Pharmacy Prior Authorization Criteria

Azole Antifungals - PA, NF

Indications for Prior Authorization

Cresemba (isavuconazonium sulfate) capsules

• For diagnosis of Invasive Aspergillosis and Invasive Mucormycosis
  Indicated for adult and pediatric patients 6 years of age and older who weight 16 kilograms (kg) and greater for the treatment of invasive mucormycosis and invasive aspergillosis. Specimens for fungal culture and other relevant laboratory studies (including histopathology) to isolate and identify causative organism(s) should be obtained prior to initiating antifungal therapy. Therapy may be instituted before the results of the cultures and other laboratory studies are known. However, once these results become available, antifungal therapy should be adjusted accordingly.

Noxafil (posaconazole) tablets

• For diagnosis of Prophylaxis of Aspergillus infection
  Indicated for prophylaxis of invasive Aspergillus infections in adult and pediatric patients 2 years of age and older who weigh greater than 40 kg, who are at high risk of developing these infections due to being severely immunocompromised, such as HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy.

• For diagnosis of Prophylaxis of Candida infection
  Indicated for prophylaxis of invasive Candida infections in adult and pediatric patients 2 years of age and older who weigh greater than 40kg, who are at high risk of developing these infections due to being severely immunocompromised, such as HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy.

• For diagnosis of Treatment of Invasive Aspergillosis
  Indicated for the treatment of invasive aspergillosis in adults and pediatric patients 13 years of age and older.

Noxafil (posaconazole) oral suspension

• For diagnosis of Prophylaxis of Aspergillus infection
  Indicated for prophylaxis of invasive Aspergillus infections in patients 13 years of age and older, who are at high risk of developing these infections due to being severely immunocompromised, such as HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy.

• For diagnosis of Prophylaxis of Candida infection
  Indicated for prophylaxis of invasive Candida infections in patients 13 years of age and older, who are at high risk of developing these infections due to being severely immunocompromised, such as HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy.

• For diagnosis of Oropharyngeal candidiasis
  Indicated for treatment of oropharyngeal candidiasis (OPC), including OPC refractory (rOPC) to itraconazole and/or fluconazole in adults and pediatric patients 13 years of age and older.

Noxafil PowderMix (posaconazole) for delayed-release oral suspension

• For diagnosis of Prophylaxis of Invasive Aspergillus and Candida Infections
  Indicated for the prophylaxis of invasive Aspergillus and Candida infections in pediatric patients 2 years of age and older who weigh 40 kg or less, who are 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.

Sporanox (itraconazole) capsules

• For diagnosis of Blastomycosis
  Indicated for the treatment of the following fungal infection in immunocompromised and non-immunocompromised patients:

  Blastomycosis, pulmonary and extrapulmonary

• For diagnosis of Histoplasmosis
  Indicated for the treatment of the following fungal infection in immunocompromised and non-immunocompromised patients:

  Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, nonmeningeal histoplasmosis

• For diagnosis of Aspergillosis
  Indicated for the treatment of the following fungal infection in immunocompromised and non-immunocompromised patients:

  Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or refractory to amphotericin B therapy

• For diagnosis of Onychomycosis of the toenail
  Indicated for the treatment of the following fungal infection in non-immunocompromised patients:

  Onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (Tinea unguium)

• For diagnosis of Onychomycosis of the fingernail
  Indicated for the treatment of the following fungal infection in non-immunocompromised patients: Onychomycosis of the fingernail due to dermatophytes (Tinea unguium)

Sporanox Pulse Pak (itraconazole)

• For diagnosis of Onychomycosis of the fingernail
  Indicated for the treatment of the following fungal infection in non-immunocompromised patients: Onychomycosis of the fingernail due to dermatophytes (Tinea unguium)

Sporanox (itraconazole) oral solution

• For diagnosis of Oropharyngeal and esophageal candidiasis
  Indicated for the treatment of oropharyngeal and esophageal candidiasis.

Tolsura (itraconazole) capsules

• For diagnosis of Blastomycosis
  Indicated for the treatment of the following fungal infection in immunocompromised and non-immunocompromised patients: Blastomycosis, pulmonary and extrapulmonary.

• For diagnosis of Histoplasmosis
  Indicated for the treatment of the following fungal infection in immunocompromised and non-immunocompromised patients: Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, nonmeningeal histoplasmosis.

• For diagnosis of Aspergillosis
  Indicated for the treatment of the following fungal infection in immunocompromised and non-immunocompromised patients: Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or refractory to amphotericin B therapy.

