Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis.
Female
Humans
Rifampin
/ adverse effects
Isoniazid
Levonorgestrel
/ adverse effects
Antitubercular Agents
/ adverse effects
Cytochrome P-450 CYP2B6
/ genetics
Pharmacogenetics
Cytochrome P-450 CYP3A
/ genetics
Contraception, Postcoital
HIV Infections
/ drug therapy
Tuberculosis
/ drug therapy
Benzoxazines
/ adverse effects
Anti-HIV Agents
/ therapeutic use
Genotype
Journal
Pharmacogenetics and genomics
ISSN: 1744-6880
Titre abrégé: Pharmacogenet Genomics
Pays: United States
ID NLM: 101231005
Informations de publication
Date de publication:
01 08 2023
01 08 2023
Historique:
medline:
12
7
2023
pubmed:
12
6
2023
entrez:
12
6
2023
Statut:
ppublish
Résumé
In AIDS Clinical Trials Group study A5375, a pharmacokinetic trial of levonorgestrel emergency contraception, double-dose levonorgestrel (3 mg, versus standard dose 1.5 mg) offset the induction effects of efavirenz or rifampin on plasma levonorgestrel exposure over 8 h post-dose (AUC 0-8h ). We characterized the pharmacogenetics of these interactions. Cisgender women receiving efavirenz- or dolutegravir-based HIV therapy, or on isoniazid-rifampin for tuberculosis, were followed after a single oral dose of levonorgestrel. Linear regression models, adjusted for BMI and age, characterized associations of CYP2B6 and NAT2 genotypes (which affect plasma efavirenz and isoniazid exposure, respectively) with levonorgestrel pharmacokinetic parameters. Of 118 evaluable participants, 17 received efavirenz/levonorgestrel 1.5 mg, 35 efavirenz/levonorgestrel 3 mg, 34 isoniazid-rifampin/levonorgestrel 3 mg, and 32 (control group) dolutegravir/levonorgestrel 1.5 mg. There were 73 Black and 33 Asian participants. Regardless of genotype, women on efavirenz and isoniazid-rifampin had higher levonorgestrel clearance. In the efavirenz/levonorgestrel 3 mg group, CYP2B6 normal/intermediate metabolizers had levonorgestrel AUC 0-8h values similar to controls, while CYP2B6 poor metabolizers had AUC 0-8h values of 40% lower than controls. In the isoniazid-rifampin group, NAT2 rapid/intermediate acetylators had levonorgestrel AUC 0-8h values similar to controls, while NAT2 slow acetylators had AUC 0-8h values 36% higher than controls. CYP2B6 poor metabolizer genotypes exacerbate the efavirenz-levonorgestrel interaction, likely by increased CYP3A induction with higher efavirenz exposure, making the interaction more difficult to overcome. NAT2 slow acetylator genotypes attenuate the rifampin-levonorgestrel interaction, likely by increased CYP3A inhibition with higher isoniazid exposure.
Identifiants
pubmed: 37306344
doi: 10.1097/FPC.0000000000000501
pii: 01213011-202308000-00002
pmc: PMC10309098
doi:
Substances chimiques
Rifampin
VJT6J7R4TR
Isoniazid
V83O1VOZ8L
efavirenz
JE6H2O27P8
Levonorgestrel
5W7SIA7YZW
Antitubercular Agents
0
Cytochrome P-450 CYP2B6
EC 1.14.14.1
Cytochrome P-450 CYP3A
EC 1.14.14.1
Benzoxazines
0
Anti-HIV Agents
0
NAT2 protein, human
EC 2.3.1.5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
126-135Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI069471
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069463
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI106701
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069521
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI068634
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069476
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI077505
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069456
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI069471
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069432
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002489
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069419
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069399
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068634
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD085887
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069518
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068636
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069423
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001857
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069453
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069494
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI069399
Pays : United States
Organisme : NIAID NIH HHS
ID : R25 AI164610
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002384
Pays : United States
Informations de copyright
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
Références
World Health Organization. Global Tuberculosis Report 2022. 2022. https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022 . [Accessed 30 January 2023].
World Health Organization. Tuberculosis in women. 2018. https://www.who.int/publications/m/item/tuberculosis-in-women . [Accessed 12 August 2022].
Pillay T, Sturm AW, Khan M, Adhikari M, Moodley J, Connolly C, et al. Vertical transmission of Mycobacterium tuberculosis in KwaZulu Natal: impact of HIV-1 co-infection. Int J Tuberc Lung Dis 2004; 8:59–69.
Curtis KM, Tepper NK, Jatlaoui TC, Berry-Bibee E, Horton LG, Zapata LB, et al. U.S. Medical eligibility criteria for contraceptive use, 2016. MMWR Recomm Rep 2016; 65:1–103.
