 7 days. Then we went to see the "specialist" who changed the dose to 500 mg tid and no prednisone. She was to do this for 5 days. On Day 4 she began showing a lot of CNS troubles. It began with shakiness, progressed to stumbling and by the next day she was unable to stand. At this point I gave her 20mg of prednisone and took her to emergency a few hours later. Her electrolytes were normal and they did the ACTH stim test. They sent us home with 10 mg of prednisone to be given once daily until we got the results. Four days later we heard that the ACTH test result was 3 and she should be taken off the Prednisone and should take Lysodren 750 mg 2 times a week. So the next day she got the 750 mg in the evening(Thursday). Friday night she slept thru the whole night, which she never does. And I woke her up on Saturday am at 5:00. She could barely hold up her head. She could not move. I finally got her to drink and eat something and gave her 10 mg Prednisone. A few hours later she could stand with help and could walk but was very ataxic. I did not take her in to the Dr. Instead I gave her 5 mg of pred at night and did the same on Sunday-10mg in thea.m. and 5 mg. at night. ON Monday I spoke with the DR. HE said, to stop the pred and just go to 500 mg of Lysodren in divided doses two times a week.after letting her rest the whole week. So on the next Monday (8-2) I gave her 250 mg Lysodren in the a.m. By afternoon she seemed a little wobbley so I only gave her 1/4 of the pill. Tuesday 2:30 a.m. she is stumbling around again so I give her 10 mg of pred and by 5:30 a.m. she is better. I talk to the Vet. He now says that she cannot tolerate the Lysodren at all and he sees this as a reaction to the medication . He recommends that she not take it at all. He is not a promotor of Ketoconazole or Anapryl. So he says we have no hope. Are CNS side effects common with Lysodren and is giving Prednisone good to help combat this during the period when the dog is taking the LYsodren..Is this safe to do? She seems to be better when she takes the Pred after the LYsodren.. IS there any danger in continuing to do the Lysodren, maybe at an even lower dose? I would be willing to put up with a day of Sable stumbling around if this was going to help her problem. Incidentely, she is an otherwise healthy dog--no heart or kidney problems. She does have bad knees from arthritis and two blown cruciates and laryngeal paralysis. I know she is old but I just can't give up so quickly. Thankyou for your time Jennifer

A: Jennifer-

Sable may be having one of several problems.

A small group of dogs who are put on Lysodren for pituitary dependent hyperadrenocorticism appear to have a rapid growth of the pituitary tumors. The theory for this occurrence is that the sudden suppression of adrenal hormone leads to a rise in ACTH levels, which over-stimulates the pituitary gland and leads to a rapid growth in tumor size. I do not know why some dogs react in this manner and others do not. It is possible that it is just coincidence that mitotane treatment is started at about the time the tumor starts to grow rapidly. The growth of the tumor leads to neurologic signs.

In other dogs, mitotane directly causes neurologic signs as a form of drug reaction. In these dogs, clinical signs of neurologic disease should disappear within a day or so after the administration of the mitotane. Usually these signs develop during the maintenance period of the medication and splitting the dose up helps. This is what the specialist recommended based on your note, but it didn't work. It is possible to split the dose up even more and give it three times a week and in some dogs, a lower dose will still provide reasonable control of the hyperadrenocorticism.

I don't understand the reluctance to try selegiline (Anipryl Rx), ketaconazole (Nizoral Rx) or even radiation treatment or surgery. In my opinion, the choice of whether or not to pursue these options is yours, not the vet's. If he is unwilling to pursue them he should be willing to refer you to someone who will. It is true that the success rate for these four options is probably less than that of mitotane. But each of these treatments has clinical studies that support their effectiveness in some patients. Since mitotane appears to be difficult for Sable to take, what harm is there in checking out the other options? I think this is particularly true for selegiline, since it is unlikely to be harmful, even if it isn't successful. Its cost can be difficult for some owners to handle but that is again your decision, not your vets.

