Amphotericin B-Lipid Suspension (Amfy®)
Amfy® is an antifungal product consisting of lipid-based amphotericin B (Nanosomal Amphotericin B) that is administered via intravenous injection. Amfy is indicated for the treatment of severe systemic and/or deep mycoses in cases where toxicity or renal failure precludes the use of conventional amphotericin B in effective doses, and in cases where prior systemic antifungal therapy has failed. Fungal infections successfully treated with amphotericin B include disseminated candidiasis and aspergillosis. Amphotericin B lipid suspension is not intended for use in common, clinically inapparent fungal diseases diagnosed only by skin tests or serological determinations.
Amfy for injection is a sterile lyophilized powder supplied it glass vial. Each vial containes 50 mg amphotericin B and is reconstituted with 46 mL water for injection and further dilution is done with 5% dextrose injection, IP. Details of dosage and administration can be found in the package insert.
About Fungal Infections
The frequency of life-threatening systemic fungal infections have increased dramatically over the past two decades, particularly among cancer, diabetic and immunocompromised patients. Cancer patients, especially organ transplantation recipients, AIDS paitents and patients with leukemia, constitute a high-risk group for the development of life-threatening systemic infections. These infections are caused by Candida, Aspergillus and Fusarium species. Candidiasis represents the most commonly reported fungal infection in cancer patients. Candida species became the fourth most commonly isolated (about 8%) blood stream pathogen in US hospitals. Candidemia alone is associated with a mortality rate above 50% in patient population.
Invasive aspergillosis is the second most common systemic fungal infection. Invasive aspergillosis is increased gradually in the recent years due to the development of new intensive chemotherapy regimens, increased use of high-dose corticosteroids, worldwide increase in solid organ and bone marrow ransplantation, and increased use of immunosuppressive drugs for autoimmune diseases. The mortality rate in cancer patients associated with aspergillus pneumonia has exceeded 80%.
About Amphotericin B
Amphotericin B, is a heptaene macrolide antibiotic that acts by binding to sterols (primarily ergosterol) in cell membranes of sensitive fungi, with subsequent leakage of intracellular contents and cell death due to changes in membrane permeability. Amphotericin B is derived from fermentation by Streptomyces nodosus and considered to be the gold standard for the treatemnt of pre-systemic and systemic fungal infections. However, the administration is limited by dose-dependent toxicities including nephrotoxicity. These toxicites can be overcome by formulation amphotericn B in a suitable carrier systems, which alters the pharmacokinetics and tissue distribution of the drug.
Amphotericin B has a molecular formula of C47H73NO17 and molecular weight of 924.09. It is practically insoluble in water, ethanol, and freely soluble in dimethyl sulfoxide. The structure of amphotericin B is shown below
Conventional Amphotericin B for Injection (Fungizone®), has several adverse effects and limitations, including nephrotoxicity, unpleasant side effects (fever, chills, and nausea). To circumvent these adverse side effects, Amphotericin B Lipid Suspension for injection (Amfy®) is developed using Nanoaqualip™ technology [Link]. These lipid excipients used in Amy are naturally occurring and considered Generally Recognized as Safe (GRAS) by US FDA.
Amphotericin B deoxycholate and other lipid-based amphotericin B drugs induce increase in hepatoxicity leading to the elevated levels of serum AST and ALT transaminases where as administration of Amfy even at high dose did not show significant increase in the serum AST and ALT transaminases levels indication less accumulation of the amphotericin B in liver. In animal model infected with aspergillus fumigatus at equal doses, Amfy resulted in 90% survival compared to 30% with Ambisome.
The key to AMFY® usage is its low toxicity. Below are some of the advantages of AMFY® .
- Proprietary Lipid Based Nanotechnology
- No use of toxic solvents during the manufacturing process
- Well differentiated Product with marketed exclusivity
- Improved clinical compliance due to significantly decrease adverse events
- Simple manufacturing process
- Lower cost of goods compared to other lipid products