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Desmopressin acetate (1-deamino-8-D-arginine vaso-pressin; DDAVP) is a syn-

thetic analogue of the antidiuretichormone vasopressin.1 It is useful fortreating bleeding disorders, such asvon Willebrand’s disease, andpolyuria related to central diabetesinsipidus (DI) in small animals.

PHARMACOLOGYDDAVP differs in structure from

endogenous vasopressin in twoplaces. The amino terminal is absentat position 1, and the D isomer re-places the L isomer at position 8.2

These differences give DDAVP moreantidiuretic potential and fewer vaso-pressor properties than vasopressin.2

They also prolong the actions ofDDAVP two- to threefold.2

The specific mechanism of actionof DDAVP is to increase reabsorp-tion of water in the collecting ductsof the kidneys.1 DDAVP binds to V2antidiuretic receptors on tubule cellsin the kidneys and stimulates an in-crease in adenylate cyclase activity,

leading to increases in cAMP con-centrations,3 which in turn increaserenal tubule permeability and freewater reabsorption.3 This results in adecrease in net urine production andan increase in urine osmolality.1 Attherapeutic doses, DDAVP does notinterfere with sodium or potassiumexcretion into the urine.1

In addition, DDAVP has a highercapacity compared with vasopressinto increase plasma coagulation factorVIII and von Willebrand’s factor(vWF) on a dose-dependent basis.2

The increases occur rapidly and ap-pear to result from stimulation andrelease of endogenous stores of factorVIII and vWF as opposed to in-creased synthesis of these agents.4

Thus when repeated doses ofDDAVP are given, the responsetends to lessen.4 DDAVP cannot beadministered orally because it is de-stroyed by the gastrointestinal tract.1

In dogs, the antidiuretic activities ofDDAVP typically begin within 1hour after administration.1 The ac-tion peaks in 2 to 8 hours and canlast up to 24 hours.1 The distributionand metabolism of DDAVP are notwell understood. In humans, intra-venous DDAVP has a terminal half-life ranging from 0.4 to 4 hours.1

INDICATIONSDDAVP is used to diagnose and

treat central DI in small animals.DDAVP coupled with a water depri-vation test can be used to differenti-ate central DI, nephrogenic DI, andpsychogenic polydipsia in animalspresenting with polyuria and poly-dipsia.2 The purpose of the waterdeprivation test is to assess the appro-priate release of endogenous vaso-pressin during dehydration and thekidneys’ response to vasopressin.2 Af-ter this test, DDAVP is given (either2 µg SC or IV or 20 µg intranasallyor conjunctivally) if the animal can-not concentrate urine after losing atleast 5% of its body weight.2 Urineosmolality is then measured every 2hours for 6 to 10 hours. If osmolalityincreases by at least 10%, central DIis strongly suspected.2

Animals with psychogenic polydip-sia should have a urine concentrationof greater than 1.035 with water dep-rivation alone. Animals with nephro-genic DI show no response toDDAVP, whereas animals with cen-tral DI have a urine concentration ofgreater than 1.035.2 Once a diagnosisof central DI is made, DDAVP is amainstay of treatment. Administra-tion of DDAVP completely corrects

Traci W. Suber, PharmDUniversity of North Carolina

P H A R M P R O F I L E

Desmopressin Acetate

962 Small Animal/Exotics Compendium December 2002

• Used to diagnose and treat central diabetes insipidus• Used to treat von Willebrand’s disease

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vasopressin deficiency and eliminatespolyuria and polydipsia both shortand long term.2

DDAVP is also used to treat vonWillebrand’s disease in breeds ofdogs in which there is a high preva-lence, such as Doberman pinschers,Shetland sheepdogs, Scottish terriers,golden retrievers, and poodles.2 Al-though the hemostatic properties ofDDAVP in cats are not well studied,when administered to normal dogsDDAVP increased plasma concentra-tions of coagulation factor VIII andvWF two- to fourfold in some stud-ies.2,5 Other studies have found moremodest increases in factor VIII andvWF in dogs, but evidence suggeststhat DDAVP corrects bleeding timeindependently of increasing vWFlevels.2,4 Thus DDAVP can be usedto increase hemostatic function inpatients with abnormal bleedingtimes even if the vWF concentra-tions do not increase dramatically.6

DDAVP is most useful when petowners are taught to administer it atthe first sign of hemorrhage, such asepistaxis or hematuria.2 DDAVP in-creases levels of vWF more than fac-tor VIII.2 Factor VIII is important inthe pathogenesis of hemophilia A,and the effects of DDAVP in the rarecases of dogs with hemophilia A areunknown.2 DDAVP could also begiven to a blood-donor dog 30 min-utes before drawing blood to increasethe concentration of vWF and factorVIII in the transfused blood if the re-cipient is deficient in these factors.2

