Ponazuril is an anticoccidial (antiprotozoal) compound with activity against several genera of the phylum Apicomplexa. Ponazuril (also known as toltrazuril sulfone) is a metabolite of the poultry antiprotozoal drug toltrazuril. It is a triazine-based drug that acts to inhibit enzyme systems in protozoa and/or decreasing pyrimidine synthesis.

Ponazuril could potentially be useful in treating Neospora caninum, Toxoplasma spp or other protozoal infections in other species (eg, dogs, cats, birds, reptiles, ruminants). One study of shelter dogs and cats with coccidiosis reported approximately 90% clearance of infection after a 3 day treatment with ponazuril; animals with low oocyst burdens appeared to respond better than those with high counts.²

Pharmacology and Pharmacokinetics

Ponazuril (also known as toltrazuril sulfone) is a metabolite of toltrazuril. The triazine class of antiprotozoals is believed to target the plastid body, an organelle found in the members of the Apicomplexa phylum, including Sarcocystis neurona. In vitro levels required to kill Sarcocystis neurona range from 0.1-1 micrograms/mL.

When administered orally to horses in water, ponazuril has a bioavailability of approximately 30% and elimination half-life of 80 hours. After daily (5 mg/kg) oral administration to horses, ponazuril reaches its peak serum levels in approximately 18 days and peak CSF levels in approximately 15 days. Peak CSF levels are 1/20th (0.21 micrograms/mL) those found in the serum. Elimination half-life from serum averages approximately 4.5 days. If ponazuril is given orally (2.2 mg/kg) dissolved in DMSO, bioavailability is significantly enhanced.³

In cattle, 5 mg/kg oral doses of ponazuril are relatively well absorbed and have an approximate elimination half-life of 58 hours.⁴

Piglets receiving a single 5 mg/kg PO dose had peak plasma levels of 5.8 micrograms/mL at 42 hours, and a terminal half-life of 135 hours.⁵

In goats, a single 10 mg/kg oral dose reached peak plasma levels of 9 micrograms/mL in 36 hours, with an average half-life of 136 hours.⁶

Ponazuril: Adverse Effects, Drug Interactions & Warnings

Field trials showed some animals developing blisters on nose and mouth or a rash/hives. Single animals developed diarrhea, mild colic, or seizures.

Successful treatment may not negate all the clinical signs associated with EPM in horses.

No drug interactions have been noted for the use of Ponazuril.

Ponazuril vs. Toltrazuril

Coccidiosis infections can be a very serious issue in kittens. Risk factors for coccidiosis include age (young kittens at least 2 weeks of age, but typically less than 6 months), stress (always a challenge in a shelter) and coinfection with other parasites.

In cases such as these, ponazuril is the preferred treatment for coccidia over toltrazuril; as a metabolite of toltrazuril, ponazuril is more efficacious and is considered a more prudent course of treatment due to the relatively frail constitution of kittens. For less critical applications, toltrazuril remains highly recommended by veterinarians.¹ Ponazuril has been widely used to treat kittens by veterinarians and in shelters without reported adverse effects at the most common dosages.

Dosages

Dogs/Cats:

Neosporosis or Toxoplasmosis (extra-label): 7.5 – 15 mg/kg PO every 24 hours for 28 days. Dose extrapolated between doses for horses and mice.⁷

Coccidiosis (extra-label):

a)20 mg/kg PO every 24 hours for 3 days.⁸

b)50 mg/kg PO every 24 hours for 3 days; extended courses (two 3-day courses) are sometimes necessary for fecal flotation results to become negative in dogs and cats with coccidiosis.²

Small Mammals:

Rabbits for adjunctive treatment of Eimeria spp (extra-label): 20 mg/kg PO every 24 hours for 7 days.⁹

Camelids (New World):

Eimeria macusaniensis (extra-label): 20 mg/kg PO every 24 hours for 3 days. Because E. macusaniensis can cause clinical disease or even death before oocysts are present in feces, prophylactic treatment should be considered in camelids that have unexplained weight loss with concurrent hypoproteinemia and without severe anemia. The commercially available paste (Marquis®) is too concentrated to be given to crias and should be diluted before being administered. Recommend diluting the paste to 100 mg/mL by taking 40 g of paste, q.s. with distilled water to 60 g total and mixing well. The paste is water-soluble and can be easily syringed into the animal.^10,11

