Whole Dog Journal's Blog December 23, 2013

Trifexis and Adverse Effects

Posted by at 05:08PM - Comments: (20)

A few weeks ago, the talk of the dog-related section of the Internet was Trifexis, the oral flea-control medication introduced a year or so ago by Elanco Animal Health. News reports alleged that more than 700 dogs have been killed by adverse reactions to this drug.

To verify that number, I looked to the FDA’s Center for Veterinary Medicine (CVM), the agency responsible for collecting and analyzing reports of adverse effects of veterinary drugs on animals. (Trifexis is an oral medication with a systemic activity. As I reported in the January issue of WDJ, systemically active insecticides and other oral medications meant for use in dogs are regulated as “drugs” by FDA CVM; in contrast, most topical pesticides are regulated in the U.S. by the Environmental Protection Agency [EPA]. The notable exceptions are Advantage Multi and Revolution; their ability to kill the L3 and L4 [larval] stages of heartworm and intestinal worms is due to a systemic action, so they are regulated by the FDA.)

The CVM maintains an “adverse drug event” (ADE) database in order “to provide an early warning or signaling system to CVM for adverse effects not detected during pre-market testing of FDA-approved animal drugs and for monitoring the performance of drugs not approved for use in animals.” CVM scientists use the ADE database to make decisions about product safety, which may include changes to the label or other regulatory action.

Analysis of the CVM ADE reports involving Trifexis are made more complicated than usual because the CVM is transitioning from compiling data from reports received on paper to an all-electronic reporting system, and the release of Trifexis occurred in the middle of that process. Some of the reports have been captured by the paper process, and some by the electronic process.

Jim Strickland, a reporter for a TV news station in Atlanta, WSB-TV 2, has been following the story closely, after he received reports from local dog owners about dogs who died following the administration of Trifexis. He was able to obtain both sets of CVM ADE reports, containing data as current as November 14, 2013, concerning Trifexis. (Here is a link to Strickland’s story, which contains links to those ADE reports: http://www.wsbtv.com/news/news/local/owners-blame-700-dog-deaths-trifexis/nb5B4/)

If you look at the reports and do some addition, you will see that indeed, there have been about 660 dog deaths reported to the CVM by owners and veterinarians who were concerned that a previous administration of Trifexis might have been involved or solely responsible. (About 392 of those were listed as “death”; 259 were “death by euthanasia.”)

But the main thing that struck me as I was looking at the reports is -- what a mess the reporting system is! Also, that there is no end to the ways that humans can screw up the administration of medications – so, there is also no end to the ways that they can screw up the reporting of adverse events.

Contained within the reports are statistics for side effects that cats (and even one fish) suffered when administered this canine medication; side effects suffered by dogs where the route of administration was “intraocular” or “ophthalmic” (both words would suggest the tablet was somehow put in the dog’s eyes) or cutaneous (on the dog’s skin); many reports in which the route of administration was not included at all; side effects suffered by humans who consumed the medication; and even side effects suffered by humans who suspected that getting the tablet on their skin was the cause.

Then there are the problems related to language. Symptoms don’t get properly tallied because various words are used to describe what is certainly the same thing: “emesis” in some reports, “vomiting” in others; “lack of efficacy” in some, “ineffectiveness” in others; “decreased appetite,” “not eating,” “anorexia” . . . the list goes on and on.

While the “paper reporting” system is older, it appears to be more accurate in these tallies, probably because CVM vets are reading the reports and translating some of these various terms into more consistent language.

The symptoms and numbers tallied in these reports can be alarming, but some perspective is needed. Along with the reports released to the WSB-TV reporter, the CVM released a statement that contained language (also found elsewhere on its website) that cautioned readers to infer too much from raw data:

“When reviewing the cumulative summaries listing, the reader should be aware that:

• For any given ADE report, there is no certainty that the reported drug caused the adverse event. The adverse event may have been related to an underlying disease, using other drugs at the same time, or other non-drug related causes. The cumulative summaries listing does not include information about underlying diseases, other drugs used at the same time, other non-drug related causes, or the final outcome of the reaction. [Editor’s note: In other words, some of these dogs should not have been given the drug, due to known adverse drug interactions or other contraindications.]

