Thursday, January 13, 2011

What Drugs Do We Use to Treat Diabetes Insipidus?

Treatment with arginine vasopressin (antidiuretic hormone of humans, dogs, and cats) or its analogues restores medullary hypertonicity and a normal urinary concentrating ability in animals with central diabetes insipidus. Historically, ADH tannate in oil, an extract of arginine vasopressin prepared from bovine and porcine pituitary glands, was administered every 2 to 3 days as needed to control polyuria and polydipsia. Because this product is no longer available, desmopressin acetate, a synthetic analogue of arginine vasopressin with prolonged and enhanced antidiuretic activity, has become the drug of choice for the treatment of central diabetes insipidus in dogs and cats.

DESMOPRESSIN PREPARATIONS
Desmopressin acetate is available in preparations for intranasal, parenteral (injectable), or oral administration (see Table below).

Nasal sprays or solutions of desmopressin

The nasal formulations are supplied with 2 different delivery systems: either a spray pump or a rhinal tube delivery system (see Table below), in which the desmopressin is “sprayed” or “blown” into the nose, respectively. Obviously, most dogs or cats will not tolerate either of these intranasal delivery methods.  Drops placed in the conjunctival sac provide a more suitable alternative for animals.

With the rhinal tube delivery formulation (DDAVP Rhinal Tube®, Sanofi Aventis), the desmopressin is packaged with a small, calibrated plastic catheter so that exact amounts of the drug can be measured and administered.  The calibrated rhinal tube has four graduation marks that measure amounts of 0.05 ml, 0.1 ml, 0.1 ml, and 0.2 ml and thereby can deliver doses of 5 to 20 µg of desmopressin).  Although this system allows for accurate dosing, it is awkward to use. In addition, because this rhinal tube delivery system is not available as a generic product, this formulation is quite expensive.

The most common intranasal formulations of desmopressin are marketed as nasal sprays or solutions equipped with compression pump that delivers 10 µg of drug with each spray. For use in dogs and cats, this spray bottle should be opened (a plier may be neccessary to break the seal) and the desmopressin solution transferred to a sterile vial; this dispensing vial then allows one to place the desmopressin drops within the animal’s conjunctival sac.

These intranasal preparations of desmopressin are generally supplied as a concentration of 100 µg/ml; depending on the size of the drop, one drop of nasal solution corresponds to 1.5 to 4 µg of desmopressin. One highly concentrated nasal solution (1.5 mg/ml) is marketed for use in hemophilia (see Table below), but it should not be used to treat animals with diabetes insipidus because of the strong likelihood of overdosage.

In most cats and smaller dogs, 1 to 2 drops of the intranasal preparation administered once or twice daily are sufficient to control polyuria and polydipsia.  Larger dogs may require up to 4 to 5 drops twice daily. Use of a tuberculin or insulin syringe allows for more accurate dosing. Application of desmopressin into the conjunctival sac may cause local irritation, as the solution is acidic. Some animals may object to the daily eye drops, making this route of administration ineffective.

Oral desmopressin tablets

The oral preparation of desmopressin is available both as a sublingual dissolve melt tablet (not suitable for treating cats) and as 0.1 mg and 0.2 mg tablets. Each 0.1 mg (100 µg) tablet is roughly comparable to 5-10 µg (1-2 large drops) of the nasal solution (see Table below).

The tablet form of desmopressin is a more cost-prohibitive alternative compared with the conjunctival or subcutaneous routes of administration. The cost of daily oral desmopressin in animals is roughly 2.5-times that of the cost of conjunctival drops, and roughly 6 times the cost of subcutaneous injections of desmopressin. For some pet owners, however, the use of a tablet form may prove to be a more convenient, or the only possible route of administration that is possible.

Injectable desmopressin solutions for SC or IV use


An injectable sterile solution of desmopressin acetate (4 µg/ml) marketed for intravenous use is available (see Table) and can be used in animals with diabetes insipidus. However, the cost of the injectable desmopressin is approximately 7 to 15 times higher per µg than the intranasal preparation, making this formulation cost-prohibitive for use in most dogs and cats.

To circumvent this cost issue, the intranasal form of desmopressin – although not designed for parenteral use – can be given subcutaneously to cats with excellent results.

