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Date Printed: June 23, 2017: 11:36 AM

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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-J1000-59

Original Effective Date: 01/01/12

Reviewed: 12/12/12

Revised: 11/01/15

Next Review: No Longer Scheduled for Routine Review (NLR)

Subject: Procarbazine (Matulane®) 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:

Procarbazine is a cell-cycle phase nonspecific antineoplastic agent which inhibits protein and nucleic acid synthesis and suppresses mitosis. Procarbazine must be converted to active metabolites; which may occur either spontaneously or by an enzymatic reaction mediated by the cytochrome P-450 system. After conversion, the precise mechanism of action is uncertain. Proposed mechanisms involve inhibition of protein synthesis by inhibiting or damaging the action of DNA, RNA or transfer RNA.

POSITION STATEMENT:

Procarbazine meets the definition of medical necessity when used for:

• Stage III and IV Hodgkin's disease

• Central nervous system cancers: Adult low-grade infiltrative supratentorial astrocytoma/oligodendroglioma, anaplastic gliomas/glioblastoma, primary CNS lymphoma

• AIDS-related B-cell lymphoma

• Diffuse large B-cell lymphoma

• Follicular lymphoma and Nodal marginal zone lymphoma

• Gastric MALT lymphoma

• Mantle cell lymphoma

• Non-gastric MALT lymphoma

• Primary cutaneous B-cell lymphoma

• Splenic marginal zone lymphoma

NOTE: Adult maximum dose is 6 mg/kg/day. Pediatric maximum dose is 100 mg per square meter of body surface per day.

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.

Adults: To minimize the nausea and vomiting experienced by a high percentage of patients beginning procarbazine therapy, single or divided doses of 2 to 4 mg/kg/day for the first week are recommended. Daily dosage should then be maintained at 4 to 6 mg/kg/day until maximum response is obtained or until the white blood count falls below 4000/cmm or the platelets fall below 100,000/cmm. When maximum response is obtained, the dose may be maintained at 1 to 2 mg/kg/day. Upon evidence of hematologic or other toxicity, the drug should be discontinued until there has been satisfactory recovery. After toxic side effects have subsided, therapy may then be resumed at the discretion of the physician, based on clinical evaluation and appropriate laboratory studies, at a dosage of 1 to 2 mg/kg/day.

Pediatric Patients: Very close clinical monitoring is mandatory. Undue toxicity, evidenced by tremors, coma and convulsions, has occurred in a few cases. Dosage, therefore, should be individualized. The following dosage schedule is provided as a guideline only. Fifty (50) mg per square meter of body surface per day is recommended for the first week. Dosage should then be maintained at 100 mg per square meter of body surface per day until maximum response is obtained or until leukopenia or thrombocytopenia occurs. When maximum response is attained, the dose may be maintained at 50 mg per square meter of body surface per day. Upon evidence of hematologic or other toxicity , the drug should be discontinued until there has been satisfactory recovery, based on clinical evaluation and appropriate laboratory tests. After toxic side effects have subsided, therapy may then be resumed.

PRECAUTIONS:

Black Box Warning

It is recommended that MATULANE be given only by or under the supervision of a physician experienced in the use of potent antineoplastic drugs. Adequate clinical and laboratory facilities should be available to patients for proper monitoring of treatment.

CNS Effects: To minimize CNS depression and possible potentiation, barbiturates, antihistamines, narcotics, hypotensive agents or phenothiazines should be used with caution. Because procarbazine exhibits some monoamine oxidase inhibitory activity, sympathomimetic drugs, tricyclic antidepressant drugs (eg, amitriptyline HCI, imipramine HCI) and other drugs and foods with known high tyramine content, such as wine, yogurt, ripe cheese and bananas, should be avoided. A further phenomenon of toxicity common to many hydrazine derivatives is hemolysis and the appearance of Heinz-Ehrlich inclusion bodies in erythrocytes.

Antabuse-like Reaction: Ethyl alcohol should not be used since there may be an Antabuse (disulfiram)-like reaction.

Teratogenic Effects: Pregnancy Category D. Procarbazine hydrochloride can cause fetal harm when administered to a pregnant woman. While there are no adequate and well-controlled studies with procarbazine hydrochloride in pregnant women, there are case reports of malformations in the offspring of women who were exposed to procarbazine hydrochloride in combination with other antineoplastic agents during pregnancy. Matulane should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant. Procarbazine hydrochloride is teratogenic in the rat when given at doses approximately 4 to 13 times the maximum recommended human therapeutic dose of 6 mg/kg/day.

