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Date Printed: December 17, 2017: 04:12 PM

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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J1000-19

Original Effective Date: 03/15/10

Reviewed: 06/12/13

Revised: 11/01/15

Subject: Tolvaptan (Samsca™) Oral

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates

DESCRIPTION:

Hyponatremia, defined as a serum sodium less than 135 mEq/L, accounts for the most frequently occurring electrolyte abnormality in the hospital. Severe hyponatremia, defined as serum sodium less than 120 mEq/L, has been reported to occur in approximately 0.2% of inpatients. If left untreated, severe hyponatremia is associated with an increase in mortality. Most persons with hyponatremia present asymptomatically; however, in severe cases when serum sodium drops below 125 mEq/L, severe hyponatremia may manifest nausea, headache, lethargy, muscle cramps, altered gait or falls, mental status changes, seizures, or coma. In persons with heart failure, the presence of hyponatremia is associated with increased risk of adverse outcomes. Early identification and appropriate treatment of hyponatremia is essential in improving outcomes.

Guidelines for managing hyponatremia are based primarily on retrospective data and expert opinion, since few prospective studies have been done. The treatment of acute and chronic hyponatremia should be based on the severity of symptoms and taking care not to raise the serum sodium level too rapidly, which can cause neurologic dysfunction.

The newest treatments for hyponatremia are arginine vasopressin (AVP) receptor antagonists. AVP—also referred to as antidiuretic hormone (ADH)—is a hormone produced by the hypothalamic-pituitary axis. The actions of AVP are mediated by 3 types of vasopressin receptor subtypes: V1A, V1B, and V2 receptors. Hyponatremia can result from inappropriate activation of the V2 receptors found in the apical membrane of the renal collecting duct leading to activation of aquaporin channels and free water retention. Conivaptan (Vaprisol┬«) and tolvaptan (Samsca┬«) are the only U.S. Food and Drug Administration (FDA)-approved vasopressin receptor antagonists. Conivaptan, a dual vasopressin antagonist, is available as an injectable formulation only, while tolvaptan is an orally active, selective V2- receptor antagonists and increases serum sodium in a controlled manner. Tolvaptan offers a mechanism-based treatment option for persons with euvolemic or hypervolemic hyponatremia who have serum sodium levels less than 125 mEq/L or persistent symptoms resistant to fluid retention. The available literature indicated tolvaptan is effective at increasing urine volume and improving symptoms of dyspnea and pedal edema in persons with acute heart failure and in the treatment of chronic hyponatremia associated with syndrome of inappropriate anti-diuretic secretion (SIADH). Trials designed to evaluate the effect of tolvaptan use on long-term clinical outcomes such as left ventricular function, worsening heart failure, morbidity, and mortality did not demonstrate an improvement over standard therapy. Additionally, these trials demonstrated a significant incidence of adverse events. Based on the available evidence, tolvaptan cannot be considered a routine therapeutic option in the management of heart failure; furthermore, there is no data available on the use of tolvaptan in acute hyponatremia, and it is not indicated in hypovolemic hyponatremia.

POSITION STATEMENT:

Tolvaptan (Samsca) meets the definition of medical necessity when ALL of the following criteria are met:

1. Member is diagnosed with EITHER of the following:

a. Hypervolemic hyponatremia

b. Euvolemic hyponatremia

2. Therapy was initiated or re-initiated in a hospital within the past month

3. Member’s hyponatremia (prior to start of therapy) is evidenced by EITHER of the following:

a. Serum sodium is <125 mEq/L

b. Less marked hyponatremia (serum sodium between 125 to 134 mEq/L) that is symptomatic (e.g., nausea, lethargy, mental status changes) and has resisted correction with fluid restriction

4. Dosage does not exceed 60 mg daily (quantity limit per 1 year: one 15 mg tablet per day for 15 mg dose, one 30 mg tablet per day for 30 mg dose; two 30 mg tablets per day for 60 mg dose)

5. Duration of treatment does not exceed 30 days

Duration of approval: 30 days

Treatment with tolvaptan meets the definition of medical necessity when used for the following designated Orphan Drug Indication (http://www.fda.gov/orphan/designat/list.htm)

1. Autosomal dominant polycystic kidney disease

Duration of approval: 30 days

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING IT’S USAGE.

FDA-approved: tolvaptan is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia [serum sodium less than 125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction], including treatment in persons with heart failure, cirrhosis, and Syndrome of Inappropriate Antidiuretic Hormone (SIADH). The recommended started dose is 15 mg once daily. The dose may be increased at intervals greater than or equal to 24 hours to 30 mg once daily. The maximum recommended dose is 60 mg once daily. Serum electrolytes (e.g., serum sodium) and volume status should be monitored.

Tolvaptan can be administered without regard to meals.

Therapy Limitations:

• Tolvaptan should not be used in members who require urgent intervention to raise serum sodium rapidly in order to prevent or treat serious neurological symptoms.

