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Private Property of Blue Cross and Blue Shield of Florida.
This medical policy (medical coverage guideline) is Copyright 2014, 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 2014 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-J1000-97

Original Effective Date: 07/15/13

Reviewed: 06/12/13

Revised: 00/00/00

Subject: Sodium Phenylbutyrate (Buphenyl®)

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.

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

DESCRIPTION:

Sodium phenylbutyrate (Buphenyl®) is a pro-drug and is rapidly metabolized to phenylacetate. Phenylacetate is a metabolically-active compound that conjugates with glutamine via acetylation to form phenylacetylglutamine. Phenylacetylglutamine then is excreted by the kidneys. On a molar basis, it is comparable to urea (each containing two moles of nitrogen). Therefore, phenylacetylglutamine provides an alternate vehicle for waste nitrogen excretion.

Sodium phenylbutyrate is used as adjunctive therapy for the chronic management of hyperammonemia in subjects with urea cycle disorders, including deficiencies in carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (ASS) enzymes. Sodium phenylbutyrate is used in individuals with neonatal-onset deficiency (i.e., complete enzymatic deficiency, presenting within the first 28 days of life) and in those with late-onset disease (i.e., partial enzymatic deficiency, presenting after the first month of life) who have a history of hyperammonemic encephalopathy.

Many individuals continue to have hyperammonemic episodes while receiving sodium phenylbutyrate therapy; however, sodium phenylbutyrate should not be used to treat acute hyperammonemia, because uncontrolled hyperammonemia can rapidly result in brain damage or death. Any episode of acute symptomatic hyperammonemia should be treated as a life-threatening emergency, and prompt use of all therapies necessary to reduce ammonia concentrations is essential. Hemodialysis is the most rapid and effective method for removing ammonia in subjects with acute neonatal hyperammonemic coma, moderate to severe episodes of hyperammonemic encephalopathy, or episodes of hyperammonemia that fail to respond to an initial course of sodium phenylacetate and sodium benzoate therapy.

POSITION STATEMENT:

Initiation of sodium phenylbutyrate (Buphenyl®) meets the definition of medical necessity when ALL of the following criteria are met:

Urea Cycle Disorders (UCDs)

• The member has a diagnosis of urea cycle disorders (UCD) involving known or proven deficiencies of ANY of the following:

- carbamylphosphate synthetase (CPS)

- ornithine transcarbamylase (OTC)

- argininosuccinic acid synthetase (AS)

• The member has documentation of protein restrictive diet.

• The drug is not being used to manage acute hyperammonemia.

• Dosage does not exceed 20 grams per day.

Continuation of glycerol phenylbutyrate therapy meets the definition of medical necessity when ALL of the following criteria are met:

• Member has a history of beneficial clinical response with sodium phenylbutyrate therapy for the treatment of urea cycle disorders.

• Member has been approved by another healthplan or member has met Florida Blue’s initial criteria for coverage.

• Dosage does not exceed 20 grams per day.

Approval duration: 1 year

Sodium phenylbutyrate meets the definition of medical necessity when used for ANY of the following designated Orphan Drug indications (http://www.fda.gov/orphan/designat/list.htm)

• Treatment of spinal muscular atrophy

• For use as an adjunct to surgery, radiation therapy and chemotherapy for the treatment of individuals with primary or recurrent malignant glioma.

• Treatment for sickling disorders, which include S-S hemoglobinopathy, S-C hemoglobinopathy, and S-thalassemia hemoglobinopathy.

Approval duration: 1 year

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 ITS USAGE.

Sodium Phenylbutyrate Tablets (500 mg): indicated for children weighing more than 20 kg and for adults.

Sodium Phenylbutyrate Powder (level teaspoon = 3 gm): indicated for oral use (via mouth, gastrostomy, or nasogastric tube) only. The powder is to be mixed with food (solid or liquid) for immediate use. When dissolved in water, sodium phenylbutyrate powder has been shown to be stable for up to one week at room temperature or refrigerated.

