Wednesday, February 26, 2014

What's the Best Route of Administration for Desmopressin in Dogs with Diabetes Insipidus?


My patient is a 10-year old, female spayed Italian greyhound suffering from diabetes insipidus that I have been treating for several years with desmopressin, with a good overall response. I'm not certain how the diagnosis of diabetes insipidus (DI) was confirmed, however, since the dog was worked up and started on desmopressin by another veterinarian.

Initially, the dog was treated with twice daily administration of desmopressin drops (0.01%) by the intraocular route. In the past 2 years, she developed severe ocular problems (uncontrolled glaucoma) and had to have both eyes enuclueated a few months ago.

Because we could no longer use the intraocular route of administration, the owner has been giving her the desmopressin intranasally. This seemed to work initially, but now polyuria and polydipsia have returned, even with 3-times-a-day intranasal treatments. Her bloodwork remains fine, with no evidence of azotemia, hypercalcemia, or hyperglycemia. The dog is showing no clinical or laboratory signs of Cushing's syndrome, and a recent low-dose dexamethasone screening test was normal.

Is there a better way to dose the desmopressin in this case? Is there anything else I should look for or rule out in this dog other than DI?

My Response:

Well, this is a first for me. I've never had a dog that was being medicated with eye drops in which both eyes had to be removed. Wow —poor dog.

Best route of administration
I've never had a dog or cat in which intranasal administration of desmopressin was successful. Intranasal formulations of desmopressin have been available for over 40 years and remain a commonly used route of administration for human patients (1,2), but most dogs just do not tolerate it very well.  Dogs tend to sneeze out the desmopressin solution before it has a chance to be absorbed from the nasal mucosa.

I'd change to either the demopressin tablets or a compounded desmopressin injectable solution (2-4). The tablets are the most expensive option, but work well in many dogs. I find that subcutaneous admintration of the desmopressin is the most effect route of administration, which also tends to be less expensive since lower doses have to be given.

You can purchase a commercially available injectable desmopressin preparation, but it's quite expensive. I generally use a compounded desmopressin injectable (0.01%) preparation, which I purchase from Wedgewood Pharmarcy. For a 5-ml vial, my cost is about $50-60. This is the cheapest price that I can find, at least with a product that works. It's already been sterilized so you don't have to do anything but start injecting it.

Other differentials for undefined polyuria and polydipsia
There are many causes for polyuria and polydipsia in the dog, almost all of which are much more common than diabetes insipidus (DI), which is a rare disorder (Table 1). Therefore, we should always question the diagnosis of DI in the adult dog, especially if an underlying cause of the DI is not apparent (e.g.,  pituitary mass).

Differential rule outs for polyuria and polydipsia in dogs and cats,
listed from most to least common (3).
It's important to realize that many dogs with polyuria will respond, at least transiently, to desmopressin, so a positive response to the drug can never be considered 100% diagnostic for DI. For example, many dogs that I suspect having mild Cushing's disease will respond to desmopressin with a decrease in thirst and urination. I will use this treatment in some of these dogs, especially if I'm not totally convinced that the cause is really Cushing's disease, but the owners need me to do something to control the polyuria.

Continued monitoring of dogs with suspected DI is recommended
So with all dogs with suspected DI, it is always a good idea to continue to monitor them for development of another disorder which could be responsible for their polyuria and polydispia  (Table 1), even when these disorders were ruled out on initial examination.

To that end, I would recommend obtaining a complete history and physical examination every 6 to 12 months. At each of these visits, I also like to monitor a complete blood count, serum chemistry panel, and complete urinalysis with culture. In many dogs with early Cushing's disease or renal disease, the diagnosis may not be obvious when they initially present for polyuria, but with time, the primary cause will become apparent.

References:
  1. Richardson DW, Robinson AG. Desmopressin. Ann Intern Med 1985;103:228-239. 
  2. Vande Walle J, Stockner M, Raes A, et al. Desmopressin 30 years in clinical use: a safety review. Curr Drug Saf 2007;2:232-238. 
  3. Nichols, R., Peterson ME. Investigation of polyuria and polydipsia In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Gloucester: British Small Animal Veterinary Association, 2012;215-220.
  4. Peterson ME. What Drugs Do We Use to Treat Diabetes Insipidus? Insights in to Veterinary Endocrinology blog post, January 13, 2011. 

2 comments:

Merrick Wolfe said...

Hi Dr. Peterson,

Thanks for this blog post -- and you also helped me in the comments section of another one, as well.

This time I do have a very specific question regarding eyedrops vs. injectable.

I started with eyedrops but the way my vet ordered it -- from a rhinal tube transferred into an eyedropper bottle -- it was messy and frustrating. And then I heard about the injectable method -- which, actually, my doctor wasn't even aware of -- and started my 13yo female Lab/Chow mix on that -- and it worked beautifully.

I then kept on reading about people still have success with the eyedrops, but when it was formulated by a compounding pharmacy, and before I committed her to a life of being poked twice a day -- and my having to buy a constant supply of needles -- I thought I'd try the eyedrops one more time with the compounding pharmacy.

I first tried one drop twice a day -- it was not doing the trick -- then two drops twice per day, which worked, then I experimented in reducing back to two drops in the AM, one in the PM and, finally, and as it is now, one drop per day and she's doing great on it. The bottle itself is horrible, I lose drops unnecessarily but that's an issue I'm going to take up with the compounding pharmacy (shame on them!).

But... your column is the second place I've seen where someone said they gave the eyedrops for a long time and it caused problems in the socket and/or removal of the eye(s). Is this something I really should be concerned about, and would you advice I go back to injectable and don't look back?

She does tolerate both methods equally well.

Dr. Mark E. Peterson said...

As long as the desmopressin is sterilized, it should not be a problem to continue with the eye drops.