ponazuril

For the treatment of equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona.

Do not use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Marquis® Antiprotozoal Oral Paste

MARQUIS is indicated for the treatment of equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona.

Marquis®(15% w/w ponazuril)Antiprotozoal Oral Paste

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. A pharmacokinetic study was conducted in eight horses to collect serum and cerebrospinal fluid (CSF) levels of ponazuril after a single dose of 5 mg/kg body weight. The estimated parameter values were used to model time concentration profiles for ponazuril in serum and CSF. The model results were used to estimate the size of the loading dose needed to support the achievement of steady state serum and CSF levels after the first dose. The appropriate loading dose, calculated on the basis of the accumulation ratio (i.e., the fold increase in serum drug concentrations once steady state conditions have been achieved) was 15 mg/kg (6.81 mg/lb) body weight. This dose represents the range of estimated accumulation ratios of 2.3 to 3.3. Thus, a three-fold loading dose (3*5 mg/kg) was selected, leading to achievement of steady state blood levels in horses after one or two days of ponazuril administration.

Marquis®(15% w/w ponazuril)Antiprotozoal Oral Paste

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

Marquis®(15% w/w ponazuril)Antiprotozoal Oral Paste

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. Post Approval Experience (2015): The following adverse events in horses are based on post-approval adverse drug experience reporting. Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data. The following adverse events have been reported: Neurologic deficits, primarily ataxia, have been reported to acutely worsen during the early treatment period. Although outcome was not always reported, in some horses the worsening of the neurologic deficits was transient. To report suspected adverse drug events, for technical assistance or to obtain a copy of the Safety Data Sheet (SDS), contact Boehringer Ingelheim Animal Health USA Inc. at 1-888-637-4251. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at www.fda.gov/reportanimalae.

Marquis®(15% w/w ponazuril)Antiprotozoal Oral Paste

Administer at a dose of 15 mg/kg (6.81 mg/lb) body weight as a loading dose for the first dose only. The loading dose is followed by a maintenance dose of 5 mg/kg (2.27 mg/lb) body weight once daily for a period of 27 additional days.

Oral

Do not use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Marquis® Antiprotozoal Oral Paste

Administer MARQUIS at a dose of 15 mg/kg (6.81 mg/lb) body weight as a loading dose for the first dose only. The loading dose is followed by a maintenance dose of 5 mg/kg (2.27 mg/lb) body weight once daily for a period of 27 additional days. Day 1: Administer a loading dose of 15 mg/kg (three times the maintenance dose) once by mouth. Because the dosage ring is calibrated by weight for the maintenance dose (5mg/kg), adjust the dosage ring to the appropriate weight and administer this 5 mg/kg dose orally, three consecutive times for a total dose of 15 mg/kg. Day 2 through 28: Administer the maintenance dose of 5 mg/kg once daily by mouth. Assembling Before administration, the syringe barrel and plunger require assembly. Ensure plunger is clean and dry. 1.End cap must be on syringe barrel when inserting plunger. 2.Carefully insert 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. 3.Return end cap to tip of paste syringe. Administering MARQUIS to the horse: Note: The paste syringe is a multi-dose package. Ensure that the correct dose is administered with each use. For the first dose only, complete steps 3 through 6 three times, then continue with steps 7 and 8. 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. 2.Determine weight of horse and ensure the horse's mouth contains no feed. 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. 4.Remove end cap from tip of syringe barrel. 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. 6.To aid swallowing of paste, immediately raise horse's head for a few seconds after dosing. 7.Clean the tip of the syringe with a clean disposable towel and return end cap to tip of syringe barrel. 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.

ORAL

Marquis®(15% w/w ponazuril)Antiprotozoal Oral Paste