• Initiation, including re-initiation, of therapy should be done in a hospital setting.

• Tolvaptan may not provide symptomatic benefit.

Dose Adjustment

Renal Impairment: no adjustment is needed for creatinine clearance > 10 mL/min. No evidence is available for use with creatinine clearance < 10 mL/min or dialysis. No benefit is expected in anuric patients.

Hepatic Impairment: moderate and severe hepatic impairment do not affect exposure to tolvaptan to a clinically relevant extent. No dose adjustment of tolvaptan is necessary.

Dosing in Special Populations: safety and effectiveness of tolvaptan in pediatric patients have not been established.

Drug Availability: tolvaptan is available as a 15- or 30 mg tablet.

PRECAUTIONS:

CONTRAINDICATIONS

• Do not administer in the following populations

- Individuals who require urgent intervention to raise serum sodium

- Individuals unable to sense or respond appropriately to thirst

- Individuals with hypovolemic hyponatremia

- Individuals who are anuric as no benefit is expected

• Do not administer concomitantly with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, etc) as supratherapeutic tolvaptan concentrations may occur.

WARNINGS

BOXED WARNINGS

• Too rapid correction of hyponatremia (e.g., greater than 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 individuals, including those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable.

• Initiate and re-initiate only in a hospital where serum sodium can be monitored closely

Monitoring: monitor serum sodium and neurologic status as serious neurologic sequelae can result from rapid correction of sodium. Monitor serum potassium in persons with potassium greater than 5 mEq/L or in individuals administered drugs known to increase potassium (e.g., ACE-Inhibitors).

Gastrointestinal bleeding: persons with cirrhosis are at a potential increased risk of gastrointestinal bleeding; use in persons with cirrhosis when the benefit of treatment outweighs the risk.

Volume status: monitor closely as dehydration and hypovolemia may require intervention.

Concomitant therapy: avoid tolvaptan use in combination with hypertonic saline, CYP3A4 inducers, and CYP3A4 inhibitors; consider dose reduction if co-administered with P-gp inhibitors.

Pregnancy and Lactation: tolvaptan is classified as pregnancy category C. Tolvaptan use in pregnant women has not been studied; however, animal data suggests the possibility of fetal malformations. Tolvaptan use in breastfeeding women has not been studied; however there is potential for serious adverse reactions in nursing infants and tolvaptan should not be used in this population.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding:

J8499

Prescription drug, oral, non-chemotherapeutic, Not Otherwise Specified

ICD-10 Diagnoses Codes That Support Medical Necessity: (Effective 10/01/15)

E87.1

Hyposmolality and/or hyponatremia

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage Products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline revised date.

Medicare Part D: Florida Blue has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

DEFINITIONS:

Euvolemic hyponatremia: that in which there is a low plasma concentration of sodium associated with low total body sodium and normal blood volume.

Hypervolemic hyponatremia: abnormal increase in the volume of circulating blood plasma with a low plasma concentration of sodium associated with low total body sodium.

RELATED GUIDELINES:

None applicable.

OTHER:

None applicable.

REFERENCES:

  1. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.;2012. URL www.clinicalpharmacilogy-ip.com Accessed 12/27/2012.
  2. Gheorghiade M, Gattis WA, O'Connor CM, et al. Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA. 2004; 291:1963-71.
  3. Kraft MD, Btaiche IF, Gordon SS, Kudsk KA. Treatment of electrolyte disorders in adult patients in the intensive care unit. Am J Health-Syst Pharm. 2005; 62:1663-82.
  4. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 12/27/2012.
  5. Patel GP, Balk RA. Recognition and treatment of hyponatremia in acutely ill hospitalized patients. Clinical Therapeutics. 2007; 29:211-29.
  6. Samsca (tolvaptan) [package insert]. Otsuka Pharmaceutical Co., Ltd. Rockville (MD): November 2012.
  7. Tolvaptan. In McEvoy GK, editor. AHFS drug information 2012 [monograph on the internet]. Bethesda (MD): American Society of Health-System Pharmacists; 2012 [cited 2012 Dec 28]. Available from http://online.statref.com Subscription required to view.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 04/08/15.

GUIDELINE UPDATE INFORMATION:

03/15/10

New Medical Coverage Guideline.

03/15/11

Review and revision; consisting of updating references.

03/15/12

Review and revision to guideline; consisting of updating references.

04/15/13

Review and revision to guideline; consisting of reformatting position statement; revising/reformatting description, dosage/administration, and precautions sections; updating references. No Longer Review.

7/15/13

Revision to guideline; consisting of revising position statement and decision tree. No Longer Review

05/11/14

Revision: Program Exceptions section updated.

05/15/15

Revision: updated billing/coding.

11/01/15

Revision: ICD-9 Codes deleted.

Date Printed: December 17, 2017: 04:12 PM