Because the nasal forms of desmopressin are not considered to be sterile, however, it is best to first sterilize the product by passing the nasal solution through a 0.2 micron bacteriostatic syringe filter. Clinically the nasal and injectable preparations of desmopressin induce indistinguishable responses when administered subcutaneously.

To make dosing easier, the desmopressin is best administered with an U-100 low-dose insulin syringe. The solution can be diluted in sterile physiologic saline to make dosing easier.

The subcutaneous route of desmopressin administration has many advantages over the other routes of administration. These advantages include the following:
  • First, drug appears to be most effective when administered via the subcutaneous route.
  • Second, the duration of action is longer after subcutaneous injection than when administered orally or via the conjunctival sac.
  • Third, because of the smaller subcutaneous doses required to control signs (about 15% and 40% of the oral and conjunctival doses, respectively), the cost of treatment is greatly reduced.
  • Fourth, many cats seem to prefer long-term subcutaneous injections to the chronic use of eye drops or oral medication.


Company Web sites for more information:
Sanofi Aventis
Ferring Pharmaceuticals
CSL Behring
Bausch and Lomb
Hospira
Teva Pharmaceuticals
Apotex Corporation

Desmopressin acetate is also available generically (many companies) and may also be known by the following synonyms and internationally registered trade names:
Concentraid®, D-Void®, Defirin®, Desmogalen®, Desmospray®, Desmotabs®, Emosint®, Minurin®, Nocutil®, Octim®, Octostim®, or Presinex®

40 comments:

eksmith48 said...

Hi Dr. Peterson,
We are using the desmopressin nasal spray as an injection for our cat with DI. I thought I came across instructions on your site a while ago for how to open the bottle for transfer to a sterile container, but I can't find it anymore. We (incl. our vet) struggled with getting it open last time we were trying to do this. Any pointers would be much appreciated.
THANKS!
EK

Dr. Mark E. Peterson said...

I don't have any secrets. It can be difficult to break the seal of the bottle. A needle-nose pliers may be needed to get the job done.

Pam said...

My vet is checking my dog for DI, can you tell me what the approx. cost is for this medicine?? thank you.

Dr. Mark E. Peterson said...

Did you read this blog post? The cost depends on the preparation used and if you use trade-name, generic, or compounded drug. The cost also depends on the dose used. Most smaller dogs can be treated for under a dollar a day; large breed dogs could be $3-4 per day depending on preparation used and dose.

chinster said...

Hello,

Thank you for your information. I purchased Desmopressin Acetate Nasal Solution 0.01% at Costco for $115. I don't really like the idea of putting it in my dog's eyes and I haven't been able to get the top off the bottle to transfer. I may try the plier suggestion. My vet wants to try this for the first few weeks and then switch to tablets. I'm thinking I should just go for the tablets. Besides cost, are there any other disadvantages? Any information you can provide would be greatly appreciated.

Dr. Mark E. Peterson said...

The tablets don't work as well as the eye drops or injectable. That's why we like to start with those methods. But you could start with the tablets, but they may not work nearly as well to control the excessive urination.

I like to use the injectable the best - I buy that at Wedgewood.com, a compounding pharmacy. They sell it in sterile vials so you don't have to pry the top of the vial off!

Jorge said...

Hello Dr. Peterson,

To apply drops into my dog's eyes is really difficult, for no saying impossible...so i am thinking in tablets but i have some doubts...for a small dog (12lb), which woul be the treatment? One tablet of 0,1mg per day or two tablets (each 12hours)?
Do we have to follow the treatment all days during his life? Or do we have to stop some time?..my dog is 9months, would I need to increase the dose, after the years?
The diabetes insipidus is an hereditary disease?
If we do not treat the diabetes insipidus but the dog has free access to fresh water, can create in a future a different disease?
Thanks a lot for your help and sorry for the high number of questions, but here in Spain, it is quite difficult to find an expert for these disease...

Dr. Mark E. Peterson said...

Most younger dogs with diabetes insipidus have a congenital form of the disorder, which will never resolve. If a dog has free access to water, as well as to a safe place to urinate, treatment is not necessary. We use desmopressin to allow dogs to be in a house or apartment where we can't have them urinating all day and night.

