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Zimeta (dipyrone injection)

This page contains information on Zimeta (dipyrone injection) for veterinary use.
The information provided typically includes the following:
  • Zimeta (dipyrone injection) Indications
  • Warnings and cautions for Zimeta (dipyrone injection)
  • Direction and dosage information for Zimeta (dipyrone injection)

Zimeta (dipyrone injection)

This treatment applies to the following species:
Company: Kindred Bio

500mg/mL injection

For intravenous use in horses

Non-steroidal anti-inflammatory drug (NSAID)

Zimeta (dipyrone injection) Caution

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


Dipyrone belongs to the pyrazolone class of non-steroidal anti-inflammatory (NSAID) drugs. Chemically, dipyrone is metamizole sodium. Each mL of this clear sterile solution for intravenous injection contains 500mg dipyrone and 10mg benzyl alcohol in water.

The structural formula of dipyrone is:

Molecular Formula: C13H16N3NaO4S • H2O

Molecular Weight: 351.4

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). The overall number of doses and duration of treatment with Zimeta is dependent on the response observed (fever reduction). Zimeta may be re-administered based on recurrence of fever for up to 3 days. Zimeta is provided in a multi-dose vial and contains a preservative.


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.


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.


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.

Horses may have experienced more than one of the observed adverse reactions during the field study. Horses may have received one or more doses of Zimeta during the field study. The control product was only administered once.

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

Adverse Reaction


(dipyrone injection)


Control Product


Elevated Serum Sorbitol Dehydrogenase (SDH)

5 (5%)

5 (16%)


3 (3%)

1 (3%)

Gastric Ulcers

2 (2%)

0 (0%)

Hyperemic Mucosa Right Dorsal Colon

1 (1%)

0 (0%)

Prolonged Activated Partial Thromboplastin Time (APTT)

1 (1%)

0 (0%)

Elevated Creatinine

1 (1%)

0 (0%)

Injection Site Reaction

1 (1%)

0 (0%)


1 (1%)

1 (3%)

Horses with elevated SDH, hypoalbuminemia, prolonged APTT, or elevated creatinine did not show associated clinical signs. One horse exhibited an exacerbation of pre-existing hypoalbuminemia after treatment; this horse also showed concurrent elevation in SDH. Two horses that received Zimeta were diagnosed with gastric ulcers. One horse that received 4 doses of Zimeta was diagnosed with grade III/IV gastric ulceration and hyperemia of the mucosa of the right dorsal colon on post-mortem examination which was performed following euthanasia due to illness unrelated to treatment (septic arthritis and cellulitis). This horse was previously treated with a different NSAID prior to enrollment in the study. A second horse that enrolled in the study due to a mandibular facial wound, and received two doses of Zimeta, was diagnosed with grade III/IV gastric ulcers 4 days following completion of the field study.

In the field study, Zimeta was used concomitantly with other therapies, including antibiotics and sedatives.

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.

Clinical Pharmacology

Dipyrone is a water soluble pyrazolone derivative that functions as a pro-drug and is immediately hydrolyzed to 4-methlyaminoantipyrine (4-MAA) following administration by any route.1 In most species, including the horse, 4-MAA is the molecule assayed for pharmacokinetics, as dipyrone is present for an extremely short period of time.2 In humans, 4-MAA is further metabolized by the liver to secondary metabolites that primarily undergo renal excretion. 4-MAA is also the molecule associated with clinical efficacy in humans. The mechanism of action to reduce pyrexia has not been fully characterized.

The mean (± SD) 4-MAA pharmacokinetic parameters after a single intravenous dose of 30 mg/kg dipyrone administered every 12 hours for 9 days to 6 adult horses were as follows: maximum concentration (Cmax) of 40,616.67 (9,917.34) ng/mL, area under the concentration vs time curve for the dosing interval (AUCtau) of 106,848.75 (12,128.88) hr*ng/mL, volume of distribution (Vz) of 1,607.43 (165.51) mL/kg, clearance at steady state (CLss) of 284.17 (36.08) mL/kg/hr, and half-life of 3.94 (0.44) hours.


One hundred and thirty-eight (138) horses were enrolled in a field effectiveness study. The field study was divided into two phases; an effectiveness phase and an extended use field safety phase.

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.

The extended use field safety phase was an open-label field study to evaluate the safety of Zimeta when administered intravenously at 30 mg/kg bodyweight to horses with pyrexia under field conditions. Eighty-seven horses from the first phase entered this phase. During the extended use field safety phase, horses may have received more than one dose of Zimeta. Most horses in the study were treated with Zimeta once per day. No horses were treated with Zimeta more than twice daily.

