Clinical pharmacology considerations and drug-drug interactions with long-acting cabotegravir and rilpivirine relevant to sub-Saharan Africa.
HIV
antiretroviral
cabotegravir
interaction
long‐acting
rilpivirine
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
25 Jun 2024
25 Jun 2024
Historique:
revised:
05
05
2024
received:
24
12
2023
accepted:
09
05
2024
medline:
26
6
2024
pubmed:
26
6
2024
entrez:
26
6
2024
Statut:
aheadofprint
Résumé
Long-acting injectable (LAI) cabotegravir and rilpivirine for HIV treatment and LAI cabotegravir for pre-exposure HIV prophylaxis are being rolled out in a multitude of countries worldwide. Due to the prolonged exposure, it can be challenging to undertake 'traditional' pharmacokinetic studies and current guidance is derived from their oral equivalents or physiologically based pharmacokinetic studies. This review aims to consider pharmacokinetic characteristics of cabotegravir and rilpivirine and describe anticipated drug-drug interactions (DDIs) with frequent concomitant medications in African settings. Relevant co-medications were identified from the WHO 2021 List of Essential Medicines. All original human and physiologically based pharmacokinetic studies published in English on PubMed, discussing DDIs with LAI cabotegravir and rilpivirine prior to April 2023, were reviewed. The Liverpool HIV interaction database was also reviewed (https://www.hiv-druginteractions.org/checker). LAI cabotegravir and rilpivirine have half-lives of 6-12 and 13-28 weeks, respectively. Cabotegravir is primarily metabolized by UDP-glucuronyltransferase (UGT)-1A1 and rilpivirine by cytochrome P450 (CYP)-3A4. LAI cabotegravir and rilpivirine themselves exhibit low risk of perpetrating interactions with co-medications as they do not induce or inhibit the major drug metabolizing enzymes. However, they are victims of DDIs relating to the induction of their metabolizing enzymes by concomitantly administered medication. Noteworthy contraindicated co-medications include rifamycins, carbamazepine, phenytoin, flucloxacillin and griseofulvin, which induce CYP3A4 and/or UGT1A1, causing clinically significant reduced concentrations of rilpivirine and/or cabotegravir. In addition to virologic failure, subtherapeutic concentrations resulting from DDIs can lead to emergent drug resistance. Clinicians should be aware of potential DDIs and counsel people receiving LAI cabotegravir/rilpivirine appropriately to minimize risk.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust Clinical Research Career Development Fellowship
ID : 222075_Z_20_Z
Organisme : Wellcome Trust Clinical Research Career Development Fellowship
ID : 222075/Z/20/Z
Organisme : Wellcome Early Career Fellowship
ID : 300088/Z/23/Z
Informations de copyright
© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Références
UNAIDS. Global HIV & AIDS statistics—fact sheet [Internet]; 2023. Available from: https://www.unaids.org/en/resources/fact-sheet
UNAIDS. South Africa [Internet]. 2023. Available from: https://www.unaids.org/en/regionscountries/countries/southafrica
Sethi AK, Celentano DD, Gange SJ, Moore RD, Gallant JE. Association between adherence to antiretroviral therapy and human immunodeficiency virus drug resistance. Clin Infect Dis. 2003;37(8):1112‐1118. doi:10.1086/378301
Swindells S, Andrade‐Villanueva JF, Richmond GJ, et al. Long‐acting cabotegravir and rilpivirine for maintenance of HIV‐1 suppression. N Engl J Med. 2020;382(12):1112‐1123. doi:10.1056/NEJMoa1904398
Spreen WR, Margolis DA, Pottage JC. Long‐acting injectable antiretrovirals for HIV treatment and prevention. Curr Opin HIV AIDS. 2013;8(6):565‐571.
