Department of Clinical Pharmacy, Isala Hospital, Zwolle, The Netherlands.
Department of Clinical Pharmacology, Isala Hospital, Zwolle, The Netherlands.
Curr Drug Saf. 2024;19(1):142-144. doi: 10.2174/1574886318666230310104322.
Phenprocoumon is a vitamin K antagonist that is widely prescribed in Europe and Latin America for the prophylaxis and treatment of thromboembolic events.
A 90-year-old female was admitted to our hospital with tonic-clonic seizures, possibly due to dementia syndrome. Valproic acid (VPA) was prescribed for the treatment of seizures. VPA is an inhibitor of cytochrome P450 (CYP) 2C9 enzymes. A pharmacokinetic interaction with phenprocoumon occurred, which is a substrate for CYP2C9 enzymes. The interaction resulted in a strong INR increase and subsequent clinically relevant bleeding in our patient. Valproic acid is not specifically mentioned in the phenprocoumon drug label as a CYP2C9 inhibitor, and in the Dutch medication surveillance database, no medication alert is shown when prescribing this combination, and no interaction with phenprocoumon has been reported so far.
When prescribing this combination, the prescriber should be warned and advised to intensify INR monitoring if the combination is to be continued.
苯丙香豆素是一种维生素 K 拮抗剂，在欧洲和拉丁美洲被广泛用于预防和治疗血栓栓塞事件。
一名 90 岁女性因强直阵挛性发作被收入我院，可能由于痴呆综合征。给予丙戊酸（VPA）治疗癫痫发作。VPA 是细胞色素 P450（CYP）2C9 酶的抑制剂。与苯丙香豆素发生药代动力学相互作用，苯丙香豆素是 CYP2C9 酶的底物。这种相互作用导致我们的患者 INR 强烈增加，并随后出现临床相关出血。苯丙香豆素药物标签中并未特别提及丙戊酸是 CYP2C9 抑制剂，在荷兰药物监测数据库中，当开具这种联合用药时不会显示药物警示，并且到目前为止还没有报告与苯丙香豆素的相互作用。
当开具这种联合用药时，如果要继续使用，应警告并建议处方医生加强 INR 监测。
