Dosing and uses of Samsca (tolvaptan)
Adult dosage forms and strengths
tablet
- 15mg
- 30mg
Hyponatremia
Indicated for hospitalized adults with clinically significant euvolemic or hypervolemic 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 SIADH
Initial: 15 mg PO qDay
Maintenance: Increase PRN after >24 hr to 30 mg qDay; may increase further, not to exceed 60 mg qDay
Not to exceed 30 days of treatment
Monitor: Serum sodium
Renal Impairment
CrCl 10-79 mL/min: No dosage adjustment required
CrCl <10 mL or dialysis: Not studied
Anuria: Contraindicated; no benefit expected
Hepatic Impairment
Moderate and severe hepatic impairment do not affect exposure to tolvaptan to a clinically relevant extent
Avoid use of tolvaptan in patients with underlying liver disease
Administration
Do not exceed 30 days of administration to minimize risk of liver injury (see Cautions)
Following discontinuation, patients should be advised to resume fluid restriction and should be monitored for changes in serum sodium and volume status
Pediatric dosage forms and strengths
Safety and efficacy not established
Samsca (tolvaptan) adverse (side) effects
>10%
Nausea (21%)
Thirst (16%)
Dry mouth (13%)
Pollakiuria (4-11%)
Urinary frequency/output increased (11%)
1-10%
GI bleeding with pre-existing cirrhosis (10%)
Weakness (9%)
Constipation (7%)
Hyperglycemia (6%)
Anorexia (4%)
Postmarketing Reports
Neurologic: Osmotic demyelination syndrome
Investigations: Hypernatremia
Immune system disorders: Hypersensitivity reactions including anaphylactic shock and rash
Warnings
Black box warnings
Initiate only in a hospital where serum sodium level can be monitored closely
Too-rapid correction of hyponatremia (eg, >12 mEq/L/24 hr) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death
In susceptible patients, including those with severe malnutrition, alcoholism, or advanced liver disease, slower rates of correction may be advisable
Contraindications
Urgent correction of hypovolemia required
Inability to feel/respond to thirst
Hypovolemic hyponatremia
Concomitant strong CYP3A4 inhibitors
Anuria
Hypersensitivity (eg, anaphylactic shock, rash generalized)
Cautions
Cirrhosis, hypovolemia, dehydration
Too rapid correction can cause serious neurologic damage (see Black box warnings)
Risk of dehydration/hypovolemia; encourage patient to drink whenever thirsty; interrupt if occurs
Osmotic demyelination syndrome reported
Risk of hyperkalemia
May need dose adjustments with concomitant moderate CYP3A4 inhibitors, CYP inducers or Pgp inhibitors (also see Contraindications)
Avoid/limit grapefruit juice consumption
Liver injury
- Can cause serious and potentially fatal liver injury; increased ALT (>3 xULN)
- Increased ALT observed in 4.4% of patients (compared with 1% taking placebo) typically starting ~3 months after therapy initiated
- Limit duration of treatment to 30 days
- If symptoms indicating liver injury occur (eg, fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice), discontinue tolvaptan
- Avoid use with underlying liver disease, including cirrhosis, because the ability to recover from liver injury may be impaired
Pregnancy and lactation
Pregnancy category: C
Lactation: not known if excreted in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Samsca (tolvaptan)
Mechanism of action
Selective vasopressin V2-receptor antagonist that causes an increase in urine water excretion that results in an increase in free water clearance (aquaresis), a decrease in urine osmolality, and a resulting increase in serum sodium concentration
Pharmacokinetics
Half-Life, Terminal: 12 hr
Absorption: >40%
Pgp substrate and inhibitor
Peak effect: 4-8 hr
Duration: At 24 hr 60% of peak serum sodium elevation is retained
Peak Plasma Time: 2-4 hr
Vd: 3 L/kg
Protein Bound: 99%
Metabolism: Hepatic through CYP3A4
Excretion: Feces
