Is Atopica Safe ? - Should I Give Atopica To My Dog ? Cyclosporine=Cyclosporin=Ciclosporin=Cyclosporin A
is Atopica ?
Ron Hines DVM PhD .
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One of the greatest heartaches a dog owner can have is a persistently itchy, uncomfortable pet. The skin of our pets just wasn’t designed to hold up to hours of chewing and scratching. In that situation, it doesn’t take long for your pet’s coat to thin and look moth-eaten. Invariable, soon after that, your pet’s natural skin barriers to bacteria and fungi infection are breached. When that occurs, pets develop that typical seborrheic skin odor, sores and scabs. It is the itch that comes first – the bacteria, fungi and yeast are just opportunistic freeloaders.
When pet owners and their veterinarians are lucky, the problem is due to fleas. Vets have great ways to deal with that. But more likely than not, when fleas are not the problem, your pet has developed atopic skin disease aka canine allergies. If you are very fortunate, those allergies will be due to ingredients in your dog’s diet. But in most cases they are not or food allergies are only a small part of the pet’s allergic condition. The most common form of allergic skin disease in dogs is caused by allergies to ordinary contaminants in your pet’s environment – contaminants that are nearly impossible to eliminate.
When humans develop allergies to environmental contaminants, the target is your respiratory system. That is because most of the chemical agents (histamines, etc.) are released by the cells that line your respiratory system causing inflammation there. (ref) That is why your eyes will itch, you will sniffle and you might even cough. But dogs are different. When they have allergies, these same inflammatory chemicals are released primarily in their skin. That is what causes them to itch. (ref)
When veterinarians are faced with allergic/atopic pets, the first things they usually dispense are soothing medicated shampoos and lotions. Itching is a self-perpetuating habit. If your pet’s problem was a one-time thing, if it is relatively minor or if it is seasonal , perhaps that, along with some oral antihistamines, will take care of the problem.
But with time, itching problems that are related to allergy tend to return and become worse. In those cases, your vet might suggest blood-based allergy testing or special low-antigen diets. Occasionally, that approach is successful - often, it is not.
Your veterinarian may then have dispensed an oral corticosteroids or given a corticosteroids injection to your pet. That probably produced a dramatic improvement. Your dog stopped itching – for a while. But it may have also peed more and gained weight. Your veterinarian was probably reluctant to repeat the therapy, telling you of the serious side effects of prolonged corticosteroid use and you probably already knew that anyway. But it is so terribly difficult to live with a scratchy, itchy, uncomfortable dog. So you probably talked the vet into repeating the steroid treatment now and then.
Veterinarians all know that the desirable effects of corticosteroids against allergic itching is very dramatic. These drugs mimic the effects of the natural corticosteroids produced every day in your pet’s adrenal glands. But they also know that corticosteroids have many undesirable side effects when they are given too frequently. Prolonged corticosteroid use leads to weight gain, decreased strength of the binding proteins (collagen) that hold the body together as well as increased blood glucose and circulating lipids (fats) that can affect your pet’s liver and pancreas. And those are only a few of the undesirable results that can occur. You can see why most veterinarians were desperate to offer their clients’ pets other options.
This lack of good options for the long-term control of canine atopy led Novartis Pharmaceutical Co. to apply for and receive an FDA permit to market cyclosporine for this problem under the trade name, Atopica. Their request was approved in August, 2003. You can read the package that Novartis submitted to the FDA here.
is a compound that naturally occurs in a fungus. It had been used in
human medicine since 1972 when it was discovered that it helped in preventing
rejection of transplanted human kidneys. (ref)
It has since become useful in treating a wide variety of autoimmune
diseases in people and in fighting organ rejection through its ability
to cripple the bodies immune system. (chiefly by
You can read the product insert furnished with the drug here.
The body’s allergic process is extremely complicated. It involves many different cells, transmitter chemicals and processes. But here is my simplified explanation:
Allergies are caused by unnecessary antibodies - antibodies your dog produces against compounds in its environment (like mold, house, dust mites or pollen) that would ordinarily be ignored. Your dog itches because those antibodies cause mast cells in its skin to release histamines. Those histamines produce inflammation that irritates the nerve endings in your dog’s skin. Mildly irritated nerve endings itch - severely irritated nerve endings are painful. It does not cause the skin damage, hair loss and skin infections that you observe – the dog does that to itself.
