Look below for quantity discounts!!!
Canadian Omeprazole can be used in Race
Horses, Greyhounds, Dogs, & Camels
Use
1 Tube for 7 days then use 1/2 tube there after.
Introduction
- Gastric ulceration is a widespread clinical finding among performance horses
in training as well as in foals. Prevalence of up to 93% has been documented
among horses in race training1 and in nearly 60% of other performance horses.
Ulcer prevalence of up to 93% has been
documented among horses in race training1
The disease complex that precipitates
ulceration of the esophageal, gastric, or duodenal mucosa in the horse is
referred to as Equine Gastric Ulcer Syndrome (EGUS). It includes both
asymptomatic and symptomatic cases; focal or multifocal ulceration of squamous
mucosa, glandular mucosa, or both; and gastritis and complications of these
disorders.3
EGUS ranges from mild erosion to craters that penetrate the mucosa
EGUS spans a spectrum of severity,
ranging from inflamed but intact epithelium to single, superficial erosions of
the mucosal surface, and from there to multiple actively hemorrhaging hyperemic
and/or necrotic craters extending beneath the mucosal surface.4 Perforation may
occur, and when it does it is usually fatal.5
Endoscopy provides a definitive
diagnosis, but it requires endoscopes of 3 meters (9.8 feet), which may not be
available in many localities. However, a variety of clinical signs, such as
reduced appetite, poor body condition, poor performance, diarrhea, and colic,
may be highly suggestive of gastric ulceration. Response to empirical antiulcer
therapy may help establish the diagnosis in the absence of endoscopy.
In addition to intensive training,
other risk factors that may predispose horses to gastric ulceration include
intermittent feeding, reduced hay intake, physical stress (such as injury,
illness, and hospitalization), other stressors (such as shipping, relocation,
and resocialization), and, possibly, high doses of some medications.
Helicobacter pylori , a bacterium that is a major factor in the development of
human ulcers, has not been isolated from horse stomachs and is not currently
considered to be a cause of horse ulcers.3
Frontiers in Treatment
EGUS is increasingly recognized as a
major problem affecting the well-being and performance of horses. Antacids,
histamine H2 antagonists, ulcer-coating agents such as sucralfate, synthetic
prostaglandins, and anticholinergics have been used to treat gastric ulcers in
horses. None of these products is approved by the FDA for use in horses, and
their effectiveness and safety have not been assessed in large-scale,
placebo-controlled trials. Limited reports of the use of these agents show
variable results, and there is no recommended dose or administration schedule.
Importantly, horses must be removed from training to achieve healing of stomach
ulcers if these agents are used.3 Omeprazole, an acid pump inhibitor, is the
most widely prescribed antisecretory ulcer medication in humans and the number
one selling prescription drug in the world. A potent suppressor of gastric acid
secretion, omeprazole is inherently long-acting and generally well-tolerated.
These are desirable characteristics in an equine medication, and formed the
initial basis of developing an omeprazole-based product for equine use.
Adapted for Equine Use
CANADIAN OMEPRAZOLEŽ (omeprazole) Oral
Paste for Equine Ulcers has been developed specifically for horses. CANADIAN OMEPRAZOLE
is administered orally by syringe. A dose of 4 mg omeprazole/kg/day has been
shown to produce maximal suppression of gastric acid secretion. Each syringe
has sufficient omeprazole paste to treat a 1250-lb horse.
What
is CANADIAN OMEPRAZOLE? - Omeprazole, the active
ingredient in CANADIAN OMEPRAZOLE, belongs to a novel class of antisecretory
compounds, the substituted benzimidazoles. Omeprazole is
5-methoxy-2-[[(4-methoxy-3, 5-dimethyl-2-pyridinyl)
methyl]sulfinyl]-1-H-benzimidazole. Its empirical formula is C17H19N3S, and its
molecular weight is 345.42. The structural formula is:
CANADIAN OMEPRAZOLE, a flavored paste,
contains 37% w/w omeprazole and is available in an adjustable-dose syringe.
Each syringe contains 2.28 g of omeprazole.
How
CANADIAN OMEPRAZOLE Works - Omeprazole
provides superior acid suppression because it most effectively shuts down acid
production in the stomach, giving the ulcer time to heal. The cells of the
stomach mucosa contain several acid-stimulating receptors, and when these
receptors are activated they switch on the H+,K+ ATPase acid pump (an enzyme
system) to secrete acid into the stomach. Omeprazole inhibits the acid pump, so
when receptors are activated the acid pump does not initiate acid secretion.
