Merck Equine Partners in Practice Magazine: Summer 2019

ISSUE NO. 2 | Summer 2019

MAGAZINE

KEEPING AN EYE ON EPM THIS SUMMER Early detection & treatment is critical to recovery 02

04

06

EXPLORING THE EFFECTIVENESS

RON'S CAMPFIRE

VET STORY NIGHT

Strangles, Noni Juice and a Jolly Old Elf

Call for Auditions!

of Protazil® (1.56% diclazuril)

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PARTNERS IN PRACTICE | Summer 2019

Featured

KEEPING AN EYE ON EPM THIS SUMMER

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pidemiologically, we know the risk of equine protozoal myeloencephalitis (EPM) is three times higher in spring and summer.1 Opossums and other wildlife that serve as hosts to the EPM-causing parasites, Sarcocystis neurona and Neospora hughesi, are more active in the summer months. Summer is also a time of heavy exercise, transport and other stressful events for horses, which can increase their risk of EPM. Up to 90% of the U.S. horse population has been exposed to S. neurona, depending on geographic location.1 Fortunately, the incidence of EPM clinical disease is low.

For those that do succumb, early disease treatment is critical

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PARTNERS IN PRACTICE | Summer 2019

to recovery. Irreversible damage to the brain or spinal cord is more likely to occur if the parasite has been present for long periods of time. Without treatment, many horses progressively deteriorate to the point of recumbency. Horses treated with an anticoccidial drug, like PROTAZIL® (1.56% diclazuril), are 10 times more likely to improve than untreated horses.1 Once the pesky parasites that cause EPM—S. neurona and N. hughesi—are ingested by the horse, they migrate from the intestinal tract into the bloodstream and cross the blood-brain barrier. Diclazuril, the active ingredient in PROTAZIL, is proven to cross the blood-brain barrier and enter the cerebrospinal fluid at levels high enough to either limit the reproduction of S. neurona protozoa or kill them outright—without a loading dose.2 This means you can achieve a rapid therapeutic effect without the need for a loading dose. PROTAZIL is proven to reach therapeutic levels within hours of administration.2

Few diseases are more frustrating than EPM. The industry continues to grapple with this “master of disguise,” including how best to definitively diagnose it in a live horse and whether any preventive strategies might be appropriate (or on the horizon). Of certainty, EPM continues to threaten horses in large numbers and because it has no single defining clinical characteristic, any neurological horse could be a candidate —making your task in managing EPM a difficult one.

Faced with a new or recurring case of EPM? Reach for PROTAZIL; it starts working fast against a disease where time matters, without a loading dose. PROTAZIL also offers added convenience as a top-dress medication, ideal for horses with a reluctance to accept oral medication. The alfalfa based PROTAZIL pellets are well-accepted by most horses and consumed without the mess, fuss and stress of a paste.

Merck Animal Health

HORSE TIPS For additional information on EPM In February 2016, the American College of Veterinary Internal Medicine published an updated consensus statement on equine protozoal myeloencephalitis (EPM), with a focus on parasite biology, diagnosis, treatment and prevention. The consensus statement is open access and can be downloaded by clicking here.

Check out our new infographic on EPM, available to download in this issue. A great tool for client education.

What veterinarians are saying about PROTAZIL®

Timely Health Tips to Share with Horse Owners

“ The Protazil treatment regimen achieves therapeutic blood levels quickly and without a loading dose. I’ve used Protazil to treat my own horses and client horses, too. Protazil is easy to use, horses find the pellets palatable plus it’s priced competitively. Protazil has an excellent safety profile, is FDAapproved and backed by Merck Animal Health. Horse owners appreciate that assurance.”

Did you know that EPM is three times more likely to occur in the spring and summer?

If your horse is showing neurological signs, talk to your veterinarian immediately. If it’s EPM, early treatment is critical to disease recovery.

Download EPM Quick Facts to learn more.

