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Marquis (Ponazuril) Information
MARQUIS Rx
(15% w/w ponazuril) Antiprotozoal Oral Paste
Bayer Corporation
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 one reusable plunger. This package
provides sufficient paste to treat one 1,200 lb (544 kg) horse for 28 days at a
dose rate of 5mg/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 a copy of the Material Safety Data Sheet (MSDS) or to
report Adverse
Reactions, call Bayer Customer Service at (800) 633-3796.
DOSAGE: Marquis (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 ensure 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 weightof 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: When the paste syringe barrel is empty, remove plunger
for re-use and assembly with a new syringe barrel. When removed, the
plunger may retain a seal from the empty paste syringe barrel. If this occurs,
remove the seal before plunger is inserted into the base of the new paste
syringe barrel. 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).
HOW SUPPLIED:
Code: 045799 Carton contains four (4) x 127 gram syringe
applicators and one (1) reusable syringe plunger
REFERENCES:
Mehlhorn, H., Ortmann-Falkenstein, G., Haberkorn, A.: (1984)
The effects of
the sym. Trianzinons on developmental stages of Eimeria
tenella, E. maxima
and E. acervulina: a light and electron microscopical study.
Zeitschr
Parsitenk 70: 173-182.
Bohrmann, R.: (1991) Treatment with toltrazuril in a natural
outbreak of
coccidiosis in calves. Dtsch. Tierarzl. Wschr. 98: 343-345.
Stafford, K.J., West, D.M., Vermunt, J.J., Pomroy, W.,
Adlington, B.A.,
Calder, S.M.: (1994) The effect of repeated doses of
toltrazuril on coccidial
oocyst output and weight gain in infected lambs. NZ Vet J
42(3): 117-119.
Haberkorn, A.G., Stoltefuss, D.I.J.: (1987) Studies on the
activity spectrum
of toltrazuril, a new anticoccidial compound. Vet. Med.
Review 1: 22-32.
Koudela, B., Vodstricilova, M., Klimes, B., Vladik, P.,
Vitovec, J.: (1991)
Application of the anticoccidiosis drug Toltrazuril in the
coccidiosis of
neonatal pigs. Veterinami medicina (Praha) 36: 657-663.
Benoit, E., Buronfosse, T., Delatour, P.: (1994) Effect of
Cytochrome P-450
1A induction on enantioselective metabolism and
pharmacokinetics of an
aryltrifluoromethyl sulfide in the rat. Chirality 6(5):
372-377.
Lindsay, D.S., Dubey, J.P., Kennedy, T.J.: (2000)
Determination of the
activity of ponazuril against Sarcocystis neurona in cell
cultures. Vet
Parasit 92: 165-169.
Furr, M., Kennedy, T.: Pharmacokinetics of ponazuril in
horses. Study 150-717
Bayer Corporation. |
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