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New Antifungal Drug : Noxafil (Posaconazole) for Use in Patients Who have Weakened Immune Systems

Bacteria, viruses and other infectious organisms live everywhere. You can find them in the air; on food, plants and animals; in the soil and in the water; and on just about every other surface — including your own body. They range in size from microscopic single-cell organisms to parasitic worms that can grow to several feet in length.

Fungi live in the air, water, soil and on plants. They can live in your body, usually without causing illness. Some fungi have beneficial uses. For example, penicillin — an antibiotic that kills harmful bacteria in your body — is derived from fungi. Fungi are also essential in making certain foods, such as bread, cheese and yogurt.Other fungi aren't as beneficial and can cause illness. One example is candida — a yeast that can cause infection. Candida can cause thrush — an infection of the mouth and throat — in infants, in people taking antibiotics and in people with impaired immune systems. It's responsible for most types of infection-induced diaper rash.Candida fungus, which lives naturally in the gastrointestinal tract. Infection occurs when a change in the body, such as surgery, causes the fungus to overgrow suddenly.

Candida vulvovaginitis, or yeast infection, is one of the most common diagnoses in American women. About three-quarters of women will have at least one yeast infection in their lives, and 40 percent have recurrent infections. The Candida yeast are often found in both women and men in the genital area, rectum and mouth.

Species of Aspergillus are without a doubt an important microorganism, both medically and commercially. Some species can cause human infection, others are important in commercial, microbial fermentations.Aspergillosis is an infection or allergic reaction caused by aspergillus — a mold (fungus) found in the environment, such as in decaying vegetation and household dust. In healthy individuals, it rarely causes problems. But aspergillus may affect people with asthma or weakened immune systems.

Some Aspergillus species cause serious disease in humans and animals, and can be pathogenic. The most common causing invasive disease are Aspergillus fumigatus and Aspergillus flavus. The most common causing allergic disease are Aspergillus fumigatus and Aspergillus clavatus. Other species are important as agricultural pathogens. Aspergillus spp. cause disease on many grain crops, especially maize, and synthesize mycotoxins including aflatoxin.

The symptoms include fever, cough, chest pain or breathlessness, which also occur in many other illnesses so diagnosis can be hard. Usually, only patients with already weakened immune systems or who suffer other lung conditions are susceptible.An aspergillus skin test can determine whether someone has been exposed to aspergillus. It's performed by injecting an aspergillus antigen under the skin. Inflammation at the injection site indicates past exposure to aspergillus.

Aspergillus can cause illness in several ways, including:

An allergic reaction (allergic bronchopulmonary aspergillosis, or ABPA) in people with asthma
A serious infection (invasive pulmonary aspergillosis) in people with weakened immune systems, such as organ transplant recipients and those receiving chemotherapy

The U.S. Food and Drug Administration recently approved Noxafil (posaconazole) to prevent fungal infections caused by certain molds and yeast-like fungus called Aspergillus and Candida. FDA approved the drug for use in patients who have weakened immune systems following bone marrow transplants and for patients with a condition (decreased white blood cell counts) that makes it difficult for the body to fight infections following chemotherapy for cancer.

"Most healthy individuals are unaffected by these common fungi," said Dr. Steven Galson, Director of FDA's Center for Drug Evaluation and Research. "However, individuals with severely weakened or abnormal immune systems may become seriously ill when exposed. These infections are often fatal for this population."

Noxafil, a new molecular entity (NME), is an antifungal drug which contains an active substance that has never before been approved for marketing in any form in the United States.

The safety and efficacy of Noxafil were evaluated in clinical trials consisting of 1,844 patients between 13 and 82 years of age. In two, randomized, controlled studies of patients who had compromised immunity and were at high risk for invasive fungal infections, those patients who received Noxafil had comparable or lower rates of invasive Aspergillus and Candida infections than those patients who received other antifungal medications.

The most common side effects in patients receiving Noxafil were nausea, vomiting, diarrhea, rash, a decrease in potassium blood levels and platelet counts, and abnormalities in liver function tests. Rare adverse events possibly related to the drug include QTc prolongation (abnormal heart rhythm) and liver function impairment.

Noxafil must be taken with a full meal or nutritional supplement (a product intended as a supplement to the diet) to allow adequate absorption of the drug into the body so it can take effect. 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.

Noxafil is manufactured by Schering Corporation, Kenilworth, NJ.