Cyclosporine (= Atopica) interferes with this extremely complex process. It prevents a certain specific group of lymphocytes (immune system cells) the helper T- lymphocytes , from transmitting chemical messages (calcineurin / interleukins) that result in histamine release from your dog's skin mast cells. Without released histamine, your pet does not itch. You can think of helper T-lymphocytes as the policemen of the body – always looking for intruders and blowing their whistle when they find them.
Atopica is usually just as effective as corticosteroids in reducing inflammation and stopping itch.
Atopica is sold in four-size capsules that should be given on an empty stomach. Veterinarians generally dispense the medication for daily use until substantial improvement in itching is noticed (about 3-6 weeks). When that happens, the dose is given only every second day. If that is sufficient in stabilizing your pet, your veterinarian may try to give Atopica even less frequently – perhaps every 3-4 days.
Not all dogs absorb Atopica or maintain blood levels of the drug equally well. Some veterinarians will follow these levels with periodic blood tests and adjust their dose schedule accordingly (ref) Others vets do not believe that blood levels accurately predict concentration of the medication in the skin and make their adjustments based on the positive response they see.
Although there are dogs, like people, who handle one medication better than another, the potential long-term side effects of Atopica are at least as severe as those of corticosteroids. They are just different side effects, they may take longer to occur and they may not be as readily apparent to you at first. You can read about some of those serious side effects when they occur in humans here.
It is not at all clear that you pet will do better long-term on Atopic than it would on a wisely- thought out program of intermittent corticosteroid (prednisone, etc.) use combined with less severe options that include topical products, nutritional management and physical intervention. (ref)
What Are These “Dangers” You Mentioned ?
Most dogs do not experience immediate side effects from Atopica. But about 30% do experience vomiting, loss of appetite, GI upsets or diarrhea. When your pet begins the drug, start lower and less frequently than your anticipated dose to try to avoid that. These immediate side effects often lessen or disappear after the pet has been on the medication a week or two.
Since most dogs seem to handle the drug just fine, owners are usually quite satisfied with their pet’s lack of itching and the lack of weight gain and frequent urination that can accompany corticosteroid use.
Atopica can cause inflammation of skin and oral surfaces. So some dogs develop thickened, swollen gums (epulis, gingival hyperplasia). (ref) Others develop reddened or tender ear flaps and some develop thickened foot pads (calluses, epidermal hyperplasia, hyperkeratosis).
Some appear to shed more while on the medication.
Veterinarians have no problem telling you what the immediate side effects of Atopic are. They are quite obvious. It is harder for them to tell you what the long-term consequences of keeping your pet on this drug might be. That is because it is very difficult to prove that any new health issue your pet experiences is do to the cyclosporine and because the drug has only been used extensively in dogs since 2003.
But the same cyclosporine (Neoral), produced by Novartis (Sandoz) has been used in humans since 1983. So there is a large body of information on its long-term side effects in people. There is no reason to believe that these side effects would be any different in dogs. So many of my reference links and warnings are based on human, not dog, studies.
I explained earlier that Atopica works by disrupting the activity of your pet’s immune system. This, unfortunately, is a double-edged sword. The same helper T-cell policemen that I told you about earlier – the ones whose activities were disrupted by Atopica, are the officers that patrol your pet’s body for invading bacteria, and other pathogens. More concerning to me, they are the same cells that look for abnormal body cells – the ones that later give rise to cancer. Atopica is not at all selective as to which helper T-cell activity it blocks.
Potential Effects On Your Pet’s Kidneys
second problem with Atopica is that the calcineurin messenger compounds
that it blocks are also found in your pet’s kidneys. So Atopica
has the potential to damage those organs as well. You can read about
Potential Effects On Your Pet’s Liver
An increase in the number of ear infections (otitis externa) appears to occur in dogs receiving cyclosporine. It is hard to sort out the cause. Most dogs with chronic skin allergies already have ear problems. It could be that rather than causing the problem, cyclosporine only weakens the pet’s natural defenses that keep those infections at bay. Whether the swollen ear flaps sometimes seen with Atopic use are due it its affect on skin or reactivated ear infections and increased scratching is unknown.