Omeprazole is the only medication approved for use in horses that acts directly
on the acid pump, preventing acid secretion no matter what receptor is
activated.6
Omeprazole was the first acid pump
inhibitor to be approved for use in humans, and is now the first and only acid
pump inhibitor approved for the treatment of stomach ulcers in horses.6 In a
pharmacokinetic study involving thirteen healthy, mixed-breed horses (8 female,
5 male) receiving multiple doses of omeprazole paste (1.8 mg/lb once daily for
15 days) in either a fed or fasted state, there was no evidence of drug
accumulation in the plasma when comparing the extent of systemic exposure
(AUC-0-infinity). When comparing the individual bioavailability data
(AUC-0-infinity, Cmax, and Tmax measurements) across the study days (doses 1
and 15 in fed animals), there was great inter- and intrasubject variability in
the rate and extent of product absorption.
The antisecretory effects of omeprazole
persist far longer than the drug's serum level, because omeprazole becomes
bound to the H+,K+ ATPase of the parietal cell, allowing it to exert its effect
for 24 hours after a single dose.7 This prolonged duration of action enables
once-daily dosing. Omeprazole, the active ingredient in CANADIAN OMEPRAZOLE, is
a potent inhibitor of gastric acid secretion. Inhibition of the acid pump by
omeprazole results in near-complete suppression of acid secretion, regardless
of stimulus, for a long period of time.6 In a study of pharmacodynamic effects
using horses with gastric cannulae, secretion of gastric acid was inhibited in
horses given 4 mg omeprazole/kg/day (1.8 mg omeprazole/lb/day). After the
expected maximum suppression of gastric acid secretion was reached (5 days),
the actual secretion of gastric acid was reduced by 99%, 95%, and 90% at 8, 16,
and 24 hours, respectively.6
Indications in Horses
CANADIAN OMEPRAZOLE is indicated for
treatment and prevention of recurrence of gastric ulcers in horses and foals 4
weeks of age and older.6
Clinical Studies With CANADIAN OMEPRAZOLE
A series of four dose-confirmation
trials, six field trials, two acceptability trials, and four safety trials was
conducted to establish the clinical utility of CANADIAN OMEPRAZOLE.6
Ulcer Scoring
Ulcers vary in their location, size,
depth, and other characteristics. A standardized scoring system is therefore
necessary to evaluate healing and to compare severity of lesions among trial
subjects. Investigators in both the dose-confirmation trials and the field
trials were trained to use a four-point scoring method.6 The higher the score,
the more severe the lesion.
Dose-Determination Trial
The benefit of CANADIAN OMEPRAZOLE for
the treatment of ulcers is based upon the capacity of its active ingredient,
omeprazole, to almost completely inhibit acid secretion.6 Initially, pharmacodynamic
experiments and field trials were conducted to assess the efficacy of various
omeprazole pastes in inhibiting gastric acid secretion using several doses.
There was a clear indication that at 3 mg/kg/day, ulcer healing and improvement
were considerably less than maximum. Further studies led to the conclusion that
treatment with CANADIAN OMEPRAZOLE given at 4 mg/kg once daily is the most
effective dose for optimal acid suppression in the horse.6
Dose Confirmation Trials
Four trials were conducted to evaluate
the efficacy of daily doses of 4 mg/kg of CANADIAN OMEPRAZOLE in treating
existing ulcers in horses and preventing their recurrence.6 The results of
these trials were pooled for statistical analysis.
Subjects
- Thoroughbred horses at least 2 years old and healthy other than the presence
of gastric ulcers were included in trials at sites in Texas, Florida, and
Kentucky. When horses followed a typical exercise schedule used by many
race-training facilities, ulcers were consistently present over a 56-day
period. Exercise consisted of galloping or running at the training track, with
distance varied according to the horse's level of training and conditioning. As
each horse's condition improved, the length of its runs was increased. Horses
were galloped for the required distance 5 days per week, and breezed (run hard
for distance) 1 day a week. Day 7 was reserved for rest.6
Horses were housed in individual stalls
throughout the trial, with feeding that met National Research Council
requirements for adult horses in training. Animals were handled in compliance
with all applicable local regulations and with due regard for their welfare.6
Methods. The dose-confirmation trials
were divided into two parts to evaluate both efficacy of treatment as well as
prevention of recurrence. In Part 1, involving 100 horses, horses within each
trial were grouped into replicates comprising four animals with similar
pretrial gastric lesion scores and gender. One randomly selected animal in each
replicate was sham dosed using an empty syringe, while the other three received
omeprazole 4 mg/kg/day. Dosing was continued for 4 weeks, with endoscopic
examination and gastric lesion scoring after 2, 3, and 4 weeks of dosing.6
In Part 2, the objective was to
determine the omeprazole dosage needed to prevent or reduce ulcer recurrence.
The animals that had received omeprazole were regrouped into new replicates of
three based on their final gastric lesion scores at the end of Part 1.
