Tolvaptan is a substrate of CYP3A4. Interaction studies give no indications for induction or clinically relevant inhibition of CYP3A4. A side effect that can be potentially porphyrinogenic through reduction in carbohydrate intake is nausea. Loss of appetite is common and nutrition should be kept under control. It is probably safe to use in acute porphyria, but is not recommended for patients with acute need for correction of hyponatremia.

Benzazepine-methylbenzamide derivative with seondary as well as cyclic tertiary amine functions.

Tolvaptan is indicated for the treatment of adult patients with hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion. Common side effects that can be confused with an acute porphyria attack are nausea and obstipation. Other common side effects are hyperglycaemia and reduced appetite. Tolvaptan has not been studied in patients with acute need for correction of serum sodium levels, and it is advised that other treatment should be considered in such cases. Anuria is a contraindication.

Significant.

Tolvaptan is a substrate of CYP3A4 and is extensively metabolised. Less than 1% of the intact drug is recovered in urine. The half-life elimination is 5-12 hours. Tolvaptan had no effect on the plasma concentration of amiodaron (Shoaf 2005) and warfarin (two CYP3A4 substrates), but it did increase the plasma concentration of lovastatin by 1.3-1.5 times. This indicates that tolvaptan has the potential to weakly inhibit CYP3A4 (SPC). These studies also indicate that tolvaptan is not an inducer of CYP3A4. It is not listed as a mechanism-based inhibitor.