Increased Number Of Tumors
Cyclosporine is known to increase the incidence of cancer. You can read the NIH statement to that effect here.
As dogs age, they all develop abnormal, pre-cancerous cells throughout their bodies – we all do. We all rely on those policemen cells to locate them, and destroy them through a process called apoptosis. (ref) Dogs and humans receiving cyclosporine are not as effective in doing that. (ref)
Novartis acknowledges that dogs on Atopica run a greater risk of developing cancers. They explain that as the drugs ability to “exacerbate sub-clinical neoplastic conditions". But they give no explanation as to how they came to the convenient conclusion that no really new tumors were formed.
Leukemias and lymphomas are lymphocyte tumors. They increase in frequency in humans receiving cyclosporine. There are articles as well that say that lymphomas increase in frequency in dogs receiving cyclosporine. But as far as I know, they are based on only a single case (ref)
Novartis reported to the FDA that the lymph nodes of dogs receiving Atopica became enlarged in 2.3% of the dogs receiving Atopica for 28 days. Lymph node enlargement (lymphadenopathy) , not related to infection, is often a prelude to lymphoma.
Effect On Blood Capillaries
Many of the potential side effects of cyclosporine are due to its potential to cause injury to the lining of small blood vessels found throughout your pet's body. (ref) That is sometimes referred to as its potential for vasculotoxicity.
Increased Susceptibility To Infections In General
Dogs and humans receiving cyclosporine appear to have reduced ability to fight infections of all kinds. That includes bacterial and fungal skin infections and urinary tract infections.
Pets can have infections and parasites that you are not aware of but that are being kept in control by its healthy immune system. If you weaken that system with medications like cyclosporine (Atopica) the animals body can loose control of them. Toxoplasma is one of those parasites, you can read about what happend to two cats that were given cyclosporine here. You can read another 2011 report of the worrisome number of side effects associated with the use of this drug in cats here.
Some dogs receiving Atopica appear weaker than usual – particularly in their hind legs. It is very hard to judge the causes of generalized weakness in pets. Sometimes, just not feeling good can be misinterpreted as weakness. But cyclosporine is known to occasionally produce muscular weakness and nerve dysfunction in human beings. (ref)
Potential Effects On Your Pet’s Pancreas
Cyclosporine also has the capacity to lower your dog’s ability to produce insulin , and so, interfere with its blood sugar metabolism. (ref)
Increased Number Of Warts (papillomas)
Veterinarians have noticed that dogs receiving Atopica may grow more warts. Warts in dogs are a benign skin tumors caused by virus (papilloma virus). (ref) This same virus might even be involved in the other skin thickening and inflammation problems occasionally seen in dogs receiving cyclosporine (ref)
Novartis submitted a list of the side effects of Atopica when they applied for FDA permission to market the drug. That study was based on the 52-week experience of thirty-two 8-10 month old laboratory beagles – not the pet population that would be receiving the drug. Nine-month-old dogs are no more representative of the pet dog population that this drug was to be marketed to than 15-year-olds are representative of the human population that takes cyclosporine. How many of us wouldn't wish to have the stamina and resistance we had at 15 ? I gave that link before here it is again.
Pay particular attention to the pathological changes that occurred in dogs receiving higher than normal doses. It is not unusual for, the side effects of short-term, high dose studies to be the same as the effects of long-term lower dose studies. (ref)
The FDA is considerably more demanding about safety studies when it comes to approving human medications than it is on pet medications. So you will find a lot more detail on the possible side effects of Atopica when Novartis markets it for humans as Nioral.
Some of Novartis’ promotional information on Atopica is highly misleading, such as the statement found on their website that “ATOPICA targets only the specific cells in the immune system that cause the allergic reaction.”(ref) Those cells have other very critical functions that will be affected as well.
Novartis' advice to veterinarians in general practice to run a few simplistic
screening tests and then hurry up getting the dogs onto Atopica is definitely
not in your pet’s best interest either. Read that promotional
If you are reading this article, I am sure you have heard and read all those suggestions before, but they can never be repeated often enough ……….
