Caspofungin Acetate
Caspofungin Acetate Prescribing Information
Caspofungin acetate for injection is an echinocandin antifungal indicated in adults and pediatric patients (3 months of age and older) for:
- Empirical therapy for presumed fungal infections in febrile, neutropenic patients. ()
1 INDICATIONS AND USAGECaspofungin acetate for injection is an echinocandin antifungal indicated in adults and pediatric patients (3 months of age and older) for:
- Empirical therapy for presumed fungal infections in febrile, neutropenic patients.
- Treatment of candidemia and the followingCandidainfections: intra-abdominal abscesses, peritonitis and pleural space infections.
- Treatment of esophageal candidiasis.
- Treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies.
1.1 Empirical Therapy for Presumed Fungal Infections in Febrile, Neutropenic PatientsCaspofungin acetate for injection is indicated as empirical therapy for presumed fungal infections in febrile, neutropenic adult and pediatric patients (3 months of age and older)
[see Clinical Studies (14.1, 14.5)].1.2 Treatment of Candidemia and OtherCandidaInfectionsCaspofungin acetate for injection is indicated for the treatment of candidemia and the following candida infections: intra-abdominal abscesses, peritonitis, and pleural space infections in adult and pediatric patients (3 months of age and older)
[see Clinical Studies (14.2, 14.5)].Caspofungin acetate for injection has not been studied in endocarditis, osteomyelitis, and meningitis due toLimitations of Use:Candida.1.3 Treatment of Esophageal CandidiasisCaspofungin acetate for injection is indicated for the treatment of esophageal candidiasis in adult and pediatric patients (3 months of age and older)
[see Clinical Studies (14.3, 14.5)].Caspofungin acetate for injection has not been approved for the treatment of oropharyngeal candidiasis (OPC). In the study that evaluated the efficacy of caspofungin in the treatment of esophageal candidiasis, patients with concomitant OPC had higher relapse rate of the OPCLimitations of Use:[see Clinical Studies (14.3)].1.4 Treatment of Invasive Aspergillosis in Patients Who Are Refractory to or Intolerant of Other TherapiesCaspofungin acetate for injection is indicated for the treatment of invasive aspergillosis in adult and pediatric patients (3 months of age and older) who are refractory to or intolerant of other therapies
[see Clinical Studies (14.4, 14.5)].Caspofungin acetate for injection has not been studied as initial therapy for invasive aspergillosis.Limitations of Use: - Treatment of candidemia and the followingCandidainfections: intra-abdominal abscesses, peritonitis and pleural space infections. ()
1 INDICATIONS AND USAGECaspofungin acetate for injection is an echinocandin antifungal indicated in adults and pediatric patients (3 months of age and older) for:
- Empirical therapy for presumed fungal infections in febrile, neutropenic patients.
- Treatment of candidemia and the followingCandidainfections: intra-abdominal abscesses, peritonitis and pleural space infections.
- Treatment of esophageal candidiasis.
- Treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies.
1.1 Empirical Therapy for Presumed Fungal Infections in Febrile, Neutropenic PatientsCaspofungin acetate for injection is indicated as empirical therapy for presumed fungal infections in febrile, neutropenic adult and pediatric patients (3 months of age and older)
[see Clinical Studies (14.1, 14.5)].1.2 Treatment of Candidemia and OtherCandidaInfectionsCaspofungin acetate for injection is indicated for the treatment of candidemia and the following candida infections: intra-abdominal abscesses, peritonitis, and pleural space infections in adult and pediatric patients (3 months of age and older)
[see Clinical Studies (14.2, 14.5)].Caspofungin acetate for injection has not been studied in endocarditis, osteomyelitis, and meningitis due toLimitations of Use:Candida.1.3 Treatment of Esophageal CandidiasisCaspofungin acetate for injection is indicated for the treatment of esophageal candidiasis in adult and pediatric patients (3 months of age and older)
[see Clinical Studies (14.3, 14.5)].Caspofungin acetate for injection has not been approved for the treatment of oropharyngeal candidiasis (OPC). In the study that evaluated the efficacy of caspofungin in the treatment of esophageal candidiasis, patients with concomitant OPC had higher relapse rate of the OPCLimitations of Use:[see Clinical Studies (14.3)].1.4 Treatment of Invasive Aspergillosis in Patients Who Are Refractory to or Intolerant of Other TherapiesCaspofungin acetate for injection is indicated for the treatment of invasive aspergillosis in adult and pediatric patients (3 months of age and older) who are refractory to or intolerant of other therapies
[see Clinical Studies (14.4, 14.5)].Caspofungin acetate for injection has not been studied as initial therapy for invasive aspergillosis.Limitations of Use: - Treatment of esophageal candidiasis. ()
1 INDICATIONS AND USAGECaspofungin acetate for injection is an echinocandin antifungal indicated in adults and pediatric patients (3 months of age and older) for:
- Empirical therapy for presumed fungal infections in febrile, neutropenic patients.
- Treatment of candidemia and the followingCandidainfections: intra-abdominal abscesses, peritonitis and pleural space infections.
- Treatment of esophageal candidiasis.
- Treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies.