Vfend (voriconazole) oral suspension, Vfend (voriconazole) tablets

• For diagnosis of Invasive Aspergillosis
  Indicated in adults and pediatric patients (2 years of age and older) for the treatment of invasive aspergillosis (IA). In clinical trials, the majority of isolates recovered were Aspergillus fumigatus. There was a small number of cases of culture-proven disease due to species of Aspergillus other than A. fumigatus.

• For diagnosis of Candidemia in Non-neutropenic Patients and Other Deep Tissue Candida Infections
  Indicated in adults and pediatric patients (2 years of age and older) for the treatment of candidemia in non-neutropenic patients and the following Candida infections: disseminated infections in skin and infections in abdomen, kidney, bladder wall, and wounds.

• For diagnosis of Esophageal Candidiasis
  Indicated in adults and pediatric patients (2 years of age and older) for the treatment of esophageal candidiasis (EC) in adults and pediatric patients 2 years of age and older.

• For diagnosis of Scedosporiosis and Fusariosis
  Indicated for the treatment of serious fungal infections caused by Scedosporium apiospermum (asexual form of Pseudallescheria boydii) and Fusarium spp. including Fusarium solani, in adults and pediatric patients (2 years of age and older) intolerant of, or refractory to, other therapy.

Criteria

Cresemba oral capsule

Prior Authorization

Length of Approval: 6 Months [17, B-D]

• Diagnosis of one of the following fungal infections: [17]
• Invasive aspergillosis
• Invasive mucormycosis
AND
• Both of the following:
• Patient is 6 years of age or older
• Patient weighs 16 kilograms or greater

Brand Sporanox capsules or generic itraconazole capsules

Prior Authorization

Length of Approval: 6 months [5, 10-12, B-D]
For diagnosis of Systemic and topical fungal infections

• Diagnosis of a systemic fungal infection (e.g., aspergillosis, histoplasmosis, blastomycosis)
OR
• All of the following:
• One of the following diagnoses:
• Tinea corporis (ring worm)
• Tinea cruris (jock itch)
• Tinea pedis (athlete's foot)
• Tinea capitis (scalp ringworm)
• Pityriasus versicolor
AND
• One of the following:
• The tinea infection is resistant to topical antifungal treatment
OR
• Trial and failure, contraindication, or intolerance to oral terbinafine [3]

Brand Sporanox capsules, generic itraconazole capsules, or Sporanox Pulse Pak

Prior Authorization

Length of Approval: 1 Month [A]
For diagnosis of Fingernail Onychomycosis

• Diagnosis of fingernail onychomycosis as confirmed by one of the following:
• Positive potassium hydroxide (KOH) preparation
• Fungal culture
• Nail biopsy
AND
• The patient’s condition is causing debility or a disruption in their activities of daily living (e.g., limitations to manual dexterity, wearing shoes, or appropriately manicuring nails) [4]
AND
• Trial and failure (of a minimum 6-week supply), contraindication, or intolerance to oral terbinafine

Brand Sporanox capsules or generic itraconazole capsules

Prior Authorization

Length of Approval: 3 Month [A]
For diagnosis of Toenail Onychomycosis

• Diagnosis of toenail onychomycosis as confirmed by one of the following:
• Positive potassium hydroxide (KOH) preparation
• Fungal culture
• Nail biopsy
AND
• The patient’s condition is causing debility or a disruption in their activities of daily living (e.g., limitations to manual dexterity, walking, standing, wearing shoes, or appropriately manicuring nails) [4]
AND
• Trial and failure (of a minimum 12-week supply), contraindication, or intolerance to oral terbinafine

Brand Sporanox oral solution or generic itraconazole oral solution

Prior Authorization

Length of Approval: 1 month [E, F]
For diagnosis of Candidiasis (esophageal or oropharyngeal)

• One of the following:
• Diagnosis of esophageal candidiasis
OR
• Diagnosis of oropharyngeal candidiasis (OPC)
AND
• One of the following:
• Trial and failure, contraindication, or intolerance to fluconazole
• Susceptibility results demonstrate resistance to fluconazole

Tolsura

Prior Authorization

Length of Approval: 6 months [5, 10-12, B-D]

• Diagnosis of one of the following fungal infections:
• Blastomycosis
• Histoplasmosis
• Aspergillosis
AND
• Trial and failure or intolerance to generic itraconazole capsules