Never begin dogs on any powerful itch-control medication if there is the slightest teeny-weeny chance that fleas may be part of the problem. Dogs that develop allergies to flea saliva only require a single flea to set of an intense itching cycle. It can be very hard to locate a single flea. The flea may not even be present on your dog by the time the itching begins. All dogs with itchy skin should be on a topical monthly flea-control product. Some do not work as well as they once did , so ask around in your area and avoid flea-infested areas like dog parks whenever you can. You can read suggestions for flea control on your pet here.
It is always wise to determine how dietary ingredients might be affecting your dog. Either put the pet on a 60-day trial of limited food ingredients it has not eaten before or feed it a diet that has been processed or manufactured to be hypoallergenic. Do not believe all the claims you read about diets – particularly if the product is sold on that website. You can find suggestions on limited ingredient diets here.
Blood Allergy Tests
I tell my clients that these blood-based tests for allergies are a waste of their time and money. The results just do not correlate with the Real World (ref) Some vets still do have the test performed by Idexx or Heska. Read one of their promotional brochure here.
Just because blood allergy tests don’t work doesn’t mean you can’t try to decrease your dog’s exposure to antigens. Try making changes in your home air filtration system, cleaning and vacuuming program and anything else that could possibly decrease the dog’s exposure. It’s always worth a try.
You should always attempt to manage itchy dogs with these products first and not stop using them even if you go on to use alternative methods. Owners of dogs that do best over long periods of time tend to use a combination of approaches to keep their pet's skin in the best condition possible. That generally includes soothing lotions, rinses and creams. Most of these products have little if any effect if they just sit on your pet's skin. They need to be massaged deep into the skin where the problem is occurring. That is because the dog's mast cells and the processes that liberate histamine from them occur in the deeper skin layers. (ref) (Wear Gloves)
Many of these products contain corticosteroids. Topical corticosteroid-containing sprays and creams are not as likely as oral corticosteroids to cause unwanted side effects in your pet’s body when they applied in reasonable amounts and according to the product's label. They are best for spot treatment of your pet’s paw-webs, axilla (armpits) and groin–areas where licking is usually worst. When they are used, they need to be massaged into the the skin until they vanish so your pet doesn't just lick them off. They include topical triamcinolone sprays (Like Genesis Topical Spray), betamethasone-containing sprays and mists and nystatin/neomycin/thiostrepton/triamcinolone products (Panalog, Anamax,etc.). Walmart sells an acceptable alternative. (ref) Dogs must not be lathered with these products because when licked off and ingested, they have the same effects as oral corticosteroid tablets.
There are other specific corticosteroid-containing veterinary sprays and lotions that owners of itchy pets rely upon. But in every case, you need to monitor your pet closely for sensitivity to the product, increased thirst and urination or weight gain. Do your best to prevent the pet from licking the products off by masaging them well into the skin. The previous two links to the inserts that accompany the products explain those side effects in detail.
Omega Fatty Acid Supplements And Ceramide-Containing Topical Products
Oral fatty acid supplements have been marketed for itchy dogs for many years. They usually contain a mixture of omega-6 and omega-3 fatty acids - compounds your dog's body can not synthesize on its own. These lipid supplemental are occasionally helpful in decreasing itching when a dog's diet does not provide them. Increasing the fat (lipid) content of the pet's diet is occasionally helpful as well when abnormalities of its digestive tract do not allow enough fats to be absorbed.
Ceramides are a special class of lipids or fats. They are found throughout the body. Those ceramides present in the skin appear to be depleted in itchy dogs. Recently, a group of topical ceramide-containing sprays and drops have become available for itchy pets. They seem to help decrease itching considerably better than the oral lipid products did. You can read about those compounds here and here. Add them to your pet's treatment plan if they appear helpful - but be cautious about exaggerated claims for the products. One of them is Spot-on.
