How Much Telazol® is Really in the Bottle? Inaccurate Labeling of Telazol From 1987–1998 and the Impact on Published Literature
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
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.
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.
1. Belant JL. Field immobilization of raccoons (Procyon lotor) with Telazol and xylazine. J Wildl Dis. 2004;40(4):787–790.
2. Belant JL. Tiletamine-zolazepam-xylazine immobilization of American marten (Martes americana). J Wildl Dis. 2005;41(3):659–663.
3. Caulkett NA, Cattet MRL, Cantwell S, Cool N, Olsen W. Anesthesia of wood bison (Bison bison athabascae) with medetomidine-telazol and xylazine-Telazol combinations. AAZV AAWV Joint Proceedings; 1998:342–346.
4. Caulkett N, Cattet MRL. Anesthesia of bears. In: Zoological Restraint and Anesthesia. Heard D, ed. Ithaca, NY: International Veterinary Information Service; 2002.
5. Chatfield J, Citino S, Munson L, Konopka S. Validation of the 13C-Urea breath test for use in cheetahs (Acinonyx jubatus) with helicobacter. J Zoo Wildl Med. 2004;35(2):137–141.
6. Citino SB, Munson L. Efficacy and long-term outcome of gastritis therapy in cheetahs (Acinonyx jubatus). J Zoo Wildl Med. 2005;36(3):401–416.
7. Deem SL, Davis R, Pacheco LF. Serologic evidence of nonfatal rabies exposure in a free-ranging oncilla (Leopardus tigrinus) in Cotapata National Park, Bolivia. J Wildl Dis. 2004;40(4):811–815.
8. Denali National Park and Preserve. Appendix J. Criteria and guidelines for handling and immobilizing bears. Bear-human conflict management plan. June 2003:94–100.
9. Gabor TM, Hellgren EC, Silvy NJ. Immobilization of collared peccaries (Tayassu tajacu) and feral hogs (Sus scrofa) with Telazol and xylazine. J Wildl Dis. 1997;33(1):161–164.
10. Grassman LI, Jr., Austin SC, Tewes ME, Silvy NJ. Comparative immobilization of wild felids in Thailand. J Wildl Dis. 2004;40(3):575–578.
11. Hall J. Fort Dodge Animal Health Technical Service: Indian Creek Parkway, Suite 400, Overland, KS, USA.
12. Hanley CS, Simmons HA, Wallace RS, Clyde VL. Erythema multiforme in a spotted hyena (Crocuta crocuta). J Zoo Wildl Med. 2005;36(3):515–519.
13. Haron AW, Ming Y, Zainudd ZZ. Evaluation of semen collected by electroejaculation from captive lesser Malay chevrotain (Tragulus javanicus). J Wildl Med. 2000;31(2):164–167.
14. Harrison TM, Mazet JK, Holekamp KE, Dubovi E, Engh AL, Nelson K, et al. Antibodies to canine and feline viruses in spotted hyenas (Crocuta crocuta) in the Masai Mara National Reserve. J Wildl Dis. 2004;40(1):1–10.
15. Haulena M, Gulland FMD. Use of medetomidine zolazepam-tiletamine with and without atipamezole reversal to immobilize captive California sea lions. J Wildl Dis. 2001;37(3):566–573.
16. Holder EH, Citino SB, Businga N, Cartier L, Brown SA. Measurement of glomerular filtration rate, renal plasma flow, and endogenous creatinine clearance in cheetahs (Acinonyx jubatus jubatus). J Zoo Wildl Med. 2004;35(2):175–178.
17. Kenny DE, Baier J, Knightly F, Steinheimer D, Getzy DM, Shelton GD. Myasthenia gravis in a polar bear (Ursus maritimus). J Zoo Wildl Med. 2004;35(3):409–411.
18. Kreeger TJ, Arnemo JM, Raath JP. Handbook of Wildlife Chemical Immobilization, International ed. Fort Collins, CO: Wildlife Pharmaceuticals, Inc.; 2002.
19. McNulty EE, Gilson SD, Houser BS, Ouse A. Treatment of fibrosarcoma in a maned wolf (Chrysocyon brachyurus) by rostral maxillectomy. J Zoo Wildl Med. 2000;31(3):394–399.
20. Miller BF, Muller LI, Doherty T, Osborn DA, Miller KV, Warren RJ. Effectiveness of antagonists for tiletamine-zolazepam/xylazine immobilization in female white-tailed deer. J Wildl Dis. 2004;40(3):533–537.
21. Miller CL, Schwartz AM, Barnhart JS, Jr., Bell MD. Chronic hypertension with subsequent congestive heart failure in a western lowland gorilla (Gorilla gorilla gorilla). J Zoo Wildl Med. 1999;30(2):262– 267.