I am a little confused by the report on the ACTH stimulation test. As I understand this test, the goal of treatment with mitotane is to produce a resting cortisol level of less than 4 ug/dl and a stimulated level that doesn't rise much from this level. So a preACTH level of 3 ug/dl and a post ACTH level of 4 ug/dl would be pretty good. Or a preACTH level of 3 ug/dl with a post ACTH level of 3 ug/dl would also be good. If this is the case, then it seems to me that there is a small chance that the signs you have seen are the result of the suppression by mitotane leading to signs of hypoadrenocorticism (Addison's disease), which can include wobbliness and incoordination in some dogs. If this is the case, then prednisone would be helpful and might have to be maintained for a few days until the adrenal glands recovered sufficiently to produce normal cortisol levels again.

At this point, I really think I'd consider changing specialists, unless you are unwilling to pursue other treatment options, too. The best option might be to ask for referral to the veterinary school in Michigan. I just can't understand the reluctance to try other available options for a pet whose owner wishes to pursue them and has taken the time to understand the odds.

Mike Richards, DVM 8/4/99

Corticosteriod side effects

Q: What are the side effects of Corticosteriods?

A: Carol-

Corticosteroids occur naturally in both dogs and cats. They are produced by the adrenal gland. They have effects on most of the body's systems. For this reason, using them therapeutically tends to produce a lot of side effects.

Cats are more resistant than dogs to the effects (and side-effects) of corticosteroids.

The most common side effects associated with the use of corticosteroids are increased drinking, urinating and appetite. These effects are less noticeable in cats than dogs but weight gain does seem to accompany the use of corticosteorids in cats pretty frequently.

Prednisone and other corticosteroids may cause other side effects, as well. Hairloss, dullness or thinning of the haircoat is occasionally seen in cats. Thinning of the skin and increased susceptibility to skin infections may occur. Panting is commonly seen in dogs as a side effect of corticosteroid use and is seen less frequently in cats, as well. We have had a couple of feline patients who developed diarrhea as a side effect of prednisone usage. Ulcers are reported to occur sometimes after corticosteroid usage but I don't recall seeing this problem in any of our patients.

Generalized immune suppression can occur, particularly at higher corticosteroid doses or with frequent administration of corticosteroids. This is the side effect that we worry the most about in cats, as there is some evidence that corticosteroids can make it possible for dormant feline leukemia virus or herpes virus infections to reappear. It is a good idea to watch carefully for signs of illness when it is necessary to use corticosteroids in a cat and to report any signs of illness to your vet as soon as possible.

Corticosteroid may lead to an increased incidence of pancreatitis in dogs but I am not sure if this problem occurs in cats. Use of cortisones makes it harder to control insulin dosages in diabetic pets and they may even help to induce diabetes in susceptible pets.

In people, corticosteroid induced pyschoses are reported. I honestly think that this occasionally occurs in pets but have no real scientific data to support that belief. Still, if your cat starts hiding out all day, is more aggressive, or exhibits any recognizable behavioral changes it would be worthwhile to report them to your vet.

There are probably other side effects that I haven't thought of. Sometimes when I look at the lists of things that corticosteroids do that aren't good for the patient it is hard to understand why we use them. But it is important to remember that they also have beneficial effects, as you have seen. As long as the beneficial effects are important and are providing an increased quality of life it seems reasonable to use corticosteroids. You just have to be careful to watch out for the pitfalls and adjust treatment plans accordingly.

Hope this helps.

Mike Richards, DVM 5/20/99

Medication side effects - Rimadyl

Q: Hi, I read with HORROR your information on arthritis medication.

1) Cartrophen is an AUSTRALIAN product made by Biopharm in Bondi, Sydney.

2) Cartrophen given every 6 months is useless according to Biopharm itself. The RECOMMENDED dosage for arthritic dogs is, initially, 1 shot every week for 4 weeks then 1 shot every 4 weeks thereafter for the dog's life. Biopharm say that the effects of Cartrophen MAY last, depending on the dog, for up to 3 months but anything over is just a waste of time for the owner and a waste of money. I have had my Chow on Cartrophen for almost 3 years and she has gone from a whimpering mess with pronounced arthritic wear noticeable in a finger probe examination and also by X-ray to a happy dog running about and playing with my other Chow and her arthritis reduced to the point where you cannot notice it by finger probe - even the VET cannot find it anymore. Cartrophen is currently undergoing FDA approval and has been undergoing same since July 98. It is expected that by July 2000, it should be a legally available drug in USA. It currently IS a legally available drug in many countries, Canada included.

