Desmopressin and the risk of hyponatremia: A population-based cohort study

Autoři: Michael Fralick aff001;  Sebastian Schneeweiss aff001;  Christopher J. D. Wallis aff002;  Emily H. Jung aff001;  Aaron S. Kesselheim aff001
Působiště autorů: Division of Pharmacoepidemiology and Pharmacoeconomics, Program On Regulation, Therapeutics, And Law (PORTAL), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America aff001;  Eliot Phillipson Clinician Scientist Training Program, Department of Medicine, University of Toronto, Toronto, Canada aff002;  Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario aff003
Vyšlo v časopise: Desmopressin and the risk of hyponatremia: A population-based cohort study. PLoS Med 16(10): e32767. doi:10.1371/journal.pmed.1002930
Kategorie: Research Article
doi: 10.1371/journal.pmed.1002930



Desmopressin was approved by the Food and Drug Administration (FDA) in 1978 for use in diabetes insipidus and bleeding disorders, but it is also prescribed off-label for patients with nocturia. Quantifying the potential risks facing adult patients taking desmopressin has taken on added importance because a new intranasal formulation of desmopressin was approved by the FDA in 2017. Like the old formulation, the main active ingredient is desmopressin acetate, but the new formulation also contains an excipient designed to enhance absorption. Our objective was to quantify the rate of hyponatremia in routine clinical care for patients prescribed the older formulation of desmopressin.

Methods and findings

We conducted a population-based new-user cohort study from 1 February 2006 to 1 February 2017 using a nationwide commercial health plan database. Patients newly prescribed the older formulation of desmopressin were propensity-score (PS)–matched to patients newly prescribed oxybutynin. As a sensitivity analysis, tamsulosin was used as the comparator rather than oxybutynin. The primary outcome was a primary position diagnosis of hyponatremia. Proportional hazard models after 1:1 PS matching were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). We identified 3,137 adults who were newly prescribed desmopressin and matched them to 3,137 adults who were newly prescribed oxybutynin. Mean age was 70, 55% were male, 13% filled a prescription for a diuretic during the baseline time period, and the mean baseline sodium prior to receiving either study drug was 140 mmol/L (normal: 135–145). The rate of hyponatremia was 146 per 1,000 person-years for adults prescribed desmopressin compared to 11 per 1,000 person-years for adults prescribed oxybutynin, corresponding to a 13-fold higher rate (HR 13.19; 95% CI 6.69, 26.01; p < 0.01). When follow-up was truncated at 30 days, a similar increased rate was observed (HR 19.41; 95% CI 7.11, 52.99; p < 0.01). A higher rate of hyponatremia was also observed with desmopressin when tamsulosin was the comparator (HR 12.10; 95% CI 6.54, 22.37; p < 0.01). Important limitations of our study include unmeasured confounding (for example, over-the-counter medication use, dietary intake), missing data (i.e., only 20% of patients had a baseline serum sodium), and a lack of data on the newer formulation of desmopressin.


Use of an older formulation of desmopressin was associated with a marked increased rate of subsequent hyponatremia compared to use of other medications indicated for lower urinary tract symptoms. Such risks should be clearly communicated to patients prescribed this formulation of desmopressin.

Klíčová slova:

Cohort studies – Comparators – Critical care and emergency medicine – Diagnostic medicine – Diuretics – Inpatients – Urology


1. Fralick M, Kesselheim AS. FDA Approval of Desmopressin for Nocturia. JAMA 2017;317:2095–2060. doi: 10.1001/jama.2017.4316 28384655

2. Ebell MH, Radke T, Gardner J. A systematic review of the efficacy and safety of desmopressin for nocturia in adults. J Urol. 2014;192(3):829–35. doi: 10.1016/j.juro.2014.03.095 24704009

3. Menon C, Berry EW, Ockelford P. Beneficial Effect of DDAVP on Bleeding Time Von Willebrand’s Disease. Lancet. 1978;312(8092):743–4. doi: 10.1016/s0140-6736(78)92749-6 80674

4. Moffatt ME, Harlos S, Kirshen AJ, Burd L. Desmopressin acetate and nocturnal enuresis: how much do we know? Pediatrics. 1993 Sep;92(3):420–5. 8361796

5. U.S. Food and Drug Administration. Desmopressin drug label. 2007 [cited 2018 Jul 1]. Available from:,018938s027,019955s013lbl.pdf.