• The accuracy of information regarding the ADE is dependent on the quality of information received from the veterinarian or animal owner.

• Accumulated ADE reports should not be used to calculate incidence rates or estimates of drug risk, because there is no accurate way to determine how many animals were given the drug, which is needed as the denominator in calculations of incidence and relative risk.

• Underreporting occurs with most adverse event reporting systems. The frequency of reporting for a given drug product varies over time, and may be greater when the drug is newly marketed, or when media publicity occurs.”

The ADEs also do not specify whether the correct dosage was administered to the dog (was the Chihuahua given the German Shepherd’s pill by mistake? did the dog eat a whole package of the medication? Did the owner misunderstand the directions and feed the wrong number of pills?), or whether the dog was already old or ill or otherwise a poor candidate for the medication.

I’m definitely concerned about the ADE reports about Trifexis – one can’t help it, when imagining all the dogs suffering all the symptoms reported in the ADEs. I strongly encourage dog owners to report any adverse effects to the CVM – as accurately as possible! – if their dogs suffer an adverse reaction to Trifexis or any other medication. And I strongly advise dog owners to take heed of the warnings we gave in the January issue – pointers on how to safely administer Trifexis and any other topical or oral flea control medication or pesticide (including many tips on what dogs should not receive these medications, and how to use them as minimally as possible). But I also recommend that the numbers be taken with a grain of salt; it’s very, very raw data.

Comments (20)

My pet has been on Trifexis since February 2014. She has been having problems since she started using it. Dumb me I trusted my vet and continued giving it. She started becoming incontinent two months ago. I again took her to the vet and he prescribed meds to help with it. Never did it dawn on me that it could possibly be connected with the drug Trifexis because he prescribed it and I would naturally assume a competent vet would know the side effects and would have taken her off it. He did not. My dog Muffin has liver and kidney damage. She is very lethargic and is not eating very well. I am so angry I could spit! Is there a class action suit on this drug? I still have Muffin but she is very ill. This is just beyond me how vets who are usually animal lovers could do this to pets. I truly believe same as with M.D.'s they get kickbacks for prescribing this poison. Muffin in the last week since her last dose has loose, yellow stools with blood and black tarry appearance interspersed. I don't want to lose her. I rescued her after my husband passed of cancer. She has been my constant companion. Help please. I hope she can be saved.

Posted by: Muffin's Mom | July 30, 2014 4:49 PM    Report this comment

I have an 8 month old German Shepherd. I've been giving him this drug for a few months now. I have noticed he gets diarrhea and a decrease in appetite. He has vomited once or twice. I did give him the drug correctly (according to his weight) and had him tested for parasites (which he was clean) because I couldn't understand why my dog was sick. Eventually it would pass, but it didn't dawn on me that this drug could be giving him these side effects! I'm very unhappy with this drug! I can't believe all the dogs affected from it and why it's still being sold and recommended by vets!

Posted by: Lisa J | July 28, 2014 11:52 AM    Report this comment

My 2 year old Rottie has been on Trifexis for a year now and has no adverse reactions at all. I questioned giving it to him when I read about all the deaths and after doing extensive research, I learned that most of the deaths of the other animals occurred because of an underlying issue. He has not lost use of his legs, his bladder control, his appetite, his eyesight, his hearing, or any other bodily function. In fact, this is quite possibly the best all in one I have ever used.

Posted by: puptch | July 25, 2014 7:36 AM    Report this comment

My 5 yr old 1st lost urine control , then went Blind, & vomited Black & Black bloody diarrhea . My 11 yr old also lost urine control , went blind & had bloody diarrhea. Both died within a month of each other AFTER given Trifexis ... It is Cruel & inhuman treatment to KILL our family members. Now I hear the company has changed there name to continue murdering out pets. This needs to stop. I lost my daughter ,my father , my husband & ,y mother all in 7 months. my 11 yr old was my daughters baby girl , I promised I would take care of for her & Trifexis KILLED HER . I hope the company & people who work for them & Vets that sold this garbage to use rot in .....

