Tolvaptan

Because of the need for a dose titration phase with close monitoring of serum sodium and volume status, treatment has to be INITIATED IN HOSPITAL. For patients at risk of overly rapid correction of sodium — e.g. patients with oncological conditions, very low baseline serum sodium, taking diuretics, or taking sodium supplementation — a dose of 7.5 mg should be considered. During titration, patients must be monitored for serum sodium and volume status: monitoring of serum sodium must start no later than 4 to 6 hours after treatment initiation, and during the first 1 to 2 days and until the dose is stabilised serum sodium and volume status must be monitored at least every 6 hours (section 4.4). To minimise the risk of too-rapid correction of hyponatraemia the increase in serum sodium should be less than 10 to 12 mmol/L per 24 hours and less than 18 mmol/L per 48 hours; if correction exceeds 6 mmol/L in the first 6 hours or 8 mmol/L in the first 6 to 12 hours, consider that correction may be overly rapid, monitor more frequently and give hypotonic fluid. Too-rapid correction can cause osmotic demyelination (dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma or death). If serum sodium improvement is inadequate, other treatment options must be considered in place of or in addition to tolvaptan — combination use may increase the risk of overly rapid correction. Treatment duration is determined by the underlying disease and its treatment. Must NOT be taken with grapefruit juice. Tablets must be swallowed without chewing with a glass of water, without regard to meals. Elderly: no dose adjustment needed. Hepatic impairment: no dose adjustment in Child-Pugh A or B; no information in severe hepatic impairment (Child-Pugh C) where dosing has to be managed cautiously with monitoring of electrolytes and volume status. Paediatric: safety and efficacy under 18 years have not been established — not recommended in the paediatric age group. Source caveats: (1) SPC section 4.5 (interactions) was not captured in the fetched bundle — clinician to review; (2) the eMC product used is a tolvaptan tablet SPC for the hyponatraemia/SIADH setting — the fetched US label is JYNARQUE (a different tolvaptan product, ADPKD) and its dosing is deliberately not reproduced here; if the ADPKD split-dose regimen is required it must be sourced from the corresponding UK SPC.