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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-J1000-98

Original Effective Date: 07/15/13

Reviewed: 12/10/14

Revised: 11/01/15

Subject: Glycerol Phenylbutyrate (Ravicti®)

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

Decision Tree

  Previous Version

DESCRIPTION:

Glycerol phenylbutyrate (Ravicti®) is a triglyceride containing 3 molecules of phenylbutyrate (PBA). Phenylacetate (PAA), the major metabolite of PBA, is the active moiety of glycerol phenylbutyrate. PAA conjugates with glutamine (which contains 2 molecules of nitrogen) via acetylation in the liver and kidneys to form phenylacetylglutamine (PAGN), which is excreted by the kidneys. On a molar basis, PAGN, like urea, contains 2 moles of nitrogen and provides an alternate vehicle for waste nitrogen excretion.

Glycerol phenylbutyrate is used as adjunctive therapy for the chronic management of hyperammonemia in subjects with urea cycle disorders (UCDs), including deficiencies in carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (ASS) enzymes.

UCDs are inherited deficiencies of enzymes or transporters necessary for the synthesis of urea from ammonia (NH3, NH4+). Absence of these enzymes or transporters results in the accumulation of toxic levels of ammonia in the blood and brain of affected individuals.

POSITION STATEMENT:

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

Urea Cycle Disorders (UCDs)

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

a. carbamylphosphate synthetase (CPS)

b. ornithine transcarbamylase (OTC)

c. argininosuccinic acid synthetase (AS)

2. The member has documentation of protein restrictive diet.

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

4. The member has failed a trial of sodium phenylbutyrate (Buphenyl®) or has a contraindication or intolerance to sodium phenylbutyrate.

5. The member is 2 years old or older.

6. Dosage does not exceed 17.5 mL (19 grams) daily.

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

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

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

3. Dosage does not exceed 17.5 mL (19 grams) daily.

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.

Glycerol phenylbutyrate oral liquid 1.1 g/mL is supplied in multi-use, 25-mL glass bottles.

Glycerol phenylbutyrate should be taken with food, administered directly into the mouth via oral syringe or dosing cup.

Switching From Sodium Phenylbutyrate to Glycerol Phenylbutrate

Individuals switching from sodium phenylbutyrate to glycerol phenylbutyrate should receive the dosage of glycerol phenylbutyrate that contains the same amount of phenylbutyric acid. The conversion is as follows:

Total daily dosage of glycerol phenylbutyrate (mL) = total daily dosage of sodium phenylbutyrate (g) x 0.86

Initial Dosage in Phenylbutyrate-Naïve Individuals:

The recommended dosage range, based upon body surface area, in individuals naïve to phenylbutyrate (PBA) is 4.5

to 11.2 mL/m2/day (5 to 12.4 g/m2/day).

For individuals with some residual enzyme activity who are not adequately controlled with protein restriction, the recommended starting dosage is 4.5 mL/m2/day.

The total daily dosage should not exceed 17.5 mL (19 grams).

PRECAUTIONS:

Contraindication:

Children less than 2 months of age may have immature pancreatic exocrine function, which could impair hydrolysis of glycerol phenylbutyrate, leading to impaired absorption of phenylbutyrate and hyperammonemia.

Known hypersensitivity to phenylbutyrate. Signs of hypersensitivity include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash.

Warnings:

The major metabolite of glycerol phenylbutyrate is phenylacetate (PAA) which is associated with neurotoxicity. Signs and symptoms of PAA neurotoxicity include somnolence, fatigue, lightheadedness, headache, dysgeusia, hypoacusis, disorientation, impaired memory, and exacerbation of preexisting neuropathy.

If symptoms of vomiting, nausea, headache, somnolence, confusion, or sleepiness are present in the absence of high ammonia or other intercurrent illnesses, reduce the glycerol phenylbutyrate dosage.

Monitor ammonia levels closely in individualss with pancreatic insufficiency or intestinal malabsorption.

Use of corticosteroids may cause the breakdown of body protein and increase plasma ammonia levels. Monitor ammonia levels closely when corticosteroids and glycerol phenylbutyrate are used concomitantly.

Hyperammonemia may be induced by haloperidol and by valproic acid. Monitor ammonia levels closely when use of valproic acid or haloperidol is necessary in UCD individuals.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

J8499

Prescription drug, oral, nonchemotherapeutic, NOS

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 which 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:

Sodium Phenylbutyrate (Buphenyl®), 09-J1000-97

OTHER:

None

REFERENCES:

  1. Clinical Pharmacology. Copyright© 2014 Elsevier. Accessed 11/21/14.
  2. Ingenix HCPCS Level II, Expert 2013.
  3. Ingenix ICD-9-CM for Physicians-Volumes 1 & 2, Expert 2013.
  4. Micromedex® 2.0, ©2014 Truven Health Analytics Inc. Accessed 11/07/14.
  5. National Urea Cycle Disorders Foundation. Copyright© 2005-2013. Available at http://www.nucdf.org/ucd.htm. Accessed 05/21/13.
  6. Ravicti® Prescribing Information. Revised February 2013.
  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 12/10/14.

GUIDELINE UPDATE INFORMATION:

07/15/13

New Medical Coverage Guideline.

01/15/15

Review and revision to guideline; consisting of position statement, references.

11/01/15

Revision: ICD-9 Codes deleted.

Date Printed: August 18, 2017: 08:02 PM