Torbugesic (Canada)

Active Ingredient: Each mL of TORBUGESIC contains 10 mg butorphanol base (as butorphanol tartrate, USP).

Preservative per mL: Benzethonium chloride 0.1 mg.

Clinical Pharmacology

Comparative Pharmacology

In animals, butorphanol has been demonstrated to be 4 to 30 times more potent than morphine and pentazocine (Talwin^®-Winthrop) respectively.¹ In humans, butorphanol has been shown to have 5 to 7 times the analgesic activity of morphine and 20 times that of pentazocine.^2,3 Butorphanol has 15 to 20 times the oral antitussive activity of codeine or dextromethorphan in dogs and guinea pigs.⁴

As an antagonist, butorphanol is approximately equivalent to nalorphine and 30 times more potent than pentazocine.¹

Cardiopulmonary depressant effects are minimal after treatment with butorphanol as demonstrated in dogs⁵, humans^6,7 and horses.⁸ Unlike the classical narcotic agonist analgesics which are associated with decreases in blood pressure, reduction in heart rate, and concomitant release of histamine, butorphanol does not cause histamine release.¹ Furthermore, the cardiopulmonary effects of butorphanol are not distinctly dose related but rather reach a ceiling effect beyond which further dosage increases result in relatively less effects.

Reproduction

Studies performed in mice and rabbits revealed no evidence of impaired fertility or harm to the fetus due to butorphanol tartrate. In the female rat, parenteral administration was associated with increased nervousness and a decreased care for the newborn, resulting in a decreased survival rate of the newborn. This nervousness was seen only in the rat species.

Equine Pharmacology

Following intravenous injection in horses, butorphanol is largely eliminated from the blood within 3 to 4 hours. The drug is extensively metabolized in the liver and excreted in the urine.

In ponies, butorphanol given intramuscularly at a dosage of 0.22 mg/kg, was shown to alleviate experimentally induced visceral pain for about 4 hours.⁹

In horses, intravenous doses of butorphanol ranging from 0.05 to 0.4 mg/kg were shown to be effective in alleviating visceral and superficial pain for at least four hours, as illustrated in the following figure:

Analgesic Effects of Butorphanol Given to Various Dosages in Horses with Abdominal Pain

*Pain threshold in butorphanol-treated colicky horses relative to placebo controls.

A definite dosage-response relationship was detected in that butorphanol dosage of 0.1 mg/kg was more effective than 0.05 mg/kg but not different from 0.2 mg/kg in alleviating deep abdominal pain.

Acute Equine Studies

Rapid intravenous, administration of butorphanol at a dosage of 2.0 mg/kg (20 times the recommended dosage) to a previously unmedicated horse resulted in a brief episode of inability to stand, muscle fasciculation, a convulsive seizure of 6 seconds duration, and recovery within three minutes. The same dosage administered after 10 successive daily 1.0 mg/kg dosages of butorphanol resulted only in transient sedative effects. During the 10 day course of administration at 1.0 mg/kg (10 times the recommended use level) in two horses, the only detectable drug effects were transient behavioural changes typical of narcotic agonist activity. These included muscle fasciculation about the head and neck, dysphoria, lateral nystagmus, ataxia, and salivation. Repeated administration of butorphanol at 1.0 mg/kg (10 times the recommended dose) every four hours for 48 hours caused constipation in one of two horses.

Subacute Equine Studies

Horses were found to tolerate butorphanol given intravenously at doses of 0.1, 0.3 and 0.5 mg/kg every 4 hours for 48 hours followed by once daily injections for a total of 21 days. The only detectable drug effects were slight transient ataxia observed occasionally in the high dosage group. No clinical, laboratory, or gross or histopathologic evidence of any butorphanol-related toxicity was encountered in the horses.

