Description:
Bayer Animal Health
Caution:
Federal (U.S.A.) Law restricts this drug to use by or on the order of a
licensed veterinarian.
For The
Treatment Of Equine Protozoal Myeloencephalitis (EPM) In Horses
For Oral Use
Only
DESCRIPTION:
Marquis® (15% w/w ponazuril) Antiprotozoal Oral Paste is supplied
in ready-to-use syringes containing 127 grams of paste. Each gram of paste
contains 150 mg of ponazuril (15% w/w). Marquis (ponazuril) is designed to
be delivered as an orally administered paste.
Each syringe
barrel of Marquis (ponazuril) contains enough paste to treat one (1) 1,200
lb (544 kg) horse for seven (7) days, at a dose rate of 5 mg/kg (2.27 mg/lb)
body weight. The plunger contains a dosage ring calibrated for a dose rate
of 5 mg/kg (2.27 mg/lb) body weight and marked for horse weight from 600 to
1,200 lbs (272 to 544 kg). The syringe barrels are packaged in units of four
with four reusable plungers. This package provides sufficient paste to treat
one 1,200 lb (544 kg) horse for 28 days at a dose rate of 5 mg/kg (2.27
mg/lb) body weight.
Ponazuril is an
anticoccidial (antiprotozoal) compound with activity against several genera
of the phylum Apicomplexa.
CHEMICAL
NOMENCLATURE AND STRUCTURE:
Ponazuril
1,3,5-Triazine-2,4,6(1H, 3H,
5H)-trione,1-methyl-3-[3-methyl-4-[4-[(trifluoromethyl)sulfonyl]
phenoxy]phenyl]-(9CI)
CLINICAL
PHARMACOLOGY: The activity
of ponazuril has been demonstrated in several Apicomplexans1-6.
Lindsay, Dubey and Kennedy7 showed that the concentration of
ponazuril necessary to kill Sarcocystis neurona in vitro was 0.1 to
1.0 µg/mL. Furr and Kennedy8 evaluated the pharmacokinetics of
ponazuril in serum and CSF in normal horses treated daily at 5 mg/kg for 28
days. The time to peak serum concentration (Tmax) was 18.20 (±5.9)
days and the maximum serum concentration (Cmax) was 5.59 (±0.92)
µg/mL. The terminal elimination half-life for serum (calculated using Day 28
to 42 data) was 4.50 (±0.57)
days. In CSF, Tmax was 15.40 (±7.9)
days and Cmax was 0.21 (±0.072)
µg/mL.
INDICATIONS:
Marquis (ponazuril) is indicated for the treatment of equine protozoal
myeloencephalitis (EPM) caused by Sarcocystis neurona.
EFFECTIVENESS
SUMMARY: A field study was
conducted at six sites with seven investigators across the United States.9
The study was conducted using historical controls. In this study, each
animal's response to treatment was compared to its pre-treatment values. The
following standardized neurologic scale was used to grade the horses:
|
0 - |
Normal, no
deficit detected |
|
1 - |
Deficit
just detected at normal gait |
|
2 - |
Deficit
easily detected and is exaggerated by backing, turning, swaying,
loin pressure or neck extension |
|
3 - |
Deficit
very prominent on walking, turning, loin pressure or neck extension |
|
4 - |
Stumbling,
tripping and falling down spontaneously |
|
5 - |
Recumbent,
unable to rise |
Improvement was
defined as a decrease of at least one grade.
Naturally-occurring clinical cases of EPM, characterized by signalment and
laboratory diagnosis, were randomly allotted to one of two treatment doses
(5 or 10 mg/kg/day for a period of 28 days), then evaluated for clinical
changes through 118 days. Acceptance into the study was based on the results
from a standardized neurological examination including radiography, serum
S. neurona IgG level determination by Western Blot (WB), and a positive
cerebrospinal fluid (CSF) for S. neurona IgG level by WB.
Response to
treatment was determined by the investigator to be acceptable when a
clinical improvement of at least one grade occurred by no later than 3
months after treatment, regardless of whether the CSF by WB was positive or
negative.
Changes in
clinical condition were evaluated first by the subjective scoring of the
investigator, then by masked assessment of videotapes of the neurological
examination. At 5 mg/kg for 28 days, 28 of 47 horses (60%) improved at least
one grade by Day 118. Seventy-five percent (75%) of those improved, that had
also been videotaped, were corroborated successes by videotape assessment.
At 10 mg/kg, 32 of 55 animals (58%) improved at least one grade by Day 118
and 56% of those improved, that had also been videotaped, were corroborated
successes using videotape assessment. With respect to the clinical
investigators' scores there was no statistical difference between 5 mg/kg
and 10 mg/kg treatment group results (p = 0.8867).