Treatments at two daily dosages (2 mg/kg/day and 4 mg/kg/day) were randomly
allocated to horses within each replicate, with the remaining horse sham dosed.
This part of the trial continued for 30 days.6 Investigators, including the
endoscopist, in these trials were kept unaware of which animals received omeprazole
and of the dosages used.6
Statistical Analysis. Changes in ulcer
score from baseline were analyzed nonparametrically using a modified Friedman's
test (Cochran-Mantel-Haenszel procedure) to assess differences between
omeprazole and control after 2, 3, and 4 weeks. Change in ulcer score over the
next 30 days was also analyzed using a modified Friedman's test, with contrasts
tested using Dunn's procedure to assess differences among omeprazole dosing
regimens. The two-sided significance level for all testing was 0.05.6
Results: Part 1. CANADIAN OMEPRAZOLE,
administered to provide omeprazole at 4 mg/kg (1.8 mg/lb) daily for 4 weeks,
effectively healed or reduced the severity of gastric ulcers in 92% of treated
horses. In comparison, 32% of sham-dosed horses exhibited healed or less severe
ulcers. All horses began the trial with gastric lesion scores >1, and the
average pretreatment lesion score was 2.2. More than 44% of the horses had
extensive, often coalescing lesions with apparent areas of deep ulceration that
resulted in a score of 3. The reduced severity of gastric ulcers compared to
baseline was significantly (P<0.01) greater for omeprazole-treated horses
than for controls at each endoscopic examination. Ulcers were healed or
improved after 4 weeks in horses treated with CANADIAN OMEPRAZOLE.6
Prevention of Recurrence: Part 2. In
the second part of the study, CANADIAN OMEPRAZOLE at either full or half doses
prevented recurrence of gastric ulcers. CANADIAN OMEPRAZOLE (given to provide
omeprazole at 4 mg/kg/day or 2 mg/kg/day) or sham dosing was given for 30 days
to treated horses that had completed the first part of the study. There was no
recurrence of ulcers among 84% of horses receiving prevention with CANADIAN OMEPRAZOLE
at either dose, whereas ulcers persisted, recurred, or became more severe in
92% of sham-dosed horses (the proportion of horses with healed ulcers or
reduced severity of ulcers was significantly higher for horses continued on
omeprazole compared to sham-dosed controls).6
The two dosages of omeprazole did not
significantly differ in their efficacy at preventing recurrence of ulcers, with
88% and 84% of horses having healed or reduced severity of ulcers at 4
mg/kg/day and 2 mg/kg/day omeprazole, respectively.6
When omeprazole treatment stopped,
ulcers recurred. At the end of 30 days, 92% of horses that stopped omeprazole
treatment had ulcers.6
Clinical Field Trials
An additional six studies were
conducted to assess the efficacy of omeprazole paste under field conditions.6
Subjects. The horses ranged in age from
4 weeks to more than 15 years, and represented a wide variety of breeds,
including Standardbreds, Thoroughbreds, Quarter Horses, Appaloosas, Paints,
Tennessee Walking Horses, ponies, warmbloods, and crossbreds. Horses enrolled
in these trials were otherwise healthy horses confirmed by gastroscopy to have
gastric ulcers. The severity of gastric ulcers was scored using the method
described in the dose-confirmation trials. Gastric ulcers were not induced
specifically, but occurred within the routine management of each facility.
Racing, other performance, and non-performance horses were included.6 Animals
were maintained on their usual diets, housing, and exercise, which varied among
sites and according to the age, condition, and occupation of the horses. Trial
sites were located in Indiana, Oklahoma, California, Illinois, Missouri, and
Tennessee.6
Methods. At each trial facility, horses
were grouped into replicates of four, based on type of activity or location.
Within each replicate, three horses were randomly selected to receive
omeprazole while the remaining horse was sham dosed. Each horse was examined
endoscopically prior to the first dose and after week 4, and gastric lesion
scores were determined. Each animal was also observed twice daily for changes
in condition and health during each trial.6
Statistical Analysis. Data including
change in gastric ulcer score, body weight, and incidence of health problems
were pooled from the six trials. Change in gastric lesion score from baseline
to week 4 were analyzed nonparametrically using a modified Friedman's test
(Cochran-Mantel-Haenszel procedure). Baseline body weight and weight gain to
weeks 2 and 4 were analyzed using mixed-model analysis of variance. In
addition, incidence of one or more health problems was also analyzed using the
Mantel-Haenszel test. The two-sided significance level for all testing was
0.05.6
Results. CANADIAN OMEPRAZOLE
administered at 4 mg/kg (1.8 mg/lb) daily for 28 days healed or reduced
severity of gastric ulcer lesion severity scores in 99% of omeprazole-treated
horses. Among treated animals, none had a lesion score that increased, and only
one animal had an unchanged score. In comparison, only 32% of sham-dosed horses
had healed ulcers or ulcers that were reduced in severity. Two thirds of the
control animals had lesion scores that remained the same or increased during
the trial. There were no adverse health effects related to medication.6
Acceptability
Trials - In the field trials, horses readily
accepted CANADIAN OMEPRAZOLE, with >99% of the nearly 3000 doses
administered with no loss of paste.6 Two additional field trials were conducted
in horses without ulcers to further assess the acceptability of the paste. Each
followed the protocols outlined for the previously described field trials, with
the omission of the requirement for preexisting ulcers. Subjects included 20
healthy Thoroughbred foals aged 11 to 16 weeks and 20 Thoroughbred yearlings at
a facility in Virginia.6
The horses readily accepted the paste.
