Zolazepam: a non-phenothiazine derivative tranquilizer of the dizepinone type,(B263, J2.3.w2)  a central nervous system depressant with anticonvulsant and antianxiety activity. (J2.5.w2)

About two-times to three-times the potency of ketamine and half the potency of phencyclidine. (J2.3.w2)

• Tiletamine: CI-634. (J2.3.w2, J2.5.w2)
• Zolazepam: Cl-716 (J2.3.w2)
• Combined: Cl-744 (J2.3.w2)

Zolazepam: 4-(o-fluorophenyl)-6,8-dihydo-1,3,8-trimethylpyrazolo[3,4-e] [1,4] diazepin-7 (1H)-one,monohydrochloride. (J2.5.w2)

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• Reconsitituted product (tiletamine plus zolazepam in a 1:1 mixture) has pH 2.2-2.8. (B263)
• Tiletamine hydrochloride pH approximately 4.0. (J2.3.w2)

Associated Techniques

• Tiletamine: a CNS depressant which produces profound analgesia and cataleptoid anaesthesia.
• Zolazepam: a tranquilizer; a central nervous system depressant with anticonvulsant and antianxiety activity. (B263, J2.3.w2, J2.5.w2)

• In Ursus maritimus - Polar bear, absorption following remote injection appears to be first-order. (J1.36.w9)

• In Ursus maritimus - Polar bear, the volume of distribution was 5.2 +/- 0.6 L/kg for tiletamine and 1.8 +/- 0.2 L/kg for zolazepm. (J1.36.w9)

• In Ursus maritimus - Polar bear, elimination following remote injection appears to be first-order, with a half-life (+/-SE) of 1.8 +/- 0.2 h for tiletamine and 1.2 +/- 0.08 h for zolazepam. Clearance was 2.1 +/- 0.3 L per hr per kg for tiletamine and 1.1 +/- 0.1 L/hour/kg for zolazepam. Only trace concentrations of the drugs or their metaboliteswere present by 24 hours after dosing, although some metabolites could be detected in trace amounts for longer periods - e.g. one of the metabolites of zolazepam was detectable in fat and muscle as long as 11 days after dosing. (J1.36.w9)

• In cats, use of chloramphenicol may result in prolonged anaesthesia with tiletamine-zolazepam. (B263)
• Use of phenothiazines in combination with tiletamine-zolazepam may result in increased respiratory and cardiac depression. (B263)
• If tiletamine-zolazepam is used, concurrent dosage of barbiturates or volatile anaesthetics may be reduced. (B263)

• Telazol^® (Fort Dodge). Tiletamine HCl (equivalent to 250 mg free base) plus zolazepam HCl (equivalent to 250 mg free base), as lyophilized powder in a 5 mL vial. Addition of 5 mL of sterile diluent (sterile water) gives a concentration of 50 mg/mL of each drug (100 mg/mL of the combined drugs). (B263)
• Note: Class III controlled substance in the USA. (B263)
• Zoletil (Virbac).
• NOTE: Labelling on Telazol^®  from 1987-1998 indicated 500 mg active drug per vial, and that reconstitution with 5 mL diluent would produce a solution containing 100 mg/mL of the two drugs combined (50 mg/mL tiletamine, 50 mg/mL zolazepam). Due to displacement when the powder in the vial is dissolved, the actual volume produced is 5.7 mL, at 100 mg/mL: Fort Dodge has confirmed that the target amounts of the drugs in the vial are 285.93 mg of each drug, i.e. 571.86 mg total combined drug per vial, to give a 100 mg/mL solution if the freeze-dried powder is reconstituted with 5 mL diluent. However, if Telazol is reconstituted using smaller volumes of diluent (as may be carried out for remote injection), and if the user is assuming 500 mg per vial (rather than the actual 571.86 mg per vial), the actual drug dosage will be underestimated by 14.4%. It is important to consider this when reconstituting Telazol, and when evaluating papers concerning Telazol, if the reconstitution technique has not been stated. (P1.2006.w2)

• Domestic dogs:
  • Diagnostic purposes 6.6-9.9 mg/kg intramuscularly
  • Minor, short duration procedures 9.9-13.2 mg/kg intramuscularly
  • If supplemental doses are required, these should be smaller than the initial dose and the total given should not exceed 26.4 mg/kg.
  • Give atropine 0.04 mg/kg concurrently to control hypersalivation. 

  (B263)

• Domestic cats:
  • 9.7-11.9 mg/kg intramuscularly for e.g. dentistry, treatment of abscesses, removal of foreign bodies. (B263)
  • 10.6-12.5 mg/kg intramuscularly for lacerations, castration.
  • 14.3-15.8 mg/kg intramuscularly for ovariohysterectomy.
  • If supplemental doses are required, these should be smaller than the initial dose and the total given should not exceed 72 mg/kg
  • Give atropine 0.04 mg/kg concurrently to control hypersalivation. 

