Noxafil/Vfend

POLICY NUMBER

L.5.01.455

Noxafil (posaconazole)

Vfend (voriconazole)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Fungal infections can be classified into different categories based on either the site of infection (mucocutaneous/local, systemic) or etiology (primary, opportunistic). Fungal pathogens may be a mold, yeast, or dimorphic fungus. Local infections typically occur on the skin, mouth, or vagina and are not usually severe while systemic fungal infections are more severe and can result in death.

Noxafil (posaconazole) is an azole antifungal that blocks the synthesis of ergosterol, a key component of the fungal cell membrane, through the inhibition of cytochrome P-450 dependent enzyme lanosterol 14α-demethylase responsible for the conversion of lanosterol to ergosterol in the fungal cell membrane. This results in an accumulation of methylated sterol precursors and a depletion of ergosterol within the cell membrane, thus weakening the structure and function of the fungal cell membrane. Noxafil (posaconazole) is indicated for the treatment of invasive aspergillosis in patients 13 years of age and older, for the prophylaxis of invasive Apergillus and Candida infections in patients at high risk of developing these infections due to being severely immunocompromised (such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) or those with hematologic malignancies with prolonged neutropenia from chemotherapy) for patients 2 years of age and older, and for the treatment of oropharyngeal candidiasis (OPC), including OPC refractory (rOPC) to itraconazole and/or fluconazole in patients 13 years of age and older.

Vfend (voriconazole) is also an azole antifungal. The primary mode of action is the inhibition of fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylation, an essential step in fungal ergosterol biosynthesis. Vfend (voriconazole) is indicated for the treatments of patients 2 and older with invasive aspergillosis, candidemia in non-neutropenic patients and other deep tissue Candida infections, esophageal candidiasis, and serious infections caused by Scedosporium apiospermum and Fusarium species, including Fusarium solani, in patients intolerant or refractory to other therapy.

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements.

  Initial Evaluation

The requested agent may be considered medically necessary when ALL of the following criteria are met:

1. ONE of the following:

   1. The individual is 2 years of age or older, and the request is for posaconazole injection or voriconazole;

   2. The individual is 2 years of age or older, weighs >40 kg, and the request is for posaconazole delayed-release tablets; OR

   3. The individual is 13 years of age or older, and the request is for posaconzole oral suspension;

2. ONE of the following:

   1. The request is for posaconazole and ONE of the following:

      1. The individual has a diagnosis of invasive Aspergillosis;

      2. The requested agent is prescribed for prophylaxis of invasive Aspergillus infection (aspergillosis) or invasive Candida infection (candidiasis) for a severely immunocompromised (e.g., post-HSCT with GVHD, hematologic malignancy with prolonged neutropenia, solid organ transplant);

      3. The individual has a diagnosis of oropharyngeal candidiasis and ONE of the following:

         1. The individual has tried and had an inadequate response to fluconazole or an alternative antifungal medication; OR

         2. The individual has an intolerance, hypersensitivity, or FDA-labeled contraindications to ALL alternative antifungal medications; OR

      4. The use of the requested agent is for an indication that is supported by compendia (e.g., NCCN Compendium™ level of evidence 1 or 2A, Infectious Disease Society of America (IDSA) Guidelines, AHFS, DrugDex level of evidence 1 or 2A, ); OR

   2. The request is for voriconazole and ONE of the following:

      1.  The individual has a diagnosis of invasive aspergillosis;

      2. The individual has a serious infection caused by Scedosporium apiospermum or Fusarium species;

      3. The individual has a documented diagnosis of esophageal candidiasis or candidemia without neutropenia and ONE of the following:

         1. The individual has tried and had an inadequate response to fluconazole or an alternative antifungal medication; OR

         2. The individual has an intolerance, hypersensitivity, or FDA-labeled contraindications to ALL alternative antifungal medications; OR

      4. The use of the requested agent is for an indication that is supported by compendia (e.g., NCCN Compendium™ level of evidence 1 or 2A, Infectious Disease Society of America (IDSA) Guidelines, AHFS, DrugDex level of evidence 1 or 2A);

3. The prescriber is an infectious disease specialist or has consulted with an infectious disease specialist;

4. The individual does NOT have any FDA labeled contraindication(s) to therapy with the requested agent; AND

5. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Length of Approval:

