Who to prophylax
"The more dangerous the infection, the greater the need for effective prophylaxis or early-intervention strategies." 29
GVHD*: A major risk factor for IFI in allogeneic HSCT† patients24,27
- IFI risk linked to severity of GVHD and requirement for potent immunosuppressive regimens24
- Corticosteroid use and GVHD are independent risk factors for IFI1
- Longer interval of susceptibility for GVHD due to use of increasingly potent immunosuppressive regimens and greater use of mismatched donor grafts39
- Increased incidence of aspergillosis associated with GVHD and its treatment27
- Aspergillosis is an increasing cause of death in HSCT patients
- 10% to 14% cumulative incidence of aspergillosis in first year after allogeneic HSCT8,19
- 32% of allogeneic HSCT patients with aspergillosis experienced a successful outcome with voriconazole for primary treatment12
- 56% mortality in HSCT patients with aspergillosis34
- GVHD and its treatment increase incidence of aspergillosis
- Potent immunosuppressive regimens and severity of GVHD both increase risk of IFIs24,27
Current guidelines recommend NOXAFIL® antifungal prophylaxis for high-risk cancer patients24,36
- High-risk patients: those with high overall infection risk, and patients with febrile neutropenia at high risk of serious complications24
- Includes patients with GVHD receiving high-dose steroids until resolution of GVHD24
- Includes HSCT recipients with GVHD at high risk for invasive aspergillosis36
* Graft-Versus-Host Disease.
† Hematopoietic stem cell transplant.
Important Safety Information
NOXAFIL® has been shown to interact with several medications, including drugs that suppress the immune system, and these reactions may be serious. The product label should be consulted when other drugs are prescribed with NOXAFIL®.
Coadministration with sirolimus or ergot alkaloids is contraindicated. Coadministration with the CYP3A4 substrates terfenadine, astemizole, cisapride, pimozide, halofantrine, or quinidine, is also contraindicated since this may result in increased plasma concentrations of these medicinal products, leading to QTc prolongation and rare occurrences of torsades de pointes.
Serious and rare fatal toxicity from cyclosporine has occurred when taken in combination with NOXAFIL® and therefore reduction of the dose of drugs like cyclosporine or tacrolimus and frequent monitoring of drug levels of these medications are necessary when taking them in combination with NOXAFIL®.
In clinical trials, there were infrequent cases of hepatic reactions (eg, mild to moderate elevations in ALT, AST, alkaline phosphatase, total bilirubin, and/or clinical hepatitis). Rarely, more severe hepatic reactions including cholestasis or hepatic failure including fatalities were reported in patients with serious underlying medical conditions (eg, hematologic malignancies) during treatment with posaconazole. Liver function tests should be monitored at the start of and during the course of therapy. Discontinuation of NOXAFIL® must be considered in patients who experience symptoms consistent with liver disease that may be attributable to NOXAFIL®.
The safety and effectiveness of NOXAFIL® in patients below the age of 13 years old have not been established.
The most common treatment-related serious adverse events (1% each) in the combined prophylaxis studies were bilirubinemia, increased hepatic enzymes, hepatocellular damage, nausea, and vomiting.
In the pooled prophylaxis safety analysis, fever, headache, anemia, diarrhea, nausea, vomiting, abdominal pain, hypokalemia, and thrombocytopenia were frequently reported treatment-emergent adverse events.
In clinical studies of OPC and refractory OPC, adverse events were reported more frequently in the pool of patients with refractory OPC. The most commonly reported serious adverse events in refractory OPC patients included fever (13%) and neutropenia (10%).