In Bears:

1) Bears general: 4-6 mg/kg gives rapid immobilization; recovery to sternal recumbency with the head up takes about two hours. (J213.4.w3). (For further details see Tiletamine-Zolazepam Anaesthesia in Bears). Species-specific suggestions:

• Ursus thibetanus - Asiatic black bear
  • Tiletamine-zolazepam, 4.4 mg/kg (B345.6.w6, B336.51.w51)
    • Ketamine 2 mg/kg as a supplemental drug if required. (B345.6.w6)
  • Tiletamine-zolazepam 2.8 - 4.4 mg/kg (D156.w2)
• Ursus americanus - American black bear
  • Tiletamine-zolazepam, 7.0 mg/kg (B345.6.w6, B336.51.w51)
    • Induction may take 20 minutes and a long time may be required for recovery. (B345.6.w6, B336.51.w51)
    • Suitable for most situations requiring safe and effective immobilisation. (J59.24.w1)
• Ursus arctos - Brown bear
  • Tiletamine-zolazepam 8.0 mg/kg (B345.6.w6)
    • Ketamine 2 mg/kg as a supplemental drug if required. (B345.6.w6)
  • Tiletamine-zolazepam 7.0-9.0 mg/kg (B336.51.w51)
  • Tiletamine-zolazepam 7-10 mg/kg  (D156.w2)
  • Tiletamine-zolazepam 3.5 +/- 1.8 mg/kg (J1.16.w14)
    • Induction time 4.0 +/- 2.0 minutes. In nine zoo bears. (J1.16.w14)
• Ursus maritimus - Polar bear
  • Tiletamine-zolazepam 8 mg/kg (B345.6.w6, B336.51.w51)
    • Ketamine 2 mg/kg as a supplemental drug if required. (B345.6.w6)
  • Tiletamine-zolazepam 8-10 mg/kg (D156.w2)
• Melursus ursinus - Sloth bear
  • Tiletamine-zolazepam 6.0 mg/kg (B345.6.w6, B336.51.w51)
    • Ketamine 2 mg/kg as a supplemental drug if required. (B345.6.w6)
  • Tiletamine-zolazepam 5.5 - 6.6 mg/kg (D156.w2)
• Tremarctos ornatus - Spectacled bear
  • Tiletamine-zolazepam 6 mg/kg (B345.6.w6, B336.51.w51)
    • Ketamine 2 mg/kg as a supplemental drug if required. (B345.6.w6)
  • Tiletamine-zolazepam 3.2-11.1 mg/kg (D156.w2)
  • Tiletamine-zolazepam 2.8 +/- 0.5 mg/kg (J1.16.w14)
    • Induction time 15.0 +/- 0.8 minutes. (J1.16.w14)
• Helarctos malayanus - Sun bear
  • Tiletamine-zolazepam 5.0 mg/kg (B345.6.w6, B336.51.w51)
  • Tiletamine-zolazepam 4.0-5.5 mg/kg (D156.w2)
  • Tiletamine-zolazepam, 4 mg/kg estimated body weight. (J17.119.w1)
    • For immobilisation of wild bears caught in culvert traps, to allow radio-collaring. Administered by pole syringe.(J17.119.w1)
  • Tiletamine-zolazepam 4.1+/-0.9 mg/kg (J1.16.w14)
    • In zoo bears. Induction time 8.7 +/- 3.0 minutes. (J1.16.w14)
  • Tiletamine-zolazepam 3-5 mg/kg (D255.6.w6e)

2) In combination with Medetomidine (see Medetomidine-Tiletamine-Zolazepam Anaesthesia in Bears):

