As various authors have pointed out, there have not been extensive investigations as to whether slowing the infusion rate of liposomal amphotericin B can reduce the risk of infusion-related reactions. Most investigations are limited to studies and case reports with protocols in place to reduce the infusion rate when patients experience an infusion reaction, not to proactively reduce infusion rates if patients are considered at risk. Generally, these reports suggest that reducing the infusion rate does ameliorate infusion-related reactions, but studies comparing rapid versus reduced rates are scarce. [1], [2], [3]
A 2021 pilot study investigated whether slowing the infusion rate of amphotericin B-containing lipid complex (Abelcet®) can reduce the risk of infusion-related reactions in pediatric patients. A total of 22 children were included for the treatment of various indications at the recommended rate of 2.5 mg/kg/hour. All but one child received a prolonged infusion rate 2-3x more than the standard infusion rate of 2 hours (e.g., 4-6 hours of prolonged infusion). Despite this, 7 of 22 patients developed a reaction (32%), with 6 of 10 patients who received 2-4 hour infusions developing the reaction. Only 1 of 14 patients who received a 5-6 hour infusion developed a reaction. Therefore, the authors suggest that a very slow infusion of 5-6 hours may be more safe in pediatric patients. Note that Abelcet® is not interchangeable with liposomal amphotericin B (AmBisome®) as they have different dosing recommendations. The results of this study on Abelcet® may not directly correlate with AmBisome®. [4]
A 1998 case series reported on three intravenous (IV) liposomal amphotericin B (AmBisome®) recipients who developed chest discomfort and pulmonary symptoms during a planned 1-hour infusion. Patient 1, a 15-year-old boy, experienced chest tightness accompanied by tremors and a reduction in oxygen saturation, all emerging shortly after the infusion began. Meanwhile, Patient 2, a 40-year-old man, developed acute dyspnea and hypoxia during the infusion, which improved after stopping the infusion and slowing down subsequent infusions to 2 hours with the next scheduled dose. Similarly, Patient 3, a 60-year-old man, complained of chest pain radiating to his groin during the infusion, which was resolved after stopping the infusion. These reactions occurred within minutes of the infusion starting and were all resolved upon discontinuation. The authors noted that the patients' reactions were not consistently related to histamine-mediated allergic responses or specific lot variations. Factors such as lipid composition, particle size, infusion rate, and concentration of the drug in the IV solution could have potentially contributed to these reported toxicities. Overall, the reports suggested that slowing the infusion rate of liposomal amphotericin B could reduce the incidence or severity of infusion reactions, as noted in patient 2. However, factors such as lipid composition and patient characteristics could have also played a role in the likelihood and severity of these reactions. The authors concluded that further investigation was needed to fully understand the mechanisms behind these infusion-related reactions and to establish optimal strategies for preventing and managing them. [5]