Brand Noxafil oral suspension or generic posaconazole oral solution

Prior Authorization

Length of Approval: 1 Month [E]
For diagnosis of Oropharyngeal Candidiasis

• Diagnosis of oropharyngeal candidiasis (OPC)
AND
• Patient is 13 years of age and older
AND
• One of the following:
• Trial and failure, contraindication, or intolerance to fluconazole
• Susceptibility results demonstrate resistance to fluconazole

Brand Noxafil oral suspension or generic posaconazole oral solution

Non Formulary

Length of Approval: 1 Month [E]
For diagnosis of Oropharyngeal Candidiasis

• Diagnosis of oropharyngeal candidiasis (OPC)
AND
• Patient is 13 years of age and older
AND
• Submission of medical records (e.g., chart notes) or paid claims documenting one of the following:
• Trial and failure, contraindication, or intolerance to fluconazole
• Susceptibility results demonstrate resistance to fluconazole

Brand Noxafil oral tablet, generic posaconazole oral tablet, Brand Noxafil oral suspension, generic posaconazole oral suspension, Noxafil PowderMix

Prior Authorization

Length of Approval: 6 Months [B-D]
For diagnosis of Prophylaxis of systemic fungal infections

• Used as prophylaxis of invasive fungal infections caused by one of the following:
• Aspergillus
• Candida
AND
• One of the following:
• For Noxafil (posaconazole) oral tablet, both of the following:
• Patient is 2 years of age and older
• Patient weighs greater than 40 kg
OR
• For Noxafil oral suspension, patient is 13 years of age and older
OR
• For Noxafil PowderMix, both of the following:
• Patient is 2 years of age and older
• Patient weighs 40 kg or less
AND
• One of the following:
• Patient is at high risk of infections due to severe immunosuppression from one of the following conditions:
• Hematopoietic stem cell transplant (HSCT) with graft-versus-host disease (GVHD)
• Hematologic malignancies with prolonged neutropenia from chemotherapy
OR
• Patient has a prior fungal infection requiring secondary prophylaxis [15, G]

Brand Noxafil oral tablet, generic posaconazole oral tablet, Brand Noxafil oral suspension, generic posaconazole oral suspension, Noxafil PowderMix

Non Formulary

Length of Approval: 6 Months [B-D]
For diagnosis of Prophylaxis of systemic fungal infections

• Used as prophylaxis of invasive fungal infections caused by one of the following:
• Aspergillus
• Candida
AND
• One of the following:
• For Noxafil (posaconazole) oral tablet, both of the following:
• Patient is 2 years of age and older
• Patient weighs greater than 40kg
OR
• For Noxafil oral suspension, patient is 13 years of age and older
OR
• For Noxafil PowderMix, both of the following:
• Patient is 2 years of age and older
• Patient weighs 40 kg or less
AND
• Submission of medical records (e.g., chart notes) documenting one of the following:
• Patient is at high risk of infections due to severe immunosuppression from one of the following conditions:
• Hematopoietic stem cell transplant (HSCT) with graft-versus-host disease (GVHD)
• Hematologic malignancies with prolonged neutropenia from chemotherapy
OR
• Patient has a prior fungal infection requiring secondary prophylaxis [15, G]

Brand Noxafil oral tablet, generic posaconazole oral tablet

Prior Authorization

Length of Approval: 3 Month(s)
For diagnosis of Treatment of systemic fungal infections

• Diagnosis of invasive aspergillosis
AND
• Patient is 13 years of age and older

Brand Noxafil oral tablet, generic posaconazole oral tablet

Non Formulary

Length of Approval: 3 Month(s)
For diagnosis of Treatment of systemic fungal infections

• Diagnosis of invasive aspergillosis
AND
• Patient is 13 years of age and older

Brand Vfend oral tablet, generic voriconazole oral tablet, Brand Vfend oral suspension, generic voriconazole oral suspension

Prior Authorization

Length of Approval: 6 Months [16, B-D]
For diagnosis of Invasive Aspergillosis

• Diagnosis of invasive aspergillosis
AND
• Patient is 2 years of age and older

Brand Vfend oral tablet, generic voriconazole oral tablet, Brand Vfend oral suspension, generic voriconazole oral suspension

Prior Authorization

Length of Approval: 6 Months [16, B-D]
For diagnosis of Serious Fungal Infections

• Diagnosis of serious fungal infections (e.g., Scedosporium apiospermum, Fusarium species including Fusarium solani)
AND
• Patient is 2 years of age and older
AND
• Patient is intolerant of, or refractory to, other therapy (e.g., amphotericin B)

