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Dacogen

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Dacogen

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Neutropenia and Thrombocytopenia

Treatment with Dacogen (decitabine injection) is associated with neutropenia and thrombocytopenia. Complete blood and platelet counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each dosing cycle. After administration of the recommended dosage for the first cycle, treatment for subsequent cycles should be adjusted [see DOSAGE AND ADMINISTRATION]. Clinicians should consider the need for early institution of growth factors and/or antimicrobial agents for the prevention or treatment of infections in patients with MDS. Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles, and may not necessarily indicate progression of underlying MDS.

Use in Pregnancy

Dacogen (decitabine injection) can cause fetal harm when administered to a pregnant woman. Based on its mechanism of action, Dacogen (decitabine injection) is expected to result in adverse reproductive effects. In preclinical studies in mice and rats, decitabine was teratogenic, fetotoxic, and embryotoxic. There are no adequate and well-controlled studies of Dacogen (decitabine injection) in pregnant women. If this drug is used during pregnancy, or if a patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while taking Dacogen (decitabine injection) [see Use in Specific Populations]

Use in Women of Childbearing Potential

Women of childbearing potential should be advised to avoid becoming pregnant while receiving Dacogen (decitabine injection) and for 1 month following completion of treatment. Women of childbearing potential should be counseled to use effective contraception during this time [see Use in Specific Populations]. Based on its mechanism of action, Dacogen (decitabine injection) can cause fetal harm if used during pregnancy.

Use in Men

Men should be advised not to father a child while receiving treatment with Dacogen (decitabine injection) , and for 2 months following completion of treatment [see Nonclinical Toxicology]. Men with female partners of childbearing potential should use effective contraception during this time. Based on its mechanism of action, Dacogen (decitabine injection) alters DNA synthesis and can cause fetal harm.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis and Impairment of Fertility

Carcinogenicity studies with decitabine have not been conducted.

The mutagenic potential of decitabine was tested in several in vitro and in vivo systems. Decitabine increased mutation frequency in L5178Y mouse lymphoma cells, and mutations were produced in an Escherichia coli lac-I transgene in colonic DNA of decitabine-treated mice. Decitabine caused chromosomal rearrangements in larvae of fruit flies.

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). In male mice given IP injections of 0.15, 0.3 or 0.45 mg/m² decitabine (approximately 0.3% to 1% the recommended clinical dose) 3 times a week for 7 weeks, decitabine did not affect survival, body weight gain or hematological measures (hemoglobin and WBC counts). Testes weights were reduced, abnormal histology was observed and significant decreases in sperm number were found at doses ≥ 0.3 mg/m². In females mated to males dosed with ≥ 0.3 mg/m² decitabine, pregnancy rate was reduced and preimplantation loss was significantly increased.

Use In Specific Populations

Pregnancy

Pregnancy Category D [see WARNINGS AND PRECAUTIONS]

Dacogen (decitabine injection) can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of Dacogen in pregnant women.

The developmental toxicity of decitabine was examined 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. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of child bearing potential should be advised to avoid becoming pregnant while taking Dacogen.

Nursing Mothers

It is not known whether decitabine or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions from Dacogen (decitabine injection) in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of Dacogen (decitabine injection) in pediatric patients have not been established.

Geriatric Use

Of the total number of patients exposed to Dacogen (decitabine injection) in the controlled clinical trial, 61 of 83 patients were age 65 and over, while 21 of 83 patients were age 75 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.

Renal Impairment

There are no data on the use of Dacogen (decitabine injection) in patients with renal dysfunction; therefore, Dacogen (decitabine injection) should be used with caution in these patients.

Hepatic Impairment

There are no data on the use of Dacogen (decitabine injection) in patients with hepatic dysfunction; therefore, Dacogen (decitabine injection) should be used with caution in these patients.

Last reviewed on RxList: 4/1/2010
This monograph has been modified to include the generic and brand name in many instances.

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