Please orient your device into the portrait position to return to the site.
​Hyponatremia in SIADH​ in Oncology SIGN UP TO STAY INFORMED

Hyponatremia is one of the most common electrolyte disorders associated with cancer1,2

In three large studies of cancer patients with hyponatremia, the rates of hyponatremia were3-6:

4.2%4

  • n = 6766 patients at admission
  • HN defined as a serum sodium level of <130 mEq/L

10.8%5

  • n = 6612 patients at admission
  • HN defined as a serum sodium level of <135 mEq/L

47%6

  • n = 3357 patients
    • 23% at admission
    • 24% acquired during hospitalization
  • HN defined as a serum sodium level <135 mEq/L

Not all of these patients will be appropriate for therapy with SAMSCA.

Hyponatremia is most often caused by SIADH in cancer patients1,7

  • SIADH is most commonly found in patients with small cell lung cancer (SCLC)3
  • SIADH has also been reported in patients with head and neck cancer3
  • SIADH in patients with cancer may be due to3:
    • Inappropriate secretion of vasopressin with malignancy
    • Agents commonly used in cancer treatment and palliative care

Certain drugs commonly used in patients with cancer are known to cause hyponatremia by inducing SIADH3

Chart showing drugs commonly used in cancer patients that are known to cause hyponatremia
* Cisplatin may also cause hyponatremia by damaging renal tubes and interfering with sodium reabsorption.
Adapted from Castillo et al, Oncologist, 2012.3

* Cisplatin may also cause hyponatremia by damaging renal tubes and interfering with sodium reabsorption.
Adapted from Castillo et al, Oncologist, 2012.3

Fluid restriction is considered the standard of care for dilutional hyponatremia8,9

Fluid restriction addresses total body water imbalance8,9

  • In some patients, hyponatremia can resist correction with fluid restriction10

Fluid Restriction can be difficult in the oncology setting3

  • Some patients with hyponatremia in SIADH experience an exaggerated need to drink due to downward resetting of the osmotic threshold for thirst11

INDICATION and IMPORTANT SAFETY INFORMATION for SAMSCA® (tolvaptan)

INDICATION:

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).

Limitations of Use:

  • Patients requiring intervention to raise serum sodium urgently to prevent or to treat serious neurological symptoms should not be treated with SAMSCA
  • It has not been established that raising serum sodium with SAMSCA provides a symptomatic benefit to patients

IMPORTANT SAFETY INFORMATION:

WARNING: INITIATE AND RE-INITIATE IN A HOSPITAL AND MONITOR SERUM SODIUM

  • SAMSCA should be initiated and re-initiated in patients only in a hospital where serum sodium can be monitored closely.
  • Too rapid correction of hyponatremia (e.g., >12 mEq/L/24 hours) 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

WARNING: NOT FOR USE FOR AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD)

  • Because of the risk of hepatotoxicity, tolvaptan should not be used for ADPKD outside of the FDA-approved REMS.

CONTRAINDICATIONS:

  • Use in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) outside of FDA-approved REMS
  • Unable to sense or respond to thirst
  • Hypovolemic hyponatremia
  • Taking strong CYP3A inhibitors
  • Anuria
  • Hypersensitivity (e.g., anaphylactic shock, rash generalized) to tolvaptan or any component of the product

Too Rapid Correction of Serum Sodium Can Cause Serious Neurologic Sequelae: During initiation and after titration monitor patients to assess serum sodium concentrations and neurologic status. Subjects with SIADH or very low baseline serum sodium concentrations may be at greater risk for too-rapid correction of serum sodium. In patients receiving SAMSCA who develop too rapid a rise in serum sodium, discontinue or interrupt treatment with SAMSCA and consider administration of hypotonic fluid. Fluid restriction during the first 24 hours with SAMSCA may increase the likelihood of overly-rapid correction of serum sodium, and should generally be avoided. Co-administration of diuretics also increases the risk of too rapid correction of serum sodium and such patients should undergo close monitoring of serum sodium.

Liver Injury: Tolvaptan can cause serious and potentially fatal liver injury. In clinical trials, cases of serious liver injury have been attributed to chronically administered tolvaptan in patients with ADPKD. Liver failure requiring transplantation has been reported in postmarketing experience with tolvaptan in ADPKD. Limit duration of therapy with SAMSCA to 30 days. Avoid use in patients with underlying liver disease, including cirrhosis, because the ability to recover may be impaired.