The usual total daily dose of sodium phenylbutyrate tablets and powder for urea cycle disorders is 450–600 mg/kg/day in subjects weighing less than 20 kg, or 9.9–13.0 g/m2/day in larger individuals. The tablets and powder are to be taken in equally divided amounts with each meal or feeding (i.e., three to six times per day).

The safety or efficacy of doses in excess of 20 grams (40 tablets) per day has not been established.

PRECAUTIONS:

Contraindication:

Sodium phenylbutyrate should not be used to manage acute hyperammonemia, which is a medical emergency.

Warnings:

Because of its high sodium content, sodium phenylbutyrate should be used with great care, if at all, in individuals with congestive heart failure or severe renal insufficiency, and in clinical states in which there is sodium retention with edema.

Adverse neurotoxic effects, principally somnolence, fatigue, and lightheadedness have been reported in cancer subjects receiving IV phenylacetate, a metabolite of sodium phenylbutyrate. Also reported were headache, dysgeusia, hypoacusis, disorientation, impaired memory, and exacerbation of existing neuropathy but less frequently.

Monitering: serum protein concentrations and plasma concentrations of ammonia, arginine, and branched-chain amino acids should be monitored and maintained within normal limits. Plasma glutamine concentrations should be maintained at less than 1000 mcmol/L. Serum phenylbutyrate, phenylacetate, and phenylacetylglutamine concentrations should be monitored periodically. Urinalysis, blood chemistry profiles, and hematologic tests should be monitored routinely.

Because sodium phenylbutyrate is metabolized in the liver and kidney, and phenylacetylglutamine is primarily excreted by the kidney, use caution when administering the drug to individuals with hepatic or renal insufficiency.

Use of sodium phenylbutyrate tablets in neonates, infants and children weighing less than 20 kg is not recommended.

Use of corticosteroids may cause the breakdown of body protein and increase plasma ammonia levels.

There have been published reports of hyperammonemia being induced by haloperidol and by valproic acid.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

J8499

Prescription drug, oral, nonchemotherapeutic, NOS

ICD-9 Diagnoses Codes That Support Medical Necessity

270.6

Disorders of urea cycle metabolism

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

E72.20

Disorder of urea cycle metabolism, unspecified

E72.22

Arginosuccinic aciduria

E72.29

Other disorders of urea cycle metabolism

E72.4

Disorders of ornithine metabolism

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) or Local Coverage Determination (LCD) was found at the time of the last guideline revised date.

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

DEFINITIONS:

Urea Cycle Disorder: a genetic disorder caused by a mutation that results in a deficiency of one of the six enzymes in the urea cycle. These enzymes are responsible for removing ammonia from the blood stream.

RELATED GUIDELINES:

Glycerol Phenylbutyrate (Ravicti ®), 09-J1000-98

OTHER:

None

REFERENCES:

  1. Buphenyl® Prescribing Information. Revised April 2009.
  2. Clinical Pharmacology. Copyright© 2013 Elsevier. Accessed 05/21/13.
  3. Ingenix HCPCS Level II, Expert 2013.
  4. Ingenix ICD-9-CM for Physicians-Volumes 1 & 2, Expert 2013.
  5. Micromedex® 2.0, ©2013 Truven Health Analytics Inc. Accessed 05/07/13.
  6. National Urea Cycle Disorders Foundation. Copyright© 2005-2013. Available at http://www.nucdf.org/ucd.htm. Accessed 05/21/13.
  7. Urea Cycle Disorders Consortium. Urea Cycle Disorders Treatment Guidelines. National Institutes of Health, Rare Diseases Clinical Research Network. Available at http://rarediseasesnetwork.epi.usf.edu/ucdc/physicians/guidelines-main.htm. Accessed 05/20/13.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 06/12/13.

GUIDELINE UPDATE INFORMATION:

07/15/13

New Medical Coverage Guideline.

Private Property of Blue Cross and Blue Shield of Florida.
This medical policy (medical coverage guideline) is copyright 2013, 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 2013 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.

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Date Printed: September 30, 2014: 05:53 PM