Keeping your pet’s toenails clipped short and ultra-smoothed will greatly reduce the amount of damage it does to its skin scratching. Dogs chew and groom themselves most at night and when they are bored and inactive. Being overweight adds to this problem. My Labrador retriever, Max, has an atopy problem. When he has flare-ups, he wears a soft muzzle at night and I massage a topical triamcinolone/bacitracin cream into any worried areas until the problem passes. This has worked well for many years. If you let the problem get out of hand, your dog’s skin odor will increase and it will smell musty as bacteria (usually staph) work their way into the worried areas. At that point, 10 days of broad spectrum antibiotic may become necessary. (although I find that staph infections usually resolve if dogs are physically prevented from scratching ,chewing and traumatizing their skin, other vets feel that certain dogs are more genetically susceptible to surface staphylococcus infections (ref)
Only a few of my clients find benadryl to be of much help in controlling canine allergic itches. When they are, it may be their sedative effects that is most helpful. Atarax (hydroxyzine)or Tavist (clemastine) (Not Tavist-D) are sometimes a bit more effective. Itching is a self-perpetuating phenomenon. Many veterinarians suggest Clemastine because its calming effect seems quite pronounced.
Acepromazine, a veterinary tranquilizer is sometimes helpful during flare-ups. It has both calming and antihistamine-like properties. (ref)
Any medication that is effective for any health problem is a combination of good effects and worrisome side effects. The only ones that are not a mixed bag of effects are those that have no effect at all. Corticosteroid medications are no different. You have to ask yourself several things before using them: Will you and your pet be happier on the medication or without it ? How severe are the potential side effects and how likely are they to occur ? Are there ways to administer the medication to lessen the chances of side effects ?
It is possible to control canine atopy over a pet’s lifetime by using corticosteroid medications, like prednisone, very carefully and judiciously.
There is usually a small window between the amount and frequency that oral corticosteroids like prednisone can be given to control most of the itching in your pet and the dose at which side effects occur. That is particularly true if you use a combination of approaches like the ones I already mentioned.
In doing so, you needs to give only enough of the drugs to eliminate the majority of symptoms – not all of them. One needs to use these medications only intermittently and at the absolutely, lowest effective dose. Pulsed, intromittent doses given only during flare-ups are considerably safer than daily doses. One needs to practice strict weight control in these pets as well to avoid the same potential problems that occur in humans taking corticosteroids over long periods. You can read about long-term management of those people here. Different dogs react to these medications differently. Through a combination of physical exams and blood chemistry exams, changes can usually be made in your pet's diet, lifestyle and medications to minimize those unwanted effects. So it should not be attempted other than under the close supervision of your veterinarian. Never consent to periodic "Depo" (methylprednisolone acetate) injections.
When a moderate corticosteroid dose is given intermittently, many of its side effects can be avoided. (ref) When too much is used or when it is used for too long without interruption, corticosteroids often lead to health problems of their own. Those include Cushing's disease, obesity, diabetes, ligamental tears and ruptures liver and eye issues and the possibility of Addison’s disease when the drug is withdrawn or stopped too abruptly.
There is probably a place for Atopica in the treatment of stubborn canine skin allergy flare-ups as well. But you need to be aware of the drug’s potential risks and monitor your dog closely when it receives it. There is no proof that dogs do any better on Atopica long term than they do on corticosteroids long term. The secret of success with either is how well the drugs are managed.
To get the full benefits of cyclosporine, your dog must be on a very strict feeding and dosing schedule. The diet should be consistent, without any deviations in amount, type of food or feeding time.
Although corticosteroids and cyclosporine both control itching, they do so in somewhat different ways. So, theoretically, your dog might be better off on a low dose of both of them than a higher dose of one or the other. But veterinarians do not know that for sure. It is a technique used by physicians that fight kidney rejection and autoimmune diseases of many sort – give multiple drugs at lower doses rather than single drugs at high doses. (ref)
To begin with, use the pharmaceutical company’s suggested doses as maximum doses. Base your actual dose on the amount, frequency and duration of medication that keeps your pet relatively symptom-free. Just do not exceed the maximum suggested doses.
Begin medications slowly and work up to the suggested dose if you need to. Never begin or withdraw a medication of this type abruptly except in a crisis or emergency situation upon the advice of your veterinarian.
Pay close attention to your dog’s ears. Many dogs with chronic atopy have chronic ear infections. Those infections can go out of control when immunosuppressive medications such as cyclosporine or corticosteroids are given.
