SUNITINIB MALATE capsule

Država: Sjedinjene Američke Države

Jezik: engleski

Izvor: NLM (National Library of Medicine)

Aktivni sastojci:

SUNITINIB MALATE (UNII: LVX8N1UT73) (SUNITINIB - UNII:V99T50803M)

Dostupno od:

Aurobindo Pharma Limited

Administracija rute:

ORAL

Tip recepta:

PRESCRIPTION DRUG

Terapijske indikacije:

Sunitinib malate capsules are indicated for the treatment of adult patients with gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate. Sunitinib malate capsules are indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC). Sunitinib malate capsules are indicated for the adjuvant treatment of adult patients at high risk of recurrent RCC following nephrectomy. Sunitinib malate capsules are indicated for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in adult patients with unresectable locally advanced or metastatic disease. None. Risk Summary Based on animal reproduction studies and its mechanism of action, sunitinib malate can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)] . There are no available data in pregnant women to inform a drug-associated risk. In animal developmental and reproductive toxicology studies, oral administration of sunitinib to pregnant rats and rabbits throughout organogenesis resulted in teratogenicity (embryolethality, craniofacial and skeletal malformations) at 5.5 and 0.3 times the combined AUC (the combined systemic exposure of sunitinib plus its active metabolite) in patients administered the recommended daily doses (RDD) of 50 mg, respectively (see Data). Advise females of reproductive potential of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated populations are 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 miscarriages in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In a female fertility and early embryonic development study, female rats were administered oral sunitinib (0.5, 1.5, 5 mg/kg/day) for 21 days prior to mating and for 7 days after mating. Embryolethality was observed at 5 mg/kg/day (approximately 5 times the combined AUC in patients administered the RDD of 50 mg). In embryo-fetal developmental toxicity studies, oral sunitinib was administered to pregnant rats (0.3, 1.5, 3, 5 mg/kg/day) and rabbits (0.5, 1, 5, 20 mg/kg/day) during the period of organogenesis. In rats, embryolethality and skeletal malformations of the ribs and vertebrae were observed at the dose of 5 mg/kg/day (approximately 5.5 times the combined AUC in patients administered the RDD of 50 mg). No adverse fetal effects were observed in rats at doses ≤3 mg/kg/day (approximately 2 times the combined AUC in patients administered the RDD of 50 mg). In rabbits, embryolethality was observed at 5 mg/kg/day (approximately 3 times the combined AUC in patients administered the RDD of 50 mg), and craniofacial malformations (cleft lip and cleft palate) were observed at ≥1 mg/kg/day (approximately 0.3 times the combined AUC in patients administered the RDD of 50 mg). Sunitinib (0.3, 1, 3 mg/kg/day) was evaluated in a pre- and postnatal development study in pregnant rats. Maternal body weight gains were reduced during gestation and lactation at doses ≥1 mg/kg/day (approximately 0.5 times the combined AUC in patients administered the RDD of 50 mg). At 3 mg/kg/day (approximately 2 times the combined AUC in patients administered the RDD of 50 mg), reduced neonate body weights were observed at birth and persisted in the offspring of both sexes during the preweaning period and in males during postweaning period. No adverse developmental effects were observed at doses ≤1 mg/kg/day. There is no information regarding the presence of sunitinib and its metabolites in human milk. Sunitinib and its metabolites were excreted in rat milk at concentrations up to 12-fold higher than in plasma (see Data) . Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with sunitinib malate and for at least 4 weeks after the last dose. Data Animal Data In lactating female rats administered 15 mg/kg, sunitinib and its metabolites were excreted in milk at concentrations up to 12-fold higher than in plasma. Sunitinib malate can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Pregnancy Testing Verify pregnancy status of females of reproductive potential prior to initiating treatment with sunitinib malate. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with sunitinib malate and for at least 4 weeks after the last dose. Males Based on findings in animal reproduction studies, advise males with female partners of reproductive potential to use effective contraception during treatment with sunitinib malate and for 7 weeks after the last dose. Infertility Based on findings in animals, sunitinib malate may impair male and female fertility [see Nonclinical Toxicology (13.1)] . The safety and effectiveness of sunitinib malate in pediatric patients have not been established. Safety and pharmacokinetics of sunitinib were assessed in an open-label study (NCT00387920) in pediatric patients 2 years to <17 years of age (n=29) with refractory solid tumors. In addition, efficacy, safety and pharmacokinetics of sunitinib was assessed in another open-label study (NCT01462695) in pediatric patients 2 years to <17 years of age (n=27) with high-grade glioma or ependymoma. The maximum tolerated dose (MTD) normalized for body surface area (BSA) was lower in pediatric patients compared to adults. Sunitinib was poorly tolerated in pediatric patients. The occurrence of dose-limiting cardiotoxicity prompted an amendment of the NCT00387920 study to exclude patients with previous exposure to anthracyclines or cardiac radiation. No responses were reported in patients in either of the trials. Apparent clearance and volume of distribution normalized for BSA for sunitinib and its active major metabolite were lower in pediatrics as compared to adults. The effect on open tibial growth plates in pediatric patients who received sunitinib malate has not been adequately studied. See Juvenile Animal Toxicity Data below. Juvenile Animal Toxicity Data Physeal dysplasia was present in cynomolgus monkeys with open growth plates treated with sunitinib for ≥3 months (3 month dosing 2, 6, 12 mg/kg/day; 8 cycles of dosing 0.3, 1.5, 6 mg/kg/day) at doses that were >0.4 times the combined AUC (the combined systemic exposure of sunitinib plus its active metabolite) in patients administered the RDD of 50 mg. The no-effect level (NOEL) was 1.5 mg/kg/day in monkeys treated intermittently for 8 cycles, but was not identified in monkeys treated continuously for 3 months. In developing rats treated continuously for 3 months (1.5, 5, and 15 mg/kg) or 5 cycles (0.3, 1.5, and 6 mg/kg/day), bone abnormalities consisted of thickening of the epiphyseal cartilage of the femur and an increase of fracture of the tibia at doses ≥5 mg/kg (approximately 10 times the combined AUC in patients administered the RDD of 50 mg). Additionally, tooth caries were present in rats at >5 mg/kg. The incidence and severity of physeal dysplasia were dose related and reversible upon cessation of treatment; however, findings in the teeth were not. In rats, the NOEL in bones was ≤2 mg/kg/day. Of the 7527 patients with GIST, RCC (advanced and adjuvant), or pNET who received sunitinib malate, 32% were 65 years and older, and 7% were 75 years and older. Patients aged 65 years of age and older had a higher incidence of Grade 3 or 4 adverse reactions (67%) than younger patients (60%). 　 In the GIST study, 73 (30%) of the patients who received sunitinib malate were 65 years and older. In the mRCC study, 152 (41%) of patients who received sunitinib malate were 65 years and older. No overall differences in safety or effectiveness were observed between these patients and younger patients. 　 In the pNET study, 22 (27%) of the patients who received sunitinib malate were 65 years and older. Clinical studies of sunitinib malate did not include sufficient numbers of patients with pNET to determine if patients 65 years of age and older respond differently than younger patients. No dose adjustment is required in patients with mild or moderate (Child-Pugh Class A or B) hepatic impairment [see Clinical Pharmacology (12.3)] . Sunitinib malate was not studied in patients with severe (Child-Pugh Class C) hepatic impairment. No dose adjustment is recommended in patients with mild (CLcr 50 to 80 mL/min), moderate (CLcr 30 to <50 mL/min), or severe (CLcr <30 mL/min) renal impairment who are not on dialysis [see Clinical Pharmacology (12.3)] . No dose adjustment is recommended for patients with end-stage renal disease (ESRD) on hemodialysis [see Clinical Pharmacology (12.3)] .