3) Rimadyl is an NSAID and as any vet with common sense and any human doctor will tell you, NSAIDs can be dangerous to LETHAL for susceptible dogs or humans. As such, Rimadyl has been the cause of the deaths of many dogs in USA and I refer you to www.srdogs.com for details of same. Recommending it without thought to that is not only dangerous for the dog but should there be an owner willing to SUE over your advice then the court aspect of it is dangerous to YOU. So far there is no 100% sure way to know which dog is susceptible and which isnt. I hope that, in future, you take the above into account when issuing information to people who write in and hope that you forward my Cartrophen information on to the person who asked you about it with the old Chow.

Chow Addiction Society Founder and Lifetime Member #1

A: Chows-

Almost every medication that is used in veterinary medicine has the potential to cause side effects. Many of them have the potential to cause death as a side effect. The list of these medications is very long. Antibiotics often have the potential to cause injury or death. Vaccinations occasionally cause sickness or death. Anesthesia will occasionally cause serious problems, including death. Non-steroidal anti-inflammatory medications can also have detrimental effects. I have treated animals dying from the effects of herbal medications administered at home and have heard unconfirmed reports, similar to much of the information on the Senior Dog site, of problems associated with the use of injectable polyglycosamines, and it seems very likely based on the injection schedule provide that Cartrophen is a polyglycosamine product--although I must emphasize that is just a guess.

While we do not specifically address this on the page on dog arthritis, we do have information on the effects of Rimadyl on the web site in several places and it is possible to find this information using the search feature of the web site. I have asked Michal to move some of this information to the dog arthritis page.

The choice of medications to use in a particular patient should always involve an evaluation of the risk to the patient versus the expected benefit. Heartworm treatment medications cause death in 1 to 2% of patients - a far greater risk than most medications, but when the effects of not treating for heartworms are considered, this seems like a small risk. Carprofen provides many dogs with the ability to move comfortably for several months to even years beyond the time they would have been able to otherwise. I inform each of my clients of the potential risk of carprofen and some elect not to use it. Most clients recognize that the benefit outweighs the risk, especially when many are considering euthanasia as an alternative to allowing their pet to live in pain.

If Cartrophen is significantly better or just as good and safer than current medications, then it will be easy to recommend it when and if it is approved in the United States. In the meantime, I am glad that carprofen is available for my patients who need to be relieved of chronic pain from arthritis right now.

Mike Richards, DVM 3/16/99

Rimadyl side effects

Q: Hi, I first wanted to say again that your web site is truly super! So much information and given in such a caring manner. I hope that you are connected to every Search Engine available on the net, so all pet owners can have access to your site. My question: In your practice, have you seen any of the negative side effects that some patients have noted with Rimadyl (serious liver damage, etc.)? The drug is not yet available up here in Canada, but I live 15 minutes from the US border and could drive my dog across to get treatments. However, before I made the decision to do so, I would want to be sure of its safety. If it were a last resort situation, then the decision to use a drug with possible serious side effects (possibly leading to death) is much easier. In a case where you want to help a dog improve his/her situation with OA, but where they are not in extreme pain, the question becomes harder. I would appreciate any further information re Rimadyl. (I did not want to repeat my Golden Retriever's history, as I included it in a previous email to you.. but .. she is 6 yrs old, and had a total hip replacement done on her right hip at age 3.The other hip is also dysplastic, but was not as bad. The orthopedic surgeon who did the surgery suspects knee problems now... slightly lax...but not serious enough to warrant surgery. He put her Piroxicam, but I did not see much improvement, and therefore tried Adaquan shots. Since the Adaquan shots, she has gotten worse..thus, my other question re Adaquan and dogs with metal hip joints. The other possibility that comes to mind to explain her increased lameness, is the fact that she is no longer on an anti-inflamatory drug.. and, even though I didn't see her improve on it, maybe it kept her from getting worse. Anyway, that's her story.. and I would appreciate any advice you might want to offer.) Again, I applaud you in your efforts to help people with their pets.Sincerely, Tina

A: Tina-

We have not seen any detrimental side effects using carprofen (Rimadyl Rx) at this time, except one dog who vomited after administration of the medication. We have had several dogs who did not seem to respond as well as we hoped. In the product literature from Pfizer the success rate was estimated at about 80% and that seems about right based on our patients.