Always give the medication at the same time each day. You can experiment with the interval between the dog’s last meal and the medication. Novartis suggests it be given on an empty stomach, but some owners find less nausea and vomiting when the medication is given with a small meal.
Some veterinarians combine Atopica with ketoconazole administration because Atopica is very expensive. Others add it because they suspect fungal skin infections. Ketoconazole is a drug that is used to treat fungal infections. Cyclosporine is not metabolized as quickly by your pet’s liver when ketoconazole is present. Although this lowers the daily cyclosporine dose, the same cyclosporine blood levels remain. So adding ketoconazole probably doesn’t alter the risks of cyclosporine side effects. Since we know that ketoconazole has the potential to lower your pet's adrenal gland cortisol production which is, itself, protective against itch (ref) , I am reluctant to give it long-term to dogs as a cost-saving measure until I know more about what the consequences might be.
There is no published data that I know of comparing the two products. But many pet owners seem equally satisfied with the results they obtain from the generic and the name-brand forms; and many people who have had kidney transplants trust their lives to the same generic cyclosporine.
There is some thought that vaccinations given to dogs taking Atopica might not be as effective. This is because Atopica might interfere with the dog’s immune response to the vaccine ingredients. You can always go to 3-year duration vaccines and taper off the dose for a period before and after vaccination. Most dogs are over-vaccinted anyway. (ref)
Because Atopica has the potential to injure your pet’s kidneys, any medication that also has the potential to injure kidneys should be avoided when taking Atopica as well as any that might alter the way cyclosporine affects the body. Those include certain antibiotics, antifungal and anti-seizure medications. Go to the Novartis product insert I linked to earlier to see them all.
Physicians think that cyclosporine injures kidneys by interfering with blood flow through the tiny vessels that nourish their filtering apparatuses (nephrons). (ref) Non-steroidal anti-inflammatory medications (NSAIDs), like Rimadyl and Previcox are widely dispensed for arthritic dogs. Many older dogs also receive Ace inhibitors, like Enalacard, for heart failure. Ace inhibitors can also reduce kidney blood flow (ref) I would hesitate to use either of those two classes of drugs and Atopica together.
Atopica should be used with caution in all dogs. But since the drug is removed from your pet’s body by its liver, dogs with liver disease should not receive it, nor should cyclosporine be used in dogs with the slightest evidence of kidney disease, heart disease, certain blood disorders or potentially malignant cancer.
(I am, by nature, cautious. Those are my personal feelings; there are veterinarians whose ideas would differ from mine.)
Your veterinarian needs to run blood tests before dispensing Atopica to be sure your pet does not have any hidden kidney, liver or heart problems or evidence of early cancer.
Then your veterinarian needs to monitor your pet’s kidneys, liver and heart while it is on the medication. You need to understand as well, that the effects of cyclosporine sometimes appear in humans long after the drug was discontinued. I would suggest that blood tests be run a month and two months after the first dose to look for acute problems and twice a year thereafter.
Checking for the potential of cancer is much harder. Novartis hints that when cancer occurs in pets taking Atopica, it only speeds the growth of cancers that are already present. Of course, that is impossible to really know. Veterinarians do not have any more good screening tests to detect early cancer than physicians do. About the best we can do is monitor your pet’s superficial lymph node size, and check its blood for the presence of any abnormal cells (Pre-leukemic syndrome). That only directly detects tumors of the lymphatic system and blood. Periodic x-rays or ultrasound examinations might also be helpful.
Since kidney damage is the most frequent serious side effect in humans taking cyclosporine, your vet needs to periodically evaluate your pet’s urine to check on the pet’s kidney function. Going by its blood BUN and creatinine levels are not enough. By the time those values rise, the pet’s kidneys are already severely damaged. The tests that pick up ongoing kidney damage earliest are the urine protein:creatinine ratio and the urine microablinuria test. You can read about them here. These are the same tests used in humans taking cyclosporine.
Drug companies are sometimes reluctant to inform the public about problems associated with their products. I wrote this article because I am troubled by the large number of clients who consult me when their pets have experienced internal health problems after receiving Atopica to treat their topical skin allergies. CADI might be a safer alterntive.