World Health Organization. Emergency contraception. 2021. https://www.who.int/news-room/fact-sheets/detail/emergency-contraception . [Accessed 5 April 2022].
World Health Organization. Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach. 2021. https://www.who.int/publications/i/item/9789240031593 . [Accessed 8 August 2022].
Williamson B, Dooley KE, Zhang Y, Back DJ, Owen A. Induction of influx and efflux transporters and cytochrome P450 3A4 in primary human hepatocytes by rifampin, rifabutin, and rifapentine. Antimicrob Agents Chemother 2013; 57:6366–6369.
Kobayashi K, Mimura N, Fujii H, Minami H, Sasaki Y, Shimada N, et al. Role of human cytochrome P450 3A4 in metabolism of medroxyprogesterone acetate. Clin Cancer Res 2000; 6:3297–3303.
Scarsi KK, Cramer YS, Rosenkranz SL, Aweeka F, Berzins B, Coombs RW, et al.; AIDS Clinical Trials Group A5316 Study Team. Antiretroviral therapy and vaginally administered contraceptive hormones: a three-arm, pharmacokinetic study. Lancet HIV 2019; 6:e601–e612.
Patel RC, Onono M, Gandhi M, Blat C, Hagey J, Shade SB, et al. Pregnancy rates in HIV-positive women using contraceptives and efavirenz-based or nevirapine-based antiretroviral therapy in Kenya: a retrospective cohort study. Lancet HIV 2015; 2:e474–e482.
Wen X, Wang JS, Neuvonen PJ, Backman JT. Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes. Eur J Clin Pharmacol 2002; 57:799–804.
Haas DW, Podany AT, Bao Y, Swindells S, Chaisson RE, Mwelase N, et al. Pharmacogenetic interactions of rifapentine plus isoniazid with efavirenz or nevirapine. Pharmacogenet Genomics 2021; 31:17–27.
Huang YS, Chern HD, Su WJ, Wu JC, Lai SL, Yang SY, et al. Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis. Hepatology 2002; 35:883–889.
Roy PD, Majumder M, Roy B. Pharmacogenomics of anti-TB drugs-related hepatotoxicity. Pharmacogenomics 2008; 9:311–321.
Ramachandran G, Swaminathan S. Role of pharmacogenomics in the treatment of tuberculosis: a review. Pharmgenomics Pers Med 2012; 5:89–98.
Holzinger ER, Grady B, Ritchie MD, Ribaudo HJ, Acosta EP, Morse GD, et al. Genome-wide association study of plasma efavirenz pharmacokinetics in AIDS Clinical Trials Group protocols implicates several CYP2B6 variants. Pharmacogenet Genom 2012; 22:858–867.
Scarsi KK, Smeaton LM, Podany AT, Olefsky M, Woolley E, Barr E, et al. Pharmacokinetics of dose-adjusted levonorgestrel emergency contraception combined with efavirenz-based antiretroviral therapy or rifampicin-containing tuberculosis regimens. Contraception 2023; 121:109951.
Cirrincione LR, Penchala SD, Scarsi KK, Podany AT, Winchester LC, Back DJ, et al. Development, validation and utilization of a highly sensitive LC-MS/MS method for quantification of levonorgestrel released from a subdermal implant in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2018; 1084:106–112.
Fletcher CV, Brundage RC, Fenton T, Alvero CG, Powell C, Mofenson LM, et al. Pharmacokinetics and pharmacodynamics of efavirenz and nelfinavir in HIV-infected children participating in an area-under-the-curve controlled trial. Clin Pharmacol Ther 2008; 83:300–306.
Winchester LC, Podany AT, Baldwin JS, Robbins BL, Fletcher CV. Determination of the rifamycin antibiotics rifabutin, rifampin, rifapentine and their major metabolites in human plasma via simultaneous extraction coupled with LC/MS/MS. J Pharm Biomed Anal 2015; 104:55–61.
US Food and Drug Administration. Bioanalytical method validation: guidance for industry. 2018. https://www.fda.gov/media/70858/download . [Accessed 12 August 2022].
Mngqibisa R, Kendall MA, Dooley K, Wu XS, Firnhaber C, McIlleron H, et al.; A5338 Study Team. Pharmacokinetics and pharmacodynamics of depot medroxyprogesterone acetate in African women receiving treatment for human immunodeficiency virus and tuberculosis: potential concern for standard dosing frequency. Clin Infect Dis 2020; 71:517–524.
Chen S, St Jean P, Borland J, Song I, Yeo AJ, Piscitelli S, et al. Evaluation of the effect of UGT1A1 polymorphisms on dolutegravir pharmacokinetics. Pharmacogenomics 2014; 15:9–16.
