Abstract

Telazol® has been produced by pharmaceutical companies owned by the American Home Products Corporation (now Wyeth Corporation) since the products inception in 1987, with distribution in the USA under the A.H. Robbins label (AH Robbins, Richmond, VA, 1987–1992), and with previous and current distribution in the USA under the label of Fort Dodge Laboratories, Inc. and Fort Dodge Animal Health (Fort Dodge, IA, 1992-present).¹¹ Telazol is a 1:1 combination of tiletamine + zolazepam supplied in freeze dried form (as a powder). From March 1987 until January 1998 Fort Dodge Telazol® was labeled to contain 500 mg of active drug per vial, with reconstitution instructions to add 5 ml of sterile water for injection to achieve a solution containing 100 mg/ml (50 mg/ml tiletamine + 50 mg/ml zolazepam).^41-43 This reconstitution technique was confusing since upon addition of 5 ml of diluent the resulting total solution in the vial was approximately 5.7 ml due to the powder dissolving into solution and expanding the fluid volume, a phenomenon known as displacement. With 500 mg of total drug per vial and a total volume of 5.7 ml the resulting solution would only contain 87.7 mg/ml (43.85 mg/ml tiletamine + 43.85 mg/ml zolazepam). Thus, the dilemma: either the amount of total Telazol labeled to be in the vial was incorrect, or the resulting solution concentration with reconstitution with 5 ml of diluent was labeled to be incorrect.

In discussions with Fort Dodge the following information was obtained. Telazol® is produced by adding a target volume of 4.12 ml of 69.4 mg/ml tiletamine + 4.12 ml of 69.4 mg/ml zolazepam into each vial. The vial is then freeze-dried producing powder in the vial totaling 285.93 mg tiletamine + 285.93 zolazepam or 571.86 mg of Telazol® (total combined drug per vial), if the exact target volumes are achieved.¹¹

Using the target values of 285.93 mg tiletamine + 285.93 zolazepam and a total reconstituted volume of 5.7 ml (taking into account displacement) the solution concentration of tiletamine is indeed accurate at 50 mg/ml and the solution concentration of zolazepam is also accurate at 50 mg/ml. With 571.86 mg of total Telazol® per vial and a total volume of 5.7 ml, the solution concentration of Telazol® is again accurate at 100 mg/ml. Thus, the actual amount of Telazol® per vial is targeted to be 572 mgA, and not 500 mg as was indicated on the 1987–1998 label, explaining the inconsistency.

After 1998 the Telazol® label and package insert were revised and no longer indicated the total amount of Telazol® per vial, but only that reconstitution with 5 ml of diluent would provide a solution containing 100 mg/ml of active ingredient (50 mg/ml tiletamine + 50 mg/ml zolazepam).^43,44 Understandably, since no alternative information has been presented, the misconception that Telazol® contains 500 mg of total drug per vial persists in the current literature despite label revisions by Fort Dodge Animal Health.^18,26

From 1987–1992 Telazol® was distributed under the AH Robbins label. With the exception of the replacement of sodium sulfate by mannitol as a buffering agent between 1992 and 1994, the production of Telazol® whether labeled as AH Robbins or Fort Dodge has been unchanged, and in the same facility or sister facilities since the inception of production in 1987.¹¹ Thus, AH Robbins Telazol® distributed from 1987–1992, labeled to contain 500 mg of total active drug per vial, also actually contained a targeted fill volume of 572 mg total Telazol® per vial. CI-744, the precursor of the commercially released product Telazol® also was produced under the same target filling values.¹¹

What is the Impact of The 1987–1998 “500 mg” Labeling on Published Species-Specific Dosages?

The impact of this inaccurate labeling will depend on the method of reconstitution used in the study. While some operators reconstitute Telazol® in the standard manner (5 ml diluent added), those working with remote injection often reconstitute Telazol® in a non-standard manner (less diluent added). This non-standard reconstitution produces a higher concentration formulation, affording a smaller injection volume if administered by hand injection or pole syringe, and if delivered remotely, allowing the use of smaller, lighter darts, which are less traumatic on impact.

Published species specific dosages (mg Telazol®/kg body weight) determined using the value of 500 mg total Telazol® in the vial, but using standard reconstitution volumes of 5 ml diluent, and basing their calculations on Telazol® at a solution concentration of 100 mg/ml are not affected by this incorrect labeling since the resulting solution did indeed contain 50 mg tiletamine + 50 mg/ml zolazepam, or 100 mg/ml Telazol®.^1,2,9,34,37

Published species specific dosages (mg Telazol®/kg body weight) determined using the value of 500 mg total Telazol® in the vial and non-standard reconstitution volumes are inaccurate, with an underestimate of the actual drug dosage by 14.4%.^{3,4,8,22,40,45}

^ATelazol® production standards allow for a 10% (±) variance in each drug. Fort Dodge Animal Health “in house” standards are more stringent, striving to produce the medication at 102–103% of the production target values-producing solution concentrations between 49–53 mg/ml each tiletamine and zolazepam, with an average of 51 mg of each drug per ml and an average displacement of solution volume by powder dissolution of 0.6 ml.¹¹

Conclusions

Readers should be cognizant of the amount of Telazol® referenced to be in the vial, and the reconstitution techniques utilized, when reviewing historic immobilization literature.^32,46 Species specific dosages calculated and published using the incorrect Telazol® amount of 500 mg per vial and non-standard reconstitution techniques should be re-evaluated using the true value of 572 mg of Telazol® per vial. Future publications utilizing Fort Dodge Animal Health Telazol® should use 572 mg as the target filling weight of drug per vial, or weigh the contents of the vial to ensure the accuracy of calculated species-specific dosage information.

Many publications using Telazol® do not provide information on reconstitution techniques and cannot be evaluated without acquiring this information through contact with the author.^{5-7,10,12-17, 19-21, 23-25, 27-31,33,35,36,38,39} It is requested that whenever publishing case reports or studies using medications that require reconstitution, authors provide the drug name, manufacturer, production facility location, and a detailed description of the reconstitution techniques utilized.

Acknowledgments

Thank you Dr. Jim Hall, Fort Dodge Animal Health for your efforts and assistance in researching historical technical information on the Telazol® product, Nira Colonero and Maggie Beheler-Amass for assistance in compiling cited reference information, and Dr. Julie Smith for your time, efforts, and advice.

© 2006 Safe-Capture International Inc. Reprinted with permission of Safe-Capture International Inc. and the authors.

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