1.1 Empirical Therapy for Presumed Fungal Infections in Febrile, Neutropenic PatientsCaspofungin acetate for injection is indicated as empirical therapy for presumed fungal infections in febrile, neutropenic adult and pediatric patients (3 months of age and older)
[see Clinical Studies (14.1, 14.5)].1.2 Treatment of Candidemia and OtherCandidaInfectionsCaspofungin acetate for injection is indicated for the treatment of candidemia and the following candida infections: intra-abdominal abscesses, peritonitis, and pleural space infections in adult and pediatric patients (3 months of age and older)
[see Clinical Studies (14.2, 14.5)].Caspofungin acetate for injection has not been studied in endocarditis, osteomyelitis, and meningitis due toLimitations of Use:Candida.1.3 Treatment of Esophageal CandidiasisCaspofungin acetate for injection is indicated for the treatment of esophageal candidiasis in adult and pediatric patients (3 months of age and older)
[see Clinical Studies (14.3, 14.5)].Caspofungin acetate for injection has not been approved for the treatment of oropharyngeal candidiasis (OPC). In the study that evaluated the efficacy of caspofungin in the treatment of esophageal candidiasis, patients with concomitant OPC had higher relapse rate of the OPCLimitations of Use:[see Clinical Studies (14.3)].1.4 Treatment of Invasive Aspergillosis in Patients Who Are Refractory to or Intolerant of Other TherapiesCaspofungin acetate for injection is indicated for the treatment of invasive aspergillosis in adult and pediatric patients (3 months of age and older) who are refractory to or intolerant of other therapies
[see Clinical Studies (14.4, 14.5)].Caspofungin acetate for injection has not been studied as initial therapy for invasive aspergillosis.Limitations of Use: - Treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies. ()
1 INDICATIONS AND USAGECaspofungin acetate for injection is an echinocandin antifungal indicated in adults and pediatric patients (3 months of age and older) for:
- Empirical therapy for presumed fungal infections in febrile, neutropenic patients.
- Treatment of candidemia and the followingCandidainfections: intra-abdominal abscesses, peritonitis and pleural space infections.
- Treatment of esophageal candidiasis.
- Treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies.
1.1 Empirical Therapy for Presumed Fungal Infections in Febrile, Neutropenic PatientsCaspofungin acetate for injection is indicated as empirical therapy for presumed fungal infections in febrile, neutropenic adult and pediatric patients (3 months of age and older)
[see Clinical Studies (14.1, 14.5)].1.2 Treatment of Candidemia and OtherCandidaInfectionsCaspofungin acetate for injection is indicated for the treatment of candidemia and the following candida infections: intra-abdominal abscesses, peritonitis, and pleural space infections in adult and pediatric patients (3 months of age and older)
[see Clinical Studies (14.2, 14.5)].Caspofungin acetate for injection has not been studied in endocarditis, osteomyelitis, and meningitis due toLimitations of Use:Candida.1.3 Treatment of Esophageal CandidiasisCaspofungin acetate for injection is indicated for the treatment of esophageal candidiasis in adult and pediatric patients (3 months of age and older)
[see Clinical Studies (14.3, 14.5)].Caspofungin acetate for injection has not been approved for the treatment of oropharyngeal candidiasis (OPC). In the study that evaluated the efficacy of caspofungin in the treatment of esophageal candidiasis, patients with concomitant OPC had higher relapse rate of the OPCLimitations of Use:[see Clinical Studies (14.3)].1.4 Treatment of Invasive Aspergillosis in Patients Who Are Refractory to or Intolerant of Other TherapiesCaspofungin acetate for injection is indicated for the treatment of invasive aspergillosis in adult and pediatric patients (3 months of age and older) who are refractory to or intolerant of other therapies
[see Clinical Studies (14.4, 14.5)].Caspofungin acetate for injection has not been studied as initial therapy for invasive aspergillosis.Limitations of Use:
Administer caspofungin acetate for injection by slow intravenous (IV) infusion over approximately 1 hour. Do not administer caspofungin acetate for injection by IV bolus administration.
- Administer by slow intravenous (IV) infusion over approximately 1 hour. Do not administer by IV bolus administration.
- Do not mix or co-infuse caspofungin acetate for injection with other medications. Do not use diluents containing dextrose (α–D-glucose).
The dosage and duration of caspofungin acetate for injection treatment for each indication are as follows:
Administer a single 70-mg loading dose on Day 1, followed by 50 mg once daily thereafter. Duration of treatment should be based on the patient's clinical response. Continue empirical therapy until resolution of neutropenia. In general, treat patients found to have a fungal infection for a minimum of 14 days after the last positive culture and continue treatment for at least 7 days after both neutropenia and clinical symptoms are resolved. If the 50-mg dose is well tolerated but does not provide an adequate clinical response, the daily dose can be increased to 70 mg.
Administer a single 70-mg loading dose on Day 1, followed by 50 mg once daily thereafter. Duration of treatment should be dictated by the patient's clinical and microbiological response. In general, continue antifungal therapy for at least 14 days after the last positive culture. Patients with neutropenia who remain persistently neutropenic may warrant a longer course of therapy pending resolution of the neutropenia.
The dose is 50 mg once daily for 7 to 14 days after symptom resolution. A 70-mg loading dose has not been studied for this indication. Because of the risk of relapse of oropharyngeal candidiasis in patients with HIV infections, suppressive oral therapy could be considered
Administer a single 70-mg loading dose on Day 1, followed by 50 mg once daily thereafter. Duration of treatment should be based upon the severity of the patient's underlying disease, recovery from immunosuppression, and clinical response.
- Administer a single 70-mg loading dose on Day 1, followed by 50 mg once daily for all indications except esophageal candidiasis.
- For esophageal candidiasis, use 50 mg once daily with no loading dose.
For all indications, administer a single 70 mg/m2loading dose on Day 1, followed by 50 mg/m2once daily thereafter.
Following calculation of the patient's BSA, the loading dose in milligrams should be calculated as BSA (m2) × 70 mg/m2. The maintenance dose in milligrams should be calculated as BSA (m2) × 50 mg/m2.
Duration of treatment should be individualized to the indication, as described for each indication in adults
- Dosing should be based on the patient's body surface area.
- For all indications, administer a single 70-mg/m
2loading dose on Day 1, followed by 50 mg/m
2once daily thereafter. - Maximum loading dose and daily maintenance dose should not exceed 70 mg, regardless of the patient's calculated dose.
Adult patients with mild hepatic impairment (Child-Pugh score 5 to 6) do not need a dosage adjustment. For adult patients with moderate hepatic impairment (Child-Pugh score 7 to 9), caspofungin 35 mg once daily is recommended based upon pharmacokinetic data
Reduce dosage for adult patients with moderate hepatic impairment (35 mg once daily, with a 70 mg loading dose on Day 1 where appropriate).