No paste was rejected by any of the horses.6
Safety Trials - CANADIAN OMEPRAZOLE was
well tolerated in controlled efficacy and safety studies.
In the previously described
dose-confirmation and field trials, no adverse effects attributable to omeprazole
treatment were noted.6
Additional safety studies were
conducted in which clinical chemistry, hematology, and physical examinations
were performed, and tissues and organs were examined at necropsy for gross
lesions. Tissue samples were also taken for histopathologic examination.6
In the first of these trials, a sham
dose-controlled safety study, 18 Thoroughbred horses (9 geldings and 9 females)
ranging in age from 4 to 20 years received 20 mg/kg/day omeprazole (5x the
recommended dose) or sham dosing for 91 days.6 In a second placebo-controlled
tolerance study, six adult Thoroughbred horses (3 gelded males and 3 females)
were treated with CANADIAN OMEPRAZOLE at a dosage of 40 mg/kg/day (10x the
recommended dose) or sham dosed for 3 weeks, then necropsied. In addition to
twice-daily observations, physical examinations were conducted on days -1, 2,
9, and 21. In both studies, no treatment-related adverse effects on the
animals' health were observed.6
A placebo-controlled study in foals
evaluated the safety of CANADIAN OMEPRAZOLE at doses of 4, 12, or 20 mg/kg (1x,
3x, or 5x the recommended dose) once daily for 13 weeks. Twenty-four Tennessee
Walking Horse foals (12 female and 12 male) ranging in age from 66 to 110 days
at study initiation were randomly assigned to treatment groups. Each foal was
observed at least twice daily, and physical examinations were conducted at
weeks 1, 2, 4, 8, and 13. Overall, CANADIAN OMEPRAZOLE given orally to young
horses at 1x, 3x, or 5x the recommended daily dose had no adverse effects on
animal health.6
Reproductive Safety
In a male reproductive safety study, 15
Thoroughbred and 5 Standardbred stallions between 3 and 12 years of age were
randomly assigned to receive CANADIAN OMEPRAZOLE at 12 mg/kg/day (3x the
recommended dose) or sham dosing for 71 days. Semen quality, reproductive
behavior, and genitalia were examined to assess breeding soundness. No
treatment-related adverse effects on semen quality, testicular volume, or
reproductive behavior were observed.6 A safety study in breeding mares has not
been conducted.
Safe for Concomitant Use
In the clinical trials, CANADIAN OMEPRAZOLE
was used concomitantly with other therapies, which included anthelmintics,
antibiotics, nonsteroidal and steroidal anti-inflammatory agents, diuretics,
tranquilizers,and vaccines. No interactions were observed.
Summary - CANADIAN OMEPRAZOLE Oral
Paste for Equine Ulcers was highly effective at healing gastric ulcers in
horses and preventing their recurrence. Efficacy was demonstrated in male and
female adult horses and foals in a variety of clinical and field settings.
CANADIAN OMEPRAZOLE was well tolerated, and its high acceptance by horses
resulted in negligible waste or underdosing. Only CANADIAN OMEPRAZOLE offers
these important and unique advantages to equine practitioners, trainers, and
owners in the treatment of gastric ulcers:
* It is a highly effective inhibitor of
acid secretion in horses, creating an intragastric environment in which ulcer
healing can occur.
* It is proven to heal and improve ulcers and prevent their recurrence, even
during training--not just alleviate their clinical signs.
* It is the only antiulcer medication for horses that elevates stomach pH
throughout the 24 hours after dosing, allowing convenient once-daily dosing.
* It is the only antiulcerant that has been exhaustively investigated for
efficacy and safety in equine use, and the only one approved by the U.S. Food
and Drug Administration for this indication.
* The paste formulation of CANADIAN OMEPRAZOLE has been developed specifically
for ease of administration, efficacy, and acceptability in horses.
