Adult Dosing

Treatment of hypervolemic/euvolemic hyponatremia

• Initial dose: 15 mg PO qd
• Titration: 30 mg PO qd, after at least 24 hrs; then 60 mg PO qd
• Max: 60 mg/day

• Avoid fluid restriction during first 24 hrs of therapy
• Monitor serum electrolytes and volume during therapy initiation and titration
• Advise patients to continue fluid intake in response to thirst

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• 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, cirrhosis, and Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

• Hypersensitivity to any of the ingredients of the product
• Situations where urgent sodium correction is required
• Inability of patient to sense or appropriately respond to thirst
• Hypovolemic hyponatremia
• Anuria
• Concomitant use of strong CYP3A inhibitors

• Initiate and re-titrate therapy only in a hospital with close monitoring of serum sodium
• Rapid correction of hyponatremia (>12 mEq/L/24 h) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death; slower rates of correction are advised in patients with severe malnutrition, alcoholism or advanced liver disease

Renal Dose Adjustment (Based on CrCl)

• 10-79 mL/minutes: No dose adjustments
• < 10 mL/minutes: Dose adjustments not defined
• Anuria: contraindicated

Hepatic Dose Adjustment

• Hepatic impairment: No dose adjustments

• Too rapid correction of serum sodium can cause osmotic demyelination resulting in serious neurologic sequelae (US Black Box Warning); increased risk in patients with SIADH or if very low baseline serum sodium concentrations. Monitor serum sodium and neurologic status. If rapid rise in serum sodium occurs, discontinue therapy and administer hypotonic fluid
• Due to the potential for increased risk of gastrointestinal bleeding in patients with cirrhosis, use in patients with cirrhosis only if benefit outweighs this risk
• Tolvaptan induces copious aquaresis; dehydration and hypovolemia may occur, especially in volume-depleted patients receiving diuretics or in fluid restriction. Advise patients to continue fluid intake in response to thirst
• Avoid use with CYP 3A inducers and moderate CYP 3A inhibitors
• Dose reduction required if co-administered with P-gp inhibitors
• Monitor serum K in patients with serum K > 5 mEq/L (> 5 mmol/L) or those taking concomitant medications known to increase serum K
• Therapy can cause serious fatal liver injury; increased ALT >3 times the upper limit of normal (ULN) and increased ALT was observed in 4.4% of patients compared with 1% taking placebo, usually starting approximately 3 months after therapy initiated
• Limit duration of treatment to 30 days and avoid use in patients with underlying liver disease, including cirrhosis, because the ability to recover from liver injury may be impaired. If symptoms indicating liver injury occur (eg, fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice) discontinue the therapy

Cautions: Use cautiously in

• Severe hepatic impairment
• Cirrhosis (increased risk of GI bleeding)
• Concomitant hypertonic saline
• Volume depletion
• Severe malnutrition
• Alcoholism
• Concomitant use of CYP3A inducers and moderate CYP3A inhibitors
• Concomitant administration of P-gp inhibitors

Pregnancy Category:C

Breastfeeding: Safety unknown; excreted in the breastmilk of lactating rats. Manufacturer recommends discontinuation of breastfeeding, or discontinuation of treatment (taking into account the importance of the drug to the mother).

• GI: Xerostomia, constipation, nausea, GI bleed (cirrhosis patients)
• CNS: Osmotic demyelination syndrome
• METABOLIC: Hyperglycemia, anorexia, hypovolemia, dehydration
• GU: Pollakiuria, polyuria
• MISC: Increased thirst, asthenia, pyrexia

• Selective vasopressin V2-receptor antagonist; antagonizes effect of vasopressin; increases urine water excretion; decreases urine osmolality
• Metabolized by liver; CYP450: 3A4 substrate; P-gp substrate/inhibitor
• Excreted by non-renal routes
• Half-life: 12 hrs

US Trade Name(s)

• Samsca

US Availability

Samsca

• TABS: 15, 30 mg

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• Samsca

UK Availability

Samsca

• TABS: 15, 30 mg

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Nutrition/Electrolytes

Electrolytes

Drug Name: Samsca 15 MG Oral Tablet

Ingredient(s): Tolvaptan

Imprint: OTSUKA;15

Color(s): Blue

Shape: Triangle

Size (mm): 7.00

Score: 1

Inactive Ingredient(s): starch, corn / hydroxypropyl cellulose / lactose monohydrate / hydroxypropyl cellulose, low substituted / magnesium stearate / cellulose, microcrystalline / fd&c blue no. 2

Drug Label Author:
Otsuka America Pharmaceutical Inc.

DEA Schedule:
Non-Scheduled

Drug Name: Samsca 30 MG Oral Tablet

Ingredient(s): Tolvaptan

Imprint: OTSUKA;30

Color(s): Blue

Shape: Round

Size (mm): 8.00

Score: 1

Inactive Ingredient(s): starch, corn / hydroxypropyl cellulose / lactose monohydrate / hydroxypropyl cellulose, low substituted / magnesium stearate / cellulose, microcrystalline / fd&c blue no. 2

Drug Label Author:
Otsuka America Pharmaceutical Inc.

DEA Schedule:
Non-Scheduled