Safety
Immunosuppressed HSCT patients with GVHD need protection25,33
Treatment-related adverse events (≥2%) in HSCT patients with GVHD25,33
| NOXAFIL® (n=301) n (%) |
Fluconazole (n=299) n (%) |
|
| Subjects reporting any adverse event | 107 (36) | 115 (38) |
| Body as a whole—general disorders | ||
| Anorexia | 3 (1) | 7 (2) |
| Dizziness | 4 (1) | 5 (2) |
| Drug level altered | 5 (2) | 2 (1) |
| Fatigue | 4 (1) | 6 (2) |
| Headache | 3 (1) | 8 (3) |
| Weakness | 3 (1) | 5 (2) |
| Cardiovascular disorders, general | ||
| Hypertension | 2 (1) | 5 (2) |
| Central and peripheral nervous system disorders | ||
| Tremor | 4 (1) | 6 (2) |
| Disorders of the eye | ||
| Vision blurred | 3 (1) | 5 (2) |
| Gastrointestinal system disorders | ||
| Abdominal pain | 4 (1) | 7 (2) |
| Constipation | 1 (<1) | 5 (2) |
| Diarrhea | 8 (3) | 12 (4) |
| Dyspepsia | 3 (1) | 6 (2) |
| Nausea | 22 (7) | 28 (9) |
| Vomiting | 13 (4) | 15 (5) |
| Liver and biliary system disorders | ||
| Bilirubinemia | 8 (3) | 5 (2) |
| GGT* increased | 9 (3) | 7 (2) |
| Hepatic enzymes increased | 8 (3) | 7 (2) |
| SGOT† increased | 8 (3) | 3 (1) |
| SGPT‡ increased | 9 (3) | 4 (1) |
| Metabolic and nutritional disorders | ||
| Phosphatase alkaline increased | 5 (2) | 5 (2) |
| Renal and urinary system disorders | ||
| Blood creatinine increased | 6 (2) | 5 (2) |
| Special senses, other disorders | ||
| Taste perversion | 3 (1) | 5 (2) |
Effective absorption even in HSCT patients with GVHD25
- NOXAFIL® oral suspension demonstrated mean steady-state plasma levels of 1.103 μg/mL (n=252/301)
GVHD class at baseline33
| Number (%) of Subjects | |
| NOXAFIL® (n=301) | |
| Acute grade 1 | 3 (1) |
| Acute grade 2 | 135 (45) |
| Acute grade 3/4 | 64 (21) |
| Chronic limited | 2 (1) |
| Chronic extensive | 96 (32) |
| Missing | 1 (<1) |
* GGT=gamma-glutamyl transpeptidase.
† SGOT=serum glutamic oxaloacetic transaminase.
‡ SGPT=serum glutamic pyruvic transaminase.
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%).