Adult patients on rifampin should receive 70 mg of caspofungin once daily. When caspofungin acetate for injection is co-administered to adult patients with other inducers of hepatic CYP enzymes such as nevirapine, efavirenz, carbamazepine, dexamethasone, or phenytoin, administration of a daily dose of 70 mg of caspofungin should be considered
Pediatric patients on rifampin should receive 70 mg/m2of caspofungin daily (not to exceed an actual daily dose of 70 mg). When caspofungin acetate for injection is co-administered to pediatric patients with other inducers of hepatic CYP enzymes, such as efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, a caspofungin acetate for injection dose of 70 mg/m2once daily (not to exceed 70 mg) should be considered
- Use 70-mg once daily dose for adult patients on rifampin.
- Consider dose increase to 70 mg once daily for adult patients on nevirapine, efavirenz, carbamazepine, dexamethasone, or phenytoin.
- Pediatric patients receiving these same concomitant medications may also require an increase in dose to 70 mg/m
2once daily (maximum daily dose not to exceed 70 mg).
Caspofungin acetate for injection 50 mg is a white to off-white lyophilized cake or powder for reconstitution in a single-dose glass vial with an aluminum band and a yellow cap. Caspofungin acetate for injection 50-mg vial contains 50 mg of caspofungin equivalent to 55.5 mg of caspofungin acetate.
Caspofungin acetate for injection 70 mg is a white to off-white lyophilized cake or powder for reconstitution in a single-dose glass vial with an aluminum band and an orange cap. Caspofungin acetate for injection 70-mg vial contains 70 mg of caspofungin equivalent to 77.7 mg of caspofungin acetate.
- Pregnancy:Based on animal data, may cause fetal harm. ()
8.1 PregnancyRisk SummaryBased on animal data, caspofungin may cause fetal harm
(see Data). There are insufficient human data to establish whether there is a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes with caspofungin use in pregnant women.In animal studies, caspofungin caused embryofetal toxicity, including increased resorptions, increased peri-implantation loss, and incomplete ossification at multiple fetal sites when administered intravenously to pregnant rats and rabbits during organogenesis at doses up to 0.8 and 2 times the clinical dose, respectively (
see Data). Advise patients of the potential risk to the fetus.The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
DataAnimal DataIn animal reproduction studies, pregnant rats dosed intravenously with caspofungin during organogenesis (gestational days [GD] 6 to 20) at 0.5, 2, or 5 mg/kg/day (up to 0.8 times the clinical dose based on body surface area comparison) showed increased resorptions and peri-implantation losses at 5 mg/kg/day. Incomplete ossification of the skull and torso and increased incidences of cervical rib were noted in offspring born to pregnant rats treated at doses up to 5 mg/kg/day. In pregnant rabbits treated with intravenous caspofungin during organogenesis (GD 7 to 20) at doses of 1, 3, or 6 mg/kg/day (approximately 2 times the clinical dose based on body surface area comparison), increased fetal resorptions and increased incidence of incomplete ossification of the talus/calcaneus in offspring were observed at the highest dose tested. Caspofungin crossed the placenta in rats and rabbits and was detectable in fetal plasma.
In peri- and postnatal development study in rats, intravenous caspofungin administered at 0.5, 2 or 5 mg/kg/day from Day 6 of gestation through Day 20 of lactation was not associated with any adverse effects on reproductive performance or subsequent development of first generation (F1) offspring or malformations in second generation (F2) offspring.
- Pediatric Use:Safety and efficacy in neonates and infants less than 3 months old have not been established. ()
8.4 Pediatric UseThe safety and effectiveness of caspofungin in pediatric patients 3 months to 17 years of age are supported by evidence from adequate and well-controlled studies in adults, pharmacokinetic data in pediatric patients, and additional data from prospective studies in pediatric patients 3 months to 17 years of age for the following indications
[see Indications and Usage (1)]:- Empirical therapy for presumed fungal infections in febrile, neutropenic patients.
- Treatment of candidemia and the followingCandidainfections: intra-abdominal abscesses, peritonitis, and pleural space infections.
- Treatment of esophageal candidiasis.
- Treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies (e.g., amphotericin B, lipid formulations of amphotericin B, itraconazole).
The efficacy and safety of caspofungin has not been adequately studied in prospective clinical trials involving neonates and infants under 3 months of age. Although limited pharmacokinetic data were collected in neonates and infants below 3 months of age, these data are insufficient to establish a safe and effective dose of caspofungin in the treatment of neonatal candidiasis. Invasive candidiasis in neonates has a higher rate of CNS and multi-organ involvement than in older patients; the ability of caspofungin to penetrate the blood-brain barrier and to treat patients with meningitis and endocarditis is unknown.
