Hyponatremiainteractions

Avoid concomitant use with: Moderate CYP3A inhibitors Strong CYP3A inducers V 2 -receptor antagonists Monitor serum potassium during concomitant therapy with: Angiotensin receptor blockers Angiotensin converting enzyme inhibitors Potassium sparing diuretics

7.1 CYP3A Inhibitors and

Inducers Strong CYP3A Inhibitors Tolvaptan's AUC was 5.4 times as large and C max was 3.5 times as large after co-administration of tolvaptan and 200 mg ketoconazole. Larger doses of the strong CYP3A inhibitor would be expected to produce larger increases in tolvaptan exposure. Concomitant use of tolvaptan with strong CYP3A inhibitors is contraindicated. Moderate CYP3A Inhibitors A substantial increase in the exposure to tolvaptan would be expected when SAMSCA is co-administered with moderate CYP3A inhibitors. Avoid co-administration of SAMSCA with moderate CYP3A inhibitors. Patients should avoid grapefruit juice beverages while taking SAMSCA. Strong CYP3A Inducers Co-administration of SAMSCA with strong CYP3A inducers reduces exposure to SAMSCA. Avoid concomitant use of SAMSCA with strong CYP3A inducers.

7.2 Angiotensin

Receptor Blockers, Angiotensin Converting Enzyme Inhibitors and Potassium Sparing Diuretics Although specific interaction studies were not performed, in clinical studies, tolvaptan was used concomitantly with beta-blockers, angiotensin receptor blockers, angiotensin converting enzyme inhibitors and potassium sparing diuretics. Adverse reactions of hyperkalemia were approximately 1 to 2% higher when tolvaptan was administered with angiotensin receptor blockers, angiotensin converting enzyme inhibitors and potassium sparing diuretics compared to administration of these medications with placebo. Serum potassium levels should be monitored during concomitant drug therapy.

7.3 V 2 -Receptor

Agonist As a V 2 -receptor antagonist, tolvaptan may interfere with the V 2 -agonist activity of desmopressin (dDAVP). Avoid concomitant use of SAMSCA with a V 2 -agonist.