Vocabria Summary Product Characteristics. ViiV Healthcare; 2021. Available from: https://www.ema.europa.eu/en/documents/product-information/vocabria-epar-product-information_en.pdf
REKAMBYS Summary of Product Characteristics. ViiV Healthcare; 2021. Available from: https://www.ema.europa.eu/en/documents/product-information/rekambys-epar-product-information_en.pdf
Markowitz M, Frank I, Grant RM, et al. Safety and tolerability of long‐acting cabotegravir injections in HIV‐uninfected men (ECLAIR): a multicentre, double‐blind, randomised, placebo‐controlled, phase 2a trial. Lancet HIV. 2017;4(8):e331‐e340. doi:10.1016/S2352‐3018(17)30068‐1
Orkin C, Schapiro JM, Perno CF, et al. Expanded multivariable models to assist patient selection for long‐acting cabotegravir + rilpivirine treatment: clinical utility of a combination of patient, drug concentration, and viral factors associated with virologic failure. Clin Infect Dis. 2023;77(10):1423‐1431. doi:10.1093/cid/ciad370
Yáñez JA, Remsberg CM, Sayre CL, Forrest ML, Davies NM. Flip‐flop pharmacokinetics—delivering a reversal of disposition: challenges and opportunities during drug development. Ther Deliv. 2011;2(5):643‐672. doi:10.4155/tde.11.19
Hodge D, Back DJ, Gibbons S, Khoo SH, Marzolini C. Pharmacokinetics and drug–drug interactions of long‐acting intramuscular cabotegravir and rilpivirine. Clin Pharmacokinet. 2021;60(7):835‐853. doi:10.1007/s40262‐021‐01005‐1
Seden K, Back D, Khoo S. Antiretroviral drug interactions: often unrecognized, frequently unavoidable, sometimes unmanageable. J Antimicrob Chemother. 2009;64(1):5‐8. doi:10.1093/jac/dkp152
Voshavar C. Protease inhibitors for the treatment of HIV/AIDS: recent advances and future challenges. Curr Top Med Chem. 2019;19(18):1571‐1598. doi:10.2174/1568026619666190619115243
Kuepfer L, Niederalt C, Wendl T, et al. Applied concepts in PBPK modeling: how to build a PBPK/PD model. CPT Pharmacometrics Syst Pharmacol. 2016;5(10):516‐531. doi:10.1002/psp4.12134
WHO Model List of Essential Medicines—22nd list, 2021 [Internet]. 2023. Available from: https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2021.02
Liverpool HIV Interactions [Internet]. 2023. Available from: https://www.hiv-druginteractions.org/checker
Scarsi KK, Havens JP, Podany AT, Avedissian SN, Fletcher CV. HIV‐1 integrase inhibitors: a comparative review of efficacy and safety. Drugs. 2020;80(16):1649‐1676. doi:10.1007/s40265‐020‐01379‐9
Patel P, Ford SL, Crauwels H, et al. 2495. Pharmacokinetics of cabotegravir (CAB) and rilpivirine (RPV) long‐acting (LA) injectables in HIV‐infected individuals through 48 weeks in the FLAIR and ATLAS phase 3 studies. Open Forum Infect Dis. 2019;6(Suppl 2):S865‐S866. doi:10.1093/ofid/ofz360.2173
Bowers GD, Culp A, Reese MJ, et al. Disposition and metabolism of cabotegravir: a comparison of biotransformation and excretion between different species and routes of administration in humans. Xenobiotica. 2016;46(2):147‐162. doi:10.3109/00498254.2015.1060372
Reese MJ, Bowers GD, Humphreys JE, et al. Drug interaction profile of the HIV integrase inhibitor cabotegravir: assessment from in vitro studies and a clinical investigation with midazolam. Xenobiotica. 2016;46(5):445‐456. doi:10.3109/00498254.2015.1081993