6. Lose G, Mattiasson A, Walter S, Lalos O, Kerrebroeck, Van P, Abrams P, et al. Clinical experiences with desmopressin for long-term treatment of nocturia. J Urol. 2004;172(3):1021–5. doi: 10.1097/01.ju.0000136203.76320.f6 15311028

7. Laureanno P, Ellsworth P. Demystifying nocturia: identifying the cause and tailoring the treatment. Urol Nurs. 2010;30(5):276–86. 21067093

8. Weiss JP, Blaivas JG, Bliwise DL, Dmochowski RR, Dubeau CE, Lowe FC, et al. The evaluation and treatment of nocturia: A consensus statement. BJU Int. 2011;108(1):6–21. doi: 10.1111/j.1464-410X.2011.10175.x 21676145

9. Van Kerrebroeck P, Abrams P, Chaikin D, Donovan J, Fonda D, Jackson S, et al. The standardisation of terminology in nocturia: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn. 2002;21(2):179–83. 11857672

10. Kowalik CG, Cohn JA, Delpe S, Reynolds WS, Kaufman MR, Milam DF, et al. Nocturia: Evaluation and Current Management Strategies. Rev Urol. 2018;20(1):1–6. doi: 10.3909/riu0797 29942194

11. Han J, Jung JH, Bakker CJ, Ebell MH, Dahm P. Desmopressin for treating nocturia in men. BJU Int. 2018;122(4):549–59. doi: 10.1111/bju.14183 29489052

12. Slawson D. Desmopressin Effective for Treating Nocturia in Adults. Am Fam Physician. 2014;90(11):796a–797.

13. Fralick M, Kim SC, Schneeweiss S, Kim D, Redelmeier DA, Patorno E. Fracture risk after initiation of use of canagliflozin: A cohort study. Ann Intern Med. 2019;170(3):155–63. doi: 10.7326/M18-0567 30597484

14. Schneeweiss S. A basic study design for expedited safety signal evaluation based on electronic healthcare data. Pharmacoepidemiol Drug Saf. 2010;19(8):858–68. doi: 10.1002/pds.1926 20681003

15. Goodman SN, Schneeweiss S, Baiocchi M. Using design thinking to differentiate useful from misleading evidence in observational research. JAMA. 2017;317(7):705–7. doi: 10.1001/jama.2016.19970 28241335

16. Connolly JG, Schneeweiss S, Glynn RJ, Gagne JJ. Quantifying bias reduction with fixed-duration versus all-available covariate assessment periods. Pharmacoepidemiol Drug Saf. 2019;28(5):665–70. doi: 10.1002/pds.4729 30786103

17. Fralick M, Sacks CA, Kesselheim AS. Assessment of Use of Combined Dextromethorphan and Quinidine in Patients with Dementia or Parkinson Disease after US Food and Drug Administration Approval for Pseudobulbar Affect. JAMA Intern Med. 2019;179(2):224–30. doi: 10.1001/jamainternmed.2018.6112 30615021

18. Movig KLL, Leufkens HGM, Lenderink AW, Egberts AC. Validity of hospital discharge International Classification of Diseases (ICD) codes for identifying patients with hyponatremia. J Clin Epidemiol. 2003;56(6):530–5. doi: 10.1016/s0895-4356(03)00006-4 12873647

19. Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009;28(25):3083–107. doi: 10.1002/sim.3697 19757444

20. Wang S, Verpillat P, Rassen J, Patrick A, Garry E, Bartels D. Transparency and reproducibility of observational cohort studies using large healthcare databases. Clin Pharm Ther. 2016;99(3):325–32. doi: 10.1002/cpt.329 26690726

21. Fralick M, Kesselheim AS, Avorn J, Schneeweiss S. Use of health care databases to support supplemental indications of approved medications. JAMA Intern Med. 2018;178(1):55–63. doi: 10.1001/jamainternmed.2017.3919 29159410

22. Kim SC, Solomon DH, Rogers JR, Gale S, Klearman M, Sarsour K, et al. Cardiovascular safety of tocilizumab versus tumor necrosis factor inhibitors in patients with rheumatoid arthritis—a multi-database cohort study. Arthritis Rheumatol. 2017;69(6):1154–64. doi: 10.1002/art.40084 28245350

Interní lékařství

Článek vyšel v časopise

PLOS Medicine

2019 Číslo 10

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…

Kurzy Doporučená témata Časopisy
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se

VIRTUÁLNÍ ČEKÁRNA ČR Jste praktický lékař nebo pediatr? Zapojte se! Jste praktik nebo pediatr? Zapojte se!