Polyuria and Polydipsia
Desmopressin is used intranasally, orally, or parenterally to prevent or control polydipsia, polyuria, and dehydration in patients with diabetes insipidus caused by a deficiency of endogenous posterior pituitary vasopressin (antidiuretic hormone) (neurohypophyseal diabetes insipidus) and to manage temporary polyuria and polydipsia associated with trauma or surgery in the pituitary region. Because of its relatively long duration of action and relative lack of adverse effects, many experts consider intranasal desmopressin the drug of choice for chronic treatment in patients with mild to severe neurohypophyseal diabetes insipidus. In children, intranasal desmopressin is preferred to vasopressin injection and to oral antidiuretic agents such as chlorpropamide because of the frequency of adverse effects of these agents in pediatric patients. Although intranasal administration of the drug is preferred for chronic therapy, parenteral administration of the drug may be useful when factors that can make nasal insufflation ineffective or inappropriate are present; these include poor intranasal absorption, nasal congestion and blockage, nasal discharge, atrophy of nasal mucosa, and severe atrophic rhinitis. In addition, parenteral administration of the drug may be preferred when the patient has an impaired level of consciousness. Parenteral administration of the drug also may be necessary during recovery from surgery or when nasal packing is present in patients who have undergone cranial surgical procedures such as transsphenoidal hypophysectomy.
Desmopressin is not effective in controlling polyuria caused by renal disease, nephrogenic diabetes insipidus, hypokalemia, or hypercalcemia. In uncontrolled studies, desmopressin had variable effectiveness in controlling polyuria secondary to administration of lithium.
Primary Nocturnal Enuresis
Desmopressin is used orally for the management of primary nocturnal enuresis. It may be used alone or as an adjunct to behavioral therapy and/or other nondrug measures, and has been shown to be effective in some cases refractory to standard therapies (e.g., imipramine, enuresis alarms).
Some desmopressin intranasal preparations (i.e., nasal solutions containing 0.1 mg of desmopressin acetate per mL) initially received approval from the US Food and Drug Administration (FDA) for the treatment of primary nocturnal enuresis. However in late 2007, FDA withdrew its prior approval for the treatment of primary nocturnal enuresis due to the risk of serious hyponatremia that may result in seizures and death, particularly in children, following a review of 61 postmarketing cases of hyponatremia-related seizures associated with the use of desmopressin. FDA requested that prescribing information for desmopressin be revised to include information about the risk of severe hyponatremia and seizures and the safe use of desmopressin, and to state that these desmopressin intranasal preparations are no longer indicated for the treatment of primary nocturnal enuresis. FDA states that the status of all other approved indications for the individual desmopressin intranasal preparations has not changed. (See Cautions: Adverse Effects and Precautions and Contraindications.)
The etiology of nocturnal enuresis is not precisely known, but appears to be related to delayed maturation of the cortical mechanisms that allow voluntary control of the micturition reflex. The condition is characterized by nocturnal incontinence without overt daytime voiding symptoms and is usually 3 times more common in boys than in girls. Primary nocturnal enuresis is diagnosed when a child never has experienced a period of consistent nighttime continence; the condition is considered secondary when nocturnal enuresis occurs in a formerly ''dry'' child, and usually is associated with an emotionally disruptive event. Treatment is not usually indicated until a child reaches the age of 6; the condition will then spontaneously remit in 15% of patients every year thereafter. The frequency of this condition in adults is less than 1%. Other possible etiologies for nocturnal enuresis (e.g., neurologic and/or spinal abnormalities, diabetes insipidus or diabetes mellitus, chronic renal failure, bacteriuria [especially in girls]) should be ruled out before initiation of drug therapy.
Controlled studies of oral desmopressin in doses of 0.2-0.6 mg daily for 2 weeks in patients 5-17 years of age with primary nocturnal enuresis indicated that patients experienced about 27-40% fewer nights of incontinence while receiving the drug versus placebo; a greater response was observed with increasing dosages up to 0.6 mg daily. In an open-label extension study of 6 months' duration in patients completing the placebo-controlled studies, 11% of patients receiving desmopressin achieved a complete or near complete response (no more than 2 nights of incontinence/2 weeks) and did not require titration to the 0. 6-mg daily dose. The majority of patients (86%) were titrated to the 0. 6-mg daily dose. When all dosage arms were combined (0.2-0.6 mg daily), 56% of patients receiving desmopressin experienced at least a 50% reduction in the number of nights of incontinence/2 weeks, while 38% of patients achieved a complete or near complete response. Although limited data demonstrate that desmopressin is effective for the control of primary nocturnal enuresis, the relapse rate after cessation of desmopressin therapy is high (with rates of nocturnal incontinence sometimes approaching incontinence rates before treatment); enuresis alarms have been observed to be the most effective treatment for nocturnal enuresis.
