To review the data examining the use of rapid infusion of amphotericin B in dextrose infusions.
Data Sources:
A MEDLINE search of the English-language literature and review of pertinent references' bibliographies was used to identify articles evaluating the effect of amphotericin B infusion rates on the incidence of adverse reactions.
Study Selection and Data Extraction:
Controlled and uncontrolled studies involving humans are reviewed; emphasis is placed on recent comparative trials. Pertinent information, as judged by the authors, was selected for discussion.
Data Synthesis:
Amphotericin B, a polyene antifungal agent with significant toxicity, remains the agent of choice for many serious fungal infections. The potential benefits of rapid administration of amphotericin B in reducing the incidence and/or severity of adverse reactions were noted soon after its introduction. Recent studies have examined the tolerability of rapid (0.75–1 h) amphotericin B infusions. Results of studies assessing the tolerability of rapid amphotericin B infusions suggest that tolerance to infusion-related reactions develops during therapy. Comparative trials have obtained variable results. The comparative trials supporting rapid amphotericin B infusion have generally used crossover designs, enrolled small numbers of patients, and excluded patients with significant renal or cardiovascular dysfunction.
Conclusions:
Rapid amphotericin B infusions should be avoided during initiation of therapy when infusion-related reactions tend to be most problematic, and in patients with cardiovascular disease, renal dysfunction, and potassium disorders because of the potential risk for cardiac arrhythmias. The literature currently available is conflicting and insufficient to support the routine use of rapid amphotericin B infusion.
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References
1.
UtzJP, BennettJE, BrandrissMW, ButlerWT, HillGJ, Amphotericin B toxicity: combined clinical staff conference at the National Institutes of Health. Ann Intern Med1964;61:334-54.
2.
SeaburyJH, DascombHE. Experience with amphotericin B for the treatment of systemic mycoses. Arch Intern Med1958;102:960-76.
3.
Drugs for treatment of fungal infections.Med Lett Drugs Ther1992;34:14-6.
4.
TerrellCL, HughesCE. Antifungal agents used for deep-seated mycotic infections. Mayo Clin Proc1992;67:69-91.
5.
GallisHA, DrewRH, PickardWW. Amphotericin B: 30 years of clinical experience. Rev Infect Dis1990;12:308-29.
6.
MadduxMS, BarriereSL. A review of complications of amphotericin-B therapy: recommendations for prevention and management. Drug Intell Clin Pharm1980;14:177-81.
7.
LinAC, GoldwasserE, BernardEM, ChapmanSW. Amphotericin B blunts erythropoietin response to anemia. J Infect Dis1990;161:348-51.
8.
FisherMA, TalbotGH, MaislinG, McKeonBP, TynanKP, StromBL. Risk factors for amphotericin B-associated nephrotoxicity. Am J Med1989;87:547-52.
9.
SeaburyJH, DascombHE. Experience with amphotericin B. Ann N Y Acad Sci1960;89:202-20.
10.
GigliottiF, ShenepJL, LottL, ThorntonD.Induction of prostaglandin synthesis as the mechanism responsible for the chills and fever produced by infusing amphotericin B. J Infect Dis1987;156:784-9.
11.
TynesBS, UtzJP, BennettJE, AllingDW. Reducing amphotericin B reactions. Am Rev Respir Dis1963;87:264-8.
12.
ChiaJKS, PollackM.Amphotericin B induces tumor necrosis factor production by murine macrophages. J Infect Dis1989;159:113-6.
13.
GraselaTH, GoodwinSD, WalawanderMK, CramerRL, FuhsDW, MoriartyVP. Prospective surveillance of intravenous amphotericin B use patterns. Pharmacotherapy1990;10:341-8.
14.
GoodpastureHC, VothDW, RomigDA, ChengD, WenglinBD, LiuC.Clinical correlations during amphotericin B therapy. J Kans Med Soc1972;73:486-90.
15.
GotzVP, RandKH, KramerBS. Effect of filtering amphotericin B infusions on the incidence and severity of phlebitis and selected adverse reactions. Drug Intell Clin Pharm1985;19:436-9.
16.
GrossMH, FulkersonWJ, MooreJO. Prevention of amphotericin B-induced rigors by dantrolene. Arch Intern Med1986;146:1587-8.
17.
Da CamaraCC, LaneTW. Dantrolene for amphotericin B-induced rigors (letter). Arch Intern Med1987;147:2220.
18.
HoltzclawBJ. Effects of extremity wraps to control drug-induced shivering: a pilot study. Nurs Res1990;39:280-3.
19.
BurksC, AisnerJ, FortnerCL, WiernikPH. Meperidine for the treatment of shaking chills and fever. Arch Intern Med1980;140:483-4.
20.
BurnettRJ, ReentsSB. Premedication for amphotericin B-induced chills (letter). Clin Pharm1989;8:836-7.
CaillotD, ChavanetP, CasasnovasO, SolaryE, ZanettaG, BuissonM, Clinical evaluation of a new lipid-based delivery system for intravenous administration of amphotericin B. Eur J Clin Microbiol Infect Dis1992;11:722-5.
