Tolvaptan

Tolvaptan blocks the action of vasopressin, the antidiuretic hormone, at V2 receptors in the kidney. The result is aquaresis: the kidneys excrete more free water, and the level of sodium in the blood climbs back towards normal. The UK SmPC for the 15 mg and 30 mg tablets limits their use to adults with hyponatraemia (low blood sodium) caused by the syndrome of inappropriate antidiuretic hormone secretion, known as SIADH. Higher-strength regimens of the same drug, sold as Jinarc, are licensed separately to slow cyst growth and kidney decline in autosomal dominant polycystic kidney disease, under specialist supervision.

The 15 mg tablets are offered in packs of 10, 20, 30, 60, 90, 120 or 180, and the 30 mg tablets in packs of 10, 20, 30, 60, 90 or 120. These are imported generic tablets that are not covered by a UK licence.

Because sodium can rise too quickly, the SmPC requires tolvaptan to be started in hospital. The first dose is 15 mg once daily, preferably in the morning, swallowed whole with water, with or without food. The dose may be increased as tolerated up to a maximum of 60 mg once daily. A lower 7.5 mg dose should be considered for people at greater risk of over-rapid correction, such as those with cancer, very low starting sodium, diuretic use or sodium supplements. Blood sodium is first checked within four to six hours of starting, then frequently over the first days. The aim is a rise of less than 10 to 12 mmol/L in 24 hours and less than 18 mmol/L in 48 hours, since faster correction can cause osmotic demyelination with serious neurological damage. Grapefruit juice must be avoided. It has not been studied where sodium has to be raised urgently, so other treatment is used in that situation, and in diabetes very high glucose causing a false low sodium reading must first be ruled out.

Tolvaptan is a prescription-only medicine in the UK. For SIADH, it is licensed as Samsca 7.5 mg, 15 mg and 30 mg tablets from Otsuka Pharmaceuticals (UK) and as generic tablets, for example from Dr. Reddy’s Laboratories. The SmPCs are on the electronic medicines compendium.

The SmPC rules out tolvaptan in anuria, volume depletion, hypovolaemic hyponatraemia, high blood sodium, in anyone unable to sense thirst, in pregnancy and while breastfeeding, and in people allergic to benzazepines. Patients need access to water and must be able to drink enough; a blocked urinary outflow, for example from an enlarged prostate, raises the risk of retention. Serious liver injury has been seen, including acute liver failure in polycystic kidney disease, so tiredness, loss of appetite, pain under the right ribs, dark urine or jaundice need prompt liver tests and the drug is stopped if injury is suspected. Strong CYP3A4 inhibitors such as ketoconazole or clarithromycin can multiply exposure, and inducers such as rifampicin sharply reduce it. Digoxin levels may rise, and desmopressin may work less well.

Thirst, a dry mouth, passing urine more often and in larger amounts, and nausea are the effects most people notice, reflecting the water loss the medicine causes. Dehydration, dizziness, weakness and high blood sugar may also occur. Your specialist decides whether tolvaptan is right for you and how the dose is adjusted.