Desmopressin and the risk of hyponatremia: A population-based cohort study
| العنوان: | Desmopressin and the risk of hyponatremia: A population-based cohort study |
|---|---|
| المؤلفون: | Michael Fralick, Emily H. Jung, Christopher J.D. Wallis, Sebastian Schneeweiss, Aaron S. Kesselheim |
| المصدر: | PLoS Medicine PLoS Medicine, Vol 16, Iss 10, p e1002930 (2019) |
| بيانات النشر: | Public Library of Science (PLoS), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Critical Care and Emergency Medicine, 030204 cardiovascular system & hematology, Hemostatics, Cohort Studies, Endocrinology, 0302 clinical medicine, Risk Factors, Medicine and Health Sciences, Medicine, Deamino Arginine Vasopressin, 030212 general & internal medicine, Diuretics, Desmopressin, Aged, 80 and over, education.field_of_study, Hazard ratio, Drugs, General Medicine, Middle Aged, Treatment Outcome, Research Design, Comparators, Engineering and Technology, Female, Nocturia, medicine.symptom, Hyponatremia, hormones, hormone substitutes, and hormone antagonists, Research Article, medicine.drug, Tamsulosin, medicine.medical_specialty, Patients, Endocrine Disorders, Urology, Population, Research and Analysis Methods, 03 medical and health sciences, Diagnostic Medicine, Internal medicine, Diabetes Mellitus, Humans, Desmopressin Acetate, Propensity Score, education, Oxybutynin, Administration, Intranasal, Aged, Proportional Hazards Models, Pharmacology, Inpatients, business.industry, medicine.disease, Health Care, Metabolic Disorders, Mandelic Acids, Electronics, business |
| الوصف: | 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. Author summary Why was this study done? Desmopressin is a medication that is sometimes used for adults who awake multiple times in the night to urinate, even though it was not previously approved for this purpose by the Food and Drug Administration (FDA). One potential risk of desmopressin is a low sodium level (also known as hyponatremia), which can be life-threatening. What did the researchers do and find? We conducted a study using a national healthcare database in the US and observed an increased risk of hyponatremia with the older formulation of desmopressin. The rate of hyponatremia was 146 per 1,000 person-years with desmopressin compared to approximately 11 per 1,000 person-years among patients who received oxybutynin. What do these findings mean? The potential increased risk of hyponatremia should be considered prior to prescribing this older formulation of desmopressin. Further observational study of the new formulation of desmopressin that was approved by the FDA in 2017, which contains the same active ingredient as the older formulation, to assess for the risk of hyponatremia is warranted. |
| تدمد: | 1549-1676 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::76e5f1b38689b8bd23dd5766e0cf17f8Test https://doi.org/10.1371/journal.pmed.1002930Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....76e5f1b38689b8bd23dd5766e0cf17f8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15491676 |
|---|