• Medetomidine 0.03 mg/kg plus tiletamine-zolazepam 3 mg/kg gives a predictable, smooth induction, excellent immobilisation and good recovery following reversal (atipamezole, 2.5 - 5 times the medetomidine dose on a mg-to-mg basis). (J213.4.w3) 
  • Helarctos malayanus - Sun bear
    • For bears rescued from bear bile farms, 0.01 mg/kg medetomidine plus 1.0 mg/kg tiletamine-zolazepam, by intramuscular injection. (V.w90)
      • This provides Stage 2/Stage3 anaesthesia for about 30-45 minutes, allowing physical examination or minor surgical procedures such as wound treatment, skin biopsy and castration. (V.w90)
      • For longer and/or more invasive procedures, anaesthesia is prolonged with inhalant anaesthesia.
      • The medetomidine is reversed with atipamezole. (V.w90)
  • Ursus americanus - American black bear: 
    • Medetomidine 52 µg/kg, Tiletamine-zolazepam 1.7 mg/kg. (D156.w2, J1.33.w16)
  • Ursus arctos - Brown bear: 
    • Medetomidine 0.06 mg/kg, Tiletamine-zolazepam 2 mg/kg. (B345.6.w6, B336.51.w51)
    • Medetomidine 35 µg/kg, Tiletamine-zolazepam 4.8 mg/kg. (D156.w2)
    • For zoo bears medetomidine 0.01 mg/kg plus tiletamine-zolazepam 1.0 mg/kg or medetomidine 0.03 mg/kg plus tiletamine-zolazepam 0.5 mg/kg. (P1.1997.w9)
    • For free-ranging brown bears in Scandinavia:
      • 20-30 kg: medetomidine 0.04 mg/kg + tiletamine-zolazepam 5.0 mg/kg. (P1.1997.w9)
        • or for 1.5 year-old cubs, darts containing medetomidine 1 mg plus tiletamine-zolazepam 125 mg. (P1.1997.w9)
      • 40-60 kg: medetomidine 0.02 mg/kg + tiletamine-zolazepam 5.0 mg/kg. (P1.1997.w9)
        • or for 2.5-year-old bears darts containing medetomidine 1 mg plus tiletamine-zolazepam 250 mg. (P1.1997.w9)
      • 80-140 kg: medetomidine 0.02 mg/kg + tiletamine-zolazepam 4.0 mg/kg. (P1.1997.w9)
        • or for adult female bears darts containing medetomidine 2 mg plus tiletamine-zolazepam 500 mg. (P1.1997.w9)
      • 200-250 kg: medetomidine 0.015 mg/kg + tiletamine-zolazepam 3.0 mg/kg. (P1.1997.w9)
        • or for adult male bears darts containing medetomidine 2.5 mg plus tiletamine-zolazepam 750 mg. (P1.1997.w9)
    • For free-ranging brown bears in Sweden and Europe, based on 575 immobilisations of 241 individual bears, the following have been recommended: (P504.2001.w5)
      • Yearlings, 15-45 kg bodyweight: 0.5 mg medetomidine + 125 mg tiletamine-zolazepam. 
      • Two-year-olds and three-year-olds, 45-70 kg bodyweight: 1 mg medetomidine plus 250 mg tiletamine-zolazepam. 
      • Adult females and subadult males, 70-120 kg: 2 mg medetomidine plus 500 mg tiletamine-zolazepam. 
      • Small adult males 120-180 kg: 3 mg medetomidine plus 750 mg tiletamine-zolazepam. 
      • Large adult males: 180-240 kg: 4 mg medetomidine plus 1,000 mg tiletamine-zolazepam.
      • All bears, if the bear is not recumbent after 15 minutes, repeat the full dose. (P504.2001.w5)
    • For bears rescued from bear bile farms, 0.01 mg/kg medetomidine plus 1.0 mg/kg tiletamine-zolazepam, by intramuscular injection. (V.w90)
      • This provides Stage 2/Stage3 anaesthesia for about 30-45 minutes, allowing physical examination or minor surgical procedures such as wound treatment, skin biopsy and castration. (V.w90)
      • For longer and/or more invasive procedures, anaesthesia is prolonged with inhalant anaesthesia.
      • The medetomidine is reversed with atipamezole. (V.w90)
  • Ursus maritimus - Polar bear:
    • Medetomidine 75 µg, Tiletamine-zolazepam 2.2 mg/kg. (D156.w2)
    • Medetomidine 34-225 µg/kg, tiletamine-zolazepam 1.14-7.43 mg/kg. (J2.30.w5)
    • Medetomidine 74.8 +/- 11.8 µg/kg medetomidine + 2.2 +/- 0.3 mg/kg tiletamine-zolazepam. (J2.30.w6)
    • Medetomidine 60 µg/kg plus tiletamine-zolazepam 2.0 mg/kg (1.0 mg/kg each) intended dose; actual medetomidine mean 70 µg/kg (median 64 µg/kg), tiletamine-zolazepam mean 2.3 mg/kg (median 2.1 mg/kg) for bears requiring only one dose for immobilization. (J1.33.w17)
    • Medetomidine 0.01 mg/kg plus tiletamine-zolazepam 1.0 mg/kg OR medetomidine 0.015 mg/kg plus tiletamine-zolazepam 0.5 mg/kg. (P1.1997.w9)
    • Medetomidine mean 74.8 +/- 11.8 µg/kg, tiletamine-zolazepam mean 2.2 +/- 0.3 mg/kg (intended dose estimated medetomidine 52 µg/kg plus tiletamine-zolazepam 0.86 mg/kg). (P20.1998.w10)
  • Ursus thibetanus - Asiatic black bear:
    • For bears rescued from bear bile farms, 0.01 mg/kg medetomidine plus 1.0 mg/kg tiletamine-zolazepam, by intramuscular injection. (V.w90)
      • This provides Stage 2/Stage3 anaesthesia for about 30-45 minutes, allowing physical examination or minor surgical procedures such as wound treatment, skin biopsy and castration. (V.w90)
      • For longer and/or more invasive procedures, anaesthesia is prolonged with inhalant anaesthesia.
      • The medetomidine is reversed with atipamezole. (V.w90)

