SAMSCA

In healthy subjects, the pharmacokinetics of tolvaptan after single doses of up to 480 mg and multiple doses up to 300 mg once daily have been examined. In hyponatremia subjects, single and multiple doses up to 60 mg have been studied.

AbsorptionIn healthy subjects, peak concentrations of tolvaptan are observed between 2 and 4 hours post-dose. Peak concentrations increase less than dose proportionally with doses greater than 240 mg. The absolute bioavailability of tolvaptan decreases with incre...

14.1 Hyponatremia In two double-blind, placebo-controlled, multi-center studies (SALT-1 and SALT-2), a total of 424 patients with euvolemic or hypervolemic hyponatremia (serum sodium <135 mEq/L) resulting from a variety of underlying causes (heart failure, liver cirrhosis, syndrome of inappropriate antidiuretic hormone [SIADH] and others) were treated for 30 days with tolvaptan or placebo, then followed for an additional 7 days after withdrawal. Symptomatic patients, patients likely to require saline therapy during the course of therapy, patients with acute and transient hyponatremia associate...

Most common adverse reactions (≥5% placebo) are thirst, dry mouth, asthenia, constipation, pollakiuria or polyuria, and hyperglycemia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Otsuka at 1-877-726-7220 or FDA at 1-800-FDA-1088 ( www.fda.gov/medwatch ). 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of anot...

SAMSCA is contraindicated in the following conditions: Patients with autosomal dominant polycystic kidney disease (ADPKD) outside of FDA-approved REMS [see Warnings and Precautions (5.2) ] Unable to sense or respond to thirst Hypovolemic hyponatremia Taking strong CYP3A inhibitors [see Warnings and Precautions (5.5) ] Anuria Hypersensitivity (e.g., anaphylactic shock, rash generalized) to tolvapta...

Liver injury: Limit treatment duration to 30 days. If hepatic injury is suspected, discontinue SAMSCA. Avoid use in patients with underlying liver disease ( 5.2 ) Dehydration and hypovolemia may require intervention ( 5.3 ) Avoid use with hypertonic saline ( 5.4 ) Avoid use with moderate to strong CYP3A inhibitors ( 5.5 ) Monitor serum potassium in patients with potassium >5 mEq/L or on drugs known to increase potassium ( 5.6 ) Urinary outflow obstruction: Urinary output must be secured ( 5.7 ) ...

7 DRUG INTERACTIONS Avoid concomitant use with: Moderate CYP3A inhibitors ( 7.1 ) Strong CYP3A inducers ( 7.1 ) V 2 -receptor antagonists ( 7.3 ) Monitor serum potassium during concomitant therapy with ( 7.2 ): 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...