Hyponatremia in SIADH
– Patient Case Video
Bindu Khanna, MD
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Hyponatremia in SIADH
Patients with hyponatremia and SIADH are at risk in the hospital
Pathogenic properties of patients with SIADH
-
Vasopressin secretion continues (even when plasma osmolality falls below the osmotic threshold that normally suppresses vasopressin), resulting in3:
— Renal reabsorption of free water
— Hyponatremia -
SIADH-induced hyponatremia can occur in:
— Elderly patients4
— Patients taking diuretics1
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SAMSCA: Increases Serum Sodium Levels
In the SALT trials on Day 4 SAMSCA increased serum sodium concentration by 4.5 mEq/L vs 0.2mEq/L for placebo. On Day 30, SAMSCA increased serum sodium concentration by 7.4 mEq/L vs 1.5 mEq/L for placebo5
SAMSCA should be initiated and re-initiated in patients only in a hospital where serum sodium can be monitored closely.
Too rapid correction of serum sodium (e.g., >12 mEq/L/24 hours) can cause serious neurologic sequelae, including osmotic demyelination syndrome (ODS).
*Data on file. Protocols 156-02-235 and 156-03-238; pooled.
In the SALT trials, SAMSCA was effective in increasing average daily serum [Na+] AUC at Day 4 and Day 30 both in patients with euvolemic hyponatremia (SIADH) and in patients with hypervolemic hyponatremia (HF and cirrhosis). In two identical, 30‑day, randomized, double-blind, placebo-controlled, multicenter studies, 424 patients with euvolemic (SIADH) or hypervolemic (HF and cirrhosis) hyponatremia were treated for 30 days with tolvaptan or placebo, then followed for an additional 7 days after withdrawal. The primary endpoint for these studies was the average daily AUC for change in serum sodium from baseline to Day 4 (tolvaptan, 4.0 mEq/L vs placebo, 0.4 mEq/L) and baseline to Day 30 (tolvaptan, 6.2 mEq/L vs placebo, 1.8 mEq/L). In SIADH patients, the mean change from baseline to Day 4 was 4.8 mEq/L in the SAMSCA group (n=85) and 0.2 mEq/L in the placebo group (n=88) (estimated treatment effect: 4.70, 95% Cl: 3.93-5.47, P<0.0001). The mean change from baseline to Day 30 was 7.4 mEq/L and 1.5 mEq/L, respectively (estimated treatment effect: 6.15, 95% Cl: 5.19-7.11, P<0.0001). Patients received either tolvaptan or placebo, at a starting dose of 15 mg. The dosage of tolvaptan or placebo was increased to 30 mg or 60 mg, if necessary.
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SAMSCA: Significant effect on fluid balance
With SAMSCA, urine output is greater than fluid intake. Thus there is a net negative fluid balance.5
*Data on file. Protocols 156-02-235 and 156-03-238; pooled.
Only subjects whose time spans in both urine collection and fluid intake were no less than 22 hours and no more than 26 hours are included. P values were derived from ANOVA model. †Fluid balance is equal to total fluid intake (oral or IV) minus urine output.
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Clinical case by Bindu Khanna, MD, Nephrologist
Insight on hyponatremia in SIADH
Patient presentation at hospitalization
72-year-old female
- Low serum sodium levels
- Fatigue
- Poor appetite
- Mild neurological symptoms
- No underlying disease state
Results*
- Serum sodium improved
- Patient was discharged
*Individual results may vary.
Subjects with SIADH may be at greater risk for too-rapid correction of serum sodium.
Hyponatremia in SIADH
– Patient Case Video
Bindu Khanna, MD
“In my experience SAMSCA has given me a satisfactory increase within 24 hours.”
Dr. Khanna
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References:
- Douglas I. Hyponatremia: why it matters, how it presents, how we can manage it. Cleve Clin J Med. 2006;73(suppl 3):S4-12.
- Han D-S, Cho B-S. Therapeutic approach to hyponatremia. Nephron. 2002;92(suppl 1):9-13.
- Wong LL, Verbalis JG. Vasopressin V2 receptor antagonists. Cardiovasc Res. 2001;51(3):391-402.
- Anpalahan M. Chronic idiopathic hyponatremia in older people due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) possibly related to aging. J Am Geriatr Soc. 2001;49(6):788-792.
- Data on file. Otsuka America Pharmaceutical, Inc.