Download Now

Daniel Yates, D.V.M. — Wilmington, Ohio

EQUINE PROTOZOAL MYELOENCEPHALITIS (EPM)

“ We have been using Protazil in our practice with excellent results. Client compliance in treatment has increased due to the ease of administration and palatability of Protazil over oral pastes. We’ve observed some horses will preferentially eat the Protazil over concentrate feeds. With increased client compliance we can achieve better treatment results with our patients and better outcomes for our clients.”

QUICK FACTS What is EPM?

Lifecycle of Sarcocystis Neurona1 1. The sarcocyst organism is ingested by the definitive host, the opossum,

EPM is an infectious, progressive neurological disease that affects horses following environmental exposure to opossum feces.

EPM can cause devastating and lasting neurological damage and any horse is susceptible.

by scavenging on intermediate hosts (cats, raccoons, skunks, armadillos, sea otters) that carry sarcocyst in skeletal muscle

2. The infective stage of the organism (the sporocysts) is passed in the

• Caused by infection with the parasite Sarcocystis neurona (S.

opossum’s feces

neurona); less frequently with Neospora hughesi (N. hughesi)1

3. The horse (dead-end host) acquires the infective sporocysts while grazing or eating contaminated feed or drinking water

• Up to 90% of the U.S. horse population has been exposed to S.

4. Once ingested by the horse, the sporocysts migrate from the intestinal

neurona, depending on geographic location1

tract into the bloodstream and cross the blood/brain barrier

• Not all horses infected with S. neurona

5. The resulting inflammatory response to sporocyst presence injures

or N. hughesi will develop disease

the horse’s central nervous system

• Cannot be spread from horse to horse

(The definitive or intermediate hosts for N. hughesi have not yet been identified.)1

Intermediate Hosts: Nine-Banded Armadillo Striped Skunk Raccoon

Definitive Host: Opossum

1. Sexual reproduction in digestive tract (intestinal epithelium)

Sarcocyst in skeletal muscle

EPM Risk Factors

1

• Exposure to wildlife; presence of opossums • Stress associated with illness, transport, strenuous exercise 2. Infective sporocyst in feces

• Young horses (1-5 years) • Horses used for western performance, racing and other strenuous activities

5.

• Immune-compromised horses of any age • Immunosuppression associated with

4.

concurrent conditions

Lesions in spinal cord and brain

• Commonly seen in late summer and fall, but can occur any time

Watch for These Signs Gait abnormalities

Diagnosis Diagnosing EPM is difficult because it can mimic other neurologic diseases.

Ataxia (incoordination)

• Complete neurologic and physical

Stumbling

exam to rule out other diseases

Muscle atrophy

• Blood and cerebrospinal

Weakness Depression Inability to chew or swallow

Greggory S. Bell, D.V.M. — Pagosa Springs, Colorado

Head tilt, ear droop Behavior change Blindness

Contact your veterinarian immediately if your horse exhibits neurological signs.

Horses that are diagnosed early and treated aggressively have the best chance for recovery.

fluid (CSF) analysis to detect antiprotozoal antibodies

3. Dead End Host: Horse ingests contaminated feedstuffs

Treatment and Recovery • An FDA-approved EPM treatment such as PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets will be prescribed to control infection

• Additional supportive treatment may be recommended based on the severity of neurologic deficits and associated complications

• 60-70% of horses show clinical improvement with early treatment1

Seizures

IMPORTANT SAFETY INFORMATION Use of Protazil® (1.56% diclazuril) Antiprotozoal Pellets is contraindicated in horses with known hypersensitivity to diclazuril. Safe use in horses used for breeding purposes, during pregnancy, or in lactating mares has not been evaluated. The safety of Protazil® (1.56% diclazuril) Antiprotozoal Pelletswith concomitant therapies in horses has not been evaluated. For use in horses only.

Do not use in horses intended for human consumption. Not for human use. Keep out of reach of children.

Brought to you by:

Talk to your veterinarian if you’re concerned about EPM and visit www.merck-animal-health-equine.com for more information on PROTAZIL®– the first and only alfalfa-based pellet EPM treatment.

Reed SM, et al. Equine Protozoal Myeloencephalitis: An Updated Consensus Statement with a Focus on Parasite Biology, Diagnosis, Treatment and Prevention. J Vet Intern Med 2016;30:491–502.