There have been reports of liver damage. All cases so far have been in Labrador retrievers but they may not be the only susceptible breed, obviously. The incidence is low but I certainly will watch my Labrador patients very closely if we use Rimadyl and I advise all clients to let me know of any changes they observe in their pets.

It may be a good idea to do some follow-up radiographs on the hips to be sure there is not a problem with the implants, too.

Good luck with this.

Mike Richards, DVM

(oh, I forgot -- what I am trying to say is that I think I would use Rimadyl without excessive worry -- but I'd pay attention to changes in appetite, vomiting, lethargy or any other signs that develop and report them promptly to your vet)

Advantage - skin reaction possible

Q: We have a 7 month old golden who has dermatitis on the back of the neck. The area affected is about 6" diameter. We are treating with Cephalexin antibiotic and Gentocin topical spray. My question regards the source of the infection. This location matches the position where we apply Advantage flea control (Imadacloprid). I have been unable to find information regarding side affects of this flea control. Can it act as a skin irritant that would lead to infection? Would you discontinue this flea control?

A: Tom- I have seen some anecdotal reports of reactions to Advantage (Rx) at the site it is put on. While this is a relatively minor problem as reactions to medications go there is still no reason to use it if it causes problems. It is possible to use Frontline (Rx) or Program (Rx) as alternatives for flea control. I would not give up on flea control entirely over a reaction to one medication.

Mike Richards, DVM

Baytril side effects

Q: I have a three year old lhasa, Pixie, diagnosed with cystitis. Culture showed e coli. Pixie has a history of drug and immunization reactions. She was treated with Clavamox and Prednisone for the cystitis. After 2 days, she developed urinary incontinence and was taken off the Prednisone on the 4th day. She continued on Clavamox for two weeks and then began vomiting each day an hour or so after medication. This continued for 3 days then vomiting became more frequent (4 times), and she refused food. She was taken off the Clavamox and Baytril was prescribed. I am fearful of Baytril since I had another Lhasa die of abdominal bleeding within 12 hours of starting Baytril. The other Lhasa was elderly (13 yrs) but vomited after taking one dose of Baytril for otitis, then continued vomiting, became lethargic and dehydrated although continued to sip Pedialyte (recommended by vet). She was admitted to hospital and died with death due to abdominal bleeding and sepsis. I expressed my concern about Baytril to my vet who also treated thedog who died. He said there was no cause for concern with Baytril and that it was one of the few drugs that could successfully treat my dog's cystitis which culture showed to be due to e coli? Can you please discuss side effects of Baytril? Is there another drug that might work for a sensitive dog prone to drug reactions? I am worried that this dog, although otherwise young and healthy, could suffer a drug reaction. Thank you, Karen

A: Karen- Enrofloxacin (Baytril Rx) is reported to cause cartilage abnormalities in growing puppies, particularly smaller breed puppies. The label insert recommends that it not be used from 2 to 8 months of age, which doesn't apply to your dog, obviously. It can cause vomiting and diarrhea in some dogs but I don't know of an antibiotic that doesn't affect at least some patients in this manner. Other than those two effects there do not seem to be side effects associated with the use of enrofloxaxin in dogs. Central nervous system effects like dizziness have been reported in humans on ciprofloxacin, a similar medication. Whether or not this occurs in dogs is hard to say.

When an adverse reaction like you saw occurs, it is natural and proper to suspect the recently administered medication. There may not be a cause and effect relationship between them, though. Bleeding disorders occur in older dogs in association with cancers, systemic illnesses, liver disease and several other conditions. There is a strong chance of a coincidental problem.

