Month: April 2021

Thoroughbreds and gastric ulcers go together like a picnic and ants. Medications like omeprazole can effectively help treat or prevent gastric ulceration and has important welfare benefits, making these drugs extremely popular in the racing industry. However, the benefits of omeprazole may be overshadowed by some potential drawbacks that may dampen its use in some cases.

Between 80 and 100% of Thoroughbreds have ulcers in the squamous or upper region of the stomach (equine gastric squamous disease, EGSD). An additional 10-60% or more of Thoroughbreds also suffering from gastric ulcers in the glandular (lower) region of the stomach (equine gastric glandular disease, EGGD).

Ulcers, which are erosions of the lining of the stomach, cause discomfort to the horse. Signs of gastric ulceration manifests in various ways such as a dull hair coat, weight loss, bruxism (grinding teeth), and poor performance.

“Squamous ulcer disease results from management practices and isn't limited to just Thoroughbreds. Feeding any horse involved in high intensity or long duration of work high grain, high carbohydrate but low roughage diets will increase the risk of disease,” said Dr. Ben Sykes from the Equine Clinic, Massey University, New Zealand.

Medications like phenylbutazone (commonly known as “bute”) or other non-steroidal anti-inflammatory drugs (NSAIDs) commonly used in horses may also contribute to the development or worsening of gastric ulcer disease although they are generally considered safe for short durations at label doses.

Given the importance of managing EGUS to optimize the health, welfare, and performance of Thoroughbreds, various medications have been developed. Sucralfate coats the ulcers to prevent further damage and allow healing, ranitidine and omeprazole decrease the acidity of the gastric juice, and misoprostol protects the lining of the glandular mucosa in the lower part of the stomach.

Manufacturers of most commercial preparations of omeprazole recommend treating ulcers with 4 mg/kg per day for four weeks. To prevent recurrence of gastric ulceration, horses can be treated longer term at a lower dose, usually 1 to 2 mg/kg per day.

Like any medication however, omeprazole doesn't always come up roses. In addition to the fact that long-term administration of any medication can be economically draining, omeprazole hasn't been tested for its long-term safety. Further, even its short-term use may not be as innocuous as one might think.

In a recent article in the journal, Equine Veterinary Education, Sykes shared four major concerns associated with omeprazole administration:

1. Rebound gastric hyperacidity. After abruptly discontinuing omeprazole, the gastric contents may become more acidic than normal, which may explain the rapid recurrence of ulcers in some horses.
2. Changes in fecal microbiome. The population of microorganisms in the equine hindgut that contribute to the overall health of the horse can be negatively affected by any medication. Omeprazole does not appear to alter the microbiome after 28 days of omeprazole administration, but the long-term effects have yet to be studied.
3. Interaction with NSAIDs. Bute and other NSAIDs can contribute to the development of gastric ulcers, and many horses treated with these medications receive omeprazole.

   “A recent study showed, however, that while omeprazole helps prevent gastric ulcers potentially caused by NSAIDs, this drug combination appears to cause hind gut issues such as small colon impactions and diarrhea that can potentially be fatal, especially when high doses of phenylbutazone are used,” said Sykes. “Considering this, my current recommendation is to avoid the co-administration of NSAIDs and omeprazole, or at least to use the lowest effective dose possible for both drugs.  If concerns about the potential for NSAIDs such as bute to cause gastric ulcers persist in a particular patient, then sucralfate is a reasonable alternative to consider.”

4. Increased fracture risk. Increased fracture risk is a significant concern with omeprazole administration in humans, both in geriatric and juvenile populations.

   “To date, no evidence exists that omeprazole has a similar effect in horses,” said Sykes. “Studies looking at the short-term effects of omeprazole on bone metabolism have found no effect of the drug. But there is data in horses that the proposed pathways that contribute to fracture risk in humans also occur with short-term omeprazole administration in the horse.”

   Long-term data are both lacking and much needed, considering the relevance of fracture risk in the racehorse industry.

In short, omeprazole is used widely both for short- and long-term use for EGUS in horses, has good reported efficacy, but may be associated with a number of important safety concerns.

“In other words, omeprazole has a high safety profile, but it does not mean omeprazole is universally safe,” Sykes said.

Ideally, veterinarians, trainers, and owners would seek to use the lowest possible dose of omeprazole that maximizes outcomes.

“Optimizing absorption will help us get more bang for our buck,” Syke said. “Giving omeprazole after fasting overnight will allow more of the drug to be absorbed compared to horses that had been fed. This means that we only need to administer about half the amount of the drug to achieve the same level of acid suppression if given when the horse has not fasted.”

As we know, though, one of the cornerstones of improving management of horses with EGUS is ensuring horses have continual access to hay. So, should we worry about withholding hay overnight? Sykes advised absolutely not.

“Horses naturally do not eat overnight even if they have ad libitum hay. Instead, they spend most of that time resting or sleeping,” he said.

Sykes therefore proposed the following tips for using omeprazole as safely and effectively as possible based on the currently available information on this drug:

• Fast horses overnight. Take away the horse's feed by 10 p.m.
• Administer omeprazole first thing in the morning before feeding and exercise. Peak absorption of omeprazole from the gastrointestinal tract into the circulation occurs around 60 minutes so the horse should remain unfed for 30 to 60 minutes after administration
• Start treating horses with only 2 mg/kg omeprazole per day. Only increase the dose to 4 mg/kg if needed (based on a lack of clinical response or gastroscopy—direct visualization of the stomach wall using a scope by a veterinarian)
• Administer other medications for gastric ulcers separate from omeprazole.

“Sucralfate, ranitidine, and misoprostol should not be administered at the same time as omeprazole. These medications will interfere in the action of omeprazole and the pH of the stomach contents will not increase as expected,” Sykes explained.

Instead, these other medications can be administered at the time of feeding, 30 to 60 minutes after omeprazole administration, or in the afternoon (omeprazole is given once a day in the morning).

“Exercising after omeprazole administration and feeding, even if just a small meal, will also increase the effectiveness of omeprazole because most of the damage to the squamous mucosa in the upper region of the stomach occurs during exercise,” Sykes said.

Overall, Sykes suggested that owners should not necessarily be deterred from using omeprazole, but should certainly cognizant of these safety issues.

“Omeprazole, like any prescription medication, should be used in a safe and responsible manner,” he said. “Implementing the recommended management changes alongside administration will help achieve either comparable or even more complete treatment responses and better outcomes with lower omeprazole doses. This not only has financial benefits but is also expected to further improve the drug's safety profile by using the minimally effective dose.”