Tolvaptan

1 INDICATIONS AND USAGE SAMSCA ® is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH).

6 ADVERSE REACTIONS 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 another drug and may not reflect the rates observed in practice. The adverse event information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

8.1 Pregnancy Risk Summary Available data with SAMSCA use in pregnant women are insufficient to determine if there is a drug-associated risk of adverse developmental outcomes. Tolvaptan did not cause any developmental toxicity in rats or in rabbits at exposures approximately 2.8 and 0.8 times, respectively, the exposure in congestive heart failure (CHF) patients at the maximum recommended human dose (MRHD) of 60 mg once daily. However, effects on embryo-fetal development occurred in both species at doses causing significant maternally toxic doses.

WARNING: (A) INITIATE AND RE-INITIATE IN A HOSPITAL AND MONITOR SERUM SODIUM (B) NOT FOR USE FOR AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD) WARNING: (A) INITIATE AND RE-INITIATE IN A HOSPITAL AND MONITOR SERUM SODIUM (B) NOT FOR USE FOR AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD) See full prescribing information for complete boxed warning. 5 WARNINGS AND PRECAUTIONS 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 ) 5.1 Too Rapid Correction of Serum Sodium Can Cause Serious Neurologic Sequelae Osmotic demyelination syndrome is a risk associated with too rapid correction of hyponatremia (e.g., >12 mEq/L/24 hours). 4 CONTRAINDICATIONS 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 gene...