Our clinical experience has been that enrofloxacin causes fewer side effects than most antibiotics. I could not say for sure that it did not cause problems in your older lhasa but I think I'd agree with your vet that a reaction is unlikely to occur again in Pixie even if it was a problem in your older dog. I can not not think of a safer antibiotic that is likely to work well for E. coli.

Mike Richards, DVM

Acetominophen and Tylenol

Tylenol and other acetominophen products are sometimes implicated in liver damage in dogs, although this appears to be a rare problem.

Advil

Advil and all ibuprofen products are very likely to cause ulcers in dogs. This can happen in as few as 1 or 2 doses with these medications.

Aspirin

It is extremely important to pay attention to your dog's eating habits when administering aspirin. Dogs have no way to tell you their stomach is upset so you must watch for signs of this. If your dog stops eating while you are giving aspirin it is important to stop giving the aspirin. If any signs of gastric ulcers develop (like blood tinged vomiting or depression) it is important to stop the aspirin.

Prednisone and diabetes

Q: Hello, I have two separate questions.

1) The first question is have you seen any reports or studies that indicate an association between the use of predisone in dogs or cats and the onset of diabetes?

A: C- It is pretty widely accepted that prednisone may predispose dogs and cats to diabetes. It is not as clear to me whether this is enhancement of an existing tendency to develop the disease or if it is an independent effect. They also can induce insulin resistance, leading to hyperglycemia. In diabetic patients, corticosteroids can make insulin regulation more difficult since they have this effect on blood sugar levels. I think this is a relatively rare side effect but it is a consideration, especially in a pet likely to already be predisposed to diabetes.

Mike Richards, DVM

Prednisone

Prednisone is known to produce a "steroid psychosis" in some people. To the best of my knowledge, no one really knows for sure if this occurs in dogs, but I believe that it does. I have seen two or three dogs with really strange behavior when they were on prednisone that cleared up consistently when they were not on prednisone.

Corticosteroids like prednisone probably do not shorten the lifespan when used judiciously. They do have several side effects, including lowering the immune response, increasing drinking, urinating and appetite and predisposing dogs to diabetes and possibly pancreatitis. Again, using prednisone every other day makes all of the side effects less likely to occur.

Mike Richards, DVM

Metronidazole and cancer

2) The second question is do you know what the clinical trials indicate as far as the association of cancer and the use of metronidazole. Thank you for your help.

A: I am not aware of any studies linking metronidazole to cancer. It is known to be teratogenic (causes birth defects) when adminstered to lab animals who are pregnant but I don't know if this occurs in dogs and cats. I have no intention of giving it to a pregnant pet, though. It can also cause neurologic signs in some pets even at the recommended dosages. These go away when the medication is withdrawn (or at least they have in the few cases we have seen).

Mike Richards, DVM

Acepromazine

Acepromazine is considered to be very safe. The average toxic dose is significantly higher than the recommended dosage (at least 20 times the dose). Despite this, acepromazine does have some significant effects that must be considered. It can cause hypotension (lowering of blood pressure). This effect may be exaggerated in Boxers and there have been anecdotal reports of death of Boxers after the use of acepromazine. In addition, acepromazine seems to make it easier for dogs with seizure disorders to have a seizure. This medication should not be used near the time of dipping or treatment with organophosphates for flea control.

Acepromazine is considered to a very safe sedative from the aspect of dosing. It has a wide margin of safety in most dogs. Recently there have been some reports of dogs with unusual sensitivity to this medication that leads to death even with smaller than normal dosages. I have used this medication for my entire career (18 years) without seeing this problem so I believe it to be rare.

Mike Richards, DVM

Amitriptylline (Elavil Rx)

The most common side effect of amitriptylline (Elavil Rx) is sedation. Some dogs also experience "dry mouth" effects from a decrease in salivation and sometimes increase their drinking, which may be an effort to combat this effect. Low blood pressure (hypotension) is possible when using amitriptylline, as well. In severe instances, this could lead to symptoms like fainting when getting up or after exercise. Constipation and urine retention have been seen in some pets on amitriptylline. Serious side effects include seizure induction and blockage of conduction in the heart but these seem to pretty rare. I have not seen either one of these effects and we have used amitriptylline for several years in our clinic.

