General Information

Vfend has been approved by the FDA for the treatment of deadly fungal infections. The medication is indicated for the primary treatment of acute invasive aspergillosis. It has also been approved as salvage therapy for rare but serious fungal infections caused by Scedosporium apiospermum and Fusarium spp. Unlike other agents, Vfend has been approved in both oral and intravenous formulations.

Invasive aspergillosis is a deadly fungal infection that occurs in immune compromised patients. The number of people at risk for infection is increasing due to more patients undergoing bone marrow transplants, solid organ transplants and aggressive chemotherapy for cancer.

Clinical Results

Vfend has been evaluated as primary or salvage therapy in 520 subjects (12 years of age and older) with infections caused by Aspergillus spp., Fusarium spp. and Scedosporium spp.

Invasive Aspergillosis

The effectiveness of Vfend as a primary therapy for invasive aspergillosis was evaluated in a randomized and controlled trial (Study 307/602). The 277-subject trial was designed to compare treatment with amphotericin B, an approved anti-fungal medication, to treatment with Vfend. The trial included subjects with solid organ transplantation, solid tumors and AIDS.

Study results demonstrated that at 12 weeks, a satisfactory global response was observed in 53% of Vfend-treated subjects, compared to 32% of amphotericin B-treated subjects. Additionally, the survival rate for Vfend treatment at Day 84 was 71%, compared to 58% for amphotericin B .

Other Disease-Causing Agents

In pooled analyses of subjects, Vfend was shown to be effective against both Scedosporium apiospermum and Fusarium spp. For Scedosporium apiospermum, a successful response to Vfend was reported in 15 of 24 subjects (63%). In those with Fusarium spp., nine of 21 (43%) were successfully treated with Vfend.

Side Effects

Adverse events (regardless of cause) reported in clinical testing include the following:

Visual disturbances

Fever

Rash

Vomiting

Nausea

Diarrhea

Headache

Sepsis

Peripheral edema

Abdominal pain

Respiratory disorder

Elevated liver function tests, rash and visual disturbances were the treatment-related adverse events that most often led to discontinuation of Vfend therapy.

Mechanism of Action

Voriconazole is a triazole anti-fungal agent. The primary mode of action of voriconazole is the inhibition of fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylation, an essential step in fungal ergosterol biosynthesis. The accumulation of 14 alpha-methyl sterols correlates with the subsequent loss of ergosterol in the fungal cell wall and may be responsible for the antifungal activity of voriconazole. Voriconazole has been shown to be more selective for fungal cytochrome P-450 enzymes than for various mammalian cytochrome P-450 enzyme systems. (from Vfend Proposed US Package Insert)