Cindi Z, Kawuma AN, Maartens G, Bradford Y, Venter F, Sokhela S, et al. Pharmacogenetics of dolutegravir plasma exposure among Southern Africans living with HIV. J Infect Dis 2022; 226:1616–1625.
Chigutsa E, Visser ME, Swart EC, Denti P, Pushpakom S, Egan D, et al. The SLCO1B1 rs4149032 polymorphism is highly prevalent in South Africans and is associated with reduced rifampin concentrations: dosing implications. Antimicrob Agents Chemother 2011; 55:4122–4127.
Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, et al.; SEARCH Collaborative Group. SLCO1B1 variants and statin-induced myopathy--a genomewide study. N Engl J Med 2008; 359:789–799.
Edelman AB, Cherala G, Blue SW, Erikson DW, Jensen JT. Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing. Contraception 2016; 94:52–57.
Neary M, Lamorde M, Olagunju A, Darin KM, Merry C, Byakika-Kibwika P, et al. The effect of gene variants on levonorgestrel pharmacokinetics when combined with antiretroviral therapy containing efavirenz or nevirapine. Clin Pharmacol Ther 2017; 102:529–536.
Haas DW, Cramer YS, Godfrey C, Rosenkranz SL, Aweeka F, Berzins B, et al.; AIDS Clinical Trials Group A5316 Study Team. Pharmacogenetic interactions between antiretroviral drugs and vaginally administered hormonal contraceptives. Pharmacogenet Genomics 2020; 30:45–53.
Watts DH, Park JG, Cohn SE, Yu S, Hitti J, Stek A, et al. Safety and tolerability of depot medroxyprogesterone acetate among HIV-infected women on antiretroviral therapy: ACTG A5093. Contraception 2008; 77:84–90.
Cohn SE, Park JG, Watts DH, Stek A, Hitti J, Clax PA, et al.; ACTG A5093 Protocol Team. Depo-medroxyprogesterone in women on antiretroviral therapy: effective contraception and lack of clinically significant interactions. Clin Pharmacol Ther 2007; 81:222–227.
Haas DW, Mngqibisa R, Francis J, McIlleron H, Robinson JA, Kendall MA, et al.; AIDS Clinical Trials Group A5338 Study Team. Pharmacogenetics of interaction between depot medroxyprogesterone acetate and efavirenz, rifampicin, and isoniazid during treatment of HIV and tuberculosis. Pharmacogenet Genomics 2022; 32:24–30.
Nanda K, Amaral E, Hays M, Viscola MA, Mehta N, Bahamondes L. Pharmacokinetic interactions between depot medroxyprogesterone acetate and combination antiretroviral therapy. Fertil Steril 2008; 90:965–971.
Kwara A, Lartey M, Sagoe KW, Court MH. Paradoxically elevated efavirenz concentrations in HIV/tuberculosis-coinfected patients with CYP2B6 516TT genotype on rifampin-containing antituberculous therapy. AIDS 2011; 25:388–390.
Dooley KE, Denti P, Martinson N, Cohn S, Mashabela F, Hoffmann J, et al.; TSHEPISO Study Team. Pharmacokinetics of Efavirenz and treatment of HIV-1 among pregnant women with and without tuberculosis coinfection. J Infect Dis 2015; 211:197–205.
Luetkemeyer AF, Rosenkranz SL, Lu D, Grinsztejn B, Sanchez J, Ssemmanda M, et al.; Adult AIDS Clinical Trials Group A5221 and A5243 Study Teams. Combined effect of CYP2B6 and NAT2 genotype on plasma efavirenz exposure during rifampin-based antituberculosis therapy in the STRIDE study. Clin Infect Dis 2015; 60:1860–1863.
Swindells S, Ramchandani R, Gupta A, Benson CA, Leon-Cruz J, Mwelase N, et al.; BRIEF TB/A5279 Study Team. One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis. N Engl J Med 2019; 380:1001–1011.
Praditpan P, Hamouie A, Basaraba CN, Nandakumar R, Cremers S, Davis AR, et al. Pharmacokinetics of levonorgestrel and ulipristal acetate emergency contraception in women with normal and obese body mass index. Contraception 2017; 95:464–469.
Natavio M, Stanczyk FZ, Molins EAG, Nelson A, Jusko WJ. Pharmacokinetics of the 1.5 mg levonorgestrel emergency contraceptive in women with normal, obese and extremely obese body mass index. Contraception 2019; 99:306–311.
National Center for Biotechnology Information. dbSNP homepage. 2022. http://www.ncbi.nlm.nih.gov/SNP/index.html . [Accessed 12 August 2022].