Amphotericin B 투여에 의한 신장 유해반응 분석
Analysis of Renal Adverse Reaction Caused by Amphotericin B
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Amphotericin B is a mainstay in the treatment of many systemic fungal infections due to its wide antifungal spectrum and low incidence of resistance. However, the use of amphotericin B is limited by its nephrotoxicity. Objectives: The objective of this study was to evaluate the incidence and risk factors of renal adverse drug reactions (ADRs) of conventional amphotericin B (Fungizone®). In addition, we compared the changes of serum creatinine (SCr)between patients who remained conventional amphotericin B and patients who were switched to liposomal amphotericin B after occurrence of renal adverse reactions. Methods: Adult hospitalized patients who reported renal adverse reactions caused by conventional amphotericin B from January 2011 to July 2012 at pharmacovigilance center in Yonsei University Healthcare System included in this study. ADRs scored as ‘doubtful’ in Naranjo probability ADR scale were excluded. We retrospectively analyzed patients’ basic clinical characteristics, concurrent diseases or nephrotoxic drugs in order to find variables that can correlate with occurrence of renal ADRs. Changes in SCr were compared between conventional amphotericin B group and liposomal amphotericin B group. Results: A total of 231 ADRs after administration of conventional amphotericin B in 75 patients were reported to pharmacovigilance center and assessed their severities as ‘possible’, ‘probable’, or ‘definite’. Renal adverse reaction was the most common ADR with incidence rate of 42% (96of 231 ADRs). Mean change in SCr from baseline was 0.26 mg/dL (change % 37.8) and statistically significant (p=0.000). Simple correlations analysis revealed that the number of concurrent diseases and number of nephrotoxic drugs were positively correlated with changes in SCr, but these results were not statistically significant. Among 43 patients who remained amphotericin B after occurrence of renal ADRs, 27 patients was administered conventional amphotericin B and 16 patients changed to liposomal amphotericin B. Mean change in SCr in amphotericin B group was 0.23 mg/dL (32.75%), whereas mean change in SCr in liposomal amphotericin B group were -0.28 mg/dL (19.38%) and difference between two groups was statistically significant (p=0.003). The numbers of patient with SCr elevation more than 30%were 9 (33.3%) in amphotericin B group and 2 (12.5%) in liposomal amphotericin B group (Odd Ratio=3.50, 95% Confidence Interval 0.65-18.85; p=0.130). Conclusion: An analysis of ADRs due to amphotericin B administration revealed significant mean changes in SCr from baseline. Switching to liposomal amphotericin B showed significant decrease in SCr compared with conventional amphotericin B
Abstract
Background: Amphotericin B is a mainstay in the treatment of many systemic fungal infections due to its wide antifungal spectrum and low incidence of resistance. However, the use of amphotericin B is limited by its nephrotoxicity. Objectives: The objective of this study was to evaluate the incidence and risk factors of renal adverse drug reactions (ADRs) of conventional amphotericin B (Fungizone®). In addition, we compared the changes of serum creatinine (SCr)between patients who remained conventional amphotericin B and patients who were switched to liposomal amphotericin B after occurrence of renal adverse reactions. Methods: Adult hospitalized patients who reported renal adverse reactions caused by conventional amphotericin B from January 2011 to July 2012 at pharmacovigilance center in Yonsei University Healthcare System included in this study. ADRs scored as ‘doubtful’ in Naranjo probability ADR scale were excluded. We retrospectively analyzed patients’ basic clinical characteristics, concurrent diseases or nephrotoxic drugs in order to find variables that can correlate with occurrence of renal ADRs. Changes in SCr were compared between conventional amphotericin B group and liposomal amphotericin B group. Results: A total of 231 ADRs after administration of conventional amphotericin B in 75 patients were reported to pharmacovigilance center and assessed their severities as ‘possible’, ‘probable’, or ‘definite’. Renal adverse reaction was the most common ADR with incidence rate of 42% (96of 231 ADRs). Mean change in