DECITABINE injection, powder, lyophilized, for solution

国家: 美国

语言: 英文

来源: NLM (National Library of Medicine)

有效成分:

DECITABINE (UNII: 776B62CQ27) (DECITABINE - UNII:776B62CQ27)

可用日期:

Hikma Pharmaceuticals USA Inc.

给药途径:

INTRAVENOUS

处方类型:

PRESCRIPTION DRUG

疗效迹象:

Decitabine for Injection is indicated for treatment of adult patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups. None. Risk Summary Based on findings from human data, animal studies, and the mechanism of action, decitabine can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) and Nonclinical Toxicology (13.1)] . Limited published data on decitabine use throughout the first trimester during pregnancy describe adverse developmental outcomes including major birth defects (structural abnormalities). In animal reproduction studies, administration of decitabine to pregnant mice and rats during organogenesis caused adverse developmental outcomes including malformations and embryo-fetal lethality starting at doses approximately 7% of the recommended human dose on a mg/m2 basis (see Data) . Advise pregnant women of the potential risk to a 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. The estimated background risk of major birth defects and miscarriage in the U.S. general population is 2% to 4% and 15% to 20% of clinically recognized pregnancies, respectively. Data Human Data A single published case report of decitabine pregnancy exposure in a 39-year old woman with a hematologic malignancy described multiple structural abnormalities after 6 cycles of therapy in the 18 th week of gestation. These abnormalities included holoprosencephaly, absence of nasal bone, mid-facial deformity, cleft lip and palate, polydactyly and rocker-bottom feet. The pregnancy was terminated. Animal Data In utero exposure to decitabine causes temporal related defects in the rat and/or mouse, which include growth suppression, exencephaly, defective skull bones, rib/sternabrae defects, phocomelia, digit defects, micrognathia, gastroschisis, micromelia. Decitabine inhibits proliferation and increases apoptosis of neural progenitor cells of the fetal CNS and induces palatal clefting in the developing murine fetus. Studies in mice have also shown that decitabine administration during osteoblastogenesis (day 10 of gestation) induces bone loss in offspring. In mice exposed to single IP (intraperitoneal) injections (0 mg/m2 , 0.9 mg/m2 and 3.0 mg/m2 , approximately 2% and 7% of the recommended daily clinical dose, respectively) over gestation days 8, 9, 10 or 11, no maternal toxicity was observed but reduced fetal survival was observed after treatment at 3 mg/m2 and decreased fetal weight was observed at both dose levels. The 3 mg/m2 dose elicited characteristic fetal defects for each treatment day, including supernumerary ribs (both dose levels), fused vertebrae and ribs, cleft palate, vertebral defects, hind-limb defects and digital defects of fore- and hind-limbs. In rats given a single IP injection of 2.4 mg/m2 , 3.6 mg/m2 or 6 mg/m2 (approximately 5%, 8%, or 13% the daily recommended clinical dose, respectively) on gestation days 9 to 12, no maternal toxicity was observed. No live fetuses were seen at any dose when decitabine was injected on gestation day 9. A significant decrease in fetal survival and reduced fetal weight at doses greater than 3.6 mg/m2 was seen when decitabine was given on gestation day 10. Increased incidences of vertebral and rib anomalies were seen at all dose levels, and induction of exophthalmia, exencephaly, and cleft palate were observed at 6.0 mg/m2 . Increased incidence of foredigit defects was seen in fetuses at doses greater than 3.6 mg/m2 . Reduced size and ossification of long bones of the fore-limb and hind-limb were noted at 6.0 mg/m2 . The effect of decitabine on postnatal development and reproductive capacity was evaluated in mice administered a single 3 mg/m2 IP injection (approximately 7% the recommended daily clinical dose) on day 10 of gestation. Body weights of males and females exposed in utero to decitabine were significantly reduced relative to controls at all postnatal time points. No consistent effect on fertility was seen when female mice exposed in utero were mated to untreated males. Untreated females mated to males exposed in utero showed decreased fertility at 3 and 5 months of age (36% and 0% pregnancy rate, respectively). Follow up studies indicated that treatment of pregnant mice with decitabine on gestation day 10 was associated with a reduced pregnancy rate resulting from effects on sperm production in the F1-generation. Risk Summary There are no data on the presence of decitabine or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions from decitabine in a breastfed child, advise women not to breastfeed while receiving decitabine and for at least 2 weeks after the last dose. Pregnancy Testing Conduct pregnancy testing of females of reproductive potential prior to initiating decitabine. Contraception Females Decitabine can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)].Advise females of reproductive potential to use effective contraception while receiving decitabine and for 6 months following the last dose. Males Advise males with female partners of reproductive potential to use effective contraception while receiving treatment with decitabine and for 3 months following the last dose [see Nonclinical Toxicology (13.1)] . Infertility Based on findings of decitabine in animals, male fertility may be compromised by treatment with decitabine. The reversibility of the effect on fertility is unknown [see Nonclinical Toxicology (13.1)]. The safety and effectiveness of decitabine in pediatric patients have not been established. Of the total number of patients exposed to decitabine in the controlled clinical trial, 61 of 83 patients were age 65 years and over, while 21 of 83 patients were age 75 years and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

產品總結:

Decitabine for Injection is a sterile, white to almost white lyophilized powder for intravenous use supplied as: NDC 0143-9385-01, 50 mg single dose vial individually packaged in a carton. Store vials at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard unused portion.

授权状态:

Abbreviated New Drug Application

产品特点

DECITABINE- DECITABINE INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
HIKMA PHARMACEUTICALS USA INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
DECITABINE FOR
INJECTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
DECITABINE FOR
INJECTION.
DECITABINE FOR INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2006
INDICATIONS AND USAGE
Decitabine for Injection is a nucleoside metabolic inhibitor indicated
for treatment of adult patients with
myelodysplastic syndromes (MDS) including previously treated and
untreated, de novo and secondary
MDS of all French-American-British subtypes (refractory anemia,
refractory anemia with ringed
sideroblasts, refractory anemia with excess blasts, refractory anemia
with excess blasts in transformation,
and chronic myelomonocytic leukemia) and intermediate-1,
intermediate-2, and high-risk International
Prognostic Scoring System groups. (1)
DOSAGE AND ADMINISTRATION
Three Day Regimen: Administer decitabine for injection at a dose of 15
mg/m by continuous
intravenous infusion over 3 hours repeated every 8 hours for 3 days.
Repeat cycle every 6 weeks. (2.1)
Five Day Regimen: Administer decitabine for injection at a dose of 20
mg/m by continuous intravenous
infusion over 1 hour repeated daily for 5 days. Repeat cycle every 4
weeks. (2.1)
DOSAGE FORMS AND STRENGTHS
For Injection: 50 mg of decitabine as a lyophilized powder in a
single-dose vial for reconstitution. (3)
CONTRAINDICATIONS
None. (4
WARNINGS AND PRECAUTIONS
Neutropenia and Thrombocytopenia: Perform complete blood counts and
platelet counts. (5.1)
Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of
reproductive potential of the potential
risk to a fetus and to use effective contraception (5.2, 8.1, 8.3)
ADVERSE REACTIONS
Most common adverse reactions (>50%) are neutropenia,
thrombocytopenia, anemia, and pyrexia. (6.1)
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT HIKMA PHARMACEUTICALS
USA INC. AT 1-
877-845-0689 OR FDA AT 1-800-F