Journal of Korean Society of Health-System Pharmacists (병원약사회지)

The Korean Society of Health-System Pharmacists (한국병원약사회)
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Effectiveness and Safety of Tolvaptan for the Management of Hyponatremia: Risk of Inadvertent Overcorrection

  • Park, Mi Seon (Department of Pharmacy, Chonbuk National University Hospital) ;
  • Park, Seung Yong (Chonbuk National University Hospital Regional Pharmacovigilance Center) ;
  • Park, Seoung Ju (Chonbuk National University Hospital Regional Pharmacovigilance Center) ;
  • Beom, Jin Seon (Department of Pharmacy, Chonbuk National University Hospital) ;
  • Ahn, Hyo Cho (Department of Pharmacy, Chonbuk National University Hospital) ;
  • Kim, Ju Sin (Department of Pharmacy, Chonbuk National University Hospital) ;
  • Lee, Heung Bum (Department of Internal Medicine, Chonbuk National University Hospital)
  • Received : 2018.02.09
  • Accepted : 2018.09.14
  • Published : 2018.12.31
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Abstract

Background : Hyponatremia is the most common electrolyte disturbance in hospitalized patients and has been associated with increased morbidity and mortality. Tolvaptan, a vasopressin receptor antagonist, is increasingly used for the treatment of euvolemic and hypervolemic hyponatremia. The aim of this study was to evaluate the effectiveness and safety of tolvaptan for the management of hyponatremia. Methods : This study was a retrospective evaluation of 106 patients who received at least one dose of tolvaptan for hyponatremia at a single tertiary academic hospital between January 2014 and June 2015. The primary endpoint was the change in serum sodium concentration after tolvaptan administration within 24 hours, with secondary endpoints of overcorrection and adverse effects. Results : The mean initial dose of tolvaptan was $20.2{\pm}7.2mg$ and the median duration of treatment was 15 days (range, 1-261 days). The maximal changes in sodium levels at 24 and 48 hours were $8.2{\pm}4.7mmol/L$ and $10.5{\pm}15.3mmol/L$, respectively. Of 99 patients in whom sodium concentrations were followed up, sodium overcorrection was observed in 26 (26.3%) patients, which was associated with concomitant use of an enzyme inhibitor (odds ratio [OR] = 4.80, 95% Cl: 1.27-18.15). However, sex, body mass index (BMI), serum albumin, a daily dose of tolvaptan, and concomitant use of hypertonic saline did not show any significant difference in overcorrection. The most commonly reported adverse effects were mild and related to aquaresis, such as polyuria, thirst, and constipation. However, severe adverse effects such as hyperkalemia, hypotension, and one death related to osmotic demyelination were also reported. Conclusions : Tolvaptan is effective for treating hyponatremia. Nevertheless, the drug should be used cautiously due to serious adverse effects related to sodium overcorrection.

Keywords

Acknowledgement

Supported by : Ministry of Food and Drug Safety

References

  1. Upadhyay A, Jaber BL, Madias NE. Incidence and prevalence of hyponatremia. Am J Med. 2006;119(7 Suppl 1):S30-35. https://doi.org/10.1016/j.amjmed.2006.05.005
  2. Miller M. Hyponatremia and arginine vasopressin dysregulation: mechanisms, clinical consequences, and management. J Am Geriatr Soc. 2006;54(2):345-353. https://doi.org/10.1111/j.1532-5415.2005.00609.x
  3. Schrier RW, Gross P, Gheorghiade M et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355(20):99-112. https://doi.org/10.1056/NEJMc061073
  4. Verbalis JG, Goldsmith SR, Greenberg A et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013;126(10 Suppl 1):S1-42.
  5. Corona G, Giuliani C, Verbalis JG et al. Hyponatremia improvement is associated with a reduced risk of mortality: evidence from a meta-analysis. PLoS One. 2015;10(4):e0124105. https://doi.org/10.1371/journal.pone.0124105
  6. Berl T. Vasopressin antagonists. N Engl J Med. 2015;372(23):2207-2216. https://doi.org/10.1056/NEJMra1403672
  7. Umbrello M, Mantovani ES, Formenti P et al. Tolvaptan for hyponatremia with preserved sodium pool in critically ill patients. Ann Intensive Care. 2016;6(1):1. https://doi.org/10.1186/s13613-015-0096-2
  8. Cyr PL, Slawsky KA, Olchanski N et al. Effect of serum sodium concentration and tolvaptan treatment on length of hospitalization in patients with heart failure. Am J Health Syst Pharm. 2011;68(4):328-333. https://doi.org/10.2146/ajhp100217
  9. Food and Drug Administration (US FDA) News Release. Samsca (tolvaptan): Drug Warning - Potential Risk of Liver Injury. Retrieved January 25, 2013. Available from: http://www.fda.gov/Safety/MedWatch/Safet yInformation/SafetyAlertsforHumanMedical Products/ucm336669.htm?source=govdelivery.
  10. Samsca (tolvaptan) package insert. Tokyo, Japan: Otsuka Pharmaceuticals Co; 2017 Mar.
  11. Shoaf SE, Bricmont P, Mallikaarjun S. Effects of CYP3A4 inhibition and induction on the pharmacokinetics and pharmacodynamics of tolvaptan, a non-peptide AVP antagonist in healthy subjects. Br J Clin Pharmacol. 2012;73(4):579-587. https://doi.org/10.1111/j.1365-2125.2011.04114.x
  12. Wolters Kluwer Clinical Drug Information, Inc. Available from: http://online.lexi.com.
  13. Aditya S, Rattan A. Vaptans: A new option in the management of hyponatremia. Int J Appl Basic Med Res. 2012;2(2):77-83. https://doi.org/10.4103/2229-516X.106347
  14. Rajan S, Srikumar S, Paul J et al. Effectiveness of single dose conivaptan for correction of hyponatraemia in post-operative patients following major head and neck surgeries. Indian J Anaesth. 2015;59(7):416-420. https://doi.org/10.4103/0019-5049.160943
  15. Adhiyaman V, Chattopadhyay I, Williams M. Once-weekly tolvaptan for chronic symptomatic hyponatremia due to syndrome of inappropriate secretion of anti-diuretic hormone. J Am Geriatr Soc. 2014;62(7):1405-1406. https://doi.org/10.1111/jgs.12917
  16. Tarhan NC, Agildere AM, Benli US et al. Osmotic demyelination syndrome in end-stage renal disease after recent hemodialysis: MRI of the brain. AJR Am J Roentgenol. 2004;182(3):809-816. https://doi.org/10.2214/ajr.182.3.1820809
  17. Singh TD, Fugate JE, Rabinstein AA. Central pontine and extrapontine myelinolysis: a systematic review. Eur J Neurol. 2014;21(12):1443-1450. https://doi.org/10.1111/ene.12571
  18. Sterns RH, Cappuccio JD, Silver SM et al. Neurologic sequelae after treatment of severe hyponatremia: a multicenter perspective. J Am Soc Nephrol. 1994;4(8):1522-1530.
  19. Torres VE, Chapman AB, Devuyst O et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012;367(25):2407-2418. https://doi.org/10.1056/NEJMoa1205511
  20. Liamis G1, Milionis H, Elisaf M. A review of drug-induced hyponatremia. Am J Kidney Dis. 2008;52(1):144-153. https://doi.org/10.1053/j.ajkd.2008.03.004