Controversy Over Trifexis Continues

[galgrey]

The following article is from the latest issue of "Dogs Naturally" magazine. I'm posting it for informational purposes . Yes, I've read the AMVA's official statement: "A summary of the pathology/necropsy reports from an independent pathologist has determined that the cause of deaths were unrelated to the administration of Trifexis®. The summary was derived from the individual pathology/necropsy reports which led attending veterinarians to also conclude that Trifexis® was not the cause of death."

 

It is not my intent to make anyone mad or start trouble here. I just want to provide this as information. If I were giving this drug to my dogs or even considering giving it, I would want to know about these deaths so I could make a more informed decision re: using it.

 

 

The Heartworm Medication Trifexis Is Causing Dog Deaths

 

There have been many reports this week of the heartworm drug Trifexis® being responsible for the deaths of 700 pets this year. That’s 120 more than have died from eating Chinese chicken jerky. And just like the jerky, veterinarians and the FDA are slow to do anything about it.

What Is Trifexis®?

 

Trifexis is a multipurpose heartworm, flea and parasite prevention medication that’s been on the market for nearly three years. It contains two active ingredients: spinosad and milbemycin oxime. In Trifexis® clinical trials, the most common adverse reactions (in order) were vomiting, depression/lethargy, pruritus, anorexia, diarrhea, trembling/shaking, ataxia, seizures, hypersalivation, skin reddening. But pet owners are reporting these reactions with alarming frequency and, so far, 700 deaths have been reported.

 

Spinosad is a broad insect pest spectrum used as a pesticide on crops since 1997. Insects treated with spinosad show involuntary muscle contractions and tremors resulting from activation of motor neurons, with prolong hyperexcitation resulting in prostration, paralysis and death in fleas – often within minutes of taking the drug.

 

Spinosad is also the active ingredient in Comfortis® and also Natroba for human head lice. It kills through both contact and ingestion but is much more effective if insects ingest it. Spinosad is not listed on US EPA list or CA Prop 65 list, which suggests it’s not been found to be carcinogenic.

 

It appears to be well known that spinosad can interact badly with ivermectin (Heartgard®). A study found ivermectin toxicity in dogs when given in conjunction with spinosad (Comfortis®). The findings suggest that spinosad increases the risk of ivermectin neurotoxicity by inhibiting the secretion of ivermectin to increase systemic drug levels and by inhibiting P-gp at the blood-brain barrier. (http://www.ncbi.nlm.nih.gov/pubmed/21321059)

 

Trifexis® and Comfortis® both carry warnings about this on their websites. Vomiting, loose stools, bloody diarrhea were the most common adverse reactions during Comfortis® trials. There are also some reports of seizure like symptoms, lethargy, weight loss and respiratory issues.

 

There are lots of anecdotal reports of dogs suffering severe vomiting, stomach issues, lethargy, lack of appetite, kidney failure, seizure-like symptoms, vestibular symptoms and death after being dosed with Comfortis®. Many of these stories can be found in the comments under this veterinary article advocating Comfortis as a wonder drug.

 

The second active ingredient in Trifexis®, milbemycin oxime (trade name Interceptor), is also used in Milbemax (with praziquantel), and Sentinel Flavor Tabs (with lufenuron). It acts by binding to glutamate gated chloride ion channels in invertebrate nerve and muscle cells, causing paralysis and death of the parasites. It may also act by disrupting the transmission of invertebrate neurotransmitters.

 

Adverse effects reported for milbemycin show (in order of frequency) 9,359 instances of it being ineffective against heartworm, vomiting (2453), diarrhea, ineffective against ascarids, depression/lethargy, ineffective against hookworms, whipworms, anorexia and many more.

Adverse Effects

Reporter Jim Strickland from Atlanta has obtained the detailed clinical reports on the adverse events from Trifexis®. In its short life, the drug has resulted in the following reports:

Emesis: 23,360 number of times reported
Lethargy: 7,366
Lack of Efficacy: 5,707
Vomiting: 4,570
Ineffective, fleas: 2,870
Diarrhea: 2,468
Behavioral disorders: 1,448
Seiaures: 1,363
Pruritis: 1,044
Anorexia: 1,028
Itching: 1,017
Ataxia: 953
Shaking: 930
Ineffective: hookworms: 916
Ineffective: heart worm larvae: 810

 

This in addition to the 700 reported deaths. However, the FDA said that while it’s heard the complaints and is monitoring the product, there’s no link between Trifexis® and the death of any dogs. The manufacturer of Trifexis®, Elanco, also states they are monitoring the deaths although there’s no indication of this on their website.

 

Keep Calm And Carry On

In the face of the recent surge of complaints, the AVMA issued the following statement:

“Today, we received an update. A summary of the pathology/necropsy reports from an independent pathologist has determined that the cause of deaths were unrelated to the administration of Trifexis®. The summary was derived from the individual pathology/necropsy reports which led attending veterinarians to also conclude that Trifexis® was not the cause of death.”

 

Who was the independent pathologist? Jeffery A Engelhardt, who was employed by the manufacturer of Trifexis®, Eli0Lilly/Elanco, from 1985-2004. It appears that he might not be as independent as the AVMA indicates.

 

So the veterinary association isn’t yet willing to act on the reports and they’re relying on information that is likely produced by the drug manufacturer. This shouldn’t come as a surprise however – when dogs and cats were getting ill and dying from tainted pet food, the veterinary associations supported the pet food manufacturers and encouraged pet owners to keep feeding kibble – a position that cost many more pets their lives.

 

Despite the AVMA’s position, the complaints of Trifexis® related deaths and adverse events continue. The Facebook page, TrifexisKillsDogs, contains many stories and updates on the product and accusations.