Torbugesic Indications

TORBUGESIC (butorphanol tartrate injection, USP) is indicated for the relief of pain associated with colic in adult horses and yearlings. Clinical studies in the horse have shown that TORBUGESIC (butorphanol tartrate injection, USP) alleviated abdominal pain associated with torsion, impaction, intussusception, spasmodic and tympanic colic, and postpartum pain.

Warning

This drug is not to be administered to horses that are to be slaughtered for use in food.

Keep out of reach of children.

Torbugesic Cautions

For use in horses only.

TORBUGESIC (butorphanol tartrate injection, USP), a potent analgesic, should be used with caution with other sedative or analgesic drugs as these are likely to produce additive effects.

Like other centrally acting compounds there may be a variation in response to TORBUGESIC (butorphanol tartrate injection, USP) between different equine breeds and between individual horses.

There are no well-controlled studies using butorphanol in breeding horses, weanlings, and foals. Therefore the drug should not be used in these groups.

Adverse Reactions

In clinical trials in horses, the most commonly observed side effect was slight ataxia which lasted 3 to 10 minutes. Marked ataxia was reported in 1.5% of the 327 horses treated. Mild sedation was reported in 9% of the horses. Extensive overdosing may cause signs of narcosis as outlined under “EQUINE PHARMACOLOGY”, (Acute Equine Studies).

Dosage

The recommended dose in the horse is 0.1 mg of butorphanol per kilogram (0.05 mg/lb) of body weight by intravenous injection. This is equivalent to 5 mL of TORBUGESIC (butorphanol tartrate injection, USP) for each 454 kg (1000 lb) body weight. Dose may be repeated as required every 3 hours for a maximum of 48 hours. Pre-clinical model studies and clinical field trials in horses demonstrate that the analgesic effects of TORBUGESIC (butorphanol tartrate injection, USP) are seen within 30 minutes following injection and persist for about 60-90 minutes.

Storage

Store at room temperature (15° to 30°C/59° to 86°F).

Supply

TORBUGESIC (butorphanol tartrate injection, USP) Veterinary Injection, 10 mg base activity per mL is available in 10 mL and 50 mL vials.

REFERENCES

1. Pircio, A.W., et al: The Pharmacology of Butorphanol, a 3, 14-Dihydroxymorphinan Narcotic Antagonish Analgesic. Arch. Int. Pharmacodyn. Ther. 220(2): 231-257, 1976.

2. Dobkin, A.B., et al: Butorphanol and Pentazocine in Patients with severe Postoperative pain. Clin. Pharmacol. Ther. 18: 547-553, 1975.

3. Gilbert, M.S., et al: Intramuscular Butorphanol and Meperidine in Postoperative pain. Clin. Pharmacol. Ther. 20: 359-364, 1976.

4. Cavanagh, R. L., et al: Antitussive Properties of Butorphanol. Arch. Int. Pharmacodyn. Ther. 220: 258-268, 1976.

5. Schurig, J.E., et al: Effect of Butorphanol and Morphine on Pulmonary Mechanics, Arterial Blood Pressure, and Venous Plasma Histamine in the Anesthetized Dog. Arch. Int. Pharmacodyn. Ther. 233: 296-304, 1978.

6. Nagashmina, H., et al: Respiratory and Circulatory Effects of Intravenous Butorphanol and Morphine. Clin. Pharm. Ther. 19: 735-745, 1976.

7. Popio, K.A., et al: Hemodynamic and Respiratory Effects of Morphine and Butorphanol. Clin. Pharm. Ther. 23: 281-287, 1978.

8. Robertson, J.T., et al: Cardiopulmonary Effects of Butorphanol Tartrate in Horses. Am. J. Vet. Res. 42: 41-44, 1981.

9. Kalpravidh, M., et al: Effects of Butorphanol, Flunixin, Levorphanol, Morphine, and Xylazine in Ponies. Am. J. Vet. Res. 45: 217-223, 1984.

Wyeth Animal Health, Division of Wyeth Canada, Guelph, Ontario N1K 1E4

^® Trademarks used under license

02174

C4540E

CPN: 1198413.2