The use of any drug carries some level of risk. When evaluating a drug for market approval, the Food and Drug Administration (FDA) weighs its benefits and potential risks. Doctors must make similar evaluations when deciding to prescribe drugs for their patients. In both cases, the level of risk must be weighed against the severity of the condition being treated. For the treatment of minor disorders, we would expect the potential risks to be minimal. Not so for life-threatening conditions, such as certain systemic fungal infections, in which treatments such as amphotericin B carry a major risk of causing severe toxicity.
AMPHOTERRIBLE. Amphotericin B (Fungizone) is an exceedingly important drug, active against a very wide range of disease-causing fungi and the first pick in the treatment of most systemic fungal infections, which before its introduction in 1956 were invariably fatal. However, amphotericin B’s downside is that it causes kidney toxicity and troubling adverse reactions associated with its intravenous infusion that may continue on a daily basis for two to four months. Referred to as amphoterrible, it may also cause liver, heart, and blood problems.
An obvious drug challenge is to maximize amphotericin B’s antifungal effects while minimizing its damaging effects to the kidneys. A similar problem exists with certain anticancer drugs, which are also toxic to organs of the body. One of the newer approaches involves the use of liposomes—laboratory-prepared microscopic bubbles that are filled with drugs and that prevent the toxic drug from collecting in the kidneys. Liposomal amphotericin B (AmBisome) and similar products have been found to be as effective as the original drug while protecting the kidneys and other sites from its deleterious effects. However, these newer preparations are so expensive that their use is restricted to patients who cannot tolerate the conventional amphotericin product.
SEE ALSO Food and Drug Administration (1906), Nystatin (1954).
Physicians prescribing amphotericin B must weigh its potential success treating life-threatening systemic fungal infections, such as Cryptococcus neoformans (pictured), against its potential for causing severe, multiple-organ toxicity, even at the recommended doses.