Background:
Hyponatraemia is a common electrolyte disorder occurring in up to 15 to 22% of hospitalised patients (1) and is associated with increased morbidity (2) and mortality (3). Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatraemia (4) and is precipitated by numerous medical conditions and medications (5). However, management of chronic SIADH remains suboptimal with limited effects of fluid restriction and underutilisation of other therapies (6). Tolvaptan, a selective oral vasopressin V2-receptor antagonist, despite its introduction more than a decade ago and its remarkable potency (7), is seldomly used likely due to the risk of overcorrection and liver function test derangement, costs, clinician non-familiarity and paucity of data in its chronic use.
Case:
84 year-old presented with nausea and generally lethargy due to chronic hypotonic hyponatraemia secondary to SIADH in setting of Mycobacterium avium complex infection on rifampicin, ethambutol and clarithromycin. Her biochemistry included: serum sodium 122mmol/L, serum osmolality 255mmol/kg, urine sodium 44mmol/L with a normal thyroid function test and 8am cortisol level. Due to the limited improvement with fluid restriction, salt tablets and intolerance of urea secondary to gastrointestinal side effects, 15mg PO tolvaptan stat was utilised with immediate however short-lived effect. The effect of rifampicin (CYP3A inducer) and clarithromycin (CYP3A inhibitor) on tolvaptan, a CYP3A substrate, was deemed to counteract each other’s effects. With tolvaptan 7.5mg PO second daily, hyponatraemia resolved without liver function test derangements and enabled relaxation of fluid restriction improving the patient’s the quality of life. Six months later, patient remains normonatraemic (139mmol/L) and is on weaning doses of tolvaptan.
Conclusion:
Long-term low dose tolvaptan may be a safe and effective treatment for chronic SIADH even in elderly comorbid patients. Tolvaptan should be considered for management of SIADH refractory to fluid restriction and second line therapies such as urea.