Ta. Nicholl et al., AMPHOTERICIN-B INFUSION-RELATED TOXICITY - COMPARISON OF 2-HOUR AND 4-HOUR INFUSIONS, The Annals of pharmacotherapy, 29(11), 1995, pp. 1081-1087
OBJECTIVE: To investigate the influence of infusion duration on infusi
on-related adverse effects (IRAEs) associated with prophylactic or tre
atment regimens of amphotericin B in patients with leukemia/bone marro
w transplant (BMT). DESIGN: Randomized, double-blind, 2-arm, complete
crossover, prospective clinical trial. SETTING: A university-affiliate
d tertiary care teaching hospital. PARTICIPANTS: The study population
consisted of 25 consecutive patients with leukemia/BMT who received 16
2 prophylactic regimen infusions and 169 treatment regimen infusions o
f amphotericin B via a central line, Prior to each infusion all patien
ts received a parenteral IRAE prophylaxis regimen of diphenhydramine 2
5 mg and hydrocortisone 25 mg, No test doses or incremental amphoteric
in B doses were administered. Patients were monitored closely for IRAE
s, which were documented by using a standardized data collection form.
MAIN OUTCOME MEASURES: The incidence and nature of IRAEs during a 6-h
our monitoring period following the initiation of each infusion was me
asured. Patients served as their own controls. IRAEs were compared acc
ording to infusion duration and therapeutic indication. RESULTS: Three
hundred and thirty-one 2- and 4-hour amphotericin B infusions were ad
ministered. We found no difference between 2- and 4-hour infusions in
the incidence and severity of IRAEs, including overall events (29% of
166 2-hour infusions vs. 25% of 165 4-hour infusions), chill scores (8
% of 166 2-hour infusions vs. 7% of 165 4-hour infusions; highest scor
e 7 vs. 6), nausea and vomiting (7% vs. 12%; highest score 4 in both g
roups), fever (3% vs. 2%), highest temperature increase (2.4 vs. 1.6 d
egrees C), systolic hypotension (6% vs. 2%), greatest decrease from ba
seline (40 vs. 62 mm Hg), diastolic hypotension (5% vs. 3%), and great
est decrease (30 vs, 28 mm Hg) (p > 0.05). Overall, IRAEs were less co
mmon in prophylactic treatment regimens (35 events [22%] in 162 infusi
ons) than in treatment regimens (55 events [32%] in 169 infusions) (p
< 0.05). CONCLUSIONS: This study demonstrates that patients with leuke
mia/BMT without myocardial or renal dysfunction who receive hydrocorti
sone and diphenhydramine as premedications can tolerate 2-hour central
line infusions of prophylactic or treatment regimens of amphotericin
B as well as 4-hour infusions.