Buscopan Sterile Solution (Canada)

Manufacturer: Boehringer

Injection for Horses

Hyoscine butylbromide (Ph. Eur.)

Sterile Solution

Veterinary Use Only

DIN 02282089

Antispasmodic/Anticholinergic

For use in horses only

Active Ingredient

Hyoscine butylbromide, 20 mg/mL.

Preservatives: Methyl parahydroxy benzoate, 1.8 mg/mL; Propyl parahydroxy benzoate, 0.2 mg/mL.

Description

Buscopan^® is an antispasmodic (spasmolytic) and anticholinergic drug which relaxes the smooth muscles of the gastro-intestinal tract. It is believed to act predominantly at the parasympathetic ganglia in the walls of the viscera of the gastro-intestinal tract. The chemical name for the active constituent of Buscopan^® is hyoscine butylbromide. It is a water soluble, white crystalline substance with a molecular weight of 440.40. Each mL of Buscopan^® contains 20 mg hyoscine butylbromide, 1.8 mg methyl parahydroxy benzoate, 0.2 mg propyl parahydroxy benzoate, 6.0 mg sodium chloride, and water for injection.

Buscopan Sterile Solution Indications

Buscopan^® is indicated for the reduction of intestinal pain associated with nonsurgical and uncomplicated colic in horses.

Dosage and Administration

Administer a single dose of 0.3 mg of hyoscine butylbromide/kg of body weight (1.5 mL Buscopan^®/100 kg body weight) by slow intravenous injection.

Dosing table: (0.3 mg/kg of body weight)

Warnings

This drug is not to be administered to horses that are to be slaughtered for use in food. Keep out of reach of children. Wash hands after use. If ingested, contact a physician immediately.

Contraindications

Buscopan^® should not be used in impaction colics associated with ileus, or in horses with glaucoma. Administration of Buscopan^® results in heart rate elevation. For this reason, this drug should not be used in horses with unstable cardiovascular status, including animals exhibiting tachycardia in association with obvious homeostatic disturbances (e.g., dehydration and volume contraction, electrolyte and/or acid-base abnormalities) or evidence of primary cardiovascular disease (e.g., myocardial disease, severe valvular dysfunction, arrhythmia). Not for use in horses with intestinal pain associated with surgical and complicated colics.

Buscopan Sterile Solution Caution

Buscopan^® is not recommended for use in nursing foals or in breeding, pregnant or lactating mares. Safety has not been demonstrated in horses less than 2 years of age or in stallions used for breeding.

Not for intramuscular or subcutaneous injection.

Not for repeated administration.

Because the administration of Buscopan^® results in heart rate elevation, heart rate cannot be used as a valid indicator of severity of pain for 30 minutes following IV injection. Effects of Buscopan^® may be potentiated by the concomitant use of other anticholinergic drugs.

The safety of this drug when administered concomitantly with other drugs has not been established. Drug compatibility should be monitored closely in horses requiring adjunct therapies. Owing to the pharmacological properties of this drug, use may be associated with marked relaxation of smooth muscles, including rectal and esophageal muscles, as well as transient delays in gastric emptying.

Adverse Reactions

Transient tachycardia and decreased borborygmal sounds last approximately 30 minutes following administration. Transient pupillary dilation may also be observed. Transient heart arrythmias have been observed in animals receiving the recommended dosage.

Clinical Pharmacology

Buscopan’s spasmolytic action is based on anticholinergic effects resulting from competitive inhibition of parasympathetic activation (via muscarinic receptors) of smooth muscle cells.¹ The major side effect is a transient, elevated heart rate.

Pharmacokinetics: Following single IV administration of ¹⁴C-Buscopan (0.4 mg/kg, side chain labelled) in 3 horses, the major route of elimination of total radioactivity was via urine and feces almost equally. The bulk of the radioactivity (>96%) was eliminated (urine and feces) within the first 48 hours post-dosing. The elimination half-life of total plasma ¹⁴C was estimated to be approximately 6 hours. Therefore, the elimination half-life of the parent drug in plasma is equal to or shorter than 6 hours.

Effectiveness

A multi-centered, North American field study was conducted to establish the clinical effectiveness of Buscopan^® (0.3 mg of hyoscine butylbromide/kg of body weight) for the reduction of intestinal pain associated with nonsurgical and uncomplicated colic in horses. A total of 217 cases were randomly assigned to the Buscopan^® or placebo group; investigators were masked with respect to treatment. Horses were excluded if: dull and depressed, in shock, or required surgical intervention. Horses were included if they showed clinical signs of colic and the investigator felt treatment with an antispasmodic was necessary. Approximately 80% of animals included in the study were diagnosed with spasmodic colic, flatulent colic and simple impaction colic.

Horses underwent a pre-treatment colic examination, with repeated exams at 5, 15, and 30 minutes following test article administration. A total colic score was assigned to each case based on 5 individual criteria (sweating, pawing, head and body movement, kicking, and desire to lie down). A general clinical impression was made at the 30-minute post-treatment evaluation. No further evaluations were performed after 30 minutes.

Quarter Horses, Arabians, and Thoroughbreds accounted for the majority of the cases. Body weights ranged from 136-772 kg with a mean of 440 kg. Ages ranged between 4 months and 35 years, with an average of 10.6 years.