The oral tablets are given to effect - I'd start with 0.1 mg once or twice a day and adjust from there,

Agnieszka Ligeza said...

Helo Dr. Peterson,
we are using the desmopressin nasal spray (Minirin) for a dog which is 8-month old. He accepts nasal administration somehow, but I'm afraid if we don't make any harm to him in that way? (e.g.don't we destroy in that way his sense of smell?)
We administer 10 mcg in the morning and 10 mcg in the evening. Shell we rather administer 20 mcg once daily?
Thank you very much for your help, but here in Poland, we can't find an experienced doctor.
With best regards
Agnieszka

Dr. Mark E. Peterson said...

The desmopressin intranasally isn't going to hurt your dog, especially if he has diabetes insipidus. Twice daily is better than once a day. It will certainly control the polyuria better than just once daily.

Agnieszka Ligeza said...

Thank you very much for your help and so quick answer. Oh, of course I forgot to mention that our dog is diagnosed with DI.

with best regards,
Agnieszka Ligęza

Agnieszka Ligeza said...

Helo Dr. Peterson,
we have just controlled the blood electrolytes in our dog, diagnosed with DI. And we got:
sodium 138,9 mmol/l (norm 139,1 156,5) L
potassium 4,3 mmol/l (norm 4,1 5,4)
chlorine 119,8 mmol/l (norm 98,7 115,6) H
calcium 9,1 mg/dl (norm 8,4 11,5)
Please tell me, if such a high chlorine and low sodium level are acceptable in DI dog ?

Thank you very much,
with kind regards,
Agnieszka Ligeza

Dr. Mark E. Peterson said...

I would not worry about these mild serum electrolyte changes. But I would recommend that you continue to monitor again in 2-3 months,.

Agnieszka Ligeza said...

Thank you very much Dr. Peterson!
It is a great relief for me.
With kind regards,
Agnieszka Ligeza

Michele Ramos said...

We have a 3 yr old dog newly diagnosed with DI and we are having a hard time treating with DDAVP. We have the 0.1mg/mL drops and he is taking 6 drops/day and it is still not fully effective. We are thinking about switching to injections and want to know how to dilute the package of drops we currently have to make it injectable. It is incredibly expensive and we want to use what we have, needles are no issue as we have had to inject other dogs with their insulin.

Dr. Mark E. Peterson said...

Most dogs with DI will partially respond to any form of desmopressin treatment. DI is a rare disorder so you should ensure that the diagnosis is really correct as a first step.

I generally turn to a compounding pharmacy to have them prepare the injectable desmopressin. This is usually cheaper (at least in the USA) than it is to buy the eye drops and use a Millipore filter to sterilize that preparation.

Dr. Mark E. Peterson said...

Most dogs with DI will partially respond to any form of desmopressin treatment. DI is a rare disorder so you should ensure that the diagnosis is really correct as a first step.

I generally turn to a compounding pharmacy to have them prepare the injectable desmopressin. This is usually cheaper (at least in the USA) than it is to buy the eye drops and use a Millipore filter to sterilize that preparation.

Iris F. said...

Dr. Peterson,
Our dog has DI and we had been treating him with desmopressin. We started dropping it into his eyes and then switched to injections when it wasn't effective. He is still drinking and urinating quite a bit and we have only a slight improveme. We have now decided to try it in the pill form but I am not hopeful. On top of that, he is on thyroid replacement and it's been difficult to get both to normal ranges. Any suggestions?
Thanks
Iris Fox

Dr. Mark E. Peterson said...

DI is a rare condition. If the desmopressin hasn't been effective, then it's highly unlikely that DI is the correct diagnosis. Talk to your vet and if they don't know, ask for a referral to a specialist.

Jeremy Easton said...

Hello, I have a 9 tear old boxer who has polyuria and polydipsia. Because he has a history of external tumors it was suggested by my Vet of 17 years that he may have one in his brain(Pituitary)causing this. She has recently put him on desmopressin (.1MG every 8 hrs). During the day all seems well and urination/water consumption is normal, but sometime over-night it must wear off and I'm waking up to urine on my carpet. I should also add he is starting to fight me a bit on taking the tablet, even in cold cuts! I have read on various posts that some people are buying the nasal spray and injecting it in cats with longer results. Is this something that can be done in dogs, possibly for the over-night does only, and if so at what rate would you suggest? Any other suggested methods? Should a diet change be considered as well? Thank you very much for your time and attention!