• Esophageal candidiasis: 1 month

• All other indications: 6 months

Renewal Evaluation

The requested agent may be approved for RENEWAL when ALL of the following criteria are met:

1. The individual has previously been approved for therapy with the requested agent through the BCBSMS PA process;

2. ONE of the following:

   1. The requested agent is being prescribed for prophylaxis of invasive Aspergillus or Candida, AND the individual continues to be severely immunocompromised (i.e., neutropenia, ongoing graft versus host disease, long term use of high dose corticosteroids [>1 mg/kg/day of prednisone or equivalent]); OR

   2. The requested agent is being prescribed for treatment of active infection, and the individual has continued indicators of active disease (i.e., continued radiologic findings, positive cultures, positive serum galactomannan assay for Aspergillus);

3. The individual does NOT have any FDA labeled contraindication(s) to therapy with the requested agent; AND

4. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Length of Approval:

• Esophageal candidiasis: 1 month

• All other indications: 6 months

Services related to delivery and/or administration of a medication which have not been approved through the BCBSMS PA review process will be considered not medically necessary.

POLICY EXCEPTIONS

State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

BCBSMS may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

Medication Failure

Medication failure is defined as disease progression at generally accepted doses as appropriate for the disease state being treated. Dosages below the recommended dose for the specific condition being treated and/or experience of common side effects of medication will not be considered medication failure or lack of response for the purpose of this review.

BCBSMS determines patient medication trials and adherence by a review of pharmacy claims data over the preceding twelve months. Additional information may be requested on a case-by-case basis to allow for proper review. If member is new to BCBSMS and pharmacy records are needed to confirm medication trials and adherence, it is the responsibility of the member and/or requesting provider to obtain said records and submit them to BCBSMS upon request. Medical records from the provider that list previously prescribed medications will not be sufficient to show medication trials or adherence.

POLICY HISTORY

01/01/2014: New policy added.

07/31/2015: Code Reference section updated for ICD-10.

05/27/2016: Policy number L.5.01.455 added. Policy Guidelines updated to add medically necessary and investigative definitions.

08/09/2016: Approved by Pharmacy & Therapeutics (P&T) Committee.

08/15/2017: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

11/01/2018: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy section updated to state that prior authorization is required. The use of samples by a Member will not be considered current or stable therapy for purposes of Medical Policy review. Initial evaluation criteria for Vfend (voriconazole) updated to add the following: "the requested agent is being prescribed for prophylaxis of invasive Aspergillus or Candida." Length of approval for oropharyngeal and esophageal candidiasis separated into two statements. Sources updated.

08/04/2020: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding Noxafil and Vfend. Revised medically necessary criteria for Noxafil and Vfend. Updated renewal evaluation criteria. Policy Guidelines updated to define medication failure and to add information regarding BCBSMS determination of patient medication trials and adherence. Sources updated.

07/13/2021: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy description updated. Policy section updated to revise initial and renewal evaluation criteria. Added statement that services related to delivery and/or administration of a medication which have not been approved through the BCBSMS PA review process will be considered not medically necessary. Policy Exceptions updated. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity." Added information regarding BCBSMS request for medical records, revised medication failure definition, and removed investigative definition. Sources updated.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

06/03/2025: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding indications for Noxafil (posaconazole). Policy statement revised to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Medically Necessary criteria updated to remove the brand names, Noxafil and Vfend. Medically necessary criteria updated regarding age requirements and requests by drug. Renewal criteria updated to add that the requested agent is being prescribed for treatment of active infection. Policy Guidelines updated regarding medication failure. Sources updated.

01/01/2026: Code Reference section updated to add new HCPCS code J1837.

SOURCE(S)

1. Kauffman CA, Vazquez JA. Oropharyngeal candidiasis in adults. In: UpToDate, Connor RF (Ed), Wolters Kluwer. Accessed on April 3, 2025.

   https://www.uptodate.com/contents/oropharyngeal-candidiasis-in-adults

2. Noxafil prescribing information. Merck Sharp & Dohme LLC. October 2024. Last accessed March 2025.

3. Patterson TF, Thompson GR III, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 63:e1-e60.

   https://doi.org/10.1093/cid/ciw326

4. Vfend prescribing information. Roerig. March 2025. Last accessed March 2025. 

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Medically Necessary Codes

CPT copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.