Impact of concurrent treatment with omeprazole on phenylbutazone‐induced equine gastric ulcer syndrome (EGUS)

Abstract

Background Phenylbutazone is commonly prescribed for treatment of various painful or inflammatory disorders in horses, but is associated with gastrointestinal (GI) adverse effects. Anecdotally, many practitioners prescribe omeprazole concurrently with phenylbutazone to reduce development of equine gastric ulcer syndrome (EGUS), but the efficacy and safety of this practice remains unknown. Objectives To evaluate the effect of omeprazole on phenylbutazone‐induced equine glandular gastric disease (EGGD) and equine squamous gastric disease (ESGD). Study design Randomised block experimental design. Methods Twenty‐two horses with EGGD and ESGD scores ≤2 were included. Horses were assigned to treatment groups: phenylbutazone (4.4 mg/kg PO q 12 h; PBZ), phenylbutazone plus omeprazole (4 mg/kg PO q. 24 h; PBZ/OME) or placebo (CON) in a randomised block design based upon initial EGGD score. Horses were treated for up to 14 days. Gastroscopy was performed weekly; CBC and biochemistry were performed at Day 0 and study end. Horses were monitored for signs of colic and/or diarrhoea. Results EGGD score increased in PBZ (median change 1, inter‐quartile range, [IQR], 0‐2) compared to PBZ/OME (median change 0, IQR −1 to 0; P = .05). PBZ/OME (6/8) had more intestinal complications than CON (0/6; difference between proportions = 75%; 95% CI, 23%‐93%; P = .03). Plasma protein concentrations decreased in PBZ, compared to CON (mean difference between groups, 14 g/L; 95% CI, 1.04‐27; P = .03). Five horses were withdrawn from the study due to intestinal complications (n = 3 PBZ/OME and n = 2 PBZ); one horse (PBZ) was withdrawn due to severe grade 4 EGGD. Main limitations Small sample size and changes in management for the 2‐3 days prior to study initiation; variable treatment duration among groups due to development of complications. Conclusions Administration of omeprazole ameliorated PBZ‐induced EGGD, but was associated with an increase in intestinal complications. Caution should be exercised when co‐prescribing NSAIDs and omeprazole in horses, particularly in association with change in management.

A free ride: Is long‐term omeprazole therapy safe and effective?

“…However, a recent study demonstrating increased complications associated with its use alongside phenylbutazone (Ricord et al . 2021), a practice that has been assumed to be safe for years, highlights that lack of evidence for an adverse effect does not preclude the possibility of an adverse effect being present. Instead, specific studies should be performed to investigate any potential adverse effects.…”

“…Complications included two fatalities from colitis in the omeprazole/phenylbutazone group (Ricord et al . 2021). The occurrence of inflammatory lesions is consistent with findings in dogs where concurrent omeprazole administration exacerbates intestinal inflammation associated with administration of carprofen (Jones et al .…”

“…It has recently been demonstrated that concurrent administration of omeprazole increases the risk of phenylbutazone‐induced gastrointestinal toxicity, over that of administration of phenylbutazone alone (Ricord et al . 2021). Reported complications in that study were impactions (small colon, n = 1; and large colon, n = 1) in 2/8 horses in the phenylbutazone only group and impactions (small colon, n = 1; and large colon, n = 1), non‐specific colic (n = 1), and diarrhoea or colitis (n = 3) in 6/8 horses in the omeprazole/phenylbutazone group (Ricord et al .…”

“…Reported complications in that study were impactions (small colon, n = 1; and large colon, n = 1) in 2/8 horses in the phenylbutazone only group and impactions (small colon, n = 1; and large colon, n = 1), non‐specific colic (n = 1), and diarrhoea or colitis (n = 3) in 6/8 horses in the omeprazole/phenylbutazone group (Ricord et al . 2021). Complications included two fatalities from colitis in the omeprazole/phenylbutazone group (Ricord et al .…”

“…However, a recent study that demonstrated an increased risk of phenylbutazone‐induced gastrointestinal disease associated with the concurrent administration of omeprazole has challenged the notion that it is universally safe (Ricord et al . 2021). Similarly, omeprazole is widely believed to be effective for long‐term administration as a preventative for equine gastric ulcer syndrome (EGUS) and it is registered for this purpose.…”