adult subjects in the same study, 2 of 8 subjects who received CANCIDAS 35 mg daily for 3 days and cyclosporine (two 3 mg/kg doses administered 12 hours apart) on Day 1 had small increases in ALT (slightly above the ULN) on Day 2. In another clinical study, 2 of 8 healthy men developed transient ALT elevations of less than 2X ULN. In this study, cyclosporine (4 mg/kg) was administered on Days 1 and 12, and CANCIDAS was administered (70 mg) daily on Days 3 through 13. In one subject, the ALT elevation occurred on Days 7 and 9 and, in the other subject, the ALT elevation occurred on Day 19. These elevations returned to normal by Day 27. In all groups, elevations in AST paralleled ALT elevations but were of lesser magnitude. In these clinical studies, cyclosporine (one 4 mg/kg dose or two 3 mg/kg doses) increased the AUC of caspofungin by approximately 35% [see Warnings and Precautions (5.1)].
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2
Registered trademark of Gilead Sciences, Inc.
3
An infusion-related adverse reaction was defined as a systemic event, such as pyrexia, chills, flushing, hypotension, hypertension, tachycardia, dyspnea, tachypnea, rash, or anaphylaxis, that developed during the study therapy infusion and one hour following infusion.
4
An infusion-related adverse reaction was defined as a systemic event, such as pyrexia, chills, flushing, hypotension, hypertension, tachycardia, dyspnea, tachypnea, rash, or anaphylaxis, that developed during the study therapy infusion and one hour following infusion.
6.2 Clinical Trials Experience in Pediatric Patients (3 months to 17 years of age)
The overall safety of caspofungin was assessed in 171 pediatric patients who received single or multiple doses of CANCIDAS. The distribution among the 153 pediatric patients who were over the age of 3 months was as follows: 104 febrile, neutropenic patients; 38 patients with candidemia and/or intra-abdominal abscesses, peritonitis, or pleural space infections; 1 patient with esophageal candidiasis; and 10 patients with invasive aspergillosis. The overall safety profile of CANCIDAS in pediatric patients is comparable to that in adult patients. Table 5 shows the incidence of adverse reactions reported in ≥7.5% of pediatric patients in clinical studies.
One patient (0.6%) receiving CANCIDAS, and three patients (11.5%) receiving AmBisome developed a serious drug-related adverse reaction. Two patients (1.2%) were discontinued from CANCIDAS and three patients (11.5%) were discontinued from AmBisome due to a drug-related adverse reaction. The proportion of patients who experienced an infusion-related adverse reaction5 was 21.6% in the group treated with CANCIDAS and 34.6% in the group treated with AmBisome.
TABLE 5: Adverse Reactions Among Pediatric Patients (0 months to 17 years of age) * — Incidence ≥7.5% for at Least One Treatment Group by System Organ Class or Preferred Term Noncomparative
Clinical Studies Comparator-Controlled Clinical Study
of Empirical Therapy
Adverse Reaction
(MedDRA v10.0 System Organ Class and Preferred Term) CANCIDAS
Any Dose
N=115
(percent) CANCIDAS
50 mg/m2†
N=56
(percent) AmBisome
3 mg/kg
N=26
(percent)
Within any system organ class, individuals may experience more than 1 adverse reaction.
*
Regardless of causality
†
70 mg/m 2 on Day 1, then 50 mg/m 2 daily for the
