Tolvaptan is now well established as a potent pharmaceutical agent for symptomatic hyponatremia from syndrome of inappropriate antidiuretic hormone secretion (SIADH), congestive heart failure and liver cirrhosis. Previous studies had recruited older (63-65 years) patients with mild renal impairment (serum creatinine, 1.3-1.4 mg/dl). A 2012 report in the Journal of Neurology, Neurosurgery & Psychiatry described tolvaptan as a “lifesaving drug”. A major outcome concern in the treatment of chronic hyponatremia is potentially fatal pontine demyelination from over-rapid correction of serum sodium >0.5 mEq/dL/h. The maximum reported correction of serum sodium within 24 hours was 13 mEq/L in a case of SIADH. We recently experienced the dramatic correction of hyponatremia at 1 mEq/dL/h over 18 hours, following 15 mg of oral tolvaptan in a 32-year old male patient with normal kidney function (serum creatinine 0.76 mg/dL), following traumatic brain injury (TBI). Tolvaptan is indeed an effective and life-saving drug for post-TBI hyponatremia. However, we strongly recommend the use of lower doses of tolvaptan (≤15 mg/d) in younger patients with more preserved renal function to avoid the development of life-threatening pontine demyelination.
Implication for health policy/practice/research/medical education:
We report a 32-year-old man who presented with progressively symptomatic hyponatremia due to the SIADH secretion complicating TBI. He responded very briskly to a low dose of the arginine vasopressin antagonist tolvaptan with normalization of hyponatremia within 18 hours from 121 mmol/L to 139 mmol/ L. His young age and normal kidney function (serum creatinine of 0.76 mg/dL, eGFR of 126 mL/min/1.73 sq. m BSA) contrasts sharply with the historical clinical trials during drug development of Tolvaptan which studied older patients with often stage III chronic kidney disease (CKD). This case report implicated that the dose of oral tolvaptan in younger patients with preserved renal function would be lower than the currently recommended standard doses of the drug. Furthermore tolvaptan should be dosed singly, with repeat daily doses only prescribed and administered after physician evaluation of response of hyponatremia to initial dose.
Please cite this paper as: Onuigbo MAC, Agbasi N. Severe symptomatic acute hyponatremia in traumatic brain injury responded very rapidly to a single 15 mg dose of oral tolvaptan; a Mayo Clinic Health System hospital experience – need for caution with tolvaptan in younger patients with preserved renal function. J Renal Inj Prev. 2017;6(1):26-29. DOI: 10.15171/jrip.2017.05