Impairment of Fertility: Azoospermia and antifertility effects associated with procarbazine administration in combination with other chemotherapeutic agents for treating Hodgkin's disease have been reported in human clinical studies. Since these patients received multicombination therapy, it is difficult to determine to what extent procarbazine hydrochloride alone was involved in the male germ-cell damage. The usual Segment I fertility/reproduction studies in laboratory animals have not been carried out with procarbazine hydrochloride. However, compounds which inhibit DNA, RNA and/or protein synthesis might be expected to have adverse effects on gametogenesis. Unscheduled DNA synthesis in the testis of rabbits and decreased fertility in male mice treated with procarbazine hydrochloride have been reported.

BILLING/CODING INFORMATION:

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

C71.0 – C71.9

Malignant neoplasm of brain

C72.9

Malignant neoplasm of central nervous system

C81.00 – C81.09

Nodular lymphocyte predominant Hodgkin lymphoma

C81.40 – C81.49

Lymphocyte-rich classical Hodgkin lymphoma

C81.10 – C81.19

Nodular sclerosis classical Hodgkin lymphoma

C81.20 – C81.29

Mixed cellularity classical Hodgkin lymphoma

C81.30 – C81.39

Lymphocyte depleted classical Hodgkin lymphoma

C81.90 – C81.99

Hodgkin lymphoma, unspecified

C83.80 – C83.89

Other non-follicular lymphoma

C83.10 – C83.19

Mantle cell lymphoma

C83.31 – C83.39

Diffuse large B-cell lymphoma

B20 with C83.31 – C83.39

Human immunodeficiency virus [HIV] disease with diffuse large B-cell lymphoma

B20 with C85.80 – C85.89

Human immunodeficiency virus [HIV] disease with other specified types of non-Hodgkin lymphoma

B20 with Z85.79

Human immunodeficiency virus [HIV] disease with personal history of other malignant neoplasms of lymphoid, hematopoietic and related tissues

C83.81

Other non-follicular lymphoma, lymph nodes of head, face, and neck

D43.2

Neoplasm of uncertain behavior of brain, unspecified

D43.4

Neoplasm of uncertain behavior of spinal cord

Z85.71

Personal history of Hodgkin lymphoma

Z85.79

Personal history of other malignant neoplasms of lymphoid, hematopoietic and related tissues

Z85.841

Personal history of malignant neoplasm of brain

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:

Autologous Bone Marrow and Stem Cell Transplantation, 02-38241-01
Bevacizumab (Avastin®) Injection, 09-J0000-66

Carboplatin (Paraplatin®) IV, 09-J0000-93

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

Gemcitabine (Gemzar®), 09-J0000-96

Granulocyte Colony Stimulating Factors, 09-J0000-62

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

Interferon alfa-n3 (Alferon N Injection®), 09-J0000-33

Interferons for Oncology Use, 09-J1000-37

Lenalidomide (Revlimid®), 09-J0000-80

Oprelvekin; Interleukin 11 (Neumega®), 09-J0000-63

Oral Antiemetic Agents, 09-J0000-55

Proton Beam Therapy, 04-77260-18

Rituximab (Rituxan®), 09-J0000-59

Topotecan HCl (Hycamtin®) Injection or Oral, 09-J1000-02

Vinorelbine Tartrate (Navelbine®) IV, 09-J1000-03

OTHER:

None

REFERENCES:

  1. Clinical Pharmacology. Copyright® 2011 Elsevier. Accessed10/27/11.
  2. DRUGDEX®. Accessed 10/27/11.
  3. Facts & Comparisons® E Answers. Accessed 10/27/11.
  4. Ingenix HCPCS Level II, Expert 2011.
  5. Ingenix ICD-9-CM for Physicians-Volumes 1 & 2, Expert 2011.
  6. Matulane® Prescribing Information. Revised February 2004
  7. NCCN Drugs & Biologics Compendium™. Accessed 10/27/11.

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 Review

05/11/14

Revision: Program Exceptions section updated.

11/01/15

Revision: ICD-9 Codes deleted.

Date Printed: June 23, 2017: 11:36 AM