Goats:

Coccidiosis (extra-label): 10 mg/kg PO once resulted in decreased oocyst counts. Goats receiving amprolium appeared to respond more favorably over the 28 day observation period than those receiving ponazuril, although the number of goats in each treatment group was small.¹²

Birds:

Cryptosporidium spp respiratory disease in falcons (extra-label): Case report of two patients: 20 mg/kg PO (as a compounded suspension) every 24 hours for 7 days.¹³

Reptiles:

Coccidiosis in Bearded dragons (extra-label): Anecdotal dosage recommendations vary considerably and include: For coccidians: 30 mg/kg PO twice 48 hours apart.¹⁴ Another recommendation is 30 – 45 mg/kg PO every 24 hours for 28 days. Daily spot cleaning of the environment with weekly deep cleaning and disinfection is essential to prevent reinfection.¹⁵

Testudine intranuclear coccidiosis (extra-label): 20 mg/kg PO every 48 hours for 3 months.¹⁶

Where to buy Ponazuril

Ponazuril is available in the U.S. through various pharmaceutical manufacturers and through veterinary custom compounding companies. 

FOR RX ONLY: A valid prescription from a licensed veterinarian is required for dispensing this medication.

²Litster AL, Nichols J, Hall K, Camp J, Mohamed AS. Use of ponazuril paste to treat coccidiosis in shelter-housed cats and dogs. Vet Parasitol. 2014;202(3-4):319-325.

³Dirikolu L, Karpiesiuk W, Lehner AF, Hughes C, Granstrom DE, Tobin T. Synthesis and detection of toltrazuril sulfone and its pharmacokinetics in horses following administration in dimethylsulfoxide. J Vet Pharmacol Ther. 2009;32(4):368-378.

⁴Dirikolu L, Yohn R, Garrett EF, Chakkath T, Ferguson DC. Detection, quantifications and pharmacokinetics of toltrazuril sulfone (Ponazuril) in cattle. J Vet Pharmacol Ther. 2009;32(3):280-288.

⁵Zou M, Guo G, Zhao Y, Zhang Q. Detection, quantifications, and pharmacokinetics of ponazuril in healthy swine. J Vet Pharmacol Ther. 2014;37(6):598-602.

⁶Love D, Gibbons P, Fajt V, Jones M. Pharmacokinetics of single-dose oral ponazuril in weanling goats. J Vet Pharmacol Ther. 2016;39(3):305-308.

⁷Greene C, Hartmannn K, Calpin J. Appendix 8: Antimicrobial Drug Formulary. In: Greene C, ed. Infectious Disease of the Dog and Cat: Elsevier; 2006:1186-1333.

⁸CAPC. Companion Animal Parasite Council Recommendations. 2017; https://www.capcvet.org/capc-recommendations/coccidia. Accessed 1/2/2017, 2017.

⁹Kelleher S. Rabbit GI Disease. Paper presented at: Proceedings: WVC2008.

¹⁰Walker P. Differential Diagnosis of Diarrhea in Camelid Crias. Paper presented at: Proceedings: ACVIM2009.

¹¹Prado ME, Ryman JT, Boileau MJ, Martin-Jimenez T, Meibohm B. Pharmacokinetics of ponazuril after oral administration to healthy llamas (Lama glama). Am J Vet Res. 2011;72(10):1386-1389.

¹²Gibbons P, Love D, Craig T, Budke C. Efficacy of treatment of elevated coccidial oocyst counts in goats using amprolium versus ponazuril. Vet Parasitol. 2016;218:1-4.

¹³Van Sant F, Stewart G. Ponazuril Used as a Treatment for Suspected Cryptosporidium Infection in 2 Hybrid Falcons. Paper presented at: Proceedings: AAV2009.

¹⁴Mitchell MA. Gastroenterology of Reptiles. Paper presented at: Proceedings: ACVC2008.

¹⁵Wright K. Bearded Dragon Medicine & Surgery. Paper presented at: Proceedings: ABVP2013.

¹⁶Boyer TH. Nasal Discharge in Tortoises. Paper presented at: Pacific Veterinary Conference : PacVet 20152015.