DDAVP, Desmopressin Acetate NOCDURNA, Desmopressin Acetate STIMATE, Desmopressin Acetate NOCTIVA, Desmopressin Acetate Form

Desmopressin acetate (DDAVP®, Stimate®, Nocdurna®) is a synthetic vasopressin analog. FDA Approved Indication(s) DDAVP and Stimate are indicated for the treatment of patients with: • Mild to moderate classic von Willebrand's disease (VWD; type I) with factor VIII (FVIII) levels greater than 5% • Hemophilia A with FVIII coagulant activity levels greater than 5% without FVIII antibodies (DDAVP only) DDAVP is also indicated for the management of central (cranial) diabetes insipidus and for the management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. Nocdurna is indicated for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void. Limitation(s) of use:
• Stimate is not indicated for the treatment of hemophilia A with FVIII coagulant activity levels equal to or less than 5%, or for the treatment of hemophilia B, or in patients who have FVIII antibodies. • DDAVP and Stimate are not indicated for the treatment of severe classic VWD (type I) and when there is evidence of an abnormal molecular form of FVIII antigen. • DDAVP is ineffective and not indicated for the treatment of nephrogenic diabetes insipidus. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that DDAVP injection, Stimate, and Nocdurna are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Polyuria and Central Diabetes Insipidus (must meet all):

1. Diagnosis of one of the following (a or b): a. Central (cranial) diabetes insipidus (referred to as arginine vasopressin deficiency); Page 1 of 8

   CLINICAL POLICY Desmopressin Acetate b. Temporary polyuria and polydipsia following head trauma or surgery in the pituitary region;

2. Prescribed by or in consultation with an endocrinologist;
   3. Age ≥ 12 years;
   4. Request is for DDAVP injection;
   5. Failure of desmopressin tablets, unless contraindicated, clinically significant adverse effects are experienced, or documentation supports inability to swallow tablets;
3. Dose does not exceed 4 mcg per day. Approval duration: Medicaid/HIM – 6 months Commercial – 6 months or to member’s renewal date, whichever is longer B. Congenital Hemophilia A (must meet all):
4. Diagnosis of congenital hemophilia A (FVIII deficiency);
   2. Prescribed by or in consultation with a hematologist;
   3. Age ≥ 3 months;
   4. Request is for DDAVP injection or Stimate for one of the following uses (a, b, or c): a. Control and prevention of bleeding episodes; b. Perioperative management; c. Routine prophylaxis to prevent or reduce the frequency of bleeding episodes;
5. FVIII coagulant activity levels are > 5%;
   6. Member does not have FVIII antibodies;
   7. Dose does not exceed any of the following (a or b): a. DDAVP injection: 0.3 mcg/kg per dose; b. Stimate: 300 mcg per day. Approval duration: Medicaid/HIM – 6 months (12 months for prophylaxis for HIM Texas) Commercial – DDAVP injection: 6 months or to member’s renewal date, whichever is longer; Stimate: 12 months
      C. Von Willebrand Disease (must meet all):
   8. Diagnosis of VWD type 1 or type 2;
   9. Prescribed by or in consultation with a hematologist;
   10. Age ≥ 3 months;
   11. Request is for DDAVP injection or Stimate for one of the following uses (a, b, or c): a. Control and prevention of bleeding episodes; b. Perioperative management; c. Routine prophylaxis to prevent or reduce the frequency of bleeding episodes;

6. FVIII coagulant activity levels are > 5%;

   6. Dose does not exceed any of the following (a or b): a. DDAVP injection: 0.3 mcg/kg per dose; b. Stimate: 300 mcg per day. Approval duration: Medicaid/HIM – 6 months (12 months for prophylaxis for HIM Texas) Commercial – DDAVP injection: 6 months or to member’s renewal date, whichever is longer; Stimate: 12 months Page 2 of 8

   CLINICAL POLICY Desmopressin Acetate D. Nocturia (must meet all):

