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EQUINE VETERINARY EDUCATION / AE / JANUARY 2020


Cook, V.L., Jones Shults, J., McDowell, M.R., Campbell, N.B., Davis, J.L., Marshall, J.F. and Blikslager, A.T. (2009) Anti-inflammatory effects of intravenously administered lidocaine hydrochloride on ischemia- injured jejunum in horses. Am. J. Vet. Res. 70, 1259-1268.


Fogle, C.A., Gerard, M.P., Elce, Y.A., Little, D., Morton, A.J., Correa, M.T. and Blikslager, A.T. (2008) Analysis of sodium carboxymethylcellulose administration and related factors associated with postoperative colic and survival in horses with small intestinal disease. Vet. Surg. 37, 558-563.


Freeman, D. (2018a) Post-operative reflux – a surgeon’s perspective. Equine Vet. Educ. 30, 671-680.


Freeman, D.E. (2018b) Fifty years of colic surgery. Equine Vet. J. 50, 423-435.


Freeman, D.E. and Schaeffer, D.J. (2010) Comparison of complications and long-term survival rates following hand-sewn versus stapled side-to-side jejunocecostomy in horses with colic. J. Am. Vet. Med. Assoc. 237, 1060-1067.


Freeman, D.E. and Schaeffer, D.J. (2011a) Comparison of complications and long-term survival rates following hand-sewn versus stapled side-to-side jejunocecostomy in horses with colic. Erratum. J. Am. Vet. Med. Assoc. 238, 65.


Freeman, D.E. and Schaeffer, D.J. (2011b) Clinical comparison between a continuous Lembert pattern wrapped in a carboxymethylcellulose and hyaluronate membrane with an interrupted Lembert pattern for one-layer jejunojejunostomy in horses. Equine Vet. J. 43, 708-713.


Freeman, D.E., Hammock, P., Baker, G.J., Foreman, J.H., Schaeffer, D.J., Richter, R.A., Inoue, O. and Magid, J.H. (2000) Short- and long-term survival and prevalence of postoperative ileus after small intestinal surgery in the horse. Equine Vet. J. 32, Suppl. 32, 42-51.


Freeman, D.E., Schaeffer, D.J. and Cleary, O.B. (2014) Long-term survival in horses with strangulating obstruction of the small intestine managed without resection. Equine Vet. J. 46, 711- 717.


Ireland, J.L., Clegg, P.D., McGowan, C.M., Platt, L. and Pinchbeck, G.L. (2011) Factors associated with mortality of geriatric horses in the United Kingdom. Prev. Vet. Med. 101, 204-218.


Little, D., Tomlinson, J.E. and Blikslager, A.T. (2005) Post operative neutrophilic inflammation in equine small intestine after manipulation and ischaemia. Equine Vet. J. 37, 329-335.


Malone, E., Ensink, J., Turner, T., Wilson, J., Andrews, F., Keegan, K. and Lumsden, J. (2006) Intravenous continuous infusion of lidocaine for treatment of equine ileus. Vet. Surg. 35, 60-66.


Morton, A.J. and Blikslager, A.T. (2002) Surgical and postoperative factors influencing short-term survival of horses following small intestinal resection: 92 cases (1994-2001). Equine Vet. J. 34,450- 454.


Nolen-Walston, R., Paxson, J. and Ramey, D.W. (2007) Evidence-based gastrointestinal medicine in horses: it’s not about your gut instincts. Vet. Clin. North. Am. Equine Pract. 23, 243-266.


Van den Boom, R., Butler, C.M. and Sloet van Oldruitenborgh-Oosterbaan, M.M. (2010) The usability of peritoneal lactate concentration as a prognostic marker in horses with severe colic admitted to a veterinary teaching hospital. Equine Vet. Educ. 22, 420-425.


Ziegler, A.L., Freeman, C.K., Fogle, C.A., Burke, M.J., Davis, J.L., Cook, V.L., Southwood, L.L. and Blikslager, A.T. (2019) Multicentre, blinded, randomised clinical trial comparing the use of flunixin meglumine with firocoxib in horses with small intestinal strangulating obstruction. Equine Vet. J. 51, 329-335.


Zimeta™ (dipyrone injection)


500mg/mL injection For intravenous use in horses Non-steroidal anti-inflammatory drug (NSAID)


CAUTION: Federal law (U.S.A.) restricts this drug to use by or on the order of a licensed veterinarian.


Before using this product, please consult the product insert, a summary of which follows:


Indication: Zimeta™ (dipyrone injection) is indicated for the control of pyrexia in horses.


Dosage and Administration: Always provide the Client Information Sheet with the prescription. Administer Zimeta by intravenous injection, once or twice daily, at 12 hour intervals, for up to three days, at a dosage of 30 mg/kg (13.6 mg/lb). See product insert for complete dosing and administration information.


Contraindications: Horses with hypersensitivity to dipyrone should not receive Zimeta. Due to the prolongation of prothrombin time (PT) and associated clinical signs of coagulopathy, dipyrone should not be given more frequently than every 12 hours.


Warnings: For use in horses only. Do not use in horses intended for human consumption. Do not use in any food producing animals, including lactating dairy animals.


Human Warnings: Care should be taken to ensure that dipyrone is not accidentally injected into humans as studies have indicated that dipyrone can cause agranulocytosis in humans.


