Podcasts

Long-term famotidine use in dogs | VETgirl Veterinary Continuing Education Podcasts

In today’s VETgirl online veterinary continuing education podcast, we review the use of long-term famotidine in dogs. How many of you have seen patients that take famotidine for weeks, months, or even years? It certainly raises the question, what impact does such chronic use have on our patients? Is it even effective? So, Tolbert et al out of University of Tennessee wanted to evaluate this in a study entitled Repeated famotidine administration results in a diminished effect on intragastric pH in dogs. In this study, they evaluated the effect of repeated famotidine administration on gastric pH and serum gastrin levels over a period of 2 weeks. The authors hypothesized that the impact of famotidine on gastric pH would diminish over time, and that its effect on day 13 would be less potent than its impact on day 1.

So, in a randomized, crossover study, the investigators studied 6 healthy beagle dogs from a research colony at the University of Tennessee. The dogs had no history of gastrointestinal disease, abnormal clinical signs, or significant changes on baseline diagnostics. They were also empirically dewormed prior to the study. The dogs were randomly assigned to two groups (3 dogs per group) to receive either a placebo or to receive 15 mg of famotidine (which ranged from a 0.98 to 1.42 mg/kg dose), every 12 hours (Side note, remember you need higher doses for famotidine to work, not the cute small dose of 0.5 mg/kg SID). After 2 weeks, the dogs had a 20-day washout period, and they were then given the alternative treatment for another 2 weeks. Medications and meals were provided at consistent times, and clinical status parameters were recorded twice daily. Additionally, a standardized fecal scoring system was used to objectively monitor fecal consistency during this time.

All dogs were placed under general anesthesia at the start of the study, and gastroesophageal endoscopy was performed. Gastric biopsies were obtained, and a pH monitoring capsule was endoscopically placed in the gastric fundus. The pH capsule was again placed on day 12 of each treatment period, as well as day 0 of the second treatment period. These were placed with sedation and radiographic guidance in order to avoid repeated anesthetic episodes. Once appropriate placement was confirmed, measurement of intragastric pH was obtained every 6 seconds for 48 hours. The manufacturer software allowed calculation of the mean pH and mean percentage time that the intragastric pH was greater than or equal to 3. Measurement of the mean percentage time is of particular interest because in human studies, the mean percentage time > 3 and mean percentage time > 4 in a 24 hour time period are parameters that have been shown to predict the ability of the tissue to heal (Burget, Bell). Additionally, the investigators measured the dogs’ serum gastrin levels on days 3 and 12 of each treatment period.

Endoscopic evaluation was normal in all dogs, with histology demonstrating helical-shaped bacteria, likely Helicobacter, in all biopsies and mild lymphoplasmacytic inflammation in 3 dogs of unknown significance. Unfortunately, there were 2 pH capsules that were eliminated from analysis due to premature detachment from the stomach. So what happened with the dogs’ gastric pH levels during treatment? In dogs receiving famotidine, the mean gastric pH was significantly decreased on days 12 and 13 as compared to days 1 and 2. Additionally, the mean percentage time >3 and mean percentage time >4 was also lower on days 12 and 13 compared to days 1 and 2. In other words, the famotidine was more effective on days 1 and 2 compared to days 12 and 13! In fact, famotidine was able to meet pH goals for treatment of certain conditions on these early days, but not at the end of the course of treatment. The pH capsule remained adhered to the stomach on day 3 in a small number of dogs, and in those dogs the pH also decreased below levels for effective treatment levels by day 3.

If comparing famotidine against the placebo, there was a significant difference in mean percentage time >3 on days 1 and 2 between the two, but no significant differences in the mean pH or mean percentage time >4. Additionally, there was no significant difference in any parameter, including mean pH, mean percentage time >3 or >4, between famotidine and placebo on days 12 or 13. The presence of gastritis did not impact the effect of famotidine on any of these measured parameters. In other words, famotidine administration led to excellent gastric acid suppression in the first 2 days of treatment, but the efficacy had declined significantly by days 12 and 13 of treatment. In fact, by days 12 and 13, there were minimal differences between famotidine and the placebo! Lastly, serum gastrin was significantly different on day 3 in the placebo group, but not on days 0 or 12, though it was still within the reference interval on all days. Not surprisingly, both treatments were well tolerated throughout the course of the study.

So, what can we take away from this VETgirl podcast? Well, this study suggests that famotidine loses efficacy over time. This is important to remember if giving oral, twice-daily, famotidine for acid suppression in dogs, as chronic administration may not have the desired efficacy. Additional studies are needed to determine if different dosages or routes of administration would have produced different results, and remember that this study was only investigating healthy dogs. Those with clinical gastrointestinal disease may have a different outcome, but this requires more investigation. In any case, use caution when using long-term famotidine! While safe, it may not work well!

References:
1. Bell NJ, Burget D, Howden CW, et al. Appropriate acid suppression for the management of gastro-oesophageal reflux disease. Digestion 1992;51(Suppl 1):59–67.
2. Burget DW, Chiverton SG, Hunt RH. Is there an optimal degree of acid suppression for healing of duodenal ulcers? A model of the relationship between ulcer healing and acid suppression. Gastroenterology 1990;99:345–351.
3. Tolbert MK, Graham A, Odunayo A, et al. Repeated famotidine administration results in a diminished effect on intragastric ph in dogs. J Vet Intern Med 2017;31(1):117-123.

Leave a Reply

Your email address will not be published. Required fields are marked *