For further information see: Medetomidine-Tiletamine-Zolazepam Anaesthesia in Bears

3) In combination with Xylazine (see: Xylazine-Tiletamine-Zolazepam Anaesthesia in Bears):

• Ursus arctos - Brown bear: 
  • Xylazine 2.4-2.8 mg/kg plus tiletamine-zolazepam 3.6-4.2 mg/kg. (J345.14.w6)
• Ursus maritimus - Polar bear:
  • Xylazine 2 mg/kg plus tiletamine-zolazepam 3 mg/kg (total drugs 5 mg/kg): 4.8 mg/kg total drugs in captive-held and 5.5 mg/kg total drugs in free-ranging wild polar bears. (J1.39.w5)

For further information see: Xylazine-Tiletamine-Zolazepam Anaesthesia in Bears

• Tiletamine-zolazepam is contraindicated in animals with pancreatic diseases or with severe cardiac or respiratory disease. (B263)
• The duration of action of the combined product may be prolonged in individuals with renal disease. (B263)
• Contraindicated for use in caesarean sections because the drugs cross the placenta and may cause respiratory depression in the newborns. (B263)
• May cause hypothermia; small animals should be monitored carefully, with supplemental heat supplied if necessary. (B263)
• The pinnal, palpebral, pedal, laryngeal and pharyngeal reflexes are not abolished, therefore tiletamine-zolazepam is not suitable on its own for surgery of these areas. (B263)
• Tiletamine-zolazepam is contraindicated for use in rabbits because of renal toxicity. (B263, J213.11.w1, J495.41.w3)
• Tiletamine-zolazepam should be avoided in large cats, particularly tigers, since it may result in seizures, permanent neurological abnormalities or fatality. (B263)
• In domestic cats, the eyes remain open and should be protected against drying by application of an appropriate ophthalmic lubricant. (B263)
• Consider reducing the dose in individuals with renal dysfunction and in elderly or debilitated individuals. (B263)

• Respiratory depression, particularly at higher dose rates of tiletamine-zolazepam; sometimes apnoea. (B263)
• There may be signs of pain after intramuscular injection of tiletamine-zolazepam; this may be related to the low pH of the product. (B263)
• In domestic dogs, tachycardia may occur commonly with the use of tiletamine-zolazepam and may last for 30 minutes. (B263)
• Athetoid movements (a constant succession of slow, writhing, involuntary movements of flexion, extension, pronation, etc.) sometimes occur in animals given tiletamine-zolazepam. Further doses should not be given to control these movements. (B263)
• In lagomorphs (rabbits, hares) tiletamine-zolazepam may cause nephrosis (not recommended for use in lagomorphs). (B263)
• Possible vomiting during emergence from tiletamine-zolazepam anaesthesia. (B263)
• Excessive salivation may occur during tiletamine-zolazepam anaesthesia. (B263)
• Recovery may be prolonged. (B263)
• Transient apnoea may occur. (B263)
• Involuntary muscle twitching may occur. (B263)
• Hypertonia, cyanosis, cardiac arrest, pulmonary oedema, muscle rigidity, hypertension and hypotension are all listed as potential side-effects by the manufacturer of Telazol®. (B263)

Tiletamine alone: side effects include convulsions (therefore not available alone). (J2.3.w2)

• The manufacturers of the tiletamine-zolazepam product Telazol® claims a two-times safety margin in domestic dogs and 4.5 times safety margin in domestic cats. (B263)
• In the event of overdose, doxapram at 5.5 mg/kg may enhance ventilation. With massive overdose, mechanically assisted ventilation and other supportive treatment should be given as indicated by symptoms seen. (B263)

• Acute toxicity (acute renal failure) has been reported in rabbits following anaesthesia. (B263, J213.11.w1)

• Contraindicated for use in caesarean sections because the drugs cross the placenta and may cause respiratory depression in the newborns. (B263)

• Not known; tiletamine-zolazepam is not recommended for use in pregnant animals. (B263)

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