XII. 参考資料
2. 海外における臨床支援情報
分類 参考：分類の概要
FDA:Pregnancy Category C
（SAVAYSA, Daiichi Sankyo,Inc., 2016年9月）
1. Animal reproduction studies have shown an adverse effect on the fetus, there are no adequate and
well-controlled studies in humans, and the benefits from the use of the drug in pregnant women may be acceptable despite its potential risks
2. There are no animal reproduction studies and no adequate and well-controlled studies in humans.
妊婦、産婦、授乳婦等に関する記載
出典 記載内容
米国の添付文書
（
SAVAYSA,
Daiichi Sankyo, Inc., 2016
年9
月）8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy
Pregnancy Category C Risk Summary
There are no adequate and well-controlled studies in pregnant women.
SAVAYSA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Human Data
In the Hokusai VTE study there were 10 pregnancy cases reported in patients receiving SAVAYSA with exposure in the first trimester and estimated duration of exposure for up to approximately 6 weeks.
Among these there were 6 live births (4 full term, 2 pre-term), 1 first-trimester spontaneous abortion, and 3 cases of elective termination of pregnancy.
Animal Data
Embryo-fetal development studies were conducted in pregnant rats and rabbits during the period of organogenesis. In rats, no teratogenic effects were seen when edoxaban was administered orally at doses up to 300 mg/kg/day, or 49 times the human dose of 60 mg/day normalized to body surface area.
Increased post-implantation loss occurred at 300 mg/kg/day, but this effect may be secondary to the maternal vaginal hemorrhage seen at this dose. In rabbits, no teratogenic effects were seen at doses up to 600 mg/kg/day (49 times the human exposure at a dose of 60 mg/day when based on AUC). Embryofetal toxicities occurred at maternally toxic doses, and included absent or small fetal gallbladder at 600 mg/kg/day, and increased post-implantation loss, increased spontaneous abortion, and decreased live fetuses and fetal weight at doses equal to or greater than 200 mg/kg/day, which is equal to or greater than 20 times the human exposure.
In a rat pre- and post-natal developmental study, edoxaban was administered
8.2 Labor and Delivery
Safety and effectiveness of SAVAYSA during labor and delivery have not been studied in clinical studies. The risks of bleeding should be balanced with the risk of thrombotic events when considering the use of SAVAYSA in this setting.
8.3 Nursing Mothers
It is not known if edoxaban is excreted in human milk. Edoxaban was excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from SAVAYSA, a decision should be made to discontinue nursing or the drug, taking into account the importance of the drug to the mother.
英国の
SPC
（Lixiana 30 mg
film-coated tablets, Daiichi Sankyo UK Limited,
2016
年8
月）4. Clinical particulars 4.3 Contraindications
• Pregnancy and breast-feeding (see section 4.6).
4.6 Fertility, pregnancy and lactation Pregnancy
Safety and efficacy of edoxaban have not been established in pregnant women.
Studies in animals have shown reproductive toxicity (see section 5.3). Due to the potential reproductive toxicity, the intrinsic risk of bleeding and the evidence that edoxaban passes the placenta, Lixiana is contraindicated during pregnancy (see section 4.3).
Women of childbearing potential should avoid becoming pregnant during treatment with edoxaban.
Breast-feeding
Safety and efficacy of edoxaban have not been established in breast-feeding women. Data from animals indicate that edoxaban is secreted into breast milk.
Therefore Lixiana is contraindicated during breast-feeding (see section 4.3). A decision must be made whether to discontinue breast-feeding or to
discontinue/abstain from therapy.
Fertility
No specific studies with edoxaban in humans have been conducted to evaluate
effects on fertility. In a study on male and female fertility in rats no effects
本邦における使用上の注意「妊婦、産婦、授乳婦等への投与」の項の記載は以下のとおりである。
【使用上の注意】｢妊婦、産婦、授乳婦等への投与｣
(1)
妊婦又は妊娠している可能性のある婦人には、治療上の有益性が危険性を上回ると判断される場合にのみ投 与すること。［妊娠中の投与に関する安全性は確立していない。動物実験（ラット）で胎児への移行が報告 されている。］(2)
授乳中の婦人には本剤投与中は授乳を避けさせること。［動物実験（ラット）で乳汁中に移行することが報 告されている。］小児等に関する記載
出典 記載内容
米国の添付文書
（
SAVAYSA,
Daiichi Sankyo, Inc., 2016
年9
月）8 USE IN SPECIFIC POPULATIONS 8.4 Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
英国の
SPC
（Lixiana 30 mg
film-coated tablets, Daiichi Sankyo UK Limited,
2016
年8
月）4. Clinical particulars
4.2 Posology and method of administration Paediatric population
The safety and efficacy of Lixiana in children and adolescents less than 18 years of age have not been established. No data are available.
本邦における使用上の注意「小児等への投与」の項の記載は以下のとおりである。
【使用上の注意】「小児等への投与」
低出生体重児、新生児、乳児、幼児又は小児に対する安全性は確立していない（使用経験がない）。
XIII. 備 考
その他の関連資料