Kuhn Alyssa K, Determan Meina L, Wright Jessica A, Matey Eric, Leung Jonathan G
Pharmacy Student, University of Wisconsin-Madison School of Pharmacy, Madison, Wisconsin.
Pharmacy Student, Texas A&M University School of Pharmacy, Kingsville, Texas.
Ment Health Clin. 2024 Jun 3;14(3):220-223. doi: 10.9740/mhc.2024.06.220. eCollection 2024 Jun.
Clozapine is primarily metabolized via cytochrome P450(CYP)1A2 and to a lesser extent CYP3A4, CYP2C19, and CYP2D6. Metabolic inhibitors of clozapine, such as fluvoxamine and ciprofloxacin, are important to recognize to avoid adverse drug events. Estrogen-containing oral contraceptives (eOCPs) are weaker CYP1A2 and CYP2C19 inhibitors but are associated with a 2-fold increase of clozapine concentrations. The potential for phenoconversion due to a CYP genetic polymorphism can add additional complexities when considering drug interactions. A case report is presented of a suspected interaction between newly initiated clozapine and a prescribed eOCP for which the patient's pharmacogenomic status was known. A 17-year-old, nonsmoking, White female with a history of schizophrenia was initiated on clozapine 12.5 mg at bedtime with a plan to increase by 25 mg every 4 days in the outpatient setting. The patient was a known rapid CYP1A2 metabolizer without identified sources of CYP1A2 induction and a CYP2C19 rapid metabolizer. Based on pharmacogenomic testing, there was no suspicion for significant gene-drug interactions. Yet, as the patient was prescribed an eOCP, a clozapine concentration was obtained after reaching 150 mg at bedtime. This steady-state clozapine concentration was found to be 560 ng/mL, correlating with worsening sedation and constipation. Given ongoing side effects, clozapine was lowered to 100 mg at bedtime; however, ongoing intolerance ultimately led to clozapine discontinuation. This case highlights the potential interaction between clozapine and eOCP in a CYP1A2 and CYP2C19 rapid metabolizer, leading to clozapine intolerance and discontinuation. The concomitant use of clozapine and eOCPs should be undertaken judiciously.
氯氮平主要通过细胞色素P450（CYP）1A2代谢，在较小程度上通过CYP3A4、CYP2C19和CYP2D6代谢。认识到氯氮平的代谢抑制剂，如氟伏沙明和环丙沙星，对于避免药物不良事件很重要。含雌激素的口服避孕药（eOCP）是较弱的CYP1A2和CYP2C19抑制剂，但与氯氮平浓度增加2倍有关。在考虑药物相互作用时，由于CYP基因多态性导致的表型转换可能性会增加额外的复杂性。本文报告了一例新开始使用氯氮平与处方eOCP之间疑似相互作用的病例，该患者的药物基因组学状态已知。一名17岁、不吸烟的白人女性，有精神分裂症病史，开始在门诊睡前服用12.5mg氯氮平，计划每4天增加25mg。该患者是已知的CYP1A2快速代谢者，未发现CYP1A2诱导源，也是CYP2C19快速代谢者。根据药物基因组学检测，没有明显的基因-药物相互作用嫌疑。然而，由于患者服用了eOCP，在睡前剂量达到150mg后检测了氯氮平浓度。发现该稳态氯氮平浓度为560ng/mL，与镇静和便秘加重相关。鉴于持续的副作用，氯氮平睡前剂量降至100mg；然而，持续的不耐受最终导致氯氮平停药。该病例突出了在CYP1A2和CYP2C19快速代谢者中氯氮平与eOCP之间的潜在相互作用，导致氯氮平不耐受和停药。氯氮平和eOCP的联合使用应谨慎进行。