Caspofungin has not been studied in pediatric patients with endocarditis, osteomyelitis, and meningitis due to
Candida. Caspofungin has also not been studied as initial therapy for invasive aspergillosis in pediatric patients.In clinical trials, 171 pediatric patients (0 months to 17 years of age), including 18 patients who were less than 3 months of age, were given intravenous caspofungin. Pharmacokinetic studies enrolled a total of 66 pediatric patients, and an additional 105 pediatric patients received caspofungin in safety and efficacy studies
[see Clinical Pharmacology (12.3)and Clinical Studies (14.5)].The majority of the pediatric patients received caspofungin at a once-daily maintenance dose of 50 mg/m2for a mean duration of 12 days (median 9, range 1-87 days). In all studies, safety was assessed by the investigator throughout study therapy and for 14 days following cessation of study therapy. The most common adverse reactions in pediatric patients treated with caspofungin were pyrexia (29%), blood potassium decreased (15%), diarrhea (14%), increased aspartate aminotransferase (12%), rash (12%), increased alanine aminotransferase (11%), hypotension (11%), and chills (11%)[see Adverse Reactions (6.2)].Postmarketing hepatobiliary adverse reactions have been reported in pediatric patients with serious underlying medical conditions
[see Warnings and Precautions (5.3)]. - Hepatic Impairment:Reduce dose for adult patients with moderate hepatic impairment (35 mg once daily, with a 70-mg loading dose on Day 1 where appropriate). No data are available in adults with severe impairment or in pediatric patients with any degree of hepatic impairment. (,
2.4 Dosage Adjustments in Patients with Hepatic ImpairmentAdult patients with mild hepatic impairment (Child-Pugh score 5 to 6) do not need a dosage adjustment. For adult patients with moderate hepatic impairment (Child-Pugh score 7 to 9), caspofungin 35 mg once daily is recommended based upon pharmacokinetic data
[see Clinical Pharmacology (12.3)]with a 70-mg loading dose administered on Day 1 where appropriate. There is no clinical experience in adult patients with severe hepatic impairment (Child-Pugh score greater than 9) and in pediatric patients with any degree of hepatic impairment.,8.6 Patients with Hepatic ImpairmentAdult patients with mild hepatic impairment (Child-Pugh score 5 to 6) do not need a dosage adjustment. For adult patients with moderate hepatic impairment (Child-Pugh score 7 to 9), caspofungin 35 mg once daily is recommended based upon pharmacokinetic data
[see Clinical Pharmacology (12.3)]. However, where recommended, a 70-mg loading dose should still be administered on Day 1[see Dosage and Administration (2.4)and Clinical Pharmacology (12.3)].There is no clinical experience in adult patients with severe hepatic impairment (Child-Pugh score greater than 9) and in pediatric patients 3 months to 17 years of age with any degree of hepatic impairment.)12.3 PharmacokineticsAdult and pediatric pharmacokinetic parameters are presented in Table 8.
DistributionPlasma concentrations of caspofungin decline in a polyphasic manner following single 1-hour IV infusions. A short α-phase occurs immediately postinfusion, followed by a β-phase (half-life of 9 to 11 hours) that characterizes much of the profile and exhibits clear log-linear behavior from 6 to 48 hours postdose during which the plasma concentration decreases 10-fold. An additional, longer half-life phase, γ-phase, (half-life of 40-50 hours), also occurs. Distribution, rather than excretion or biotransformation, is the dominant mechanism influencing plasma clearance. Caspofungin is extensively bound to albumin (~97%), and distribution into red blood cells is minimal. Mass balance results showed that approximately 92% of the administered radioactivity was distributed to tissues by 36 to 48 hours after a single 70-mg dose of [3H] caspofungin. There is little excretion or biotransformation of caspofungin during the first 30 hours after administration.
MetabolismCaspofungin is slowly metabolized by hydrolysis and N-acetylation. Caspofungin also undergoes spontaneous chemical degradation to an open-ring peptide compound, L-747969. At later time points (≥5 days postdose), there is a low level (≤7 picomoles/mg protein, or ≤1.3% of administered dose) of covalent binding of radiolabel in plasma following single-dose administration of [3H] caspofungin, which may be due to two reactive intermediates formed during the chemical degradation of caspofungin to L-747969. Additional metabolism involves hydrolysis into constitutive amino acids and their degradates, including dihydroxyhomotyrosine and N-acetyl-dihydroxyhomotyrosine. These two tyrosine derivatives are found only in urine, suggesting rapid clearance of these derivatives by the kidneys.
ExcretionTwo single-dose radiolabeled pharmacokinetic studies were conducted. In one study, plasma, urine, and feces were collected over 27 days, and in the second study plasma was collected over 6 months. Plasma concentrations of radioactivity and of caspofungin were similar during the first 24 to 48 hours postdose; thereafter drug levels fell more rapidly. In plasma, caspofungin concentrations fell below the limit of quantitation after 6 to 8 days postdose, while radiolabel fell below the limit of quantitation at 22.3 weeks postdose. After single intravenous administration of [3H] caspofungin, excretion of caspofungin and its metabolites in humans was 35% of dose in feces and 41% of dose in urine. A small amount of caspofungin is excreted unchanged in urine (~1.4% of dose). Renal clearance of parent drug is low (~0.15 mL/min) and total clearance of caspofungin is 12 mL/min.
Special PopulationsRenal ImpairmentIn a clinical study of single 70-mg doses, caspofungin pharmacokinetics were similar in healthy adult volunteers with mild renal impairment (creatinine clearance 50 to 80 mL/min) and control subjects. Moderate (creatinine clearance 31 to 49 mL/min), severe (creatinine clearance 5 to 30 mL/min), and end-stage (creatinine clearance less than 10 mL/min and dialysis dependent) renal impairment moderately increased caspofungin plasma concentrations after single-dose administration (range: 30 to 49% for AUC). However, in adult patients with invasive aspergillosis, candidemia, or other
Candidainfections (intra-abdominal abscesses, peritonitis, or pleural space infections) who received multiple daily doses of caspofungin 50 mg, there was no significant effect of mild to end-stage renal impairment on caspofungin concentrations. No dosage adjustment is necessary for patients with renal impairment. Caspofungin is not dialyzable, thus supplementary dosing is not required following hemodialysis.Hepatic ImpairmentPlasma concentrations of caspofungin after a single 70-mg dose in adult patients with mild hepatic impairment (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 impairment 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 impairment.
Adult patients with moderate hepatic impairment (Child-Pugh score 7 to 9) who received a single 70-mg dose of caspofungin 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 impairment based upon these pharmacokinetic data
[see Dosage and Administration (2.4)].There is no clinical experience in adult patients with severe hepatic impairment (Child-Pugh score greater than 9) or in pediatric patients with any degree of hepatic impairment.
GenderPlasma 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.
RaceRegression analyses of patient pharmacokinetic data indicated that no clinically significant differences in the pharmacokinetics of caspofungin were seen among Caucasians, Blacks, and Hispanics. No dosage adjustment is necessary on the basis of race.
Geriatric PatientsPlasma concentrations of caspofungin in healthy older men and women (65 years of age and older) 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
Candidainfections (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 PatientsCaspofungin acetate for injection 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 (less than 3 months of age)]
[see Use in Specific Populations (8.4)].Pharmacokinetic parameters following multiple doses of caspofungin in pediatric and adult patients are presented in Table 8.