Proizvod sažetak:

Sunitinib Malate Capsules, 12.5 mg are supplied as hard gelatin capsule with red opaque cap and red opaque body imprinted ‘S12.5’ on body with white ink and plain cap, containing yellow to orange granules; available in:                 Bottles of  28 capsules                                                       NDC 59651-464-28                 Cartons of 28 Capsules (4 x 7 Unit-Dose)                         NDC 59651-464-29 Sunitinib Malate Capsules, 25 mg are supplied as hard gelatin capsule with olive green opaque cap and red opaque body imprinted ‘S25’ on body with white ink and plain cap, containing yellow to orange granules; available in:                 Bottles of  28 capsules                                                        NDC 59651-465-28                 Cartons of 28 Capsules (4 x 7 Unit-Dose)                          NDC 59651-465-29 Sunitinib Malate Capsules, 37.5 mg are supplied as hard gelatin capsule with light green opaque cap and light green opaque body imprinted ‘S37.5’ on body with black ink and plain cap, containing yellow to orange granules; available in:                 Bottles of  28 capsules                                                       NDC 59651-466-28                 Cartons of 28 Capsules (4 x 7 Unit-Dose)                         NDC 59651-466-29 Sunitinib Malate Capsules, 50 mg are supplied as hard gelatin capsule with olive green opaque cap and olive green opaque body imprinted ‘S50’ on body with black ink and plain cap, containing yellow to orange granules; available in:                Bottles of  28 capsules                                                         NDC 59651-467-28                Cartons of 28 Capsules (4 x 7 Unit-Dose)                           NDC 59651-467-29 Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Status autorizacije:

Abbreviated New Drug Application

Svojstava lijeka

SUNITINIB MALATE - SUNITINIB MALATE CAPSULE
AUROBINDO PHARMA LIMITED
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
SUNITINIB MALATE
CAPSULES SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
SUNITINIB MALATE
CAPSULES.
SUNITINIB MALATE CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 2006
WARNING: HEPATOTOXICITY
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
HEPATOTOXICITY MAY BE SEVERE, AND IN SOME CASES FATAL. MONITOR HEPATIC
FUNCTION AND
INTERRUPT, DOSE REDUCE, OR DISCONTINUE SUNITINIB MALATE AS RECOMMENDED
_[SEE_
_WARNINGS AND PRECAUTIONS (5.1)]._
INDICATIONS AND USAGE
Sunitinib malate is a kinase inhibitor indicated for:
treatment of adult patients with gastrointestinal stromal tumor (GIST)
after disease progression on or
intolerance to imatinib mesylate. (1.1)
treatment of adult patients with advanced renal cell carcinoma (RCC).
(1.2)
adjuvant treatment of adult patients at high risk of recurrent RCC
following nephrectomy. (1.3)
treatment of progressive, well-differentiated pancreatic
neuroendocrine tumors (pNET) in adult patients
with unresectable locally advanced or metastatic disease. (1.4)
DOSAGE AND ADMINISTRATION
GIST and Advanced RCC:
The recommended dosage is 50 mg orally once daily for the first 4
weeks of each 6-week cycle
(Schedule 4/2). (2.1)
Adjuvant Treatment of RCC:
The recommended dosage is 50 mg orally once daily for the first 4
weeks of a 6-week cycle (Schedule
4/2) for a maximum of 9 cycles. (2.2)
pNET:
The recommended dosage is 37.5 mg orally once daily. (2.3)
DOSAGE FORMS AND STRENGTHS
Capsules: 12.5 mg, 25 mg, 37.5 mg, 50 mg sunitinib (3)
CONTRAINDICATIONS
None (4)
WARNINGS AND PRECAUTIONS
Hepatotoxicity: Fatal liver failure has been observed. Monitor liver
function tests at baseline, during
each cycle, and as clinically indicated. Interrupt sunitinib malate
for Grade 3 hepatotoxicity until
resolution to Grade ≤1 or baseline and resume sunitinib malate at a
reduced dose; discontinue if no
reso