Amphotericin B Side Effects

ADVERSE REACTIONS The following adverse events are based on the experience of 592 adult patients (295 treated with amphotericin B liposome for injection and 297 treated with amphotericin B deoxycholate) and 95 pediatric patients (48 treated with amphotericin B liposome for injection and 47 treated with amphotericin B deoxycholate) in Study 94-0-002, a randomized double-blind, multicenter study in febrile, neutropenic patients.

Amphotericin B liposome for injection and amphotericin B were infused over two hours.

The incidence of common adverse events (incidence of 10% or greater) occurring with amphotericin B liposome for injection compared to amphotericin B deoxycholate, regardless of relationship to study drug, is shown in the following table: Empirical Therapy Study 94-0-002 Common Adverse Events Adverse Event by Body System Amphotericin B Liposome for Injection N=343 % Amphotericin B N=344 % Body as a Whole Abdominal pain 19.8 21.8 Asthenia 13.1 10.8 Back pain 12 7.3 Blood product transfusion reaction 18.4 18.6 Chills 47.5 75.9 Infection 11.1 9.3 Pain 14 12.8 Sepsis 14 11.3 Cardiovascular System Chest pain 12 11.6 Hypertension 7.9 16.3 Hypotension 14.3 21.5 Tachycardia 13.4 20.9 Digestive System Diarrhea 30.3 27.3 Gastrointestinal hemorrhage 9.9 11.3 Nausea 39.7 38.7 Vomiting 31.8 43.9 Metabolic and Nutritional Disorders Alkaline phosphatase increased 22.2 19.2 ALT (SGPT) increased 14.6 14 AST (SGOT) increased 12.8 12.8 Bilirubinemia 18.1 19.2 BUN increased 21 31.1 Creatinine increased 22.4 42.2 Edema 14.3 14.8 Hyperglycemia 23 27.9 Hypernatremia 4.1 11 Hypervolemia 12.2 15.4 Hypocalcemia 18.4 20.9 Hypokalemia 42.9 50.6 Hypomagnesemia 20.4 25.6 Peripheral edema 14.6 17.2 Nervous System Anxiety 13.7 11 Confusion 11.4 13.4 Headache 19.8 20.9 Insomnia 17.2 14.2 Respiratory System Cough increased 17.8 21.8 Dyspnea 23 29.1 Epistaxis 14.9 20.1 Hypoxia 7.6 14.8 Lung disorder 17.8 17.4 Pleural effusion 12.5 9.6 Rhinitis 11.1 11 Skin and Appendages Pruritus 10.8 10.2 Rash 24.8 24.4 Sweating 7 10.8 Urogenital System Hematuria 14 14 Amphotericin B liposome for injection was well tolerated.

Amphotericin B liposome for injection had a lower incidence of chills, hypertension, hypotension, tachycardia, hypoxia, hypokalemia, and various events related to decreased kidney function as compared to amphotericin B deoxycholate.

In pediatric patients (16 years of age or less) in this double-blind study, amphotericin B liposome for injection compared to amphotericin B deoxycholate, had a lower incidence of hypokalemia (37% versus 55%), chills (29% versus 68%), vomiting (27% versus 55%), and hypertension (10% versus 21%).

Similar trends, although with a somewhat lower incidence, were observed in open-label, randomized Study 104-14 involving 205 febrile neutropenic pediatric patients (141 treated with amphotericin B liposome for injection and 64 treated with amphotericin B deoxycholate).

Pediatric patients appear to have more tolerance than older individuals for the nephrotoxic effects of amphotericin B deoxycholate.

The following adverse events are based on the experience of 244 patients (202 adult and 42 pediatric patients) of whom 85 patients were treated with amphotericin B liposome for injection 3 mg/kg, 81 patients were treated with amphotericin B liposome for injection 5 mg/kg and 78 patients were treated with amphotericin B lipid complex 5 mg/kg in Study 97-0-034, a randomized, double-blind, multicenter study in febrile, neutropenic patients.

Amphotericin B liposome for injection and amphotericin B lipid complex were infused over two hours.

The incidence of adverse events occurring in more than 10% of subjects in one or more arms, regardless of relationship to study drug, are summarized in the following table: Empirical Therapy Study 97-0-034 Common Adverse Events Adverse Event by Body System Amphotericin B Liposome for Injection 3 mg/kg/day N=85 % Amphotericin B Liposome for Injection 5 mg/kg/day N=81 % Amphotericin B Lipid Complex 5 mg/kg/day N=78 % Body as a Whole Abdominal pain 12.9 9.9 11.5 Asthenia 8.2 6.2 11.5 Chills/rigors 40 48.1 89.7 Sepsis 12.9 7.4 11.5 Transfusion reaction 10.6 8.6 5.1 Cardiovascular System Chest pain 8.2 11.1 6.4 Hypertension 10.6 19.8 23.1 Hypotension 10.6 7.4 19.2 Tachycardia 9.4 18.5 23.1 Digestive System Diarrhea 15.3 17.3 14.1 Nausea 25.9 29.6 37.2 Vomiting 22.4 25.9 30.8 Metabolic and Nutritional Disorders Alkaline phosphatase increased 7.1 8.6 12.8 Bilirubinemia 16.5 11.1 11.5 BUN increased 20 18.5 28.2 Creatinine increased 20 18.5 48.7 Edema 12.9 12.3 12.8 Hyperglycemia 8.2 8.6 14.1 Hypervolemia 8.2 11.1 14.1 Hypocalcemia 10.6 4.9 5.1 Hypokalemia 37.6 43.2 39.7 Hypomagnesemia 15.3 25.9 15.4 Liver function tests abnormal 10.6 7.4 11.5 Nervous System Anxiety 10.6 7.4 9 Confusion 12.9 8.6 3.8 Headache 9.4 17.3 10.3 Respiratory System Dyspnea 17.6 22.2 23.1 Epistaxis 10.6 8.6 14.1 Hypoxia 7.1 6.2 20.5 Lung disorder 14.1 13.6 15.4 Skin and Appendages Rash 23.5 22.2 14.1 The following adverse events are based on the experience of 267 patients (266 adult patients and 1 pediatric patient) of whom 86 patients were treated with amphotericin B liposome for injection 3 mg/kg, 94 patients were treated with amphotericin B liposome for injection 6 mg/kg and 87 patients were treated with amphotericin B deoxycholate 0.7 mg/kg in Study 94-0-013 a randomized, double-blind, comparative multicenter trial, in the treatment of cryptococcal meningitis in HIV-positive patients.