Prior Auth Protocol

FDA Approved Indications:

Prophylaxis of invasive Aspergillus and Candida infections in patients 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
Oral Suspension: Treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis refractory to itraconazole and/or fluconazole

Health Net Approved Indications and Usage Guidelines:

Patient is not concurrently on any of the following medications: sirolimus, CYP3A4 substrates (e.g., pimozide, quinidine), HMG-CoA Reductase Inhibitors primarily metabolized through CYP3A4 (e.g., atorvastatin, simvastatin) or ergot alkaloids (e.g., ergotamine, dihydroergotamine).

AND

Prophylaxis of invasive Aspergillus and Candida infections

Authorization is requested by an infectious disease, oncologist, or HIV/AIDS specialist physician

OR

Discharge from hospital for continuation of therapy

Treatment of oropharyngeal candidiasis

Authorization is requested by an infectious disease, oncologist, or HIV/AIDS specialist physician

OR

Discharge from hospital for continuation of therapy

OR

Failure or clinically significant adverse effects to one of the following: clotrimazole troches, nystatin suspension, fluconazole

Treatment of allergic bronchopulmonary aspergillosis

Failure or clinically significant adverse events to itraconazole or voriconazole

Coverage is Not Authorized For:

Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.

General Information:

A variety of dosing regimens of 800 mg/day were given in two to four divided doses during clinical studies for treatment of certain refractory invasive fungal infections in immunocompromised patients refractory to or intolerant of conventional antifungal therapy.
Cases of elevated cyclosporine levels resulting in rare serious adverse events, including nephrotoxicity and leukoencephalopathy, and death were reported in clinical efficacy studies. Dose reduction and more frequent clinical monitoring of cyclosporine and tacrolimus should be performed when Noxafil therapy is initiated. Use of sirolimus is contraindicated due to the sirolimus blood levels increasing nine fold. Concomitant administration of posaconazole with CYP3A4 substrates such as simvastatin, pimozide and quinidine are also contraindicated due to increased plasma concentrations. Concomitant use of efavirenz, rifabutin, or phenytoin with posaconazole should be limited to patients for whom the potential benefit outweighs the risk. Increased monitoring of digoxin, glipizide, vinka alkaloids, calcium channel blockers, metaclopramide gastric acid suppressors with posaconazole and appropriate dose adjustments are recommended.
Liver function tests should be evaluated at the start of and during the course of therapy. Discontinuation of Noxafil should be considered if clinical signs and symptoms are consistent with development of liver disease.
Noxafil is indicated with a IIb rating by Micromedex as salvage therapy for the treatment of allergic bronchopulmonary aspergillosis. This use is also supported by The Sanford Guide to Antimicrobial Therapy.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
Clotrimazole troches	Oropharyngeal candidiasis 1 lozenge (10 mg) PO 5 times per day	5 lozenges (50 mg)/day
Fluconazole (Diflucan^R)	Prevention of candidasis-Bone Marrow Transplant 400 mg PO or IV once daily Vaginal candidiasis 150 mg PO as a single dose if uncomplicated, 150 mg PO every 72 hr for 3 doses if complicated Esophageal candidiasis 200 mg PO or IV on the first day, then 100 mg once daily Candida UTI and peritonitis 50-200 mg PO or IV per day Cryptococcal meningitis 400 mg PO or IV on the first day, then 200 mg once daily for 10 to 12 weeks after the cerebrospinal fluid becomes culture negative. For suppression of relapse of cryptococcal meningitis in patients with HIV infection use 200 mg PO once daily Systemic candidiasis (candidemia, disseminated candidiasis, pneumonia) Up to 400 mg PO or IV once daily Oropharyngeal candidiasis 200 mg PO on day 1 then 100 mg PO QD for 14 days	400 mg/day
Itraconazole (Sporanox^R)*	Blastomycosis or Histoplasmosis, disseminated 200 mg PO daily, up to 200 mg twice daily Aspergillosis invasive, refractory 200 mg PO 3 times daily for 3 days, then 200 mg PO daily Esophageal candidiasis 100-200 mg (10-20 mL) swish/swallow daily Oropharyngeal candidiasis 200 mg (20 mL) swish/swallow daily	600 mg/day Oral Solution: Safety & efficacy beyond 6 months is unknown Note: Capsules and oral solution are not interchangeable
Nystatin suspension	Oropharyngeal candidiasis 4 - 6 mL (400,000 to 600,000 units) PO 4 times a day	2.4 MU per day
Voriconazole (Vfend^R)*	Invasive Aspergillosis, Candidemia in other nonneutropenic patients and other deep tissue Candida infections, Scedopporiosis and Fusariosis 6 mg/kg IV every 12 hours for 2 doses then either 3 -4 mg/kg IV every 12 hours or 200 mg PO every 12 hours (> 40 kg) or 100 mg PO every 12 hours (< 40 kg) Esophageal candidiasis 200 mg PO every 12 hr (3 40 kg) or 100 mg every 12 hr (< 40 kg); treat for a minimum of 14 days and until 7 days after resolution of symptoms	800 mg/day

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Noxafil	Prophylaxis of invasive fungal infections: Oral Suspension: 200 mg (5 mL) PO three times a day Delayed Release Tablets: 300 mg PO twice a day on day 1 then 300 mg once daily Oropharyngeal candidiasis: Oral Suspension: Loading dose of 100 mg (2.5 mL) PO twice a day on the first day, then 100 mg (2.5 mL) daily Oropharyngeal candidiasis refractory to itraconazole and/or fluconazole: Oral Suspension: 400 mg (10 mL) PO twice a day Treatment of allergic bronchopulmonary aspergillosis: Oral Suspension: 200 mg (5 mL) PO four times daily until stabilization of disease then 400 mg (10 mL) twice daily thereafter	Prophylaxis of invasive fungal infections Length of Benefit Oropharyngeal Candidiasis 14 days Oropharyngeal Candidiasis refractory to itraconazole and/or fluconazole Length of Benefit Treatment of non-allergic bronchopulmonary aspergillosis Length of Benefit

Product Availability:

Noxafil 40 mg/ml oral suspension, 105 ml of oral suspension in a 123 ml bottle (glass amber type IV) with a measuring spoon (polystyrene) with 2 graduations: 2.5 ml and 5 ml
Noxafil IV solution: 300mg/16.7 ml (18 mg/ml)

Delayed Release Capsules 100 mg

References:

1. Noxafil [Prescribing Information] Whitehouse Station, NJ: Merck and Company, Inc; November 2015.
2. Micromedex^R Healthcare Series [Internet database]. Greenwood village, Colo: Thomson Healthcare. Updated periodically. Accessed January 8, 2016.
3. Keating G. Posaconazole. Drugs. 2005;65:1553-1567.
4. Sporanox [Prescribing Information] Olen, Belgium: Janssen Pharmaceutica; April 2015.
5. Vfend [Prescribing Information] New York, NY: Pfizer; February 2015.
6. Diflucan [Prescribing Information]. New York, NY: Pfizer; October 2014.
7. Sanford JP. The Sanford Guide to Antimicrobial Therapy. 40th edition. Sperryville, VA: Antimicrobial Therapy, Inc; 2011.
8. Restrepo A, Tobon A, Clark B et al. Salvage treatment of histoplasmosis with posaconazole. J Infect 2007; 54:319-327.
9. Ulmann AJ, Cornely A, Burchardt A, et al. Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection. Antimicrob Agents Chemother 2006; 50:658-666.