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Date Printed: June 23, 2017: 06:30 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-J1000-58

Original Effective Date: 01/01/12

Reviewed: 12/12/12

Revised: 11/01/15

Subject: Altretamine (Hexalen®) Capsules

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:

Altretamine, formerly known as hexamethylmelamine, is a synthetic cytotoxic antineoplastic s-triazine derivative. The precise mechanism by which altretamine exerts its cytotoxic effect is unknown, although a number of theoretical possibilities have been studied. Structurally, altretamine resembles the alkylating agent triethylenemelamine, yet in vitro tests for alkylating activity of altretamine and its metabolites have been negative. Altretamine is efficacious for certain ovarian tumors resistant to classical alkylating agents. Metabolism of altretamine is a requirement for cytotoxicity. Synthetic monohydroxymethylmelamines and products of altretamine metabolism in vitro and in vivo can form covalent adducts with tissue macromolecules including DNA, but the relevance of these reactions to antitumor activity is unknown.

POSITION STATEMENT:

Altretamine meets the definition of medical necessity when used to treat ovarian cancer and the dose does not exceed 260 mg/m2 and the following criteria is followed:

• Used as a single agent following first-line therapy with a cisplatin (Platinol®) based and an alkylating agent (e.g., cyclophosphamide; melphalan) based combination or an alkylating agent.

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.

Normal Dosage

Ovarian cancer, Persistent or recurrent disease; monotherapy as second-line after cisplatin or alkylating agent-based combination.

The dose of altretamine for ovarian cancer is 260 milligrams/square meter/day given orally for 14 or 21 consecutive days. The cycle is repeated every 28 days. Administer in 4 divided doses after meals and at bedtime.

Temporarily discontinue (for 14 days or more) and restart at 200 milligrams/square meter/day if any of the following conditions exist [10]:

• Gastrointestinal intolerance not responsive to symptomatic measures

• White blood cell count less than 2000 cells/cubic millimeter or a granulocyte count less than 1000 cells/cubic millimeter

• Platelets less than 75,000 cells/cubic millimeter

• Progressive neurotoxicity

Discontinue altretamine altogether if neurologic symptoms fail to stabilize on the reduced dose schedule.

PRECAUTIONS:

Black Box Warning

Administer only under the supervision of a physician experienced in the use of antineoplastic agents.

Monitor peripheral blood counts at least monthly, prior to the initiation of each course of altretamine therapy and as clinically indicated.

Because of the possibility of altretamine-related neurotoxicity, perform neurologic examination regularly during administration.

CONTRAINDICATIONS

Altretamine capsules are contraindicated in members who have shown hypersensitivity to it. Altretamine capsules should not be employed in members with preexisting severe bone marrow depression or severe neurologic toxicity. Altretamine capsules have been administered safely, however, to members heavily pretreated with cisplatin and/or alkylating agents, including members with preexisting cisplatin neuropathies. Careful monitoring of neurologic function in these members is essential.

ADVERSE REACTIONS

Gastrointestinal

With continuous high-dose daily altretamine capsules, nausea and vomiting of gradual onset occur frequently. Although in most instances these symptoms are controllable with anti-emetics, at times the severity requires altretamine capsules dose reduction or, rarely, discontinuation of altretamine capsules therapy. In some instances, a tolerance of these symptoms develops after several weeks of therapy. The incidence and severity of nausea and vomiting are reduced with moderate-dose administration of altretamine capsules.

Neurotoxicity

Peripheral neuropathy and central nervous system symptoms (mood disorders, disorders of consciousness, ataxia, dizziness, vertigo) have been reported. They are more likely to occur in patients receiving continuous high-dose daily altretamine capsules than moderate-dose altretamine capsules administered on an intermittent schedule. Neurologic toxicity has been reported to be reversible when therapy is discontinued.

Hematologic

Altretamine capsules causes mild to moderate dose-related myelosuppression. Leukopenia below 3000 WBC/mm3 occurred in <15% of members on a variety of intermittent or continuous dose regimens.

Laboratory Tests: Peripheral blood counts should be monitored at least monthly, prior to the initiation of each course of altretamine capsules, and as clinically indicated.

Drug Interactions:

Concurrent administration of altretamine capsules and antidepressants of the MAO inhibitor class may cause severe orthostatic hypotension.

Pyridoxine should not be administered with altretamine capsules and/or cisplatin.

Pediatric Use: The safety and effectiveness of altretamine capsules in children have not been established.

BILLING/CODING INFORMATION:

HCPCS Coding

J8999

Prescription drug, oral, chemotherapeutic, NOS

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

C48.1

Malignant neoplasm of specified parts of peritoneum

C48.2

Malignant neoplasm of peritoneum, unspecified

C48.8

Malignant neoplasm of overlapping sites of retroperitoneum and peritoneum

C56.0 – C57.4

Malignant neoplasm of ovary and other and unspecified female genital organs including fallopian tube, broad ligament, round ligament, parametrium and uterine adnexa, unspecified.

Z85.43

Personal history of malignant neoplasm of ovary

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:

No guideline specific definitions apply.

RELATED GUIDELINES:

Bevacizumab (Avastin®) Injection, 09-J0000-66
Docetaxel (Taxotere®) IV, 09-J0000-95

Doxorubicin HCl Liposome (Doxil®) IV, 09-J0000-91

Gemcitabine (Gemzar®), 09-J0000-96

Genetic Testing for Hereditary Breast or Ovarian Cancer, 05-82000-30

Gonadotropin Releasing Hormone Analogs and Antagonists, 09-J0000-48

Intensity-Modulated Radiation Therapy (IMRT), 04-77260-22

Irinotecan HCl (Camptosar®) IV, 09-J0000-99

Paclitaxel and Paclitaxel (protein-bound) IV, 09-J1000-05

Positron Emission Tomography (PET Scans) Oncologic Applications, 04-78000-17

Topotecan HCl (Hycamtin®) IV, 09-J1000-02

OTHER:

None

REFERENCES:

  1. Clinical Pharmacology. Copyright® 2012 Elsevier. Accessed 10/30/12.
  2. DRUGDEX®. Accessed 10/30/12.
  3. Facts & Comparisons® E Answers. Accessed 10/30/12.
  4. Hexalen Prescribing Information. Revised November 2003.
  5. Ingenix HCPCS Level II, Expert 2012.
  6. Ingenix ICD-9-CM for Physicians-Volumes 1 & 2, Expert 2012.
  7. NCCN Drugs & Biologics Compendium™. Accessed 10/30/12.

COMMITTEE APPROVAL:

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

GUIDELINE UPDATE INFORMATION:

01/01/12

New Medical Coverage Guideline.

01/15/13

No longer reviewed.

05/11/14

Revision: Program Exceptions section updated.

Date Printed: June 23, 2017: 06:30 PM