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®