Table 8: Pharmacokinetic Parameters Following Multiple Doses of Caspofungin 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)Harmonic Mean ± jackknife standard deviationCI
(mL/min)PEDIATRIC PATIENTSAdolescents, 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 ± 5.5 Children, Aged 2-11 years 9 50 mg/m2 120.0 ± 33.4 16.1 ± 4.2 1.7 ± 0.8 8.2 ± 2.4 6.4 ± 2.6 Young Children, Aged 3-23 months 8 50 mg/m2 131.2 ± 17.7 17.6 ± 3.9 1.7 ± 0.7 8.8 ± 2.1 3.2 ± 0.4 ADULT PATIENTSAdults with Esophageal Candidiasis 6N=5 for C
1hr and AUC
0-24hr; N=6 for C
24hr50 mg 87.3 ± 30.0 8.7 ± 2.1 1.7 ± 0.7 13.0 ± 1.9 10.6 ± 3.8 Adults receiving Empirical Therapy 119N=117 for C
24hr; N=119 for C
1hr50 mgFollowing an initial 70-mg loading dose on day 1 -- 8.0 ± 3.4 1.6 ± 0.7 -- -- Drug Interactions [see Drug Interactions (7)]Studies
in vitroshow that caspofungin acetate is not an inhibitor of any enzyme in the cytochrome P (CYP) system. Caspofungin is not a substrate for P-glycoprotein and is a poor substrate for CYP enzymes.In clinical studies, caspofungin did not induce the CYP3A4 metabolism of other drugs. Clinical studies in adult healthy volunteers also demonstrated that the pharmacokinetics of caspofungin are not altered by itraconazole, amphotericin B, mycophenolate, nelfinavir, or tacrolimus. Caspofungin has no effect on the pharmacokinetics of itraconazole, amphotericin B, or the active metabolite of mycophenolate.
In two adult clinical studies, cyclosporine (one 4 mg/kg dose or two 3 mg/kg doses) increased the AUC of caspofungin by approximately 35%. Caspofungin did not increase the plasma levels of cyclosporine. There were transient increases in liver ALT and AST when caspofungin and cyclosporine were co-administeredCyclosporine:[see Warnings and Precautions (5.2)].Caspofungin reduced the blood AUC0-12of tacrolimus (FK-506, Prograf®) by approximately 20%, peak blood concentration (Cmax) by 16%, and 12-hour blood concentration (C12hr) by 26% in healthy adult subjects when tacrolimus (2 doses of 0.1 mg/kg 12 hours apart) was administered on the 10th day of caspofungin 70 mg daily, as compared to results from a control period in which tacrolimus was administered alone. For patients receiving both therapies, standard monitoring of tacrolimus whole blood trough concentrations and appropriate tacrolimus dosage adjustments are recommended.Tacrolimus:A drug-drug interaction study with rifampin in adult healthy volunteers has shown a 30% decrease in caspofungin trough concentrationsRifampin:[see Dosage and Administration (2.5)].Other Inducers of Hepatic CYP EnzymesResults from regression analyses of adult patient pharmacokinetic data suggest that co-administration of other hepatic CYP enzyme inducers (e.g., efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine) with caspofungin may result in clinically meaningful reductions in caspofungin concentrations. It is not known which drug clearance mechanism involved in caspofungin disposition may be inducibleAdults:[see Dosage and Administration (2.5)].In pediatric patients, results from regression analyses of pharmacokinetic data suggest that co-administration of dexamethasone with caspofungin may result in clinically meaningful reductions in caspofungin trough concentrations. This finding may indicate that pediatric patients will have similar reductions with inducers as seen in adultsPediatric patients:[see Dosage and Administration (2.5)].
Caspofungin acetate for injection is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis) to any component of this product
The following serious adverse reactions are discussed in detail in another section of the labeling:
- Hypersensitivity[see Warnings and Precautions (5.1)]
- Hepatic Effects[see Warnings and Precautions (5.2)]
- Elevated Liver Enzymes During Concomitant Use With Cyclosporine[see Warnings and Precautions (5.3)]
- Adults:Most common adverse reactions (incidence 10% or greater) are diarrhea, pyrexia, ALT/AST increased, blood alkaline phosphatase increased, and blood potassium decreased.
- Pediatric Patients:Most common adverse reactions (incidence ≥10%) are pyrexia, diarrhea, rash, ALT/AST increased, blood potassium decreased, hypotension, and chills.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of caspofungin cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.
The overall safety of caspofungin was assessed in 1865 adult individuals who received single or multiple doses of caspofungin: 564 febrile, neutropenic patients (empirical therapy study); 382 patients with candidemia and/or intra-abdominal abscesses, peritonitis, or pleural space infections (including 4 patients with chronic disseminated candidiasis); 297 patients with esophageal and/or oropharyngeal candidiasis; 228 patients with invasive aspergillosis; and 394 individuals in phase I studies. In the empirical therapy study patients had undergone hematopoietic stem-cell transplantation or chemotherapy. In the studies involving patients with documented
In the randomized, double-blinded empirical therapy study, patients received either caspofungin 50 mg/day (following a 70-mg loading dose) or AmBisome®(amphotericin B liposome for injection, 3 mg/kg/day). In this study clinical or laboratory hepatic adverse reactions were reported in 39% and 45% of patients in the caspofungin and AmBisome groups, respectively. Also reported was an isolated, serious adverse reaction of hyperbilirubinemia. Adverse reactions occurring in 7.5% or greater of the patients in either treatment group are presented in Table 2.
