Study of incidence of amphotericin B side effects and nephrotoxicity risk factors in patients under chemotherapy.

Simin O Mashayekhi, Mohammadreza Sattari, Nasrin Maleki, Iraj Asvadi-Kermani, Vahid Ghahremanfar. Hematology research center, Tabriz Pharmacy Faculty, Tabriz University of Medical Sciences, Tabriz, Iran, Clinical Pharmacy, 51664-14766, Iran

Drugs used for treatment of cancer have cytotoxic effects with an inhibitory effect on bone marrow. This is more true for therapeutic agents used in hemopoietic cancers treatment. The drug regimens used to treat these types of cancer includes several medicines with simultaneous inhibitory effects on bone marrow. The consequences of this inhibition, is a decrease in production of defence cells and therefore reduced body\'s ability to fight pathogens. Presence of infection in the body is usually associated with fever and the fever due to bone marrow suppression is called febrile neutropenia. One of the most important drugs in treatment of febrile neutropenia is amphotericin B. This medicine has some immediate side effects such as: hypothermia, hyperthermia, hypotension, hypertension, nausea, diarrhoea, muscle and joint pain or irritability. There are also a series of side effects related to its toxicity of this drug such as: liver disorders, peripheral neuropathy, nephrotoxicity, anaemia and increased renal potassium excretion that causes hypokalaemia and hypomagnesaemia. The aim of the present study was to examine prevalence of side effects amphotericin B in patients with neutropenia fever.

In this study, 100 hospitalized patients who were receiving amphotericin B were enrolled to the study. Only antifungal medication given to these patients was amphotericin B. A questionnaire was designed and completed by the information in patients\' records and direct questions from patients. Student t test and regression analysis was used to examine the data. The results of this study showed that a total of 44% of the subjects were female. Their mean age was 38.6 ±16.5 years old (23-77). The cause of hospitalization was acute lymphoblastic leukaemia (74%), acute myeloid leukaemia (18%) and non-Hodgkin\'s lymphoma (8%). Amphotericin dosage was 211.2 ± 130.1 mg (25-600 mg). 100 patients treated with amphotericin B, suffered a series of side effects. The most common side effects included: fever (83%), headache (79%), myalgia (60%), dizziness (57%), restlessness (54%), joint pain (52%), diarrhoea (46%). the differences between serum creatinine level before amphotericin administration and the last day of its administration was significant (P<0.05) and number of patients with serum creatinine level of more than normal range increased from 35 patients to 76 patients. Increase in cumulative dose of amphotericin B, caused a rise in serum urea concentration. These are indication of nephrotoxicity. Treatment duration and cumulative dose of amphotericin B had no significant effects on serum potassium and sodium concentrations and blood cell count. One of the most important side effects of amphotericin B that limits its usage is nephrotoxicity. There are several methods that can be employed to reduce nephrotoxicity of amphotericin B. Liposomal formulation of amphotericin B has the lowest nephrotoxicity. In Iran non-lipid form of amphotericin is used routinely and therefore it is recommended to use other formulations. There are also other methods that can be employed for reducing amphotericin B nephrotoxicity. Examples of such methods are slow infusion rate and administration sodium, potassium and magnesium salts prior to amphotericin B administration.