23.
ChavanetPY, GarryI, CharlierN, CaillotD, KistermanJP, D'athisM, Trial of glucose versus fat emulsion in preparation of amphotericin for use in HIV infected patients with candidiasis. BMJ1992;305:921-5.
24.
Lopez-BeresteinG, FainsteinV, HopferR, MehtaK, SullivanMP, KeatingM, Liposomal amphotericin B for the treatment of systemic fungal infections in patients with cancer: a preliminary study. J Infect Dis1985;151:704-10.
25.
Lopez-BeresteinG, BodeyGP, FrankelLS, MehtaK.Treatment of hepatosplenic candidiasis with liposomal-amphotericin B. J Clin Oncol1987;5:310-7.
26.
TollemarJ, RingdenO, TydenG.Liposomal amphotericin-B (AmBisome) treatment in solid organ and bone marrow transplant recipients. Efficacy and safety evaluation. Clin Transpl1990;4:167-75.
27.
Package insert. Amphotericin B for injection. Princeton, NJ: Bristol-Myers Squibb, August1993.
28.
DeMonacoHJ, McGovernB.Transient asystole associated with amphotericin B infusion. Drug Intell Clin Pharm1983;17:547-8.
29.
SolerJA, IbanezL, ZuazuJ, JuliaA.Bradycardia after rapid intravenous infusion of amphotericin B (letter). Lancet1993;341:372-3.
30.
CravenPC, GremillionDH. Risk factors of ventricular fibrillation during rapid amphotericin B infusion. Antimicrob Agents Chemother1985;27:868-71.
31.
FieldsBT, BatesJH, AbernathyRS. Effect of rapid intravenous infusion on serum concentrations of amphotericin B. Appl Microbiol1971;22:615-7.
32.
BarreutherAD, DodgeRR, BlondeauxAM. Administration of amphotericin B (letter). Drug Intell Clin Pharm1977;11:368-9.
33.
TaralaRA, SmithJD. Cryptococcosis treated by rapid infusion of amphotericin B (letter). Br Med J1980;281:28.
34.
CampbellGD. Using amphotericin B. Intern Med1982;3:95-102.
35.
SpitzerTR, CregerRJ, FoxRM, LazarusHM. Rapid infusion of amphotericin B: effective and well-tolerated therapy for neutropenic fever. Pharmatherapeutica1989;5:305-11.
36.
ClearyJD, WeisdorfD, FletcherCV. Effect of infusion rate on amphotericin B-associated febrile reactions. Drug Intell Clin Pharm1988;22:769-72.
37.
OldfieldEC, GarstPD, HostettlerC, WhiteM, SamuelsonD.Randomized, double-blind trial of 1- versus 4-hour amphotericin B infusion durations. Antimicrob Agents Chemother1990;34:1402-6.
38.
ArningM, DresenB, SchneiderW.Influence of infusion time on the acute toxicity of amphotericin B: results of a randomized double-blind study. Recent Results Cancer Res1991;121:347-52.
39.
EllisME, Al-HokailAA, ClinkHM, PadmosMA, ErnstP, SpenceDG, Double-blind randomized study of the effect of infusion rates on toxicity of amphotericin B. Antimicrob Agents Chemother1992;36:172-9.
40.
CruzJM, PeacockJE, LoomerL, HolderLW, EvansGW, PowellBL, Rapid intravenous infusion of amphotericin B: a pilot study. Am J Med1992;93:123-30.
41.
CockcroftDW, GaultMH. Prediction of creatinine clearance from serum creatinine. Nephron1976;16:31-41.
42.
DaviesHD, MatlowA, KingS, KorenG.Effect of infusion rates on toxicity of amphotericin B (letter). Antimicrob Agents Chemother1992;36:2573-4.
43.
KintzelPE, KennedyPE. Stability of amphotericin B in 5% dextrose injection at concentrations used for administration through a central venous line. Am J Hosp Pharm1991;48:283-5.
44.
DrutzDJ. Rapid infusion of amphotericin B: is it safe, effective, and wise (editorial)? Am J Med1992;93:119-21.
45.
AguadoJM, HidalgoM, MoyaI, AlcazarJM, JimenezMJ, NoriegaAR. Ventricular arrhythmias with conventional and liposomal amphotericin (letter). Lancet1993;342:1239.
46.
GoogeJH, WalterspielJN. Arrhythmia caused by amphotericin B in a neonate (letter). Ped Infect Dis J1988;7:73.
47.
WalkerR, MilfordD, DerbyshireP.Bradycardia after amphotericin, irradiation, and anthracycline (letter). Lancet1992;340:380.
48.
BowlerWA, WeissPJ, HillHE, HoffmeisterKA, FleckRP, BlackyAR, Risk of ventricular dysrhythmias during 1-hour infusions of amphotericin B in patients with preserved renal function. Antimicrob Agents Chemother1992;36:2542-3.