7. Diagnosis of nocturia due to nocturnal polyuria;
   2. Age ≥ 18 years;
   3. Request is for Nocdurna;
   4. Dose does not exceed 1 tablet per day and one of the following (a or b): a. 27.7 mcg for women; b. 55.3 mcg for men. Approval duration: 12 months E. Other diagnoses/indications (must meet 1 or 2):
8. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
9. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. All Indications in Section I (must meet all):

10. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);

    2. Member is responding positively to therapy;
    3. If request is for a dose increase, new dose does not exceed any of the following (a, b, or c): a. DDAVP injection: 4 mcg per day for polyuria or diabetes insipidus and 0.3 mcg/kg per dose for hemophilia A or VWD; b. Stimate: 300 mcg per day; c. Nocdurna: 1 tablet per day and one of the following (i or ii): i. 27.7 mcg for women;
       ii. 55.3 mcg for men. Page 3 of 8

    CLINICAL POLICY Desmopressin Acetate Approval duration: Medicaid/HIM – 12 months Commercial – DDAVP injection: 6 months or to member’s renewal date, whichever is longer; Stimate/Nocdurna: 12 months B. Other diagnoses/indications (must meet 1 or 2):

11. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

12. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid, or evidence of coverage documents.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key DDAVP: 1-deamino-8-D-arginine vasopressin FVIII: factor VIII SIADH: syndrome of inappropriate eGFR: estimated glomerular filtration rate FDA: Food and Drug Administration antidiuretic hormone VWD: von Willebrand disease Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose 1.2 mg/day desmopressin acetate oral tablets (DDAVP®)
    Polyuria and Central Diabetes Insipidus 0.05 mg PO BID, titrated to a maintenance dose in the range of 0.1-1.2 mg divided into 2-3 daily doses as needed to obtain adequate antidiuresis Page 4 of 8

    CLINICAL POLICY Desmopressin Acetate Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
    o Stimate: none reported o DDAVP injection, Nocdurna: hyponatremia or a history of hyponatremia; polydipsia; concomitant use with loop diuretics or systemic/inhaled glucocorticoids; renal impairment with an eGFR below 50 mL/min/1.73 m2; SIADH secretion; during illnesses that can cause fluid or electrolyte imbalance; heart failure; uncontrolled hypertension o DDAVP injection: hypersensitivity to desmopressin acetate or to any of the components of DDAVP Injection • Boxed warning(s):
    o Stimate: none reported o DDAVP injection, Nocdurna: hyponatremia Appendix D: General Information • The American Urology Association defines nocturnal polyuria as the production of • greater than 20 to 33% of total 24-hour urine output during the period of sleep, which is age-dependent with 20% for younger individuals and 33% for elderly individuals.
    In 2022, the Endocrine Society along with various international endocrine societies proposed to change the name of this disorder from central diabetes insipidus to arginine vasopressin deficiency. V. Dosage and Administration Drug Name Desmopressin injection (DDAVP)
    Desmopressin nasal spray (Stimate)
    Desmopressin sublingual tablet (Nocdurna) 2 to 4 mcg IV or SC daily, as one or two divided doses Indication Dosing Regimen Central diabetes insipidus Hemophilia A, VWD Hemophilia A, VWD Nocturnal polyuria One spray per nostril
    Women: 27.7 mcg PO QD one hour before bedtime 0.3 mcg/kg IV or SC as needed Maximum Dose 4 mcg/day 0.3 mcg/kg/dose 300 mcg/dose Women: 27.7 mcg/day; Men: 55.3 mcg/day VI. Product Availability
    Drug Name Desmopressin injection (DDAVP)
    Desmopressin nasal spray (Stimate)
    Men: 55.3 mcg PO QD one hour before bedtime Availability Single-dose ampule: 4 mcg/mL (1 mL) Multi-dose vial: 4 mcg/mL (10 mL) Bottle with spray pump: 25 sprays of 150 mcg (2.5 mL) Page 5 of 8

    CLINICAL POLICY Desmopressin Acetate Drug Name Desmopressin sublingual tablet (Nocdurna) Availability Sublingual tablets: 27.7 mcg, 55.3 mcg VII.