Posted by: DeathbyTrifexis | July 23, 2014 9:17 PM    Report this comment

My dog is a three year old mix hound and she lost the use of her back legs and can no longer walk due to the use of Trifexis this medication should be taken off the shelf so many dogs are dying getting sick or losing the use of their legs from this its horrible

Posted by: debpeir13 | July 17, 2014 8:03 AM    Report this comment

I was about to administer triflexis for the first time to my border collie today but I decided to do a quick search online first - I'm glad I did, I found multiple sites warning that dogs had died from this drug. I don't care how low the chance is that my dog will suffer ill effects, if there's even a small chance I am not taking that risk. I'm going to go down to my vet and get a refund for the triflexis. Question is, what can I use instead? I was only Prescribed triflexis because frontline and advantix no longer work (fleas are immune or resistant to the poison). The only alternatives where I live are triflexis and comfortis, both orally administrated (which I don't want to use after hearing about the dog deaths). Is there a natural remedy I can use? Otherwise the only option is to let him suffer and do a weekly bath to lower the numbers of fleas.

Posted by: Miss Cellany | June 9, 2014 5:06 AM    Report this comment

Reply to Patrick_67

Could you supply your site regarding collies please? I want to read the other post you mentioned. Thank you!

Posted by: Karen N | May 30, 2014 3:02 PM    Report this comment

We put our six months poodle on Trifexis. He has been on it for six weeks. He has grown a red button on his right paw. He is jumpy. My ten year Jack Russel (female) has become solitary. I have never put these dogs or any previous dogs on any strong preventatives. After all my research, I am taking my dogs off Trifexis. The stats admit that Trifexis was released during the time of accumulation of paper reports of incidences and computer reports there was a problem getting the reports of findings combined because of fusing the two systems which left inadequate time for info to be stabilized because of the system compilations and the research lack.

Posted by: Page | May 30, 2014 11:45 AM    Report this comment

Response to Angelic

I am French and I have an important site on Collie. A site mainly dedicated to the health problems of the breed. A mutation in MDR1 gene makes Colley (and a dozen other breeds) sensitive to many chemical molecules, including Ivermectin. MDR1 protects the brain (CNS) against many toxic molecules (xenobiotics).

I launched an alert on 14/08/2011 on Comfortis and active molecule that is spinosad.

The findings suggest that spinosad, by inhibiting MDR1 action at the blood-brain barrier, increases the risk of neurotoxicity for many molecules (xenobiotics).

The TRIFEXIS uses spinosad + milbemycin oxime . However, the milbemycin is a molecule of the same family as Ivermectin. The milbemycin also interacts with MDR1 .

Perhaps many accidents could be explained by this action that the TRIFEXIS can produce at the blood-brain barrier. All adverse effects are neurological signs: vomiting , depression, lethargy , anorexia , trembling / shaking , ataxia , seizures , hypersalivation

I will shortly issue a warning about the TRIFEXIS because these two molecules bound to MDR1 . The risk of unintended interaction with other chemicals controlled by MDR1 molecules are important. And, especially as spinosad has a long duration of action.

Patrick

Posted by: Patrick_67 | May 10, 2014 3:23 PM    Report this comment

Hi, I found the comments very interesting. We have used Frontline for years with no adverse affects. I wonder if it makes a difference whether the dog is large or small? I am in animal rescue and I have always adopted large dogs. Right now I have an American Rottweiler and a yellow lab, both neutered. It seems that the seizures and other complications, even death, are in small dogs. Since I have used Frontline for years, on other dogs that have crossed over from old age and NEVER had a problem, I am sticking with it. We use Heart Guard for heartworms. Our Vet recommends year round protection but here in Michigan there are no mosquitoes or fleas in the winter. (especially THIS winter, 2014) I also feel that it gives my dog's liver a break for a few months. Money is not a factor. Every March or April we have the blood test just to be sure and then treat them until winter rears it's ugly head again. I NEVER BUY ANYTHING THAT WILL BE CONSUMED FROM CHINA!!!