Dehydration and Hypovolemia: In patients who develop medically significant signs or symptoms of hypovolemia, discontinuation is recommended. Dehydration and hypovolemia can occur, especially in potentially volume-depleted patients receiving diuretics or those who are fluid restricted

Co-administration with Hypertonic Saline: Not recommended

Drug Interactions – CYP3A Inhibitors: Tolvaptan is a substrate of CYP3A. Moderate to strong CYP3A inhibitors can lead to a marked increase in tolvaptan concentrations. Do not use SAMSCA with strong inhibitors of CYP3A and avoid concomitant use with moderate CYP3A inhibitors. Patients should avoid grapefruit juice beverages while taking SAMSCA

Hyperkalemia or Drugs that Increase Serum Potassium: Monitor serum potassium levels in patients with a serum potassium >5 mEq/L and in patients receiving drugs known to increase serum potassium levels

Acute Urinary Retention with Outflow Obstruction: Patients with partial obstruction of urinary outflow have an increased risk of developing acute retention. Do not administer tolvaptan in patients with uncorrected urinary outflow obstruction.

Adverse Reactions: The most common adverse reactions (SAMSCA incidence  ≥5% more than placebo, respectively): thirst (16% vs 5%), dry mouth (13% vs 4%), asthenia (9% vs 4%), constipation (7% vs 2%), pollakiuria or polyuria (11% vs 3%) and hyperglycemia (6% vs 1%)

Gastrointestinal Bleeding in Patients with Cirrhosis: In patients with cirrhosis in the hyponatremia trials, GI bleeding was reported in 10% of tolvaptan-treated patients vs 2% for placebo

Other Drug Interactions:

  • Strong CYP3A Inducers: Co-administration of SAMSCA with strong CYP3A inducers reduces exposure to SAMSCA. Avoid concomitant use of SAMSCA with strong CYP3A inducers
  • Angiotensin Receptor Blockers, Angiotensin Converting Enzyme Inhibitors and Potassium Sparing Diuretics: In clinical studies, adverse reactions of hyperkalemia were approximately 1 to 2% higher when tolvaptan was administered with angiotensin receptor blockers, angiotensin converting enzyme inhibitors and potassium sparing diuretics compared to administration of these medications with placebo. Serum potassium levels should be monitored during concomitant drug therapy.
  • V2-Receptor Agonist: Tolvaptan interferes with the V2-agonist activity of desmopressin (dDAVP). Avoid concomitant use of SAMSCA with a V2-agonist

Pregnancy and Lactation: Based on animal data, SAMSCA may cause fetal harm. Advise women not to breastfeed during treatment with SAMSCA.

To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch)

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.

 

 

References:

1
Onitilo AA, Kio E, Doi SAR. Tumor-related hyponatremia. Clin Med Res. 2007;5(4):228-237.
2
Sarhill N, Walsh D, Nelson K, Davis M. Evaluation and treatment of cancer-related fluid deficits: volume depletion and dehydration. Support Care Cancer. 2001;9(6):408-419.
3
Castillo JJ, Vincent M, Justice E. Diagnosis and management of hyponatremia in cancer patients. Oncologist. 2012;17(6):756-765.
4
Hampshire PA, Welch CA, McCrossan LA, Francis K, Harrison DA. Admission factors associated with hospital mortality in patients with haematological malignancy admitted to UK adult, general critical care units: a secondary analysis of the ICNARC Case Mix Programme Database. Crit Care. 2009;13(4):R137.
5
Waikar SS, Mount DB, Curhan GC. Mortality after hospitalization with mild, moderate, and severe hyponatremia. Am J Med. 2009;122(9):857-865.
6
Doshi SM, Shah P, Lei X, Lahoti A, Salahudeen AK. Hyponatremia in hospitalized cancer patients and its impact on clinical outcomes. Am J Kidney Dis. 2012;59(2):222-228.
7
Raftopoulos H. Diagnosis and management of hyponatremia in cancer patients. Support Care Cancer. 2007;15(12):1341-1347.
8
Douglas I. Hyponatremia: why it matters, how it presents, how we can manage it. Cleve Clin J Med. 2006;73(suppl 3):S4-S12.
9
Berl T. Treatment of the syndrome of inappropriate antidiuretic hormone secretion and the emergence of vasopressin antagonists for hyponatremic disorders. Nephrol Rounds. 2007;5(5):2-6. http://nephrologyrounds.org/crus/usneph0507.pdf. Accessed May 22, 2013.
10
Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013;126(10 suppl 1):S1-S4.
11
Smith D, Moore K, Torney W, Baylis PH, Thompson CJ. Downward resetting of the osmotic threshold for thirst in patients with SIADH. Am J Physiol Endocrinol Metab. 2004;287(5):E1019-E1023. doi: 10.1152/ajpendo.00033.24.

© 2021 Otsuka America Pharmaceutical, Inc.

May 2021
07US21EBP0001