| Adverse Reactions | Caspofungin70 mg on Day 1, then 50 mg once daily for the remainder of treatment; daily dose was increased to 70 mg for 73 patients. N=564 (percent) | AmBisome3 mg/kg/day; daily dose was increased to 5 mg/kg for 74 patients. N=547 (percent) |
|---|---|---|
| Within any system organ class, individuals may experience more than 1 adverse reaction. | ||
All Systems, Any Adverse Reaction | 95 | 97 |
Investigations | 58 | 63 |
| Alanine Aminotransferase Increased | 18 | 20 |
| Blood Alkaline Phosphatase Increased | 15 | 23 |
| Blood Potassium Decreased | 15 | 23 |
| Aspartate Aminotransferase Increased | 14 | 17 |
| Blood Bilirubin Increased | 10 | 14 |
| Blood Magnesium Decreased | 7 | 9 |
| Blood Glucose Increased | 6 | 9 |
| Bilirubin Conjugated Increased | 5 | 9 |
| Blood Urea Increased | 4 | 8 |
| Blood Creatinine Increased | 3 | 11 |
General Disorders and Administration Site Conditions | 57 | 63 |
| Pyrexia | 27 | 29 |
| Chills | 23 | 31 |
| Edema Peripheral | 11 | 12 |
| Mucosal Inflammation | 6 | 8 |
Gastrointestinal Disorders | 50 | 55 |
| Diarrhea | 20 | 16 |
| Nausea | 11 | 20 |
| Abdominal Pain | 9 | 11 |
| Vomiting | 9 | 17 |
Respiratory, Thoracic and Mediastinal Disorders | 47 | 49 |
| Dyspnea | 9 | 10 |
Skin and Subcutaneous Tissue Disorders | 42 | 37 |
| Rash | 16 | 14 |
Nervous System Disorders | 25 | 27 |
| Headache | 11 | 12 |
Metabolism and Nutrition Disorders | 21 | 24 |
| Hypokalemia | 6 | 8 |
Vascular Disorders | 20 | 23 |
| Hypotension | 6 | 10 |
Cardiac Disorders | 16 | 19 |
| Tachycardia | 7 | 9 |
The proportion of patients who experienced an infusion-related adverse reaction (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) was significantly lower in the group treated with caspofungin (35%) than in the group treated with AmBisome (52%).
To evaluate the effect of caspofungin and AmBisome on renal function, nephrotoxicity was defined as doubling of serum creatinine relative to baseline or an increase of greater than or equal to 1 mg/dL in serum creatinine if baseline serum creatinine was above the upper limit of the normal range. Among patients whose baseline creatinine clearance was greater than 30 mL/min, the incidence of nephrotoxicity was significantly lower in the group treated with caspofungin (3%) than in the group treated with AmBisome (12%).
In the randomized, double-blinded invasive candidiasis study, patients received either caspofungin 50 mg/day (following a 70-mg loading dose) or amphotericin B 0.6 to 1 mg/kg/day. Adverse reactions occurring in 10% or greater of the patients in either treatment group are presented in Table 3.
| Adverse Reactions | Caspofungin 50 mgPatients received caspofungin 70 mg on Day 1, then 50 mg once daily for the remainder of their treatment. N=114 (percent) | Amphotericin B N=125 (percent) |
|---|---|---|
| Within any system organ class, individuals may experience more than 1 adverse reaction. | ||
All Systems, Any Adverse Reaction | 96 | 99 |
Investigations | 67 | 82 |
| Blood Potassium Decreased | 23 | 32 |
| Blood Alkaline Phosphatase Increased | 21 | 32 |
| Hemoglobin Decreased | 18 | 23 |
| Alanine Aminotransferase Increased | 16 | 15 |
| Aspartate Aminotransferase Increased | 16 | 14 |
| Blood Bilirubin Increased | 13 | 17 |
| Hematocrit Decreased | 13 | 18 |
| Blood Creatinine Increased | 11 | 28 |
| Red Blood Cells Urine Positive | 10 | 10 |
| Blood Urea Increased | 9 | 23 |
| Bilirubin Conjugated Increased | 8 | 14 |
Gastrointestinal Disorders | 49 | 53 |
| Vomiting | 17 | 16 |
| Diarrhea | 14 | 10 |
| Nausea | 9 | 17 |
General Disorders and Administration Site Conditions | 47 | 63 |
| Pyrexia | 13 | 33 |
| Edema Peripheral | 11 | 12 |
| Chills | 9 | 30 |
Respiratory, Thoracic and Mediastinal Disorders | 40 | 54 |
| Tachypnea | 1 | 11 |
Cardiac Disorders | 26 | 34 |
| Tachycardia | 8 | 12 |
Skin and Subcutaneous Tissue Disorders | 25 | 28 |
| Rash | 4 | 10 |
Vascular Disorders | 25 | 38 |
| Hypotension | 10 | 16 |
Blood and Lymphatic System Disorders | 15 | 13 |
| Anemia | 11 | 9 |
The proportion of patients who experienced an infusion-related adverse reaction (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) was significantly lower in the group treated with caspofungin (20%) than in the group treated with amphotericin B (49%).
To evaluate the effect of caspofungin and amphotericin B on renal function, nephrotoxicity was defined as doubling of serum creatinine relative to baseline or an increase of greater than or equal to 1 mg/dL in serum creatinine if baseline serum creatinine was above the upper limit of the normal range. In a subgroup of patients whose baseline creatinine clearance was greater than 30 mL/min, the incidence of nephrotoxicity was significantly lower in the group treated with caspofungin than in the group treated with amphotericin B.
In a second randomized, double-blinded invasive candidiasis study, patients received either caspofungin 50 mg/day (following a 70-mg loading dose) or caspofungin 150 mg/day. The proportion of patients who experienced any adverse reaction was similar in the 2 treatment groups; however, this study was not large enough to detect differences in rare or unexpected adverse reactions. Adverse reactions occurring in 5% or greater of the patients in either treatment group are presented in Table 4.
