Amphotericin B infusion-related toxicity: comparison of two- and four-hour infusions.
OBJECTIVE
To investigate the influence of infusion duration on infusion-related adverse effects (IRAEs) associated with prophylactic or treatment regimens of amphotericin B in patients with leukemia/bone marrow transplant (BMT).


METHODS
Randomized, double-blind, 2-arm, complete crossover, prospective clinical trial.


METHODS
A university-affiliated tertiary care teaching hospital.


METHODS
The study population consisted of 25 consecutive patients with leukemia/BMT who received 162 prophylactic regimen infusions and 169 treatment regimen infusions of amphotericin B via a central line. Prior to each infusion all patients received a parenteral IRAE prophylaxis regimen of diphenhydramine 25 mg and hydrocortisone 25 mg. No test doses or incremental amphotericin B doses were administered. Patients were monitored closely for IRAEs, which were documented by using a standardized data collection form.


METHODS
The incidence and nature of IRAEs during a 6-hour monitoring period following the initiation of each infusion was measured. Patients served as their own controls. IRAEs were compared according to infusion duration and therapeutic indication.


RESULTS
Three hundred and thirty-one 2- and 4-hour amphotericin B infusions were administered. 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 score 7 vs. 6), nausea and vomiting (7% vs. 12%; highest score 4 in both groups), fever (3% vs. 2%), highest temperature increase (2.4 vs. 1.6 degrees C), systolic hypotension (6% vs. 2%), greatest decrease from baseline (40 vs. 62 mm Hg), diastolic hypotension (5% vs. 3%), and greatest decrease (30 vs. 28 mm Hg) (p > 0.05). Overall, IRAEs were less common in prophylactic treatment regimens (35 events [22%] in 162 infusions) than in treatment regimens (55 events [32%] in 169 infusions) (p < 0.05).


CONCLUSIONS
This study demonstrates that patients with leukemia/BMT without myocardial or renal dysfunction who receive hydrocortisone 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.
Nicholl
T A
TA
Department of Pharmacy, Vancouver Hospital and Health Sciences Centre, British Columbia, Canada.
Nimmo
C R
CR
Shepherd
J D
JD
Phillips
P
P
Jewesson
P J
PJ
D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016026:Bone Marrow Transplantation; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004361:Drug Tolerance; D005260:Female; D006785:Hospitals, University; D006801:Humans; D016867:Immunocompromised Host; D007262:Infusions, Intravenous / Q000379:methods; D007938:Leukemia / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000517:prevention & control; D011446:Prospective Studies; D013997:Time Factors
D000935:Antifungal Agents; D000666:Amphotericin B