Amphotericin B is notorious for causing unpleasant infusion-related reactions (some patients call it ‘amphoterrible’) including fevers (51%), chills (28%), nausea (18%), headache (9%) and thrombophlebitis (5%).
Patients on higher doses are also particularly at risk of nephrotoxicity: around half of patients on 10-15 mg/kg/day AmBisome will have >1.5x serum creatinine (Walsh et al, 2001).
Various lipid formulations are available that are less toxic than the deoxycholate form (reviewed by Hamill, 2013), but care must be taken to communicate which formulation and dosage has been prescribed where multiple forms are available (read a case commentary from the US DHHS about the root causes of a mix-up).
How to minimise side effects
- Carry out a 1 mg test dose
- Slow the rate of infusion (2-6 hours, deoxycholate formulation)
- Monitor the infusion site for signs of phlebitis
- Maintaining adequate vitamin D levels may protect against nephrotoxicity (Ferreira et al, 2019)
- Evidence for pretreatment with e.g. acetaminophen/corticosteroids is mixed (e.g. Goodwin et al, 2019; Paterson et al, 2008).
L-AmB and diphenhydramine
I: Chest pain, dyspnoea, and hypoxia (~20%, mainly first 5 minutes)
II: Flank pain, abdominal pain, and leg pain (~10%, first 5 minutes)
III: Flushing and urticaria (~12%, towards end of infusion)
In each case, symptoms were rapidly relieved by interrupting the L-AmB infusion and administering 1 mg/kg diphenhydramine. Pretreatment with 1 mg/kg diphenhydramine may be given 30 minutes before infusion.