Prior Auth Protocol

FDA Approved Indications:

Primary Nocturnal Enuresis (oral DDAVP only):
- May be used alone or as an adjunct to behavioral conditioning or other nonpharmacological intervention.
Central Cranial Diabetes Insipidus (intranasal, oral, and parenteral DDAVP):
- Antidiuretic replacement therapy in the management of central cranial (neurogenic) diabetes insipidus and for management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. Ineffective for the treatment of nephrogenic diabetes insipidus.
Hemophilia A (parenteral DDAVP; Stimate):
- Hemophilia A with Factor VIII coagulant activity levels > 5%. Dexmopressin also will stop bleeding in hemophilia A patients with episodes of spontaneous or trauma-induced injuries such as hemarthroses, intramuscular (IM) hematomas, or mucosal bleeding.
von Willebrand's disease (Type I) (parenteral DDAVP; Stimate):
- Mild-to-moderate classic von Willebrand's disease (Type I) with Factor VIII levels > 5%. Desmopressin will also stop bleeding in mild-to-moderate von Willebrand's patients with episodes of spontaneous or trauma-induced injuries such as hemarthroses, IM hematomas, or mucosal bleeding.

Health Net Approved Indications and Usage Guidelines:

For DDAVP

Primary Nocturnal Enuresis (tablets only)

Failure of at least a three month trial of bed-wetting monitor

Central Cranial Diabetes Insipidus (Redirect to California Children's Services [CCS] if <21 years of age)

Diagnosis of central cranial diabetes insipidus

For Stimate

Diagnosis of Hemophilia A

OR

Diagnosis of von Willebrand's disease (Type I)

Coverage is Not Authorized For:

Nasal spray and rhinal tube formulations for Primary Nocturnal Enuresis.
Patients with hyponatremia or a history of hyponatremia
Treatment of nephrogenic diabetes insipidus.
Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section unless there is sufficient documentation of efficacy and safety in the published literature.

General Information:

In December 2007, Sanofi Aventis sent a letter to healthcare professionals stating that the nasal spray and rhinal tube formulations of DDAVP are no longer indicated for Primary Nocturnal Enuresis. There was also a warning and precaution regarding hyponatremia, fluid restriction, and a recommendation to supervise administration in children. Unless properly diagnosed and treated, hyponatremia can be fatal.
Per the package insert, DDAVP is ineffective for the treatment of nephrogenic diabetes insipidus.
Per the package insert, Stimate should not be used to treat patients with Type IIB von Willebrand's disease since platelet aggregation may be induced.
Micromedex Class IIa for a urine concentration test. Intranasal desmopressin (20-40 mcg) is an adequate alternative to vasopressin for testing maximal renal concentrating capacity

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
Imipramine	Childhood Enuresis: Initially, 25 mg/day PO 1 hour before bedtime. If a satisfactory response is not obtained within 1 week, increase up to 50 mg/night if < 12 years of age; up to 75 mg/night if > 12 years of age. Do not exceed 2.5 mg/kg/day. In early-night bedwetters, it may be more effective given earlier and in divided amounts (25 mg midafternoon and at bedtime). Institute a drug-free period after an adequate trial with favorable response. Gradually tapering dosage may reduce tendency to relapse. Children who relapse after discontinuation do not always respond to a subsequent course.	A dose > 75 mg/day does not enhance efficacy and increases side effects.

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
DDAVP [oral]	Primary Nocturnal Enuresis Adults and children over 6 years of age Patients begin at 0.2 mg PO at HS. The dose may be adjusted upward to a maximum dose of 0.6 mg. Central Diabetes Insipidus Adults and Children It is recommended that patients be started on doses of 0.05 mg PO (1/2 of the 0.1 mg tablet) BID and individually adjusted to their optimum therapeutic dose, range of 0.1 mg to 1.2 mg divided in two or three daily doses.	Primary Nocturnal Enuresis One year Central Diabetes Insipidus Length of Benefit
DDAVP [nasal]	Central Diabetes Insipidus Adults: 10 to 40 mcg (0.1 to 0.4 mL) INTRANASALLY daily, either as a single dose or divided into 2 or 3 doses; most adults require 20 mcg (0.2 mL) daily in 2 divided doses Children (aged 3 months to 12 years): 5 to 30 mcg (0.05 to 0.3 mL) intranasally daily in 1 or 2 divided doses.	Length of Benefit
DDAVP [injection]	Central Diabetes Insipidus Adults: 2 to 4 mcg daily by direct IV/SC usually in 2 divided doses. Hemophilia A and von Willebrands Disease 0.3 mcg/kg diluted in 50 mL of sterile physiological saline and infused slowly by IV over 15 to 30 minutes	Length of Benefit
Stimate [nasal]	Hemophilia A and von Willebrand's Disease Patients greater than 50 kg: One spray per nostril to provide a total dose of 300 mcg Patients less than 50 kg: One spray in one nostril to provide a total dose of 150 mcg	Length of Benefit

Product Availability:

DDAVP Tablet: 0.1 mg and 0.2 mg

DDAVP Nasal Spray: 0.1 mL/spray (10 mcg/spray); 5 mL bottle

DDAVP Nasal (Rhinal) Tube: Calibrated 0.2, 0.15, 0.1 and 0.05 mL doses; 2.5 mL bottle

DDAVP Injection: 4 mcg/mL, 1 mL single-dose vials and 10 mL multi-dose vials.

Stimate Nasal Spray: 0.1 mL/spray (150 mcg/spray): 2.5 mL bottle

References:

1. DDAVP Tablets [Prescribing information] Bridgewater, NJ: sanofi-aventis U.S. LLC; July 2007.

2. DDAVP Nasal Spray [Prescribing information] Bridgewater, NJ: sanofi-aventis U.S. LLC; July 2007.

3. DDAVPRhinal Tube [Prescribing information] Bridgewater, NJ; sanfoi-aventis U.S. LLC; October 2011.

4. DDAVP Injection [Prescribing information] Bridgewater, NJ: sanfoi-aventis U.S. LLC; July 2007.

5. Stimate Nasal Spray [Prescribing information] King of Prussia, PA: CSL Behring LLC;June 2013.

6. Hjalmas K, Arnold T, Bower W, Caione P, Chiozza LM, Von Gontard A, et al. Nocturnal Enuresis: An International Evidence Based Management Strategy. Journal of Urology. 171(6, Part 2 of 2):2545-2561, June 2004

7. Fritz G, Rockney R, Bernet W, Arnold V, Beitchman J, et al. AACAP staff Practice Parameter for the Assessment and Treatment of Children and Adolescents With Enuresis. Journal of the American Academy of Child & Adolescent Psychiatry. 43:1540-1550. December 2004.

8. DDAVP. American Hospital Formulary Service Drug Information. AHFS Web site. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed July 1,2015

9. Micromedex^R Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed July 1, 2015.