SCr from baseline was 0.26 mg/dL (change % 37.8) and statistically significant (p=0.000). Simple correlations analysis revealed that the number of concurrent diseases and number of nephrotoxic drugs were positively correlated with changes in SCr, but these results were not statistically significant. Among 43 patients who remained amphotericin B after occurrence of renal ADRs, 27 patients was administered conventional amphotericin B and 16 patients changed to liposomal amphotericin B. Mean change in SCr in amphotericin B group was 0.23 mg/dL (32.75%), whereas mean change in SCr in liposomal amphotericin B group were -0.28 mg/dL (19.38%) and difference between two groups was statistically significant (p=0.003). The numbers of patient with SCr elevation more than 30%were 9 (33.3%) in amphotericin B group and 2 (12.5%) in liposomal amphotericin B group (Odd Ratio=3.50, 95% Confidence Interval 0.65-18.85; p=0.130). Conclusion: An analysis of ADRs due to amphotericin B administration revealed significant mean changes in SCr from baseline. Switching to liposomal amphotericin B showed significant decrease in SCr compared with conventional amphotericin B
참고문헌 (20)
- Freifeld AG, "Clinical practice guideline for the use of antimicrobial agents in neutropenic patientswith cancer: 2010 update by the infectious diseases society of America", Clinical Infectious Diseases, 52, pp.e56~e93 (2011)
- Pappas PG, "Clinical practice guidelines for the managementof candidiasis: 2009 update by the infectious diseases society of America", Clinical Infectious Diseases, 48, pp.503~535 (2009)
- Miceli MH, "Safety and efficacy of liposomal amphotericin B for the empirical therapy of invasive fungal infections in immunocompromisedpatients", Infection and Drug Resistance, 5, pp.9~16 (2012)
- Laniado-Laborn R, "Amphotericin B: side effects and toxicity", Rev IberoamMicol, 26(4), pp.223~227 (2009)
- Tiphine M, "Amphotericin B and its new formulations: pharmacologic characteristics, clinical efficacy, and tolerability", Transpl Infect Dis, 1(4), pp.273~283 (1999)
- Deray G, "Amphotericin B nephrotoxicity", Journal of Antimicrobacterial Chemotherapy, 49(suppl1), pp.37~41 (2002)
- Shigemi A, "Safety analysis of liposomal amphotericin B in adult patients: anemia, thrombocytopenia, nephrotoxicity, hepatotoxicity and hypokalemia", International Jouranl of Antimicrobial Agents, 38, pp.417~420 (2011)
- Safdar A, "Drug-induced nephrotoxicity caused by amphotericin B lipid complex and liposomal amphotericin B", Medicine(Baltimore), 89(4), pp.236~244 (2010)
- Patel GP, "L. An evaluation of hepatotoxicity and nephrotoxicity of liposomal amphotericin B(l-amb)", Toxicology investigation, 7, pp.12~15 (2011)
- Sawaya BP, "Amphotericin B nephrotoxicity: the adverse consequences of altered membrane properties", Journal of the American Society of Nephrology, 6(2), pp.154~164 (1995)
- Ostrosky-Zeichner L, "Amphotericin B: time for a new “gold standard”", Clin Infect Dis, 37, pp.415~425 (2003)
- Blau IW, "Review of comparative studies between conventional and liposomal amphotericin b (Ambisome®) in neutropenic patients with fever of unknown origin and patients with systemic mycosis", Mycoses, 43(9-10), pp.325~332 (2000)
- "Health Insurance Review and Assessment Service Website"[URL]
- Naranjo CA, "A method for estimating the probability of adverse drug reactions", Clin Pharmacol Ther, 30, pp.239~245 (1981)
- Azaz-Livshits T, "Computerized surveillance of adverse drug reactions in hospital: pilot study", Br. J ClinPharmacol, 45, pp.309~314 (1998)
- Ullmann AJ, "Prospective study of amphotericin B formulations in immunocompromised patients in 4 european countries", Clin Infect Dis, 43(4), pp.e29~e38 (2006)
- Bates DW, "Correlates of acute renal failure in patients receiving parenteral amphotericin B", Kidney Int, 60(4), pp.1452~1459 (2001)
- Hamill RJ, "Comparison of 2 doses of liposomal amphotericin B and conventional amphotericin B deoxycholate for treatment of AIDSassociated acute cryptococcal meningitis: a randomized, double-blind clinical trial of efficacy and safety", Clin Infect Dis, 51(2), pp.225~232 (2010)
- 권정미, "Fungizone 에서 AmBisome 으로의 약물 전환에 따른 환아의 신기능 변화", 병원약사회지, 24(2), pp.1~7 (2007), 한국병원약사회
- Tiphine M, "Amphotericin B and its new formulations: pharmacologic characteristics, clinical efficacy, and tolerability", Transpl Infect Dis, 1(4), pp.273~283 (1999)