Total colic scores decreased throughout the 30-minute post-treatment observation period for both Buscopan^® and placebo. Scores were significantly lower (p≤0.001) for the Buscopan^®-treated horses. Also, 88% of the Buscopan^®-treated horses were rated by a veterinarian as a “success” (excellent, good, or moderate reduction in pain). This was significantly greater (p≤0.0001) than the 42% success rate for the placebo group.

The effectiveness of Buscopan^® was also supported by the overall improvement in the behavioural attitudes of the horses. A significantly higher percentage of Buscopan^®-treated horses were rated as “alert/calm” at 15 and 30 minutes post-treatment (p≤0.01) and were less likely to be “nervous/restless” (p<0.01) than were placebo-treated animals. A comparable number of cases for both the Buscopan^® and placebo groups were classified as “violent” or “drowsy/depressed” at all time points.

Post-treatment heart rates were significantly elevated for Buscopan^®-treated horses compared to the placebo-treated horses, as expected due to Buscopan’s parasympatholytic effects. At each post-treatment interval through 30 minutes, heart rates in horses treated with Buscopan^® were elevated over those of placebo horses (p≤0.0011). Within Buscopan^®-treated horses, heart rates were elevated at 5 and 15 minutes (p<0.0001), but were lower at 30 minutes compared to either 5 or 15 minutes (p<0.0001).

Animal safety: Target animal safety was evaluated in several studies; including dose tolerance, target animal safety, hemodynamics, and field safety. With the exception of the field safety study (performed on horses being treated for colic), data was derived from healthy mature horses, 2-17 years of age. Safety has not been demonstrated in foals or young horses. The pharmacological effects seen in the safety studies were consistent with those of anticholinergic drugs (see above).

In a tolerance study, four horses were administered 10 times the recommended Buscopan^® dosage (300 mg/100 kg) and were examined at 10 minutes and then at 1, 2, 3, 4, 24, and 72 hours post-injection. All horses temporarily experienced dilated and fixed pupils at 10 minutes post-injection. Normal pupillary light reflex returned in two horses at 4 hours and in the other two horses at 24 hours post-injection. Heart rates were increased at 10 and 60 minutes, but had returned to normal range at 2 hours post-injection. Oral mucous membranes were dry at 10 minutes, but were normal at 2 hours. Gut motility, as judged by auscultated borborygmi, was absent at 10 minutes post-injection, but had returned to baseline frequency and intensity by 3 hours in 2 horses and by 4 hours in the remaining horses. There were two incidences of colic, with one horse showing mild colic at 10 minutes, and another with mild colic at 11 hours. Both colic episodes were transient and required no medication. There were no drug associated changes in CBC, blood coagulation, or serum chemistry. Neither were there any drug-related gross or histopathological changes.

In a target animal safety study, Buscopan^® was evaluated in two phases. In the first phase, the drug was administered intravenously at a dose of 1, 3, and 5 times the recommended level (0.30, 0.90 and 1.50 mg hyoscine butylbromide per kg of body weight) once daily for three consecutive days. In the second phase, it was given at the recommended therapeutic dose (0.30 mg hyoscine butylbromide per kg of body weight) at hourly intervals for three consecutive hours. Control groups were used in both phases. Horses receiving Buscopan^® tended to have transient, reduced intensity of auscultated borborygmi, which can be attributed to the intended therapeutic effect of the drug. Decreased frequency and intensity of borborygmi were observed at 5 and 15 minutes post-injection and became less evident at 30 minutes. There was no evidence of gut stasis or colic. In general, increased dosages were associated with lower defecation frequencies over the observation period. Pupillary dilation, an expected pharmacological response to this class of drug (anticholinergic) was not observed in the target animal safety study when the recommended dosage was administered. This was likely related to the longer time after treatment at which the initial observations were made. However, as the dosage increased, the light reflex shifted from normal to dilated. In any event, this study shows that any effect on pupillary light response is indeed transient. Likewise, the expected transient effect on heart rate was not observed in this study as observations were not made until after the primary pharmacological activity for the drug had passed (1-4 hrs). There were no drug associated findings with respect to blood analyses, nor were there any effects evident at necropsy and histopathology.

A hemodynamic parameter study was conducted in a pony. Buscopan^® administration resulted in a brief rise in cardiac output which was of shorter duration than heart rate changes. There was a brief fall in left atrial pressure and a more sustained fall in right atrial pressure that was evident for the duration of the study (1 hr). While no changes in cardiac rhythm were recorded, transient heart arrhythmias have been observed in animals receiving the recommended dosage. None of the hemodynamic changes were marked and would be of little clinical significance in a normal animal. However, in an animal with significantly reduced cardiovascular functional capacity, the changes would take on greater significance, since there may be insufficient functional reserve capacity to tolerate the inefficiencies and increased cardiac workload invoked by the drug-induced hemodynamic changes.

Storage

Store at controlled room temperature 15-30°C.

How Supplied

Buscopan^® Sterile Solution is supplied in 50 mL multi-dose vials.

Reference:

¹Roelvinck, M.E.J., et al. 1991. Analgesic and spasmolytic effects of dipyrone, hyoscine-N-butylbromide and a combination of the two in ponies. Veterinary Record 129 (17):378-380

Boehringer Ingelheim (Canada) Ltd., 5180 South Service Road, Burlington, Ontario L7L 5H4

81326348

81312886, R.2

370121L-01-1011

NAC No.: 12300591