Dr. Mark E. Peterson said...

I discuss injectable desmopressin in this blog post. The easiest way to use that is to have a compounded pharmacy make it up for you so you don't have to sterilize it. The injectable form is most effective form.

Jeremy Easton said...

Thank you very much for the quick response. However, the main point I was trying to ask (and I may have rambled on a bit) is that I have read on a few posts that people have purchased the nasal spray, popped the cap, and injected it in Cats? Would this method also apply to dogs if it was a sterilized nasal formula?

Dr. Mark E. Peterson said...

Yes, same for dogs and cats...

Trina Redgwell said...

Hi there, I have a 3 year old welsh pony with suspected D I. We have done a water consumption test and he drank 78 litres over 24 hours. My question is, is there any effective treatment for equines and can they be treated successfully, whilst still having purpose? He is a harness pony - a very good one at that - I am still hoping it is boredom related. It would be devastating to lose him. Thank You.

Dr. Mark E. Peterson said...

I have no idea if a pony can develop DI, but I don't know why not. This blog is written for dogs and cats. Remember, however, that DI is not a fatal disease as long as water is always available. Your pony certainly needs a workup so talk to your vet.

Trina Redgwell said...

Thank you, he is in for further testing today. Apparently very rare in equines, however with a small management change he is concentrating urine so hopefully not as bad as we feared. Thank you for replying, very little information available on this topic. Thanks again.

Scott p said...

Dr Peterson,

We have a 90 lb dog that was recently diagnosed with DI. It looks like oral tablets will run ~$300/month, so we are looking for a more cost effective option such as injectible Desmopressin. Does Wedgewood Pet RX sell the nasal solution in a sterile vials? I assume that the "injection solution" is just that - the nasal solution in injectible form. Is that right?

Dr. Mark E. Peterson said...

Wedgewood sells a sterile injectable solution. I am not certain where they get the desmopressin from, but it works.

Laurie Smith said...

Hello Dr. Peterson. First of all, thank you so much for maintaining this blog and responding to people who post questions. I have found it to be so helpful. I have a 13.5 year old, 20 lb. boston terrier who was diagnosed with hypothyroid at age 9 and cushings at age 10.5. We have been managing him well on soloxine and trilostane, but about a year ago, he developed polydipsia/polyuria. It took nearly a year of testing/adjusting meds and ruling out other things (though I don't know if we ruled out the rare infections you refer to in other posts) before we landed on Diabetes Insipidus as the likely culprit. Other than his bucket of endocrine issues, he's happy and healthy, thin and active (walking at least 20 miles a week), and really quite youthful.

Here's the issue:

1) We started on oral tabs, which seemed to work at first, and then stopped working about 3-4 weeks in.
2) We then switched to eye drops, which worked wonderfully for about 6 weeks, and now their effectiveness seems to be waning too. Also, it's so expensive - a $120 ml bottle from our compounding pharmacy lasts us 3 weeks!
3) As noted above, this is a boston terrier. They have eye troubles as it is, so I'm very concerned about corneal edema or other issues. I have heard of dogs having to have their eyes removed because of this. Also, the buggie-ness of his eyes means he blinks alot of the drops out (even though I am dropping it into the conjunctiva).

Based on all of this, I think it's time to go to injectable desmo. Do you agree? What is the dosage for a 20 lb dog if you're injecting it (he currently gets 2 drops, 2x daily, at 5:30 am and pm). Based on what I've read here, I know I can get sterile injectable from Wedgewood, but will it be obvious to my vet how to prescribe it?

Thank you again - so much - for the insight provided on this page. It's really a godsend to those of us who have complex pups.









Dr. Mark E. Peterson said...

Yes, injectable desmopressin works the best. But if your dog really has Cushing's, the polyuria is probably due to that disease. We don't generally see Cushing's and DI together unless the pituitary tumor in huge and invasive. Talk to your vet about a referral for better workup, including imaging.

Laurie Smith said...