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2 Giralda Farms • Madison, NJ 07940 • merck-animal-health-usa.com • 800-521-5767 Copyright © 2019 Intervet Inc., d/b/a/ Merck Animal Health, a subsidiary of Merck & Co., Inc. All rights reserved. US/Equine/EPM Infographic/June 2019

4218_Protazil_Infographic_v9.indd 1

7/9/19 5:12 PM

Reed SM, et al. Equine Protozoal Myeloencephalitis: An Updated Consensus Statement with a Focus on Parasite Biology, Diagnosis, Treatment and Prevention. J Vet Intern Med 2016;30:491–502.

1

Hunyadi L, Papich MG, Pusterla N. Pharmacokinetics of a lowdose and FDA-labeled dose of diclazuril administered orally as a pelleted top dressing in adult horses. J of Vet Pharmacology and Therapeutics (accepted) 2014, doi: 10.111/jvp.12176.

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IMPORTANT SAFETY INFORMATION: Use of Protazil® (1.56% diclazuril) is contraindicated in horses with known hypersensitivity to diclazuril. Safe use in horses used for breeding purposes, during pregnancy, or in lactating mares has not been evaluated. The safety of Protazil® (1.56% diclazuril) with concomitant therapies in horses has not been evaluated. For use in horses only. Do not use in horses intended for human consumption. Not for human use. Keep out of reach of children.

Summer Spring 2019 | PARTNERS IN PRACTICE

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Ron's Campfire

RON’S CAMPFIRE NEW!

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here are no greater stories to be told than those of the practicing equine veterinarian. And if you’ve attended Vet Story Night at AAEP the last two years, you’ve heard some of the best. That is exactly what inspired our new section, Ron’s Campfire. Storytelling comes in many forms—whether on stage with a microphone, or at the tip of a pencil (or keyboard), equine veterinarians not only have scientifically gifted minds, they are also talented writers and storytellers.

If you have a story or blog you’d like to share, we’d love to feature it in a future issue.

Please email Ron McDaniel (ron.mcdaniel@merck.com) to learn more or submit contributions.

Vet Stories

Welcome

This issue of Ron’s Campfire features an original blog piece by Robert H. Koontz, D.V.M. Strangles, Noni Juice and a Jolly Old Elf About 10:30 one night I got a call from what sounded like a very old Amish man. He explained, "My name is Joseph Miller and I own the health food store in town. My horse is awful sick, can you come out and see him?" I didn't feel too bad about going out on the call.

The football game I was watching was going badly for my team, besides it was a very nice December evening.

It just started to snow as I pulled into the driveway.

Large, fluffy flakes floated leisurely from the sky.

A hunched over little man with a long, white beard sprung from behind the barn door and ran to my truck.

The pipe he smoked had a long wooden handle and puffs of gray smoke fluttered from the bowl.

Maybe I was caught up in the season, but I thought this hunchbacked little man with the long white beard, standing outside smoking a pipe while large snowflakes fell atop his head, looked very much like Santa Claus.

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PARTNERS IN PRACTICE | Summer 2019

As he ushered me into the barn he pointed the handle of the long wooded pipe at me, cocked his head, and with a knowing grin whispered, "If I could give you a potion that would cure all your patients, you'd be interested wouldn't you?" I have had people offer me magic cure-all concoctions before, so I politely said, "sure" without much interest and began to examine my patient.

It didn't take long to diagnose strangles in this three-year-old buggy horse.

When I pulled the thermometer, it read 105.1 degrees. His head was hanging nearly to the ground. He had no interest in his surroundings, and his eyes were lifeless. This horse was indeed "awful sick."

Dr. Rob Koontz

The little man persisted, "My medication is wonderful stuff. Why it cures cancer, kidney ailments, asteria, liver ailments, lameness, colic, infection, consumption and fever."

many testimonials from others that had been similarly cured. He was of the opinion that if I would start using Noni Juice in my veterinary practice that I could stop all equine suffering.