 

Beth Timms said her dog, Gizmo, was lethargic, suffered vertigo, seizures and a 106 degree fever after her vet prescribed the dog’s first ever dose of Trifexis®. “We had to let her go. We had to have her put her to sleep. I killed my dog,” she said.

 

Much of the media attention began with seven Vizsla puppies that were born in June 2013. While four of these puppies are thriving and have never had Trifexis®, three puppies each got their one and only dose of Trifexis® in early to mid September. One died within six days while two were dead within three weeks. Each puppy died of heart inflammation. The cause of death is still being researched, but the only common element is the Trifexis®.

 

Trifexis is also marketed under the private label Vethical ComboGuard for VCA vet clinics. Vethical also has a Comfortis® equivalent called Acuguard.

Edited November 29, 2013 by galgrey

[MaryJane]

Thank you for posting this - I also saw it on some of my other news feeds. It's alarming and as yet, hard to tell where it is coming from but, there does seem to be some correlation with the Trifexis.

[Charlies_Dad]

I don't think it's a coincidence. Others will counter this with some of their own wisdom but that is not going to convince me otherwise. You do everything to keep your pup healthy and this is what happens. Drug companies are just that, a company and a company is in the business to make money. A drug manufacturer will do anything to deny it and or prevent the spread of this news and the AVMA will stand right by them as there again is a lot of money involved.

[KF_in_Georgia]

So far, the FDA has not been able to figure out how chicken jerky treats have killed 600+ pets, but most of us believe there's a correlation between the treats and the pet deaths and have stopped feeding our pets the jerky treats.

 

So I'm not impressed when the FDA and Elanco (the manufacturer) say there's no correlation between Trifexis and the deaths of 700+ pets. I have a hard time believing in that big a coincidence.

[JJNg]

It's alarming and as yet, hard to tell where it is coming from but, there does seem to be some correlation with the Trifexis.

 

There is a good bit of information about the cases where this "is coming from" on the Internet, including full necropsy reports and interviews with the owners about the course of clinical signs. The majority of the recent publicity has all traced back to a single news station in Atlanta. Looking critically at the details of the cases, I'm not convinced of the alleged correlation to Trifexis.

 

All meds have the potential for side effects, and I don't automatically discount client claims. But just because an owner is convinced that Trifexis killed their dog doesn't make it true, especially when the necropsy shows otherwise. Also, keep in mind that the American public seems to have a tendency toward paranoia, and Internet publicity often results in a rash of people joining in and making incorrect assumptions. For example, claims of dog food A making dogs sick start getting spread around the internet. Suddenly every time a dog that is eating food A gets sick, the owner blames it on the food. The original illness may or may not have been even due to the food, and it may have only been specific signs like vomiting and diarrhea. But before you know it, every conceivable illness is blamed on the food, and the reports start flooding in. So the large number of reports is often not a coincidence, nor proof of correlation, but more of a snowball effect.

 

This phenomenon has happened on more than one occasion, and may have played a role in the FDA recall of the 6-month injectable HW preventative Proheart. Interesting when you consider that Proheart (including a higher dose 12-month formula) was never recalled in Europe or Australia and was never shown to cause all the problems claimed by American owners. This type of overreaction also makes it even more difficult to discern which, if any, of the reports of side effects are real.

 

Here are some more thoughts about Trifexis that I posted to my clinic Facebook page:

 

Many of you have probably been seeing all the concerns about Trifexis on the Internet lately. It seems that all of the recent negative publicity goes back to a single news station in Atlanta. I have to wonder, what do they have against Trifexis? Why do they seem set on spreading paranoia based primarily on unsubstantiated owner claims to villify a perfectly good product?

 

Anyone who knows me knows that I'm conservative with medication and take potential side effects seriously. I also never discount reports and claims of side effects, regardless of the source, but they need to be evaluated critically. Just because an owner is convinced that something caused their pet's illness or death doesn't make it true. The longer I'm in practice, the more cases I see where people just make the wrong assumptions of cause and effect. I remember one case of parvo where the owner thought the bloody diarrhea was caused by the dog eating part of a rose bush.

 

What I find frustrating is that these news articles blaming Trifexis for the deaths of numerous dogs are not backed by any medical or scientific evidence. In fact, they include copies of necropsy reports that show the deaths to be from completely different and unrelated causes that haven't been connected with Trifexis.

 

Most drugs that have toxic effects cause specific signs, and there is some pattern to the problems which are related to how the chemical interacts with organ systems. The side effects proven to be caused by Trifexis/Comfortis, which mostly include vomiting, lethargy, and diarrhea have been pretty well documented. These recent reports blame Trifexis for such a variety of signs that, from a scientific standpoint, it makes no sense. Almost reminds me of holistic remedies that are claimed to cure everything under the sun, except this is the opposite - a medication is being blamed for causing just about every side effect you can imagine.

 

We have been using and recommending Trifexis for the almost 3 years it's been available, and Comfortis for 2-3 years prior to that. We have seen the occasional dog who can't tolerate it, but all problems have been mild and resolve without treatment. Here in the southeast, Comfortis/Trifexis is probably the most effective flea medication we have available.

 

I have also found Elanco/Eli Lilly to be an excellent company to work with, one that believes in the doing the right thing and doesn't puts the bottom line above all else. I'm sure they are investigating all reports of problems, and I'll be keeping a close eye out for any additional info. Perhaps further research will indicate a need for caution in pets with specific underlying problems, or of certain breeds. But my clinical experience over the past few years would indicate that this is not a dangerous product in general, and it is one that I still use in my own dogs and my fosters.

Edited December 2, 2013 by JJNg