DACOGEN- decitabine injection, powder, lyophilized, for solution

Valsts: Amerikas Savienotās Valstis

Valoda: angļu

Klimata pārmaiņas: NLM (National Library of Medicine)

Aktīvā sastāvdaļa:

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

Pieejams no:

Otsuka America Pharmaceutical, Inc.

SNN (starptautisko nepatentēto nosaukumu):

DECITABINE

Kompozīcija:

DECITABINE 50 mg in 20 mL

Ievadīšanas:

INTRAVENOUS

Receptes veids:

PRESCRIPTION DRUG

Ārstēšanas norādes:

DACOGEN 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, DACOGEN can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) and Nonclinical Toxicology (13.1)] . Limited published data on DACOGEN 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 18th 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, 0.9 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, 3.6 or 6 mg/m2 (approximately 5%, 8%, or 13% the daily recommended clinical dose, respectively) on gestation days 9-12, 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 DACOGEN in a breastfed child, advise women not to breastfeed while receiving DACOGEN and for at least 2 weeks after the last dose. Pregnancy Testing Conduct pregnancy testing of females of reproductive potential prior to initiating DACOGEN. Contraception Females DACOGEN 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 DACOGEN 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 DACOGEN 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 DACOGEN. The reversibility of the effect on fertility is unknown [see Nonclinical Toxicology (13.1)]. The safety and effectiveness of DACOGEN in pediatric patients have not been established. Of the total number of patients exposed to DACOGEN 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.

Produktu pārskats:

DACOGEN for injection is a sterile, white to almost white lyophilized powder for intravenous use supplied as: 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].

Autorizācija statuss:

New Drug Application

Produkta apraksts

DACOGEN- DECITABINE INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
OTSUKA AMERICA PHARMACEUTICAL, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
DACOGEN SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR DACOGEN.
DACOGEN (DECITABINE) FOR INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2006
INDICATIONS AND USAGE
DACOGEN 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 DACOGEN 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 DACOGEN 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 OTSUKA AMERICA
PHARMACEUTICAL, INC. AT
1-800-438-9927 OR FDA AT 1-800-FDA-1088 OR WWW.FDA.GOV/MEDWATCH.
USE IN SPECIFIC POPULATIONS
Lactat