"Wow," I replied noncommittally, and continued to work on my patient.

When I looked under the jaw, I saw what I expected, two tell-tale swollen lymph nodes. It was strangles all right.

I continued to treat my patient.

I established drainage of the lymph nodes. I also gave him flunixin meglumine to reduce the temperature.

I felt confident that after my treatment this horse would feel better soon. While I was explaining this to Mr. Miller, he suddenly interrupted me. "I think a lot of this horse," the old man mused, "he deserves some Noni Juice."

While I treated my patient, Mr. Miller informed me that just four years ago he could barely walk due to "the cancer in his legs." I don't know what he was like four years ago but on that night, he was bouncing off the walls. Then he asked, "Young man, do you know how old I am?"

Without waiting for a response from me he answered, "I am 84 years old. I'm 84 years old and I look like I'm 60, I no longer have cancer, and I am no longer lame," he stated proudly. "I have one medicine to thank for it; Noni Juice!" he pronounced.

The little man went on to explain that Noni Juice was a tropical juice that could cure any human or animal ailment. It had cured him, and he had

I could see that this man really wanted me to give his horse the wonderful potion. Well, I reasoned, what could it hurt? I passed a nasogastric tube and poured a bottle of Noni Juice directly into the horse's stomach. I then packed up my equipment, said goodbye to Mr. Miller, and went home to bed.

The next day I stopped by the Miller Farm to check on the young horse.

As expected, he was doing much better.

Mr. Miller burst into the barn cackling, "See; see I told you the Noni Juice would

cure him!" I was informed that just one hour after the administration of Noni Juice my patient was improving.

I thought, but did not point out, that it was also one hour after my treatment when the horse started feeling better.

"Yes, yes," I said. "He is much better."

The jolly old fellow pointed his pipe at me and tried to convince me that I should throw away all the "old-fashioned" medications that I was currently using and start using Noni Juice exclusively.

I doubt the "amazing medication" helped.

Many times, I have seen horses with strangles make remarkable recoveries when I administered the exact same medical treatment without the Noni Juice. I don't know if Mr. Miller was just a health food salesman or if he was a jolly old elf, but despite the spry man's assertions, I think I will stick with my more traditional treatments.

Dr. Koontz is the chief executive officer of Conley & Koontz Equine Hospital in Columbia City, Ind. Read more stories from Dr. Koontz on his blog, Rob’s View from the Passenger Seat.

Summer 2019 | PARTNERS IN PRACTICE

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Merck Animal Health Business Tips

Did You Know?

THE DICHOTOMIES OF PRACTICE: COMMANDING A FEE FOR YOUR SERVICES

VET STORY NIGHT, BENEFITING THE AAEP FOUNDATION

I

n this issue, Dani McVety, D.V.M., Co-founder and CEO of Lap of Love Veterinary Hospice, shares a few tips to help support the value of your services with clients. Because, let’s face it, while few in veterinary medicine are motivated by money, as business owners you must command a fee for your services.

It’s simply not reasonable to provide low cost high service. Use the following verbal priming tips to help handle challenging client conversations.

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INSTEAD OF…

TRY…

(ESTIMATE FOR TREATMENT) I KNOW THIS SEEMS LIKE A LOT OF MONEY.

I hear you. The best medicine can cost a little more.

WE DON’T TAKE PAYMENT PLANS.

We aren’t in a position to offer payment plans.

I KNOW YOU CAN’T AFFORD THIS.

If price is your biggest concern, here are two great non-profit clinics in the area whose business model supports a lower cost option.

I KNOW YOU CAN’T AFFORD THIS.

Doing nothing may be more expensive.

YOUR PRICES ARE 30% MORE THAN EVERYONE ELSE.

That sounds about right.

YOU FORGOT YOUR WALLET?

What do you suggest?

PARTNERS IN PRACTICE | Summer 2019

CALL FOR AUDITIONS!

A

fter reading the piece from Dr. Rob Koontz earlier in this issue, and based on your own experience as a veterinarian, you’ll likely agree equine veterinarians have some of the best stories out there.