Thank you, Dr. Peterson, for your comments. Here's what we've done in workup thus far:
1. retested thyroid levels to fine tune dosage
2. retested ACTH Stim (annually) to ensure Cushing's is adequately controlled (always gets a good reading at his trilostane dosage, have followed protocol for 3 years)
3. Abdominal ultrasound, which found xanthine stones in the bladder. We had them removed. This did not improve the symptoms.
4. Urinalysis, which found nothing (not sure they tested for rare infections, only the standard ones). We did put him on clavamox just in case. No improvement in symptoms.

At this stage, our DVM thought DI might be it, and consulted an endocrinologist here in SoCal. This person listened to the case and suspected DI, saying it does happen due to the tumor growth that might be expected when a dog lives for several years with cushing's (even though there are no other brain tumor symptoms).

We elected to forgo an MRI because Rex is older and has a heart murmur, so we're not excited about any unnecessary anesthesia. As I noted, the desmo helps for several weeks, and then seems to stop working.

Given all we've already done and ruled out, what would you suggest for further workup. Or, would you suggest trying the injectable desmopressin to see if that addresses the issue?

Thank you again for your help and insight. Even our vet feels a bit like he's flying blind here, and the endocrinologist we consulted seems to feel it's DI.

Happy to have my vet contact your office for an official consult if that is an option for us.

Dr. Mark E. Peterson said...

So try the injectable desmporessin. There is no set dosage. Your vet should start low and adjust accordingly.

Kim Rogers said...

Our 14 yr old llasa apso mix has recently started with the extreme drinking and urinating. A full blood workup and normal physical checkup showed everything good but the urine test came back with the specific gravity of urine very low. And so we tested again today after withholding water for 12 hrs and getting a first morning specimen. The vet just called to say this result was even lower than the one before. He highly suggests DI but is wanting to rule out two more things. He's suggesting we need to to test for Leptospirosis ($75) and do a culture ($114) to rule out a UTI. We spent $240 already on the above testing. My husband has stage IV Melanoma and our funds are limited. We love this little guy to pieces but you begin to wonder when you just need to say no. I am very interested in the DDAVP by injection (I've had to give my husband subcutaneous injections so am very comfortable with the process). What I don't want to have to do is pay another $200 for tests that seem silly with no other symptoms or blood results that would even suggest some type of infection. I read about a suggestion called a DDAVP trial to see if the symptoms leave when the drug is administered and return when the trial is stopped. This makes sense to me. I've learned with our journey with my husband to be proactive about our care and I'm feeling the need to do the same here. Do you agree with me? Anything I'm missing? I've read all the above and plan to research buying the compound from Wedgewood. Is that marketed to the general public? Thanks so much! You've already been a huge help! Also, did I read That DI is not a life threatening disease - just requires lots of water to drink and plenty of potty times?

Dr. Mark E. Peterson said...

Your vet is recommending the correct steps. If your dog has lepto or an UTI, both are treatable. If not treated, progression of kidney disease will occur.

Idiopathic DI is not common (in fact, it is extremely rare(, especially in 14 yr old dogs. The desmopressin may control clinical signs in a number of different problems (yes, the injectable is best) but this drug does not cure anything.

Petlover said...

I have a 16 week old male lab puppy they believe to have DI. Had previous uti and 3 weeks of clavamox. Seemed to get better than contiued thirst and urinating began again. No uti with urinalysis waiting on culture. Blood work normal. Mild glucose elevated, dilute urine and low serum protein. Active puppy gaining weight full of energy. Currently 35.7 pounds. What can I expect. He does hold it when crated at night. Can I restrict water before bedtime.

Dr. Mark E. Peterson said...

No you should not restrict water with DI.

Angie Atkinson said...

I have a 13 year old boxer with di. Have been treating him with desmopressin oral for several months now.I never intended to stop the peeing but more control his drinking obsession for comfort measure. It works to a degree although i havent given the full recommended dose as yet cos lower dose produced results.can i expect the dose to become less effective with time?or is it a case òf if it works,the dose needed will remain the same?

Dr. Mark E. Peterson said...

If it's not completely working, then mostly likely the main problem isn't primary DI. Talk to your vet.

n Pomerantz said...

Will desmopressin resolve PU/PD caused by untreated cushing's disease?

Dr. Mark E. Peterson said...

Yes, it may lessen the PUPD, but generally will not resolve it completely. And the effect may not last forever.