CAUTIONSSide effects of DDAVP are un-

common in small animals. Cautionshould be used when administeringDDAVP to German shorthairedpointers.2 Type II von Willebrand’sdisease is common in this breed, andDDAVP administration could resultin thrombocytopenia when given toa patient with type II disease.2 Cau-tion is also needed when administer-ing DDAVP to patients at risk for

thrombotic events.1 DDAVP is safeto use in dogs with central DI. Possi-ble water intoxication, induced by adysfunctional inhibitory thirst mech-anism, is the major complication ofDDAVP use in patients with centralDI, but this problem is uncommon.2

Likewise, hypersensitivity reactionsare possible but uncommon.1

The safety of DDAVP for use incanine pregnancy has not been estab-lished.1 However, no harmful fetaleffects were seen when 125 timesnormal human doses were adminis-tered to rats and rabbits.1

ACUTE TOXICITYOverdose may result in fluid reten-

tion or overload and subsequent hy-ponatremia.1 If this occurs, appropriatetreatment includes dose reduction andfluid restriction.1 Monitoring of elec-trolytes is recommended.1

DRUG INTERACTIONSConcomitant administration of

chlorpropamide, carbamazepine,clofibrate, fludrocortisone, or ureahas the potential to increase the an-tidiuretic effects of DDAVP and putthe patient at risk for wateroverload.1 The antidiuretic effect ofDDAVP may be decreased with con-comitant administration of lithium,epinephrine, demeclocycline, he-parin, or alcohol.1

DOSAGE AND ADMINISTRATIONIn small animals, DDAVP can be

administered intravenously, subcuta-neously, intranasally, or intraconjuc-tivally. The intraconjunctival route ispreferred for animals with central DI

Compendium December 2002 Desmopressin 963

because of ease of administration.2

Parenteral use is recommended for-patients with von Willebrand’s dis-ease because of the need for higherconcentrations.1,2 For treating centralDI in dogs, the recommended doseis one to four drops of intranasal so-lution once or twice daily applied tothe conjunctiva indefinitely.2 Thedose should be adjusted to controlsigns of polyuria and polydipsia.1

Parenteral dosing is reserved for pa-tients not responding to or toleratingDDAVP intraconjunctivally or in-tranasally.2 The intranasal formula-tion is safe for parenteral use, and thedose is 0.5 to 2 µg IV or SCq12–24h.2 Appropriate dosing forcats with central DI is one to twodrops of the intranasal preparationintraconjunctivally q12–24h.1

For von Willebrand’s disease, theappropriate canine dosage is 1 µg/kgSC, and the effect lasts 3 to 4 hours.Subsequent doses within 24 hoursdo not add benefit.1 DDAVP canalso be used intravenously in thesepatients but must be diluted in 0.9%normal saline and given over 20 to30 minutes.2

PREPARATIONSDDAVP is available as a nasal solu-

tion containing 10 µg/0.1 ml or 1.5mg/ml.1 The former is available in2.5- and 5-ml bottles and comes witheither two calibrated rhinal tube ap-plicators (1.5 to 4 µg per drop) or anasal compression pump that delivers10 µg of DDAVP in each spray.2 The1.5-mg/ml concentration is manufac-tured only in 2.5-ml bottles.1

DDAVP as a parenteral injection

• DDAVP is a lifelong treatment, not a cure.

• DDAVP should be administered at the first sign of hemorrhage in vonWillebrand’s disease.

• Both the nasal solution and injectable product should be refrigerated.

• Monitor your pet for swelling.

Client Counseling Information

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is available in 1-ml ampules and 10-ml multiple-dose vialsat a concentration of 4 µg/ml.1 DDAVP tablets (0.1 and0.2 mg) are also available but are not recommended be-cause they are destroyed in the gastrointestinal tract.1

STORAGE AND HANDLINGRefrigeration is recommended for both nasal and par-

enteral DDAVP solutions.1 However, an unopened bottle ofnasal solution is stable for 3 weeks at room temperature.1

DDAVP should not be frozen. Tablets should be stored atroom temperature.

REFERENCES1. Plumb DC: Veterinary Drug Handbook, ed 3. Ames, Iowa State

University Press, 1999, pp 203–205.

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Desmopressin (continued from page 963) 2. Nichols R, Hohenhaus AE: Use of the vasopressin analoguedesmopressin for polyuria and bleeding disorders. JAVMA 205(2):168–173, 1994.

3. Kraus KH: The use of desmopressin in diagnosis and treatmentof diabetes insipidus in cats. Compend Contin Educ Pract Vet9(7):752–755, 1987.

4. Mansell PD, Parry BW: Changes in factor VIII: Coagulant ac-tivity and von Willebrand factor antigen concentration aftersubcutaneous injection of desmopressin in dogs with mild he-mophilia A. J Vet Intern Med 5(3):191–194, 1991.

5. Johnstone IB, Crane S: The effects of desmopressin on hemo-static parameters in the normal dog. Can J Vet Res 50:265–271,1986.

6. Johnstone IB: Desmopressin enhances the binding of plasmavon Willebrand factor to collagen in plasmas from normal dogsand dogs with type I von Willebrand’s disease. Can Vet J 40:645–648, 1999.