WARNING:
For use in animals only. Not for use in horses intended for food. Not for
human use. Keep out of the reach of children.
PRECAUTIONS:
Prior to treatment, EPM should be distinguished from other diseases that may
cause ataxia in horses. Injuries or lameness may also complicate the
evaluation of an animal with EPM. In most instances, ataxia due to EPM is
asymmetrical and affects the hind limbs.
Clinicians should
recognize that clearance of the parasite by ponazuril may not completely
resolve the clinical signs attributed to the natural progression of the
disease. The prognosis for animals treated for EPM may be dependent upon the
severity of disease and the duration of the infection prior to treatment.
The safe use of
Marquis (ponazuril) in horses used for breeding purposes, during pregnancy,
or in lactating mares, has not been evaluated. The safety of Marquis (ponazuril)
with concomitant therapies in horses has not been evaluated.
ADVERSE
REACTIONS: In the field
study, eight animals were noted to have unusual daily observations. Two
horses exhibited blisters on the nose and mouth at some point in the field
study, three animals showed a skin rash or hives for up to 18 days, one
animal had loose stools throughout the treatment period, one had a mild
colic on one day and one animal had a seizure while on medication. The
association of these reactions to treatment was not established.
ANIMAL SAFETY
SUMMARY: Marquis (ponazuril)
was administered to 24 adult horses (12 males and 12 females) in a target
animal safety study. Three groups of 8 horses each received 0, 10, or 30
mg/kg (water as control, 2X and 6X for a 5 mg/kg [2.27 mg/lb] dose). Horses
were dosed after feeding. One half of each group was treated for 28 days and
the other half for 56 days followed by necropsy upon termination of
treatment. There were several instances of loose feces in all animals in the
study irrespective of treatment, sporadic inappetence and one horse at
10 mg/kg (2X) lost weight while on test. Loose feces were treatment related.
Histopathological findings included moderate edema in the uterine epithelium
of three of the four females in the 6X group (two treated for 28 days and
one for 56 days).
For customer
service or to obtain product information, including Material Safety Data
Sheet, call 1-800-633-3796. For medical emergencies or to report adverse
reactions, call 1-800-422-9874.
DOSAGE:
Marquis (15% w/w ponazuril) is to be used at a dose of 5 mg/kg (2.27 mg/lb)
body weight once daily for a period of 28 days.
|
ADMINISTRATION:
Paste syringe assembly:
Before administration, the syringe barrel and plunger require
assembly. Ensure plunger is clean and dry. |
 |
|
Step 1. |
End cap
must be on syringe barrel when inserting plunger. |
|
Step 2. |
Carefully
insert reusable plunger into base of syringe barrel until it snaps
into place, then remove end cap and gently apply pressure to the
plunger until paste is seen at the tip of the syringe barrel. |
|
|
Step 3. |
Return end
cap to tip of paste syringe. |
|
|
Administering Marquis (ponazuril) to the horse: |
|
NOTE: |
The paste
syringe is a multi-dose package. Ensure that the correct dose is
administered with each use. |
|
Step 1. |
Remove end
cap and gently apply pressure to the plunger until paste is seen at
the tip of the syringe barrel. Return end cap to tip of paste
syringe. |
|
Step 2. |
Determine
weight of horse and insure the horse's mouth contains no feed. |
 |
|
Step 3. |
To measure
dose, dosage ring collar and barrel collar should be flush. Hold
plunger and rotate dosage ring with the other hand to the weight of
the horse. |
|
Step 4. |
Remove end
cap from tip of syringe barrel. |
|
Step 5. |
The
selected dose of paste should be deposited onto the back and top of
the horse's tongue. Introduce tip of paste syringe into the side of
the horse's mouth at the space between the front (incisor) and back
(molar) teeth. Deposit paste on the horse's tongue by depressing the
plunger of the syringe as far as the dose ring permits. Remove tip
of syringe from horse's mouth. |
|
|
Step 6. |
To aid
swallowing of paste, immediately raise horse's head for a few
seconds after dosing. |
|
Step 7. |
Clean the
tip of the syringe with a clean disposable towel and return end cap
to tip of syringe barrel. |
 |
|
Step 8. |
For the
next daily dose, repeat steps 1-7. |
|
NOTE: |
At the
end of the prescribed treatment period, partially used syringes
should be discarded. |
|
STORAGE: Store at
Controlled Room Temperature 15-30° C (59-86° F). |
|