In 2017 at the annual AAEP convention, Merck Animal Health introduced a new idea inspired by the popular “open mic” concept to provide veterinarians a platform to share the hilarious and unbelievable stories of everyday veterinary medicine.

Dr. Koontz’s story is a prime example of what Vet Story Night is all about – an evening of fun and entertaining storytelling with your peers. Best of all, proceeds from Vet Story Night benefit the AAEP Foundation.

We’re looking forward to Denver, where once again some of the best storytellers in our profession will make us laugh until it hurts. Do you have a hilarious story to share?

Contact Ron McDaniel at ron.mcdaniel@merck.com or (479) 366-2236 to learn more about Vet Story Night 2019.

Auditions are currently taking place.

Stay tuned for more details and ticket information through the 2019 AAEP Convention page of AAEP.org.

VET STORY

NIGHT

LIVE

I MUSTACHE YOU TO

JOIN ME

Meet the Veterinary Professional Services Team

CHRISTINA S. TAYLOR, BS, RVT Equine Professional Services Salisbury, Maryland christina.taylor2@merck.com

Q&A

Tell us a little bit about your horse background.

My interest and passion for horses began in college. I leased a horse in college (strictly trail riding); cleaned horse stalls throughout college (I love the smell, no I really, really do!); and I went to (watch) every mule and draft horse team competition I could. I even participated in a round up on my cousin’s ranch.

Well, life happens and my ability to fit horses in after college just wasn’t meant to be, so I never became an official “horse person,” but my love for horses never ended. I guess I felt like all of the other livestock needed my love, too, because horses got love from so many people already. And my career has given me the opportunity to be involved in both production and companion animal care, which I’m grateful for.

If you were a horse, what type of horse would you be?

The breed would not be important to me. I think being the companion for a blind horse would be such a rewarding position and give you a great purpose in life!

Best horse advice you’ve ever received?

“Hold on tight!”

Best veterinary advice you’ve ever received?

I know its cliché but a vet I worked for told me, “People don't want to know how much you know, they want to know how much you care.”

Outside of the equestrian/veterinary world, what is your favorite hobby?

Going to the beach, every season of the year.

How long have you been working for Merck Animal Health?

27 years.

What is your favorite part of being on the equine veterinary professional services team?

Unequivocally, the people. Each person on the team is virtuous, humble, kind, ethical and, above all, a horse lover.

If there were one thing you would want customers to know about you, what would it be?

I am here to help them in any way I can to help keep horses healthy; that I truly care.

Summer 2019 | PARTNERS IN PRACTICE

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NAC N0.: 1047378.2

WARNINGS For use in horses only. Do not use in horses intended for human consumption. Not for human use. Keep out of reach of children.

PROTAZIL®

Intervet/Merck Animal Health ANTIPROTOZOAL PELLETS (1.56% DICLAZURIL) FOR ORAL USE IN HORSES ONLY CAUTION Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian.

NADA #141-268, Approved by FDA DESCRIPTION Diclazuril, (±)-2,6-dichloro-α-(4chlorophenyl)-4(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)yl) benzeneacetonitrile, has a molecular formula of C17H9CI3N4O2, a molecular weight of 407.64, and a molecular structure as follows:

Diclazuril is an anticoccidial (antiprotozoal) compound with activity against several genera of the phylum Apicomplexa. PROTAZIL® (diclazuril) is supplied as oral pellets containing 1.56% diclazuril to be mixed as a top-dress in feed. Inert ingredients include dehydrated alfalfa meal, wheat middlings, cane molasses and propionic acid (preservative).

INDICATIONS PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets are indicated for the treatment of equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona in horses.

DOSAGE AND ADMINISTRATION Dosage: PROTAZIL® (1.56% diclazuril) is administered as a top dress in the horse’s daily grain ration at a rate of 1 mg diclazuril per kg (0.45 mg diclazuril/lb) of body weight for 28 days. The quantity of PROTAZIL® necessary to deliver this dose is 64 mg pellets per kg (29 mg pellets/lb) of body weight.

Administration: To achieve this dose, weigh the horse (or use a weigh tape).