Brand Vfend oral tablet, generic voriconazole oral tablet, Brand Vfend oral suspension, generic voriconazole oral suspension

Prior Authorization

Length of Approval: 1 Month [H, 16]
For diagnosis of Candidemia in non-neutropenic patients and other deep tissue Candida infections

• Diagnosis of one of the following:
• Candidemia
• Deep tissue Candida infection (e.g., disseminated in skin, infection in abdomen, kidney, bladder wall, and wounds)
AND
• Patient is non-neutropenic
AND
• Patient is 2 years of age and older
AND
• One of the following:
• Trial and failure, contraindication or intolerance to fluconazole [I]
• Susceptibility results demonstrate resistance to fluconazole [K]

Brand Vfend oral tablet, generic voriconazole oral tablet, Brand Vfend oral suspension, generic voriconazole oral suspension

Prior Authorization

Length of Approval: 1 Month [H, 16]
For diagnosis of Esophageal Candidiasis

• Diagnosis of esophageal candidiasis
AND
• Patient is 2 years of age and older
AND
• One of the following:
• Trial and failure, contraindication, or intolerance to fluconazole
• Susceptibility results demonstrate resistance to fluconazole

P & T Revisions

2024-01-17, 2023-09-29, 2023-08-22, 2023-01-24, 2022-12-09, 2022-07-05, 2022-01-21, 2021-10-26, 2021-08-03, 2021-05-20, 2021-01-28, 2021-01-20, 2019-12-17, 2019-10-28

References

1. Sporanox Capsules Prescribing Information. Janssen Pharmaceuticals, Inc.; Titusville, NJ. November 2023.
2. Sporanox Oral Solution Prescribing Information. Janssen Pharmaceuticals, Inc.; Titusville, NJ. November 2023.
3. Ely J, Rosenfeld S, Stone M. Diagnosis and Management of Tinea Infections. Aafp.org. https://www.aafp.org/afp/2014/1115/p702.html. Published 2014. Accessed October 28, 2019
4. Gupta A, Mays R. The Impact of Onychomycosis on Quality of Life: A Systematic Review of the Available Literature. Skin Appendage Disord. 2018;4(4):208-216. doi:10.1159/000485632
5. Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1-50.
6. Stevens DA, Kan VL, Judson MA, et al. Practice Guidelines for Diseases Caused by Aspergillus. Clin Infect Dis. 2000;30:696-709.
7. McEvoy GK. AHFS Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc; 2005.
8. Sigurgeirsson B, Olafsson JH, Steinsson JP, et al. Long-term effectiveness of treatment with terbinafine vs. itraconazole in onychomycosis: a 5-year blinded prospective follow-up study. Arch Dermatol. 2002;138:353-7.
9. Roberts DT, Taylor WD, Boyle J. Guidelines for treatment of onychomycosis. Br J Dermatol. 2003;148:402-410.
10. Chapman SW, Dismukes WE, Proia LA, et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:1801-1812.
11. Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45:807-825.
12. Patterson TF, Thompson GR, 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(4):e1-60.
13. Tolsura Prescribing Information. Mayne Pharma; Greenville, NC. July 2023.
14. Noxafil Prescribing Information. Merck Sharp & Dohme Corp.; Whitehouse Station, NJ. October 2023.
15. Per Clinical Consultation with an Infectious Disease Specialist. January 24, 2014.
16. Voriconazole Tablet Prescribing Information. Ajanta Pharma Limited.; Bridgewater, NJ. November 2022.
17. Cresemba Prescribing Information. Astellas Pharma US., Inc. Northbrook, IL. December 2023.
18. Vfend Prescribing Information.Roerig. New York, NY. November 2022.