Desmopressin acetate is used intranasally or parenterally for the management of spontaneous or trauma-induced bleeding episodes such as hemarthrosis, intramuscular hematoma, or mucosal bleeding in patients with mild hemophilia A. The drug is designated an orphan drug by the US Food and Drug Administration (FDA) for use in this condition. Desmopressin acetate also is used parenterally or intranasally to maintain hemostasis during surgical procedures and postoperatively in patients with hemophilia A. The drug is not indicated for patients with hemophilia B or those with factor VIII antibodies. Desmopressin acetate generally is indicated in patients with hemophilia A whose plasma factor VIII activity is greater than 5%. Although use of desmopressin may be justified in certain clinical situations in patients with hemophilia A whose factor VIII activity is between 2-5%, these patients should be carefully monitored if the drug is used. Desmopressin is ineffective in patients with severe hemophilia A.
The National Hemophilia Foundation's Medical and Scientific Advisory Council (MASAC) currently recommends that parenteral or intranasal desmopressin be used whenever possible for the treatment of mild hemophilia A. When desmopressin does not provide adequate treatment, patients should be treated with antihemophilic factor (recombinant) or antihemophilic factor (human). MASAC states that cryoprecipitate is not recommended as a treatment alternative for the management of hemophilia A. Despite the fact the donor units used to prepare cryoprecipitate are screened for antibody to HIV-1, HIV-2, hepatitis C virus, and hepatitis B surface antigen (HBsAg), cryoprecipitate may still be infectious for several reasons, including the several months' delay in seroconversion after HIV or hepatitis C infection.
von Willebrand Disease
Desmopressin acetate is used intranasally or parenterally for the management of spontaneous or trauma-induced bleeding episodes in patients with mild to moderate type 1 von Willebrand disease. The drug is designated an orphan drug by the FDA for use in this condition. The drug also is used parenterally to maintain hemostasis during surgical procedures and postoperatively in these patients. MASAC and other experts state that desmopressin acetate is the treatment of choice for the management of mild to moderate type 1 von Willebrand disease, especially those whose plasma factor VIII activity is greater than 5%. Patients least likely to respond to the drug are those with severe homozygous von Willebrand disease whose factor VIII and factor VIII/von Willebrand factor activities are less than 1%; the response of other patients may be variable depending on the type of molecular defect associated with their disease. Desmopressin acetate is not indicated for patients with severe type 1 von Willebrand disease or when there is evidence of an abnormal molecular form of factor VIII antigen. Bleeding time, factor VIII and ristocetin cofactor activities, and von Willebrand factor antigen should be monitored during desmopressin therapy to ensure that an adequate response is being achieved. If individuals with type 1 disease become transiently unresponsive to desmopressin acetate, many experts recommend use of antihemophilic factor (human) preparations rich in von Willebrand factor (i.e., Alphanate, Humate-P, Koate-DVI).
Desmopressin acetate may be effective for the management of bleeding in some, but not all, individuals with type 2A, 2M, or 2N von Willebrand disease. Although desmopressin acetate reportedly has been used effectively in some patients with type 2B von Willebrand disease, the drug usually is not used in these individuals because of an increased risk of thromboembolic events. Desmopressin acetate is ineffective for the management of bleeding in individuals with type 3 von Willebrand disease. Experts generally recommend use of antihemophilic factor (human) preparations rich in von Willebrand factor if prevention or control of bleeding is necessary in individuals with type 2A, 2M, or 2N von Willebrand disease who do not respond to desmopressin acetate or when prevention or control of bleeding is considered necessary in those with type 2B or type 3 von Willebrand disease (e.g., in surgical situations). These antihemophilic factor (human) preparations are particularly useful for the management of von Willebrand disease in pediatric patients who are too young to receive desmopressin acetate.
(See Cautions: Pediatric Precautions.)Cryoprecipitate should not be used in the management of von Willebrand disease except in emergency, life- or limb-threatening situations when desmopressin acetate or appropriate preparations of antihemophilic factor (human) are not available.
Intranasal desmopressin has been used in adults and children to evaluate the ability of the kidneys to concentrate urine. Use of the drug for this purpose is easier and more rapid but may be less accurate than the Mosenthal concentrating test.
Intranasal desmopressin has been used in a small number of patients with sickle cell anemia to induce hyponatremia for the prevention and treatment of sickle cell crisis; however, further studies are needed to establish the safety and efficacy of the drug for this condition. In a few patients, chronic hyponatremia induced by desmopressin reduced the frequency of painful crises, and acutely induced hyponatremia shortened the duration of crises; however, successful therapy requires strict dietary regulation and patient supervision. Because of the need for further studies and the potential complications of hyponatremia (e.g., seizures), use of intranasal desmopressin for the management of patients with sickle cell disease should be limited to severely afflicted patients who can be treated and evaluated in a strictly supervised setting.
In one randomized, placebo-controlled study in uremic patients with prolonged bleeding times and hemorrhagic tendencies, IV desmopressin increased factor VIII activity and reduced bleeding time; in some additional uremic patients who received IV desmopressin before surgery or renal biopsy, bleeding time was reduced and associated with normal hemostasis.