Scoop up PROTAZIL® to the level (cup mark) corresponding to the dose for the horse’s body weight using the following chart: Weight Range of Horses

mLs of

(lb)

Pellets

275-524

20

525-774

30

775-1024

40

1025-1274

50

1275-1524

60

1525-1774

70

1775-2074

80

One 2.4-lb bucket of PROTAZIL® will treat one 1274-lb horse for 28 days. One 10-lb bucket of PROTAZIL® will treat five 1100lb horses for 28 days.

CONTRAINDICATIONS Use of PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets is contraindicated in horses with known hypersensitivity to diclazuril.

PRECAUTIONS The safe use of PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets in horses used for breeding purposes, during pregnancy, or in lactating mares has not been evaluated.

The safety of PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets with concomitant therapies in horses has not been evaluated.

ADVERSE REACTIONS There were no adverse effects noted in the field study which could be ascribed to diclazuril. To report suspected adverse reactions, to obtain a MSDS, or for technical assistance call 1-800-224-5318.

CLINICAL PHARMACOLOGY The effectiveness of diclazuril in inhibiting merozoite production of Sarcocystis neurona and S. falcatula in bovine turbinate cell cultures was studied by Lindsay and Dubey (2000).1 Diclazuril inhibited merozoite production by more than 80% in cultures of S. neurona or S. falcatula treated with 0.1 ng/mL diclazuril and greater than 95% inhibition of merozoite production (IC95) was observed when infected cultures were treated with 1.0 ng/mL diclazuril. The clinical relevance of the in vitro cell culture data has not been determined.

PHARMACOKINETICS IN THE HORSE The oral bioavailability of diclazuril from the PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets at a 5 mg/kg dose rate is approximately 5%. Related diclazuril concentrations in the cerebrospinal fluid (CSF) range between 1% and 5% of the concentrations observed in the plasma. Nevertheless, based upon equine pilot study data, CSF concentrations are expected to substantially exceed the in vitro IC95 estimates for merozoite production (Dirikolu et al., 1999)2. Due to its long terminal elimination half-life in horses (approximately 43-65 hours), diclazuril accumulation occurs with once-daily dosing. Corresponding steady state blood levels are achieved by approximately Day 10 of administration.

EFFECTIVENESS Two hundred and fourteen mares, stallions, and geldings of various breeds, ranging in age from 9.6 months to 30 years, were enrolled in a multi-center field study. All horses were confirmed EPM-positive based on the results of clinical examinations and laboratory testing, including CSF Western Blot analyses. Horses were administered PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets at doses of 1, 5, or 10 mg diclazuril/kg body weight as a top-dress on their daily grain ration for 28 days. The horses were then evaluated for clinical changes via a modified Mayhew neurological scale on Day 48 as follows: 0. Normal, neurological deficits not detected.

1. Neurological deficits may be detectable at normal gaits; signs exacerbated with manipulative procedures (e.g., backing, turning in tight circles, walking with head elevation, truncal swaying, etc.).

2. Neurological deficit obvious at normal gaits or posture; signs exacerbated with manipulative procedures.

3. Neurological deficit very prominent at normal gaits: horses give the impression they may fall (but do not) and buckle or fall with manipulative procedures.

The Science of Healthier Animals 8

2 Giralda Farms • Madison, NJ 07940 • merck-animal-health-equine.com • 800-521-5767 Copyright © 2019 Intervet Inc., d/b/a/ Merck Animal Health, a subsidiary of Merck & Co., Inc. All rights reserved. US-Equine-Summer PIP Newsletter – July 2019

PARTNERS IN PRACTICE | Summer 2019

4. Neurological deficit is profound at normal gait: horse frequently stumbles or trips and may fall at normal gaits or when manipulative procedures were utilized.

5. Horse is recumbent, unable to rise.

Each horse’s response to treatment was compared to its pre-treatment values.

Successful response to treatment was defined as clinical improvement of at least one grade by Day 48 ± conversion of CSF to Western Blot-negative status for S. neurona or achievement of Western Blotnegative CSF status without improvement of 1 ataxia grade.

