| <P style="TEXT-INDENT: 31.5pt; LINE-HEIGHT: 150%; TEXT-ALIGN: left" align=left><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">英国药品和健康产品管理局（</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">MHRA</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">）在</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">2010</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">年</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">11</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">月的《药物安全更新》上报道了口服二膦酸盐可能导致食管癌风险。</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-INDENT: 31.5pt; LINE-HEIGHT: 150%; TEXT-ALIGN: left" align=left><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">虽然尚无充分的证据表明口服二膦酸盐可导致食管癌，但因其对食道造成刺激，使用时应严格按照说明书的指导服用，同时，一旦出现食道刺激如吞咽疼痛、吞咽困难、胸痛、胃灼热等，应及时告知医生。医生在给个别患有食管慢性炎伴腺上皮化生（</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">Barrett</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">食管）的病人处方阿仑膦酸或伊班膦酸时，因充分衡量利弊。</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-INDENT: 31.5pt; LINE-HEIGHT: 150%; TEXT-ALIGN: left" align=left><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">口服二膦酸盐用于治疗骨质疏松症、佩吉特病（</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">Paget</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">’</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">s disease</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">）以及骨相关的癌症。欧洲药品管理局（</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">EMA</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">）人用药品委员会药物警戒工作组（</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">PhVWP</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">）对已发表的二膦酸盐片剂与食管癌风险的相关研究进行评估后得出结论：口服二膦酸盐增加食管癌风险。已有明确的证据证明含氮二膦酸盐可致食管刺激和反应。</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">Green</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">等</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">[1]</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">与牛津大学的癌症流行病学机构合作对口服二膦酸盐增加食管癌风险进行了研究。</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-INDENT: 31.5pt; LINE-HEIGHT: 150%; TEXT-ALIGN: left" align=left><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">研究结果表明口服二膦酸盐超过</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">5</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">年的患者比未服用二膦酸盐的患者患食管癌的风险小幅增加。在</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">60-79</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">岁的人群中，口服二膦酸盐</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">5</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">年，食管癌的发病率由之前的</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">0.5</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">名每</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">1000</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">名女性、</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">1.5</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">名每</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">1000</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">名男性增加到</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">1</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">名每</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">1000</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">名女性、</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">3</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">名每</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">1000</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">名男性。但其他研究并未发现此相关风险。</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-INDENT: 31.5pt; LINE-HEIGHT: 150%; TEXT-ALIGN: left" align=left><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">虽然</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">Green</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">等与牛津大学的癌症流行病学机构的研究也有很多局限性，其他的研究也未找到支持口服二膦酸盐与食管癌风险的证据，但</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">MHRA</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">仍然建议专业医护人员及患者在使用口服二膦酸盐时：</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="LAYOUT-GRID-MODE: char; TEXT-INDENT: 28pt; LINE-HEIGHT: 150%; TEXT-ALIGN: left" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: Wingdings">l</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">阿仑膦酸盐及口服伊班膦酸盐不适用于食管异常和</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">或其他延迟食管排空的因素，如食管狭窄或迟缓不能的患者；利塞膦酸盐在这些患者中应谨慎使用。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="LAYOUT-GRID-MODE: char; TEXT-INDENT: 28pt; LINE-HEIGHT: 150%; TEXT-ALIGN: left" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: Wingdings">l</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">阿仑膦酸盐、口服伊班膦酸盐以及利塞膦酸盐在近期曾有过或正有上消化道问题的患者中应谨慎使用。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="LAYOUT-GRID-MODE: char; TEXT-INDENT: 28pt; LINE-HEIGHT: 150%; TEXT-ALIGN: left" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: Wingdings">l</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">对于明确患有食管慢性炎伴腺上皮化生的患者，处方医师应对患者逐个进行使用阿仑膦酸盐及口服伊班膦酸盐的利弊的衡量。</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="LAYOUT-GRID-MODE: char; TEXT-INDENT: 28pt; LINE-HEIGHT: 150%; TEXT-ALIGN: left" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: Wingdings">l</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">建议患者应严格遵循说明书剂量服用。早上起床后立即在空腹的情况下用大于</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">200ml</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">清水将整片药片服下。服药后应保持至少</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">30</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">分钟或</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">1</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">小时的直立状态，同时不能进食、饮水和服用其他说明书中规定的不能服用的药物。</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="LAYOUT-GRID-MODE: char; TEXT-INDENT: 28pt; LINE-HEIGHT: 150%; TEXT-ALIGN: left" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: Wingdings">l</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">如果患者出现食管刺激的症状如吞咽疼痛、吞咽困难、胸痛、胃灼热或胃灼热加重等，应停止服药并向医生寻求治疗。</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="LAYOUT-GRID-MODE: char; TEXT-INDENT: 28pt; LINE-HEIGHT: 150%; MARGIN-RIGHT: 38.6pt; TEXT-ALIGN: left" align=left><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">参考信息：</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="LAYOUT-GRID-MODE: char; TEXT-INDENT: 28pt; LINE-HEIGHT: 150%; MARGIN-RIGHT: 38.6pt; TEXT-ALIGN: left" align=left><SPAN style="LINE-HEIGHT: 150%">1.</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??"> Green J, et al. BMJ 2010; 341: c4444</SPAN></P>
<P style="LAYOUT-GRID-MODE: char; TEXT-INDENT: 28pt; LINE-HEIGHT: 150%; TEXT-ALIGN: right" align=right><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">（英国</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: ??">MHRA</SPAN><SPAN style="FONT-SIZE: 11.5pt; LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">网站）</SPAN></P> |
