volving patients with documented Candida infections, the majority of the patients had serious underlying medical conditions (e.g., hematologic or other malignancy, recent major surgery, HIV) requiring multiple concomitant medications. Patients in the noncomparative Aspergillus studies often had serious predisposing medical conditions (e.g., bone marrow or peripheral stem cell transplants, hematologic malignancy, solid tumors or organ transplants) requiring multiple concomitant medications.
Empirical Therapy
In the randomized, double-blinded empirical therapy study, patients received either CANCIDAS 50 mg/day (following a 70-mg loading dose) or AmBisome®2 (amphotericin B liposome for injection, 3.0 mg/kg/day). In this study clinical or laboratory hepatic adverse reactions were reported in 39% and 45% of patients in the CANCIDAS and AmBisome groups, respectively. Also reported was an isolated, serious adverse reaction of hyperbilirubinemia considered possibly related to CANCIDAS. Adverse reactions occurring in ≥7.5% of the patients in either treatment group are presented in Table 2.
TABLE 2: Adverse Reactions Among Patients with Persistent Fever and Neutropenia * — Incidence ≥7.5% for at Least One Treatment Group by System Organ Class or Preferred Term Adverse Reaction
(MedDRA v10.1 System Organ Class and Preferred Term) CANCIDAS†
N=564 (percent) AmBisome‡
N=547 (percent)
Within any system organ class, individuals may experience more than 1 adverse reaction.
*
Regardless of causality
†
70 mg on Day 1, then 50 mg daily for the remainder of treatment; daily dose was increased to 70 mg for 73 patients.
‡
3.0 mg/kg/day; daily dose was increased to 5.0 mg/kg for 74 patients.
All Systems, Any Adverse Reaction 95.2 97.3
Cardiac Disorders 16.3 18.6
Tachycardia 7.4 9.3
Gastrointestinal Disorders 50.4 55.2
Abdominal Pain 8.5 10.8
Diarrhea 20.2 15.9
Nausea 11.3 19.9
Vomiting 9.2 17.4
General Disorders and Administration Site Conditions 57.1 63.3
Chills 22.5 30.9
Mucosal Inflammation 6.0 7.5
Edema Peripheral 10.6 12.4
Pyrexia 27.1 29.1
Infections and Infestations 44.9 42.0
Pneumonia 11.3 9.9
Investigations 57.6 63.1
Alanine Aminotransferase Increased 18.1 20.1
Aspartate Aminotransferase Increased 14.2 17.4
Bilirubin Conjugated Increased 5.1 9.1
Blood Albumin Decreased 7.4 7.5
Blood Alkaline Phosphatase Increased 14.5 22.9
Blood Bilirubin Increased 10.3 13.7
Blood Creatinine Increased 3.4 11.3
Blood Glucose Increased 6.4 8.8
Blood Magnesium Decreased 7.1 9.0
Blood Potassium Decreased 15.2 22.5
Blood Urea Increased 3.9 7.9
Metabolism and Nutrition Disorders 21.3 24.1
Hypokalemia 6.4 8.2
Nervous System Disorders 25.4 27.4
Headache 10.5 12.1
Respiratory, Thoracic and Mediastinal Disorders 46.5 48.8
Cough 10.6 10.2
Dyspnea 9.2 9.7
Rales 6.9 7.7
Skin and Subcutaneous Tissue Disorders 42.2 37.3
Rash 16.0 13.5
Vascular Di