Posted by: Unknown | February 3, 2014 6:02 PM    Report this comment

I believe my own eyes and I had my Gizmo (Yorkie) given a clean bill of health by a Vet ,on my way out I was handed a Trifexis tablet to give him. He was acting fine till the night I gave him that tablet,as soon as I did he ran acting funny and vomitted 3 times. Next day wasn't acting right,became lethargic,couldn't eat,or drink,couldn't move his back legs.Next stage was blood in his stool,seizures etc.The pain that he suffered was horrible, I even had him in a Vet Hospital on IV etc. Still I couldn't save my precious baby, I still hurt and will never forget that what I thought was the right thing ,give him a pill from a Vet and now he is gone, Trifexis shouldn't have been put on the market without more testing.The people from Elanco are still denying what is going on ,,how can they sleep at night. Do people really think we are pooring our hearts out on face book for nothing.. Think the video's on there aren't real,,,give me a break ,,we are doing these in memory of our precious little ones who aren't hear and don't have a way of standing up for themselves.

Posted by: angelic | February 1, 2014 5:36 PM    Report this comment

Thank you for the balanced report. A restrained and thoughtful approach is hard to come by these days.

Posted by: Elaine K | December 27, 2013 2:30 PM    Report this comment

I'd like to see a report on heart worm pills like the report on food.

Posted by: carolthequilter | December 25, 2013 8:02 PM    Report this comment

I don't think I'm paranoid, but I do think we are at "war" w/China. The more we buy from that country, with their care-less attitude toward other's health and well-being, the more they win. I will not knowingly buy products made in China and I am careful when reading labels. I will pay more and buy USA made AND assembled. A few years ago, I was purchasing garden rocks and found some real beauties for my garden. As I was about to pay, the clerk mentioned that they were imported from China. That stopped the sale. Why should I care about rocks that certainly would not be ingested? I care because I will not support a society that does not support the human/animal condition. Read those labels!

Posted by: Rochelle | December 25, 2013 8:38 AM    Report this comment

I have yet to find a "satisfactory" flea treatment.

The old 'washes' tended to be very limited, especially when used on dogs with a dense undercoat. They also tended to make the dogs sick.

The flea collars make ME feel sick heaven's knows what they do to dogs that are wearing them.

Swimming in the ocean works well -- for dogs that WILL go in the water and saturate themselves to the skin.

Initially fipramil seemed to do a wonerful job, but recently I've found that a couple of weeks after applying the various spot-ons for ticks, we have a flea plague :-(

So I use Spinosad. So far with no ill-effects (except freedom from fleas! :-) But I do not think that I would use it regularly.

From the reported problems I've heard here it seems to be due to long term regular use.

Posted by: Jenny H | December 25, 2013 2:23 AM    Report this comment

Thanks for writing an interesting article with such a balanced view. It is true, we need to keep things in perspective. In Australia we have Comfortis and Panoramis, which also contain Spinosad. Initially my clinic was reluctant to recommend the product, as there already seemed to be so many good flea treatments available with proven track records. More and more clients kept coming in and asking for Comfortis, as they had bought it elsewhere online and loved it. Eventually we caved, and have so far had no adverse events reported.

That being said, I think it is definitely true to say that no drug is 100% safe, and unfortunately the same can be said for 'natural' things too. A pet or human can have an adverse reaction to anything, whether that be a so-called natural thing such as something in their food, a herb, a vitamin, a plant, or an essential oil and I think we need to keep any reaction in perspective. I could develop a severe anaphylactic reaction to an insect bite. If that happened 2 hours after I administered a flea treatment to my pet I would definitely blame the flea treatment. That is human nature, but it is not science.