| Adverse Reactions | Caspofungin 50 mgPatients received caspofungin 70 mg on Day 1, then 50 mg once daily for the remainder of their treatment. N=104 (percent) | Caspofungin 150 mg N=100 (percent) |
|---|---|---|
| Within any system organ class, individuals may experience more than 1 adverse event | ||
All Systems, Any Adverse Reaction | 83 | 83 |
General Disorders and Administration Site Conditions | 33 | 27 |
| Pyrexia | 6 | 6 |
Gastrointestinal Disorders | 30 | 33 |
| Vomiting | 11 | 6 |
| Diarrhea | 6 | 7 |
| Nausea | 5 | 7 |
Investigations | 28 | 35 |
| Alkaline Phosphatase Increased | 12 | 9 |
| Aspartate Aminotransferase Increased | 6 | 9 |
| Blood potassium decreased | 6 | 8 |
| Alanine Aminotransferase Increased | 4 | 7 |
Vascular Disorders | 19 | 18 |
| Hypotension | 7 | 3 |
| Hypertension | 5 | 6 |
Adverse reactions occurring in 10% or greater of patients with esophageal and/or oropharyngeal candidiasis are presented in Table 5.
| Adverse Reactions | Caspofungin 50 mgDerived from a comparator-controlled clinical study. N=83 (percent) | Fluconazole IV 200 mg N=94 (percent) |
|---|---|---|
| Within any system organ class, individuals may experience more than 1 adverse reaction. | ||
All Systems, Any Adverse Reaction | 90 | 93 |
Gastrointestinal Disorders | 58 | 50 |
| Diarrhea | 27 | 18 |
| Nausea | 15 | 15 |
Investigations | 53 | 61 |
| Hemoglobin Decreased | 21 | 16 |
| Hematocrit Decreased | 18 | 16 |
| Aspartate Aminotransferase Increased | 13 | 19 |
| Blood Alkaline Phosphatase Increased | 13 | 17 |
| Alanine Aminotransferase Increased | 12 | 17 |
| White Blood Cell Count Decreased | 12 | 19 |
General Disorders and Administration Site Conditions | 31 | 36 |
| Pyrexia | 21 | 21 |
Vascular Disorders | 19 | 15 |
| Phlebitis | 18 | 11 |
Nervous System Disorders | 18 | 17 |
| Headache | 15 | 9 |
In an open-label, noncomparative aspergillosis study, in which 69 patients received caspofungin (70-mg loading dose on Day 1 followed by 50 mg daily), the following adverse reactions were observed with an incidence of 12.5% or greater: blood alkaline phosphatase increased (22%), hypotension (20%), respiratory failure (20%), pyrexia (17%), diarrhea (15%), nausea (15%), headache (15%), rash (13%), alanine aminotransferase increased (13%), aspartate aminotransferase increased (13%), blood bilirubin increased (13%), and blood potassium decreased (13%). Also reported in this patient population were pulmonary edema, ARDS (adult respiratory distress syndrome), and radiographic infiltrates.
The overall safety of caspofungin was assessed in 171 pediatric patients who received single or multiple doses of caspofungin. 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 caspofungin in pediatric patients is comparable to that in adult patients. Table 6 shows the incidence of adverse reactions reported in 7.5% or greater of pediatric patients in clinical studies.
One patient (0.6%) receiving caspofungin, and three patients (12%) receiving AmBisome developed a serious drug-related adverse reaction. Two patients (1%) were discontinued from caspofungin and three patients (12%) were discontinued from AmBisome due to a drug-related adverse reaction. The proportion of patients who experienced an infusion-related adverse reaction (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) was 22% in the group treated with caspofungin and 35% in the group treated with AmBisome.
| Noncomparative Clinical Studies | Comparator-Controlled Clinical Study of Empirical Therapy | ||
|---|---|---|---|
| Adverse Reactions | Caspofungin Any Dose N=115 (percent) | Caspofungin 50 mg/m270 mg/m 2 on Day 1, then 50 mg/m 2 once daily for the remainder of the treatment. N=56 (percent) | AmBisome 3 mg/kg N=26 (percent) |
| Within any system organ class, individuals may experience more than 1 adverse reaction. | |||
All Systems, Any Adverse Reaction | 95 | 96 | 89 |
Investigations | 55 | 41 | 50 |
| Blood Potassium Decreased | 18 | 9 | 27 |
| Aspartate Aminotransferase Increased | 17 | 2 | 12 |
| Alanine Aminotransferase Increased | 14 | 5 | 12 |
| Blood Potassium Increased | 3 | 0 | 8 |
General Disorders and Administration Site Conditions | 47 | 59 | 42 |
| Pyrexia | 29 | 30 | 23 |
| Chills | 10 | 13 | 8 |
| Mucosal Inflammation | 10 | 4 | 4 |
| Edema | 3 | 4 | 8 |
Gastrointestinal Disorders | 42 | 41 | 35 |
| Diarrhea | 17 | 7 | 15 |
| Vomiting | 8 | 11 | 12 |
| Abdominal Pain | 7 | 4 | 12 |
| Nausea | 4 | 4 | 8 |
Infections and Infestations | 40 | 30 | 35 |
| Central Line Infection | 1 | 9 | 0 |
Skin and Subcutaneous Tissue Disorders | 33 | 41 | 39 |
| Pruritus | 7 | 6 | 8 |
| Rash | 6 | 23 | 8 |
| Erythema | 4 | 9 | 0 |
Vascular Disorders | 24 | 21 | 19 |
| Hypotension | 12 | 9 | 8 |
| Hypertension | 10 | 9 | 4 |
Metabolism and Nutrition Disorders | 22 | 11 | 23 |
| Hypokalemia | 8 | 5 | 4 |
Cardiac Disorders | 17 | 13 | 19 |
| Tachycardia | 4 | 11 | 19 |
Nervous System Disorders | 13 | 16 | 8 |
| Headache | 5 | 9 | 4 |
Musculoskeletal and Connective Tissue Disorders | 11 | 14 | 12 |
| Back Pain | 4 | 0 | 8 |
Blood and Lymphatic System Disorders | 10 | 2 | 15 |
| Anemia | 2 | 0 | 8 |
The overall safety of caspofungin was assessed in 2036 individuals (including 1642 adult or pediatric patients and 394 volunteers) from 34 clinical studies. These individuals received single or multiple (once daily) doses of caspofungin, ranging from 5 mg to 210 mg. Full safety data is available from 1951 individuals, as the safety data from 85 patients enrolled in 2 compassionate use studies was limited solely to serious adverse reactions. Adverse reactions which occurred in 5% or greater of all individuals who received caspofungin in these trials are shown in Table 7.
