Division of Medical Affairs, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Ther Clin Risk Manag. 2013;9:259-71. doi: 10.2147/TCRM.S43151. Epub 2013 May 27.
Omeprazole, a proton pump inhibitor (PPI), is widely used for the treatment of dyspepsia, peptic ulcer, gastroesophageal reflux disease, and functional dyspepsia. Polypharmacy is common in patients receiving omeprazole. Drug toxicity and treatment failure resulting from inappropriate combination therapy with omeprazole have been reported sporadically. Systematic review has not been available to address the pharmacokinetic drug-drug interaction (DDI) profile of omeprazole with adverse consequences, the factors determining the degree of DDI between omeprazole and comedication, and the corresponding clinical risk management.
Literature was identified by performing a PubMed search covering the period from January 1988 to March 2013. The full text of each article was critically reviewed, and data interpretation was performed.
Omeprazole has actual adverse influences on the pharmacokinetics of medications such as diazepam, carbamazepine, clozapine, indinavir, nelfinavir, atazanavir, rilpivirine, methotrexate, tacrolimus, mycophenolate mofetil, clopidogrel, digoxin, itraconazole, posaconazole, and oral iron supplementation. Meanwhile, low efficacy of omeprazole treatment would be anticipated, as omeprazole elimination could be significantly induced by comedicated efavirenz and herb medicines such as St John's wort, Ginkgo biloba, and yin zhi huang. The mechanism for DDI involves induction or inhibition of cytochrome P450, inhibition of P-glycoprotein or breast cancer resistance protein-mediated drug transport, and inhibition of oral absorption by gastric acid suppression. Sometimes, DDIs of omeprazole do not exhibit a PPI class effect. Other suitable PPIs or histamine 2 antagonists may be therapeutic alternatives that can be used to avoid adverse consequences. The degree of DDIs associated with omeprazole and clinical outcomes depend on factors such as genotype status of CYP2C19 and CYP1A2, ethnicity, dose and treatment course of precipitant omeprazole, pharmaceutical formulation of object drug (eg, mycophenolate mofetil versus enteric-coated mycophenolate sodium), other concomitant medication (eg, omeprazole-indinavir versus omeprazole-indinavir-ritonavir), and administration schedule (eg, intensified dosing of mycophenolate mofetil versus standard dosing).
Despite the fact that omeprazole is one of the most widely prescribed drugs internationally, clinical professionals should enhance clinical risk management on adverse DDIs associated with omeprazole and ensure safe combination use of omeprazole by rationally prescribing alternatives, checking the appropriateness of physician orders before dispensing, and performing therapeutic drug monitoring.
质子泵抑制剂（PPI）奥美拉唑被广泛用于治疗消化不良、消化性溃疡、胃食管反流病和功能性消化不良。接受奥美拉唑治疗的患者常采用联合用药。已有报道称，由于奥美拉唑与其他药物联合使用不当导致药物毒性和治疗失败。目前尚未对奥美拉唑与不良后果相关的药代动力学药物相互作用（DDI）特征、决定奥美拉唑与合并用药相互作用程度的因素以及相应的临床风险管理进行系统评价。
通过在 1988 年 1 月至 2013 年 3 月期间进行 PubMed 检索来确定文献。对每篇文章的全文进行严格审查，并进行数据分析。
奥美拉唑对安定、卡马西平、氯氮平、茚地那韦、奈非那韦、阿扎那韦、利匹韦林、甲氨蝶呤、他克莫司、霉酚酸酯、氯吡格雷、地高辛、酮康唑、口服铁补充剂等药物的药代动力学有实际的不良影响。同时，由于依非韦伦和圣约翰草、银杏、茵栀黄等草药可能会显著诱导奥美拉唑的消除，预计奥美拉唑的治疗效果不佳。DDI 的发生机制涉及细胞色素 P450 的诱导或抑制、P-糖蛋白或乳腺癌耐药蛋白介导的药物转运抑制以及胃酸抑制对口服吸收的抑制。有时，奥美拉唑的 DDIs 不表现出 PPI 类药物的作用。其他合适的 PPI 或组胺 2 拮抗剂可能是可替代的治疗选择，可用于避免不良后果。与奥美拉唑相关的 DDI 程度和临床结局取决于 CYP2C19 和 CYP1A2 的基因型状态、种族、诱导奥美拉唑的剂量和疗程、对象药物的药物制剂（例如，霉酚酸酯与肠溶性霉酚酸酯钠）、其他伴随药物（例如，奥美拉唑-茚地那韦与奥美拉唑-茚地那韦-利托那韦）和给药方案（例如，霉酚酸酯的强化剂量与标准剂量）等因素。
尽管奥美拉唑是全球应用最广泛的药物之一，但临床医生应加强对与奥美拉唑相关的不良 DDI 的临床风险管理，通过合理处方替代药物、在配药前检查医嘱的合理性以及进行治疗药物监测来确保奥美拉唑的安全联合使用。