Mike Richards, DVM

Corticosteroids

Corticosteroids like prednisone probably do not shorten the lifespan when used judiciously. They do have several side effects, including lowering the immune response, increasing drinking, urinating and appetite and predisposing dogs to diabetes and possibly pancreatitis. Using prednisone every other day makes all of the side effects less likely to occur.

Mike Richards, DVM

Heartgard (Rx) and Interceptor (Rx)

Heartgard (Rx) and Interceptor (Rx) both come under a lot of scrutiny as potential causes of immune medicated hemolytic anemia (IMHA) and immune mediated thrombocytopenia (ITP) because they are often the only medications that a pet is on when these occur. There is no evidence at this time of an increase in the cases of IMHA or ITP in dogs on these preventatives. That doesn't mean new information won't come to light at some future time but I honestly do not suspect these medications as culprits in these diseases.

Mike Richards, DVM

Program - side effects

Q: I have a 12 year old (18 lbs. Schnauzer) and a 3 year old (75 lbs. collie) - The collie is presently on heartworm medication and hypothyroid medication (2 pills daily - .05mm each) - the collie is prone to seizures approximately every 8-9 weeks, we believe from the hypothyroidism. Will putting the collie on The Program flea control pill monthly cause any reaction or side effects with the other medications the dog is on? Would it be safe? And the 12 year old is on no medications but on a special diet due to fatty stones just surgically removed. I want my animals safe and I don't like giving them medications unless absolutely necessary. Frontline flea control was expensive and did not work for my animals last flea season. Topical treatments are just not enough and I am suspicious that some of the flea bombs and dips that I have used in the past may have been toxic enough to have caused these seizures in my collie. The seizures have only been noticable since January of this year. Thank you for your time. Please respond. RJ in Pennsylvania

A: RJ - There is no evidence that I am aware of that Program (Rx) will induce or facilitate seizures. It should be safe to use in this situation and does not interact with the medications listed.

It is always hard to figure out what is causing seizures and many times it is impossible to do so. That leaves a lot of room for guessing at causes. It is probably unlikely that previous insecticide use is the cause of the seizures but it is probably possible. Hypothyroidism has been implicated as a cause of seizures but it is probably not a common cause, either. Supplementation of thyroid hormone should reduce the incidence of seizures if hypothyroidism is the underlying cause.

The topical version (vs. the spray version) of Frontline (Rx) has been more successful on long haired breeds such as collies, for us. If Program does not control the fleas you might consider trying this - or using both Program and Frontline or Advantage (Rx).

I hope that the seizures do diminish as time goes on.

Mike Richards, DVM

NSAID medications

Most NSAID medications are much more likely to cause ulcers in dogs then they are in people.

Acetaminophen is probably safe for most dogs but it causes liver damage in a small percentage of them. It should NEVER be used in cats as it almost always causes severe liver damage in this species. Due to the slight increase in potential for side effects in dogs and the severe consequences of people thinking that it might be OK to use in cats, almost all vets are reluctant to recommend this medication.

Aspirin seems safe to use in most dogs but does cause ulcers or gastrointestinal upset in some dogs.

Advil and all ibuprofen products are very likely to cause ulcers in dogs. This can happen in as few as 1 or 2 doses with these medications.

Ketoprofen has been advocated by some vets for short-term use in situations such as post-surgical pain but advise against long term use and other vets report high incidences of ulcers associated with its use for more than 3 to 5 days. Naproxen seems to have some advocates and other doubters, as well.

Mike Richards, DVM

Ovaban

Ovaban has been implicated for predisposing dogs to uterine infections in intact female dogs. The side effects that I am aware of for megestrol acetate (Ovaban Rx) in dogs are weight gain, changes in hair color, uterine infections, enlargement of the mammary glands (sometimes with milk production) and rarely mammary cancer. Weight gain is common but the other effects are less likely to occur in any individual dog.

Mike Richards, DVM


,

Michael Richards, D.V.M. co-owns a small animal general veterinary practice in rural tidewater Virginia. Dr. Richards graduated from Iowa State University's College of Veterinary Medicine in 1979, and has been in private practice ever since. Dr. Richards has been the director of the PetCare Forum...

 

Comments