No drug company (or Vet!) wants to hurt pets. There is no financial reason and it is ridiculous to say that Vets are in on a conspiracy with drug companies to support unsafe products! We all get into this industry to help animals...and we like to base all our actions on the available scientific research.

One of the most common 'natural' products I see as a vet used inappropriately is Tea Tree oil. This can be very toxic if ingested (such as when your pet grooms), and is contained in many products, such as animal shampoos for its antibacterial properties. Usually the concentration is minimal, so it is relatively safe, but of course that concentration is also completely ineffective and will not kill bacteria at all.

I think with all the information on the internet we are all wise enough to know that we can't trust everything we read. A very well-meaning person on the internet claiming to have a 'natural' solution to fleas has essentially a study group of one or two on which to base their safety data. Administering garlic to your pets is toxic, do not use this a flea preventative! If you want to use something safe, use good old fashioned vacuuming, sunlight and washing of bedding at more than 60 degrees Celsius before you spray your pet with anything weird or give them a 'natural' product.

Posted by: Unknown | December 24, 2013 11:47 PM    Report this comment

There is NO safe chemical product. There are plenty of safe, all natural products that will repel and/or kill fleas, lice, mites, pests on our pets. Our dogs picked up lice from a trip to a groomer. No way did we have time to shampoo and nit pick them daily so I searched online and found that neem seed oil kills pests and their eggs. Works for fleas, lice, mites and more. This website has the information: www.discoverneem.com. We added 1 oz of raw neem seed oil to 1.5 oz of liquid peppermint castile shampoo; kept it all sudsy on the dogs for 10-11 minutes, rinsed well. Repeated that 2 more time every 7 days. After the first shampoo, they weren't itching any longer. It killed all the buggers and was safe for the dogs. Be sure to protect their eyes with either a drop of mineral oil or Puralube eye ointment in each eye before lathering them up. The website has instructions on making a natural spray that works as a repellant and we use that when the dogs go anywhere they could pick up critters. Neem oil smells a bit like garlic so we add either geranium, lemon grass or citronella essential oil to the spray mix; smells so nice then. It really works, they haven't had any fleas or other pests. To put it on the head/face area, we spray it on our hands and rub on their fur. You need to make the shampoo mix fresh each time as it only lasts for 8 hours.

Years ago, my sister put a topical flea product on her small dog; she didn't know they were toxic and her stupid vet told her it was safe. 2 hours later, her dog had a seizure. She calls the vet who says it can't be from the product, must be a coincidence...but he tells her to bathe the dog really well and then bring him in. The dog has never had another seizure and my sister learned the hard way that 1)no chemical is safe, no matter who says it is; 2) conventional vets don't know much.

Posted by: YorkieMom | December 24, 2013 2:41 PM    Report this comment

About 6 months ago a friend working in a repro clinic in FLorida mentioned that Trifexis was the cause of neonatal deaths and some other repro problems and was not recommended. About that time a 9 month old terrier pup I had sold was obviously showing signs of Failure to Thrive and I mentioned Trifexis - turns out that she was on it so I asked that something else be given - within two months she had gained 2 pounds and her coat was beaching thicker and glossy.

Posted by: Carol O | December 24, 2013 11:11 AM    Report this comment

China rears it's ugly head again. I cannot believe people are so dumb to keep buying products from China. PROTECT YOUR PETS!!!

Posted by: Norm Starr | December 24, 2013 10:38 AM    Report this comment

A grain of salt? If you love your pets, avoid poisoning them with this Toxic drug! Try proving to Elanco that your dog was harmed. All you can do is prove what it isnt... They will still say maybe its your water?? Nice try, I only give her bottled water.

The reports are very vague as they ask for symptoms before the final diagnosis is made. The updates are not reported. Sadly your dog will suffer long term effects of this poison, providing they make it. I still have my darling, but not because they helped me. She will have permanent damage as many will. Your vet listens to the sales people at Elanco, Trifexis is made in China. Be safe not sorry!

Posted by: Salli J | December 24, 2013 10:19 AM    Report this comment

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