Very often, it causes a serious reaction soon after infusion (within 1 to 3 hours), consisting of high fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, dyspnea and tachypnea, drowsiness, and generalized weakness. The violent chills and fevers have caused the drug to be nicknamed "shake and bake". The precise etiology of the reaction is unclear, although it may involve increased prostaglandin synthesis and the release of cytokines from macrophages. Deoxycholate formulations (ABD) may also stimulate the release of histamine from mast cells and basophils. Reactions sometimes subside with later applications of the drug. This nearly universal febrile response necessitates a critical (and diagnostically difficult) professional determination as to whether the onset of high fever is a novel symptom of a fast-progressing disease, or merely the effect of the drug. To decrease the likelihood and severity of the symptoms, initial doses should be low, and increased slowly. Paracetamol, pethidine, diphenhydramine, and hydrocortisone have all been used to treat or prevent the syndrome, but the prophylactic use of these drugs is often limited by the patients condition.Intravenously administered amphotericin B in therapeutic doses has also been associated with multiple organ damage. Kidney damage is a frequently reported side effect, and can be severe and/or irreversible. Less kidney toxicity has been reported with liposomal formulations (such as AmBisome) and it has become preferred in patients with preexisting renal injury.
It has been a highly effective drug for over fifty years in large part because it has a low incidence of drug resistance in the pathogens it treats. This is because amphotericin B resistance requires sacrifices on the part of the pathogen that make it susceptible to the host environment, and too weak to cause infection. Antiprotozoal
Amphotericin B is used for life-threatening protozoan infections such as visceral leishmaniasis and primary amoebic meningoencephalitis. Spectrum of susceptibility
The following table shows the amphotericin B susceptibility for a selection of medically important fungi. Available formulations
Intravenous
Amphotericin B alone is insoluble in normal saline at a pH of 7. Therefore, several formulations have been devised to improve its intravenous bioavailability. Lipid-based formulations of amphotericin B are no more effective than conventional formulations, although there is some evidence that lipid-based formulations may be better tolerated by patients and may have fewer adverse effects. Deoxycholate
The original formulation uses sodium deoxycholate to improve solubility. Amphotericin B deoxycholate (ABD) is administered intravenously. As the original formulation of amphotericin, it is often referred to as "conventional" amphotericin. Liposomal
In order to improve the tolerability of amphotericin and reduce toxicity, several lipid formulations have been developed. Liposomal formulations have been found to have less renal toxicity than deoxycholate, and fewer infusion-related reactions. They are more expensive than amphotericin B deoxycholate.AmBisome (LAMB) is a liposomal formulation of amphotericin B for injection and consists of a mixture of phosphatidylcholine, cholesterol and distearoyl phosphatidylglycerol that in aqueous media spontaneously arrange into unilamellar vesicles that contain amphotericin B.