Hepatic Insufficiency

Plasma concentrations of caspofungin after a single 70-mg dose in adult patients with mild hepatic insufficiency (Child-Pugh score 5 to 6) were increased by approximately 55% in AUC compared to healthy control subjects. In a 14-day multiple-dose study (70 mg on Day 1 followed by 50 mg daily thereafter), plasma concentrations in adult patients with mild hepatic insufficiency were increased modestly (19 to 25% in AUC) on Days 7 and 14 relative to healthy control subjects. No dosage adjustment is recommended for patients with mild hepatic insufficiency. Adult patients with moderate hepatic insufficiency (Child-Pugh score 7 to 9) who received a single 70-mg dose of CANCIDAS had an average plasma caspofungin increase of 76% in AUC compared to control subjects. A dosage reduction is recommended for adult patients with moderate hepatic insufficiency based upon this pharmacokinetic data [see Dosage and Administration (2.4)]. There is no clinical experience in adult patients with severe hepatic insufficiency (Child-Pugh score >9) or in pediatric patients with any degree of hepatic insufficiency.

Gender

Plasma concentrations of caspofungin in healthy adult men and women were similar following a single 70-mg dose. After 13 daily 50-mg doses, caspofungin plasma concentrations in women were elevated slightly (approximately 22% in area under the curve [AUC]) relative to men. No dosage adjustment is necessary based on gender.

Geriatric

Plasma concentrations of caspofungin in healthy older men and women (≥65 years of age) were increased slightly (approximately 28% AUC) compared to young healthy men after a single 70-mg dose of caspofungin. In patients who were treated empirically or who had candidemia or other Candida infections (intra-abdominal abscesses, peritonitis, or pleural space infections), a similar modest effect of age was seen in older patients relative to younger patients. No dosage adjustment is necessary for the elderly [see Use in Specific Populations (8.5)].

Pediatric

CANCIDAS has been studied in five prospective studies involving pediatric patients under 18 years of age, including three pediatric pharmacokinetic studies [initial study in adolescents (12-17 years of age) and children (2-11 years of age) followed by a study in younger patients (3-23 months of age) and then followed by a study in neonates and infants (<3 months)] [see Use in Specific Populations (8.4)].

Pharmacokinetic parameters following multiple doses of CANCIDAS in pediatric and adult patients are presented in Table 7.

TABLE 7: Pharmacokinetic Parameters Following Multiple Doses of CANCIDAS in Pediatric (3 months to 17 years) and Adult Patients 
Population
N

Daily
Dose Pharmacokinetic Parameters
(Mean ± Standard Deviation)
AUC0-24hr
(μg·hr/mL) C1hr
(μg/mL) C24hr
(μg/mL) t1/2(hr)* CI(mL/min)
*
Harmonic Mean ± jackknife standard deviation
†
N=5 for C 1hr and AUC 0-24hr; N=6 for C 24hr
‡
N=117 for C 24hr; N=119 for C 1hr
§
Following an initial 70-mg loading dose on day 1 
PEDIATRIC PATIENTS
Adolescents, Aged 12-17 years 8 50 mg/m2 124.9 ± 50.4 14.0 ± 6.9 2.4 ± 1.0 11.2 ± 1.7 12.6 &plus