Overall, 1665 of the 1951 (85%) patients/volunteers who received caspofungin experienced an adverse reaction.
| Adverse ReactionsWithin any system organ class, individuals may experience more than 1 adverse event. | Caspofungin (N = 1951) | |
|---|---|---|
| n | (%) | |
All Systems, Any Adverse Reaction | 1665 | (85) |
Investigations | 901 | (46) |
| Alanine Aminotransferase Increased | 258 | (13) |
| Aspartate Aminotransferase Increased | 233 | (12) |
| Blood Alkaline Phosphatase Increased | 232 | (12) |
| Blood Potassium Decreased | 220 | (11) |
| Blood Bilirubin Increased | 117 | (6) |
General Disorders and Administration Site Conditions | 843 | (43) |
| Pyrexia | 381 | (20) |
| Chills | 192 | (10) |
| Edema Peripheral | 110 | (6) |
Gastrointestinal Disorders | 754 | (39) |
| Diarrhea | 273 | (14) |
| Nausea | 166 | (9) |
| Vomiting | 146 | (8) |
| Abdominal Pain | 112 | (6) |
Infections and Infestations | 730 | (37) |
| Pneumonia | 115 | (6) |
Respiratory, Thoracic, and Mediastinal Disorders | 613 | (31) |
| Cough | 111 | (6) |
Skin and Subcutaneous Tissue Disorders | 520 | (27) |
| Rash | 159 | (8) |
| Erythema | 98 | (5) |
Nervous System Disorders | 412 | (21) |
| Headache | 193 | (10) |
Vascular Disorders | 344 | (18) |
| Hypotension | 118 | (6) |
Clinically significant adverse reactions, regardless of causality or incidence which occurred in less than 5% of patients are listed below.
- anemia, coagulopathy, febrile neutropenia, neutropenia, thrombocytopeniaBlood and lymphatic system disorders:
- arrhythmia, atrial fibrillation, bradycardia, cardiac arrest, myocardial infarction, tachycardiaCardiac disorders:
- abdominal distension, abdominal pain upper, constipation, dyspepsiaGastrointestinal disorders:
- asthenia, fatigue, infusion site pain/pruritus/swelling, mucosal inflammation, edemaGeneral disorders and administration site conditions:
- hepatic failure, hepatomegaly, hepatotoxicity, hyperbilirubinemia, jaundiceHepatobiliary disorders:
- bacteremia, sepsis, urinary tract infectionInfections and infestations:
- anorexia, decreased appetite, fluid overload, hypomagnesemia, hypercalcemia, hyperglycemia, hypokalemiaMetabolic and nutrition disorders:
- arthralgia, back pain, pain in extremityMusculoskeletal, connective tissue, and bone disorders:
- convulsion, dizziness, somnolence, tremorNervous system disorders:
- anxiety, confusional state, depression, insomniaPsychiatric disorders:
- hematuria, renal failureRenal and urinary disorders:
- dyspnea, epistaxis, hypoxia, tachypneaRespiratory, thoracic, and mediastinal disorders:
- erythema, petechiae, skin lesion, urticariaSkin and subcutaneous tissue disorders:
- flushing, hypertension, phlebitisVascular disorders:
The following additional adverse reactions have been identified during the post-approval use of caspofungin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Gastrointestinal disorders:pancreatitis
- Hepatobiliary disorders:hepatic necrosis
- Skin and subcutaneous tissue disorders: erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, and skin exfoliation
- Renal and urinary disorders:clinically significant renal dysfunction
- General disorders and administration site conditions:swelling and peripheral edema
- Laboratory abnormalities:gamma-glutamyltransferase increased
- Hypersensitivity: Anaphylaxis, possible histamine-mediated adverse reactions, including rash, facial swelling, angioedema, pruritus, sensation of warmth or bronchospasm, and cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with use of caspofungin acetate for injection. Discontinue caspofungin acetate for injection at the first sign or symptom of a hypersensitivity reaction and administer appropriate treatment. ()
5.1 HypersensitivityAnaphylaxis and other hypersensitivity reactions have been reported during administration of caspofungin.
Possible histamine-mediated adverse reactions, including rash, facial swelling, angioedema, pruritus, sensation of warmth or bronchospasm have been reported.
Cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some with a fatal outcome, have been reported with use of caspofungin
[see Adverse Reactions (6.2)].Discontinue caspofungin at the first sign or symptom of a hypersensitivity reaction and administer appropriate treatment.
- Hepatic Effects:Can cause abnormalities in liver enzymes. Isolated cases of hepatic dysfunction, hepatitis, or hepatic failure have been reported. Monitor patients who develop abnormal liver enzymes for evidence of worsening hepatic function, and evaluate risk/benefit of continuing caspofungin acetate for injection. ()
5.2 Hepatic EffectsLaboratory abnormalities in liver function tests have been seen in healthy volunteers and in adult and pediatric patients treated with caspofungin. In some adult and pediatric patients with serious underlying conditions who were receiving multiple concomitant medications with caspofungin, isolated cases of clinically significant hepatic dysfunction, hepatitis, and hepatic failure have been reported; a causal relationship to caspofungin has not been established. Monitor patients who develop abnormal liver function tests during caspofungin therapy for evidence of worsening hepatic function and evaluated for risk/benefit of continuing caspofungin therapy.
- Elevated Liver Enzymes During Concomitant Use with Cyclosporine: Limit use to patients for whom potential benefit outweighs potential risk. Monitor patients who develop abnormal liver function tests (LFTs) during concomitant use with caspofungin acetate for injection. ()
5.3 Elevated Liver Enzymes During Concomitant Use With CyclosporineElevated liver enzymes have occurred in patients receiving caspofungin and cyclosporine concomitantly. Only use caspofungin and cyclosporine in those patients for whom the potential benefit outweighs the potential risk. Patients who develop abnormal liver enzymes during concomitant therapy should be monitored and the risk/benefit of continuing therapy should be evaluated.