22. Millspaugh JJ, Brundige GC, Jenks JA, Tyner CL, Hustead DR. Immobilization of rocky mountain elk with Telazol and xylazine hydrochloride, and antagonism by yohimbine hydrochloride. J Wildl Dis. 1995;31(2):259–262.
23. Munson L, Terio KA, Worley M, Jago M, Bagot-Smith A, Marker L. Extrinsic factors significantly affect patterns of disease in free-ranging and captive cheetah (Acinonyx jubatus) populations. J Wildl Dis. 2005;41(3):542–548.
24. Munson L, Marker L, Dubovi E, Spencer JA, Evermann JF, O’Brien SJ. Serosurvey of viral infections in free-ranging Namibian cheetahs (Acinonyx jubatus). J Wildl Dis. 2004;40(1):23–31.
25. Murray S, Monfort SL, Ware L, McShea WJ, Bush M. Anesthesia in female white-tailed deer using Telazol and xylazine. J Wildl Dis. 2000;36(4):670–675.
26. Nielsen L. Chemical Immobilization of Wild and Exotic Animals. Ames, IA: State University Press; 1999.
27. Olsen SC, Rhyan J, Gidlewski T, Goff J, Stoffregen WC. Safety of Brucella abortus strain RB51 in black bears. J Wildl Dis. 2004;40(3):429–433.
28. Onuma M. Immobilization of sun bears (Helarctos malayanus) with medetomidine-zolazepam-tiletamine. J Zoo Wildl Med. 2003;34(2):202–205.
29. Poole KG, Elkin BT, Pisz T, Elkin KE, Robertson D, Sabourin ML. Surgical plating of a fractured radius and ulna in a wild Canada lynx. J Wildl Dis. 1998;34(2):365–368.
30. Pulley ACS, Roberts JA, Lerche NW. Four preanesthetic oral sedation protocols for rhesus macaques (Macaca mulatta). J Zoo Wildl Med. 2004;35(4):497–502.
31. Read MR, McCorkell RB. Use of azaperone and zuclopenthixol acetate to facilitate translocation of white-tailed deer (Odocoileus virginianus). J Zoo Wildl Med. 2002;33(2):163–165.
32. Schobert E. Telazol use in wild and exotic animals. Vet Med. 1987;82:1080–1088.
33. Semple HA, Gorecki DK, Farley SD, Ramsay MA. Pharmacokinetics and tissue residue of telazol in free-ranging polar bears. J Wildl Dis. 2000;36(4):653–662.
34. Shindle DB, Tewes ME. Immobilization of wild ocelots with tiletamine and zolazepam in southern Texas. J Wildl Dis. 2000;36(3):546–550.
35. Sleeman JM, Cameron K, Mudakikwa AB, Nizeyi J, Anderson S, Cooper JE, et al. Field anesthesia of free-living mountain gorillas (Gorilla gorilla Beringei) from the Virunga volcano region, Central Africa. J Zoo Wildl Med. 2000;31(1):9–14.
36. Stamper MA, Norton T, Spodnick G, Marti J, Loomis M. Hypospadias in a polar bear (Ursus maritimus). J Zoo Wildl Med. 1999;30(1):141–144.
37. Stoskopf MK, Meyer RE, Jones M, Baumbarger DO. Field immobilization and euthanasia of American opossum. J Wildl Dis. 1999;35(1):145–149.
38. Suedmeyer WK, Ludlow C, Layton C, Dennis J, Miller M. Primary lymphangiectasia in a dingo (Canis Familiaris dingo). J Zoo Wildl Med. 2004;35(4):572–575.
39. Sutherland-Smith M, Campos JM, Cramer C, Thorstadt C, Toone W, Morris PJ. Immobilization of Chacoan peccaries (Catagonus wagneri) using medetomidine, Telazol, and ketamine. J Wildl Dis. 2004;40(4):731–736.
40. Sweitzer RA, Ghneim GS, Gardner IA, Van Vuren D, Gonzales BJ, Boyce WM. Immobilization and physiological parameters associated with chemical restraint of wild pigs with Telazol and xylazine hydrochloride. J Wildl Dis. 1997;33(2):198–205.
41. Telazol Product Insert: A.H. Robbins: March 1987.
42. Telazol Product Insert: Fort Dodge Laboratories: Rev June 1994.
43. Telazol Product Insert: Fort Dodge Animal Health: Rev January 1998.
44. Telazol Product Insert: Fort Dodge Animal Health: Rev September 2003.
45. Walter WD, Leslie DM, Jr., Herner-Thogmartin JH, Smith KG, Cartwright ME. Efficacy of immobilizing free-ranging elk with Telazol and xylazine hydrochloride using transmitter-equipped darts. J Wildl Dis. 2005;41(2):395–400.
46. Woodbury MR, ed. The Chemical Immobilization of Wildlife. The Canadian Association of Zoo and Wildlife Veterinarians. 1996.