University of Toronto, Toronto General Hospital, Faculty of Pharmacy, Toronto, ON, Canada.
Expert Opin Drug Metab Toxicol. 2013 May;9(5):559-72. doi: 10.1517/17425255.2013.772579. Epub 2013 Feb 21.
Significant advances in antiretroviral therapy have transformed HIV into a chronic manageable disease, and millions of women living with HIV now have the opportunity to reconsider their reproductive choices, be it contraception or pregnancy planning. Hormonal contraceptives are metabolized by cytochrome P450 isoenzymes and sulfate and glucuronide conjugation in the liver. Many antiretrovirals have inducing or inhibiting effects on the cytochrome P450 system. As such, the pharmacokinetics of hormonal contraceptives can be affected by antiretroviral therapy with potential for significant clinical impact.
This article presents the pharmacology and metabolism of selected antiretrovirals and hormonal contraceptives, and highlights the potential interactions between these two classes of drugs. Furthermore, the authors present the pharmacokinetic evidence of interactions from available clinical trials, product monographs, and international conference abstracts.
Drugs most likely to interact with combined oral contraceptives, transdermal and implant contraceptives include protease inhibitors, the NNRTIs efavirenz and nevirapine, and cobicistat-boosted elvitegravir. There do not appear to be significant pharmacokinetic interactions with depo-medroxyprogesterone or intrauterine systems and antiretrovirals, although further study is needed. Clinicians working with HIV-positive women need to know the significance of these interactions in order to properly counsel patients and prevent unplanned pregnancies.
抗逆转录病毒疗法的重大进展将 HIV 转变为一种可慢性控制的疾病,现在数以百万计的 HIV 感染者有机会重新考虑他们的生育选择,无论是避孕还是妊娠计划。激素避孕药在肝脏中通过细胞色素 P450 同工酶和硫酸盐及葡萄糖醛酸缀合代谢。许多抗逆转录病毒药物对细胞色素 P450 系统具有诱导或抑制作用。因此,激素避孕药的药代动力学可能会受到抗逆转录病毒治疗的影响,从而产生潜在的重大临床影响。
本文介绍了选定的抗逆转录病毒药物和激素避孕药的药理学和代谢,并强调了这两类药物之间可能存在的相互作用。此外,作者还介绍了现有临床试验、产品说明书和国际会议摘要中药物相互作用的药代动力学证据。
最有可能与口服避孕药、透皮贴剂和植入避孕药发生相互作用的药物包括蛋白酶抑制剂、NNRTI 类药物依非韦伦和奈韦拉平,以及考比司他增强的艾维雷韦。与去甲孕二烯酮或宫内节育系统和抗逆转录病毒药物似乎没有明显的药代动力学相互作用,但仍需要进一步研究。与 HIV 阳性女性合作的临床医生需要了解这些相互作用的意义,以便为患者提供适当的咨询并防止意外怀孕。