Animal Safety: A pilot laboratory study was conducted in 31 adult horses, ages 3 years to 20 years, with naturally occurring fever (due to respiratory disease or other infectious process) to evaluate the effectiveness of a non-final market formulation of dipyrone injection at a dose of 30 mg/kg intravenously. One horse developed soft feces after treatment with one dose of dipyrone injection and a second horse developed bloody nasal discharge and died one day after receiving one dose of dipyrone injection. Necropsy findings for the horse that died documented severe pleuropneumonia; however, due to the potential effects of dipyrone on platelet aggregation and function, the occurrence of bloody nasal discharge and progression of disease in this horse may be related to treatment. There were no substantive differences between the non-final market formulation used in this pilot study and Zimeta.

A laboratory safety study was conducted in which Zimeta was administered via intravenous catheter to 32 healthy adult horses at 0, 30, 60, and 90 mg/kg (0, 1, 2, and 3X the recommended dose) three times a day (TID), every 8 hours, for 9 consecutive days. Horses in the control group were administered placebo (saline).

The most common post-treatment observations were cough, depression, tachypnea or dyspnea, epistaxis, nasal discharge, inappetence, loose manure, colic and fever. Many of these clinical signs were associated with infectious respiratory disease, which affected horses in all treatment groups. One horse in the 3X group died. This horse had pleuropneumonia and observations of epistaxis for 46 hours with increasing dyspnea prior to spontaneous death, and associated prolongations in both prothrombin time (PT) and activated partial thromboplastin time (APTT). Another horse in the 3X group had nasal discharge with epistaxis that resolved prior to study completion, with associated prolongations in both PT and APTT on Day 8. This horse also had clinical signs and necropsy findings consistent with pneumonia and coagulopathy including: hemorrhage from previous catheter site, renal abscessation with hemorrhage, and petechial and ecchymotic hemorrhage of the ileum. Overall, PT was statistically significantly prolonged for the horses in the 2X and 3X dose groups when compared to control horses (p=0.0037).

Other treatment-related effects included an increase in liver weight and an elevation in total bilirubin. These findings were not associated with clinical signs or liver pathology. On necropsy, duodenal erosion was present in one 3X TID horse. Stomach (non-glandular) erosions were present in one control horse and two 1X TID horses. Stomach (non-glandular) ulcers were present in one control horse and one 2X TID horse. No erosions or ulcerations were identified in the large intestine. On histopathology, there were three 1X TID horses, two 2X TID horses, and three 3X TID horses with minimal or mild renal tubular dilation. One 1X TID horse and two 3X TID horses had minimal renal tubular mineralization. These histopathology changes were not associated with changes on gross necropsy, in clinical pathology or clinical signs of renal dysfunction.

Due to the prolongation of PT and associated clinical signs of coagulopathy, this study did not demonstrate an adequate margin of safety when Zimeta was administered IV three times daily (every 8 hours).

To further evaluate the effects of Zimeta on coagulation, an additional laboratory study was conducted. Zimeta was administered via intravenous catheter to 32 healthy adult horses at 0, 30, 60, and 90 mg/kg (0, 1, 2, and 3X the recommended dose) every 12 hours (BID) for 9 consecutive days, and at 30 and 60 mg/kg (1X and 2X the recommended dose) TID for 9 consecutive days. Horses in the control group were administered placebo (saline). The most common treatment-related adverse effects were anorexia, depression, and loose feces. Seven horses in Zimeta treatment groups experienced one or more of these adverse effects, as compared to no horses in the control group. One horse in the 2X TID group had varying degrees of depression, loose feces and colic for multiple days during the study, which resolved with hand walking.

At the completion of the study, horses were healthy when returned to the source herd. There was an upward numerical trend in the PT which suggested a treatment effect of dipyrone injection on prolongation of PT; however, the overall treatment effect was not significant (p=0.1131). There was no evidence of clinical signs related to coagulopathy. This study supported the conclusion that there is an adequate margin of safety when Zimeta is administered at 30 mg/kg IV twice daily (every 12 hours) for three days.

For pharmacokinetic results see summary in Clinical Pharmacology section.


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

For a copy of the Safety Data Sheet (SDS) or 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. 09-2019


1 Levy M, Zylber-Katz E, Rosenkranz B. Clinical Pharmacokinetics of Dipyrone and its Metabolites. Clin Pharmacokinet. 1995; 28(3):216-231.

2 Metamizole Summary Report. Committee for Veterinary Medicinal Products: The European Agency for the Evaluation of Medicinal Products. June 2003.


CPN: 1988001.0

Customer Service:   1-888-608-2542
Telephone:   650-692-2577
Every effort has been made to ensure the accuracy of the Zimeta (dipyrone injection) information published above. However, it remains the responsibility of the readers to familiarize themselves with the product information contained on the US product label or package insert.

Copyright © 2021 Animalytix LLC. Updated: 2021-10-04