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PLoS Med. 2019 Oct 21;16(10):e1002930. doi: 10.1371/journal.pmed.1002930. eCollection 2019 Oct.

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

Author information

1
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.
2
Eliot Phillipson Clinician Scientist Training Program, Department of Medicine, University of Toronto, Toronto, Canada.
3
Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario.

Abstract

BACKGROUND:

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.

CONCLUSIONS:

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.

Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: SS is the principal investigator of investigator-initiated grants to the Brigham and Women’s Hospital from Vertex, and Boehringer Ingelheim unrelated to the topic of this study. He is a consultant to WHISCON and to Aetion, a software manufacturer of which he owns equity. His interests were declared, reviewed, and approved by the Brigham and Women’s Hospital and Partners HealthCare System in accordance with their institutional compliance policies. AK is an Academic Editor on PLOS Medicine’s editorial board. SS, and AK are Faculty members at the Division of Pharmacoepidemiology and Pharmacoeconomics, which funded access to the data at the Optum database. MF, CW, and EH have declared that they do not have any competing interests.

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