Not for use in humans. Keep this and all drugs out of reach of children. In case of accidental exposure, contact a physician immediately. Direct contact with the skin should be avoided. If contact occurs, the skin should be washed immediately with soap and water. As with all injectable drugs causing profound physiological effects, routine precautions should be employed by practitioners when handling and using loaded syringes to prevent accidental self-injection.


Precautions: Horses should undergo a thorough history and physical examination before initiation of any NSAID therapy.


As a class, NSAIDs may be associated with platelet dysfunction and coagulopathy. Zimeta has been shown to cause prolongation of coagulation parameters in horses. Therefore, horses on Zimeta should be monitored for clinical signs of coagulopathy. Caution should be used in horses at risk for hemorrhage.


As a class, NSAIDs may be associated with gastrointestinal, renal, and hepatic toxicity. Sensitivity to drug-associated adverse events varies with the individual patient. Consider stopping therapy if adverse reactions, such as prolonged inappetence or abnormal feces, could be attributed to gastrointestinal toxicity. Patients at greatest risk for adverse events are those that are dehydrated, on diuretic therapy, or those with existing renal, cardiovascular, and/or hepatic dysfunction. Concurrent administration of potentially nephrotoxic drugs should be carefully approached or avoided. Since many NSAIDs possess the potential to produce gastrointestinal ulcerations and/or gastrointestinal perforation, concomitant use of Zimeta with other anti-inflammatory drugs, such as NSAIDs or corticosteroids, should be avoided. The influence of concomitant drugs that may inhibit the metabolism of Zimeta has not been evaluated. Drug compatibility should be monitored in patients requiring adjunctive therapy.


The safe use of Zimeta in horses less than three years of age, horses used for breeding, or in pregnant or lactating mares has not been evaluated. Consider appropriate washout times when switching from one NSAID to another NSAID or a corticosteroid.


Adverse Reactions: Adverse reactions reported in a controlled field study of 138 horses of various breeds, ranging in age from 1 to 32 years of age, treated with Zimeta (n=107) or control product (n=31) are summarized in Table 1. The control product was a vehicle control (solution minus


dipyrone) with additional ingredients added to maintain masking during administration.


Table 1: Adverse Reactions Reported During the Field Study with Zimeta


Adverse Reaction


Elevated Serum Sorbitol Dehydro- genase (SDH)


Hyperemic Mucosa Right Dorsal Colon


Prolonged


Activated Partial Thromboplastin Time (APTT)


Elevated Creatinine 1 (1%) 0 (0%) 1 (1%) 0 (0%)


Injection Site Reaction


Anorexia 1 (1%) 1 (3%)


See Product Insert for complete Adverse Reaction information.


Information for Owners or Person Treating Horse: A Client Information Sheet should be provided to the person treating the horse. Treatment administrators and caretakers should be aware of the potential for adverse reactions and the clinical signs associated with NSAID intolerance. Adverse reactions may include colic, diarrhea, and decreased appetite. Serious adverse reactions can occur without warning and, in some situations, result in death. Clients should be advised to discontinue NSAID therapy and contact their veterinarian immediately if any signs of intolerance are observed.


Effectiveness: The effectiveness phase was a randomized, masked, controlled, multicenter, field study conducted to evaluate the effectiveness of Zimeta™ (dipyrone injection) administered intravenously at 30 mg/kg bodyweight in horses over one year of age with naturally occurring fevers. Enrolled horses had a rectal temperature ≥102.0°F. A horse was considered a treatment success if 6 hours following a single dose of study drug administration the rectal temperature decreased ≥2.0°F from hour 0, or the temperature decreased to normal (≤101.0°F).


One hundred and thirty-eight horses received treatment (104 Zimeta and 34 control product) and 137 horses (103 Zimeta and 34 control product) were included in the statistical analysis for effectiveness. At 6 hours post-treatment, the success rate was 74.8% (77/103) of Zimeta treated horses and 20.6% (7/34) of control horses. The results of the field study demonstrate that Zimeta administered at 30 mg/kg intravenously was effective for the control of pyrexia 6 hours following treatment administration.


Refer to the Product Insert for complete Effectiveness information.


Storage Information: Store at Controlled Room Temperature 20° and 25°C (68° and 77°F); with excursions permitted between 15° and 30°C (59° and 86°F). Protect from light. Multi-dose vial. Use within 30 days of first puncture.


How Supplied: Zimeta is available as a 500mg/mL solution in a 100mL, multi-dose vial.


Approved by FDA under NADA # 141-513 NDC 86078-245-01


Manufactured for: Kindred Biosciences, Inc. 1555 Bayshore Hwy, Suite 200, Burlingame, CA 94010


To report adverse reactions call Kindred Biosciences, Inc. at 1-888-608-2542.


Zimeta™ is a trademark of Kindred Biosciences, Inc.


©2019 Kindred Biosciences, Inc. All rights reserved.


Rev. 11-2019 KB50002_ZIV-BS-1


ZimetaTM (dipyrone injection) (N=107)


Control Product (N=31)


5 (5%) 5 (16%)


Hypoalbuminemia 3 (3%) 1 (3%) Gastric Ulcers


2 (2%) 0 (0%) 1 (1%) 0 (0%)


1 (1%) 0 (0%)


© 2019 EVJ Ltd


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