Forty-two horses were initially evaluated for effectiveness and 214 horses were evaluated for safety. Clinical condition was evaluated by the clinical investigator’s subjective scoring and then corroborated by evaluation of the neurological examination videotapes by a masked panel of three equine veterinarians.

Although 42 horses were evaluated for clinical effectiveness, corroboration of clinical effectiveness via videotape evaluation was not possible for one horse due to missing neurologic examination videotapes. Therefore, this horse was not included in the success rate calculation.

Based on the numbers of horses that seroconverted to negative Western Blot status, and the numbers of horses classified as successes by the clinical investigators, 28 of 42 horses (67%) at 1 mg/kg were considered successes. With regard to independent expert masked videotape assessments, 10 of 24 horses (42%) at 1 mg/kg were considered successes. There was no clinical difference in effectiveness among the 1, 5, and 10 mg/kg treatment group results.

Adverse events were reported for two of the 214 horses evaluated for safety. In the first case, a horse was enrolled showing severe neurologic signs. Within 24 hours of dosing, the horse was recumbent, biting, and exhibiting signs of dementia.

The horse died, and no cause of death was determined. In the second case, the horse began walking stiffly approximately 13 days after the start of dosing. The referring veterinarian reported that the horse had been fed grass clippings and possibly had laminitis.

ANIMAL SAFETY PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets were administered to 30 horses (15 males and 15 females, ranging from 5 to 9 months of age) in a target animal safety study. Five groups of 6 horses each (3 males and 3 females) received 0, 5 (5X), 15 (15X), 25 (25X) or 50 (50X) mg diclazuril/kg (2.27mg/lb) body weight/day for 42 consecutive days as a topdress on the grain ration of the horse. The variables measured during the study included: clinical and physical observations, body weights, food and water consumption, hematology, serum chemistry, urinalysis, fecal analysis, necropsy, organ weights, gross and histopathologic examinations.

The safety of diclazuril top-dress administered to horses at 1 mg/kg once daily cannot be determined based solely on this study because of the lack of an adequate control group (control horses tested positive for the test drug in plasma and CSF). However, possible findings associated with the drug were limited to elevations in BUN, creatinine, and SDH and less than anticipated weight gain.

Definitive test article-related effects were decreased grain/top-dress consumption in horses in the 50 mg/kg group.

In a second target animal safety study, PROTAZIL® (1.56% diclazuril) Antiprotozoal

Pellets were administered to 24 horses (12 males and 12 females, ranging from 2 to 8 years of age). Three groups of 4 horses/ sex/group received 0, 1, or 5 mg diclazuril/ kg body weight/day for 42 days as a topdress on the grain ration of the horse. The variables measured during the study included physical examinations, body weights, food and water consumption, hematology, and serum chemistry. There were no test article-related findings seen during the study.

STORAGE INFORMATION Store between 15°C to 30°C (59°F to 86°F).

HOW SUPPLIED PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets are supplied in 2.4-lb (1.1 kg) and 10-lb (4.5 kg) buckets.

REFERENCE 1. Lindsay, D. S., and Dubey, 1. J. P. 2000.

Determination of the activity of diclazuril against Sarcocystis neurona and Sarcocystis falcatula in cell cultures.

J. Parasitology 86(1):164-166.

2. Dirikolu, L., Lehner, F., Nattrass, C., Bentz, B. G., Woods, W. E., Carter, W. E., Karpiesiuk, W. G., Jacobs, J., Boyles, J., Harkins, J. D., Granstrom, D. E. and Tobin, T. 1999. Diclazuril in the horse: Its identification and detection and preliminary pharmacokinetics. J. Vet. Pharmacol. Therap. 22:374-379.

Intervet Inc d/b/a Merck Animal Health, 556 Morris Avenue, Summit, NJ 07901 Copyright © 2014 Intervet Inc., a subsidiary of Merck & Co. Inc. All rights reserved.

2.4 lbs (1.1 kg)

07-2014

10 lbs (4.5 kg)

09-2011