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End Notes

1. Fingernail infections are usually reevaluated 18 weeks or longer after completion of therapy. Toenail infections are usually reevaluated 6-9 months after completion of therapy. [5] Indeed, considering that toenails can take 12 to 18 months to grow out, many clinicians consider that 1 year is too short to assess clinical effectiveness. [6] Reports of long-term follow-up of treated patients have recently been presented, suggesting that positive mycology at 12 and 24 weeks after commencement of therapy are poor prognostic signs and may indicate a need for retreatment or for a change of drug. [8]
2. The optimal duration of therapy for aspergillosis has not been defined. Most clinicians treat infections (pulmonary) until resolution or stabilization of clinical and radiographic manifestations. The IDSA recommends a minimal treatment period of 6 – 12 weeks in immunocompetent patients for invasive conditions. [11]
3. According to the IDSA guidelines for aspergillosis, duration of therapy for most conditions for aspergillosis has not been optimally defined. Most experts attempt to treat pulmonary infection until resolution or stabilization of all clinical and radiographic manifestations. Other factors include site of infection (e.g., osteomyelitis), level of immunosuppression, and extent of disease. Reversal of immunosuppression, if feasible, is important for a favorable outcome for invasive aspergillosis.” [11]
4. According to the IDSA guidelines for the treatment of aspergillosis, both Amphotericin B and itraconazole are listed as second line treatment options for the treatment of invasive disease. [11]
5. For fluconazole-refractory OPC, either itraconazole or posaconazole for up to 28 days is recommended. For fluconazole-refractory esophageal candidiasis, itraconazole or voriconazole for 14 to 21 days is recommended. [3, 5]
6. Patients may be expected to relapse shortly after discontinuing therapy with Sporanox oral solution. Limited data on the safety of long-term use (> 6 months) of Sporanox Oral Solution are available at this time. [2]
7. NCCN recommends secondary prophylaxis with an appropriate antifungal agent in patients with prior chronic disseminated candidiasis or with invasive filamentous fungal infection during subsequent cycles of chemotherapy or HSCT. In patients with invasive aspergillosis before HSCT, antifungal therapy for more than a month and resolution of radiologic abnormalities correlate with a lower likelihood of post-transplant recurrence of infection. Secondary prophylaxis with a mold-active agent is advised for the entire period of immunosuppression. Secondary prophylaxis is generally administered for the duration of immunosuppression. Per recommendation from an infectious disease specialist, posaconazole is used for secondary prophylaxis of prior fungal infections. [15]
8. Voriconazole prescribing information states that for candidemia in non-neutropenic patients and other deep tissue Candida infections, patients should be treated for at least 14 days following resolution of symptoms or following last positive culture, whichever is long. For esophageal candidiasis, patients should be treated for a minimum of 14 days and for at least 7 days following resolution of symptoms. [16]
9. According to the 2016 IDSA guideline for candidemia in nonneutropenic patients, fluconazole, intravenous or oral, is an acceptable alternative to an echinocandin (e.g., caspofungin, micafungin, anidulafungin) in patients who are not critically ill and who are considered unlikely to have fluconazole-resistant Candida species. Voriconazole is effective for candidemia, however, offers little advantage over fluconazole as the initial therapy. [5]
10. According to the 2016 IDSA guideline for the treatment of esophageal candidiasis, oral fluconazole 200-400 mg for 14 to 21 days is strongly recommended (high-quality evidence). Intravenous fluconazole may be used in patients who cannot tolerate oral therapy. For fluconazole-refractory disease, voriconazole either intravenous or oral is recommended. [5]
11. Of the Candida species, C. krusei and C. glabrata are the two species with higher likelihood of fluconazole-resistance for serious candida infections due to widespread azole treatment. In these cases, voriconazole may be used as oral therapy in patients with infections due to C. krusei or fluconazole-resistant, voriconazole-susceptible C. glabrata infections. [5]

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Revision History

• 2024-01-17: 2024 UM Annual Review. Updated age criteria for Cresemba based on expanded indication. Addition of posaconazole oral suspension to criteria. Background updates
• 2023-09-29: Addition of Cresemba 74.5mg capsules
• 2023-08-22: GPI clean up
• 2023-01-24: 2023 UM Annual Review. Updated NF criteria to require submission of medical records to align with NF SOP.
• 2022-12-09: Added new product, Noxafil Powdermix to guideline.
• 2022-07-05: Addition of NF criteria for Noxafil
• 2022-01-21: 2022 UM Annual Review.
• 2021-10-26: Added new PA criteria for Brand Vfend/generic voriconazole and Cresemba oral formulations, to be effective 1/1/2022.
• 2021-08-03: Added criteria for new Noxafil tablet indication.
• 2021-05-20: Addition of EHB formulary to guideline, no changes to criteria
• 2021-01-28: Added new PA criteria for Noxafil (posaconazole) oral formulations.
• 2021-01-20: 2021 UM Annual Review.
• 2019-12-17: 2020 UM Annual Review. Removed Onmel criteria and product from list as RxClaims obsolete date is 02/21/2020. Updated references.
• 2019-10-28: Updated criteria for Nov 2019 P&T - SL - 10.28.19

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