CASPOFUNGIN ACETATE injection, powder, lyophilized, for solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

CASPOFUNGIN ACETATE (UNII: VUW370O5QE) (CASPOFUNGIN - UNII:F0XDI6ZL63)

Available from:

Athenex Pharmaceutical Division, LLC.

INN (International Name):

caspofungin acetate

Composition:

caspofungin acetate 50 mg in 10.8 mL

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Caspofungin 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)]. Caspofungin 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)] . Limitations of Use : Caspofungin acetate for injection has not been studied in endocarditis, osteomyelitis, and meningitis due to Candida. Caspofungin 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)] . Limitations of Use : 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 OPC [see Clinical Studies ( 14.3)] . Caspofungin 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)] . Limitations of Use : Caspofungin acetate for injection has not been studied as initial therapy for invasive aspergillosis. Caspofungin is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis) to any component of this product [see Adverse Reactions ( 6)]. Risk Summary Based 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. Data Animal Data In 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. Risk Summary There are no data on the presence of caspofungin in human milk, the effects on the breast-fed child, or the effects on milk production. Caspofungin was found in the milk of lactating, drug-treated rats. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for caspofungin and any potential adverse effects on the breastfed child from caspofungin or from the underlying maternal condition. The 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 following Candida infections: 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/m 2 for 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)]. Clinical studies of caspofungin did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Although the number of elderly patients was not large enough for a statistical analysis, no overall differences in safety or efficacy were observed between these and younger patients. Plasma concentrations of caspofungin in healthy older men and women (65 years of age and older) were increased slightly (approximately 28% in AUC) compared to young healthy men. A similar effect of age on pharmacokinetics was seen in patients with candidemia or other Candida infections (intra-abdominal abscesses, peritonitis, or pleural space infections). No dose adjustment is recommended for the elderly; however, greater sensitivity of some older individuals cannot be ruled out. 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 [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. No dosage adjustment is necessary for patients with renal impairment. Caspofungin is not dialyzable; thus, supplementary dosing is not required following hemodialysis [see Clinical Pharmacology ( 12.3)].

Product summary:

Caspofungin Acetate for Injection is supplied as follows: Caspofungin Acetate for Injection is a lyophilized white to off-white powder/cake for intravenous infusion in a vial with an aluminum flip off seal and plastic cap. Storage Conditions Store refrigerated between 2° and 8°C (36° and 46°F). Sterile, Nonpyrogenic, Lyophilized. The container closure is not made with natural rubber latex. There are no preservatives or bacteriostatic agents in this product.

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

CASPOFUNGIN ACETATE- CASPOFUNGIN ACETATE INJECTION, POWDER,
LYOPHILIZED,
FOR SOLUTION
ATHENEX PHARMACEUTICAL DIVISION, LLC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
CASPOFUNGIN ACETATE
FOR INJECTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION
FOR CASPOFUNGIN
ACETATE FOR INJECTION.
CASPOFUNGIN ACETATE FOR INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2001
INDICATIONS AND USAGE
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)
Treatment of candidemia and the following _Candida_infections:
intra-abdominal abscesses, peritonitis
and pleural space infections. ( 1)
Treatment of esophageal candidiasis. ( 1)
Treatment of invasive aspergillosis in patients who are refractory to
or intolerant of other therapies. ( 1)
DOSAGE AND ADMINISTRATION
_Important Administration Instructions for All Patients ( 2.1):_
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).
_Dosage in Adults [18 years of age and older] ( 2.2):_
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.
_Dosage in Pediatric Patients [3 months to 17 years of age] ( 2.3):_
Dosing should be based on the patient's body surface area.
For all indications, administer a single 70 mg/m
loading dose on Day 1, followed by 50 mg/m
once
daily thereafter.
Maximum loading dose and daily maintenance dose should not exceed 70
mg, regardless of the
patient's calculated dose.
_Dosage Adjustments in Patients with Hepatic Impairment ( 2.4):_
Reduce dosage for adult patien