Safety
Power and safety in an oral suspension25
Safety profile25
- Most frequently reported adverse events were GI related
- Changes in liver function were minor, transient, and rarely led to discontinuation
- Rarely, more severe hepatic reactions including cholestasis or hepatic failure including fatalities were reported in patients with serious underlying medical conditions
- Visual disturbances were 1%, similar in incidence to fluconazole
| Special Populations | Recommended Action |
| Patients with renal impairment | No dosage adjustment required. Due to the variability in exposure, patients with severe renal impairment should be monitored closely for breakthrough IFIs |
| Patients with severe diarrhea or vomiting | Monitor closely for breakthrough fungal infections |
| Patients with hepatic impairment | NOXAFIL® should be used with caution in patients with hepatic impairment. Discontinuation of NOXAFIL® must be considered in patients who experience symptoms consistent with liver disease that may be attributable to NOXAFIL® |
Treatment-related adverse events (≥2%) in AML and MDS patients with neutropenia6,25
| NOXAFIL® (n=304) n (%) |
Fluconazole/ Itraconazole (n=298) n (%) |
Fluconazole (n=240) n (%) |
Itraconazole (n=58) n (%) |
|
| Subjects reporting any adverse event | 102 (34) | 101 (34) | 71 (30) | 30 (52) |
| Body as a whole—general disorders | ||||
| Headache | 5 (2) | 1 (<1) | 0 | 1 (2) |
| Gastrointestinal system disorders | ||||
| Abdominal pain | 9 (3) | 9 (3) | 8 (3) | 1 (2) |
| Constipation | 3 (1) | 7 (2) | 7 (3) | 0 |
| Diarrhea | 20 (7) | 21 (7) | 12 (5) | 9 (16) |
| Dyspepsia | 5 (2) | 3 (1) | 3 (1) | 0 |
| Mucositis NOS* | 7 (2) | 0 | 0 | 0 |
| Nausea | 22 (7) | 25 (8) | 17 (7) | 8 (14) |
| Vomiting | 14 (5) | 20 (7) | 14 (6) | 6 (10) |
| Heart rate and rhythm disorders | ||||
| QT/QTc prolongation | 12 (4) | 9 (3) | 5 (2) | 4 (7) |
| Liver and biliary system disorders | ||||
| Bilirubinemia | 7 (2) | 8 (3) | 5 (2) | 3 (5) |
| GGT† increased | 5 (2) | 2 (1) | 1 (<1) | 1 (2) |
| Hepatic enzymes increased | 7 (2) | 3 (1) | 3 (1) | 0 |
| SGOT‡ increased | 6 (2) | 5 (2) | 4 (2) | 1 (2) |
| SGPT§ increased | 7 (2) | 5 (2) | 4 (2) | 1 (2) |
| Metabolic and nutritional disorders | ||||
| Hypokalemia | 9 (3) | 6 (2) | 5 (2) | 1 (2) |
| Skin and subcutaneous tissue disorders | ||||
| Rash | 9 (3) | 11 (4) | 10 (4) | 1 (2) |
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) |
* NOS=not otherwise specified.
† 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%).
