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desmopressin (deamino-arginine vasopressin, dDAVP, dDVP, Noctiva, Stimate, Minirin)

Indications: 1) diabetes insipidus a) 10-40 ug (0.1-0.4 mL)/day intranasally divided QD/BID/TID b) 2-4 ug/day IV/SC in divided doses 2) bleeding associated with hemophilia A or Type I von Willebrand's disease a) 150-300 ug intranasally b) 0.3 ug/kg IV over 15-30 minutes c) 30 minutes prior to surgery 3) alternative to platelet transfusion when platelet dysfunction contributes to bleeding, for example: a) uremia b) cardiopulmonary bypass 4) enuresis [6]; nocturnal polyuria [7] 5) desmopressin associated with less intracranial hemorrhage expansion in antiplatelet-associated intracranial hemorrhage but no change in clinical outcome [9] Contraindications: - no longer approved for nocturnal enuresis, reports of serious hyponatremia [5] - Noctiva approved for nocturnal polyuria (March 2017) [7] - Type I von Willebrand's disease [10] - not for use in patients with serum sodium < 135 meq/L [8] Pregnancy category: B Safety in lactation: ? Dosage: Injection: 4 ug/mL (1 mL) DDAVP nasal spray: 1) 10 ug/metered dose 2) 100 ug/mL (100 ug = 400 IU), 5 mL Nasal spray (Stimate): 1) 1 spray/nostril (300 ug total) 2) for individuals < 50 kg, use 150 ug total or less 3) 10 & 150 ug/spray (1.5 mg/mL, 2.5 mL) DDAVP tablets: 0.1 & 0.2 mg Pharmacokinetics: - elimination: liver, kidney Adverse effects: 1) intranasal - conjunctivitis - transient headache - dizziness - nasal congestion 2) parenteral a) not common (1-10%) - abdominal cramps, vulval pain, facial flushing, headache (transient), rhinitis, dizziness, pain at the site of injection b) uncommon (< 1%) - hypertension, hyponatremia [10] c) thrombosis (rare) 3) other: severe hyponatremia, seizures [4,5,8] Laboratory: - absence of hyperresponsiveness of platelet aggregation to ristocetin indicates DDAVP administration is safe - 24 hour urine volume to confirm nocturnal polyuria [7] - serum sodium must be > 135 meq/L [8] Mechanism of action: 1) structurally-related to arginine-vasopressin 2) elicits greater antidiuretic response than does arginine-vasopressin 3) causes dose-dependent increase in activities of: a) factor VIII activator b) factor VIII-related antigen c) ristocetin cofactor 4) causes release of factor VIII & von Willebrand factor (vWF) from endothelial cells

General

vasopressin (antidiuretic hormone, ADH) endocrine agent

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. FDA MedWatch http://www.fda.gov/medwatch/safety/2007/safety07.htm#Desmopressin
  5. Prescriber's Letter 15(1): 2008 New Precautions for Use of Desmopressin Acetate (DDAVP, DDVP, Minirin, and Stimate) Detail-Document#: 240112 (subscription needed) http://www.prescribersletter.com
  6. Deprecated Reference
  7. FDA News Release. March 3, 2017 FDA approves first treatment for frequent urination at night due to overproduction of urine https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm544877.htm - Fralick M, Kesselheim AS. FDA Approval of Desmopressin for Nocturia. JAMA. 2017;317(20):2059-2060 Free full text Free PMC Article http://jamanetwork.com/journals/jama/article-abstract/2617966
  8. Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
  9. Feldman EA, Meola G, Zyck S et al. Retrospective assessment of desmopressin effectiveness and safety in patients with antiplatelet-associated intracranial hemorrhage. Crit Care Med 2019 Sep 24; PMID: 31567345
  10. Connell NT, James PD, Brignardello-Petersen R et al. ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease. Blood Adv 2021 Jan 12; 5:301 PMID: 33496750 PMCID: PMC7839375 Free PMC article https://ashpublications.org/bloodadvances/article/5/1/301/474884/ASH-ISTH-NHF-WFH-2021-guidelines-on-the-management
  11. NOCTIVA (desmopressin acetate) nasal spray, for intranasal use. Prescribing Information http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201656lbl.pdf