Who to prophylax
"Chemotherapy-induced neutropenia places cancer patients at increased risk for infection … Diagnosing infection in a patient with neutropenia is complicated by the fact that many of the usual signs and symptoms of infection are muted or absent because of the neutropenia." 16
Neutropenia: A major risk factor for IFI in hematologic cancer24,27
- IFI risk is related to the severity and duration of neutropenia—frequency and severity of infection is inversely proportional to neutrophil count24
- Decreased integrity of host defense mechanisms places patients with hematologic malignancies at high risk of life-threatening infections24
- Risk of IFI is substantially higher in patients with hematologic malignancies than in those with solid tumors5,15
- Up to 25% incidence of IFI in patients with leukemia15
- 50% mortality in neutropenic patients with aspergillosis14
- Candida and Aspergillus spp. are the most common fungal pathogens isolated from neutropenic patients, representing 90% of all IFIs in this group15
- Patients with hematologic malignancies, including AML,* are at high risk of invasive aspergillosis3,21,29
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 complications
- AML and MDS† patients with neutropenia24
- Patients with AML or MDS at high risk for invasive aspergillosis36
* Acute myelogenous leukemia.
† Myelodysplastic syndrome.
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%).