Landovitz RJ, Li S, Eron JJ, et al. Tail‐phase safety, tolerability, and pharmacokinetics of long‐acting injectable cabotegravir in HIV‐uninfected adults: a secondary analysis of the HPTN 077 trial. Lancet HIV. 2020;7(7):e472‐e481. doi:10.1016/S2352‐3018(20)30106‐5
Crauwels HM, Van Heeswijk R, Kestens D, et al. The pharmacokinetic (PK) interaction between omeprazole and TMC278, an investigational non‐nucleoside reverse transcriptase inhibitor (NNRTI). J Int AIDS Soc. 2008;11(1):1‐2. doi:10.1186/1758‐2652‐11‐S1‐P239
Weiss J, Haefeli WE. Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug‐metabolising enzymes in vitro. Int J Antimicrob Agents. 2013;41(5):484‐487. doi:10.1016/j.ijantimicag.2013.01.004
Jackson AGA, Else LJ, Mesquita PMM, et al. A compartmental pharmacokinetic evaluation of long‐acting rilpivirine in HIV‐negative volunteers for pre‐exposure prophylaxis. Clin Pharmacol Ther. 2014;96(3):314‐323. doi:10.1038/clpt.2014.118
Penrose KJ, Parikh UM, Hamanishi KA, et al. Selection of rilpivirine‐resistant HIV‐1 in a seroconverter from the SSAT 040 trial who received the 300‐mg dose of long‐acting rilpivirine (TMC278LA). J Infect Dis. 2016;213(6):1013‐1017. doi:10.1093/infdis/jiv528
EDURANT® (rilpivirine) tablets, package insert. 2021. Available from: www.fda.gov/medwatch
la Porte C. Inhibitory quotient in HIV pharmacology. Retrovirology. 2010;7(Suppl 1):I9. doi:10.1186/1742‐4690‐7‐S1‐I9
Krishna R, East L, Larson P, et al. Effect of metal‐cation antacids on the pharmacokinetics of 1200 mg raltegravir. J Pharm Pharmacol. 2016;68(11):1359‐1365. doi:10.1111/jphp.12632
Kiser JJ, Bumpass JB, Meditz AL, et al. Effect of antacids on the pharmacokinetics of raltegravir in human immunodeficiency virus‐seronegative volunteers. Antimicrob Agents Chemother. 2010;54(12):4999‐5003. doi:10.1128/AAC.00636‐10
World Health Organization. Rapid advice: antiretroviral therapy for HIV infection in adults and adolescents—November 2009. 2009.
Bruchfeld J, Correia‐Neves M, Kallenius G. Tuberculosis and HIV coinfection. Cold Spring Harb Perspect Med. 2015;5(7):a017871. doi:10.1101/cshperspect.a017871
Dorman SE, Nahid P, Kurbatova EV, et al. Four‐month rifapentine regimens with or without moxifloxacin for tuberculosis. New Engl J Med. 2021;384(18):1705‐1718. doi:10.1056/NEJMoa2033400
WHO operational handbook on tuberculosis: module 4: treatment: drug‐susceptible tuberculosis treatment [Internet]. 2023. Available from: https://www.who.int/publications/i/item/9789240050761
Ford SL, Sutton K, Lou Y, et al. Effect of rifampin on the single‐dose pharmacokinetics of oral cabotegravir in healthy subjects. Antimicrob Agents Chemother. 2017;61(10):P239. doi:10.1186/1758‐2652‐11‐S1‐P239
Ford SL, Sutton K, Lou Y, et al. Effect of rifampin on the single‐dose pharmacokinetics of oral cabotegravir in healthy subjects. Antimicrob Agents Chemother. 2017;61(10):e00487‐17. doi:10.1128/AAC.00487‐17
Rajoli RKR, Curley P, Chiong J, et al. Predicting drug–drug interactions between rifampicin and long‐acting cabotegravir and rilpivirine using physiologically based pharmacokinetic modeling. J Infect Dis. 2019;219(11):1735‐1742. doi:10.1093/infdis/jiy726
Bettonte S, Berton M, Stader F, Battegay M, Marzolini C. Management of drug‐drug interactions between long‐acting cabotegravir and rilpivirine and comedications with inducing properties: a modeling study. Clin Infect Dis. 2023;76(7):1225‐1236. doi:10.1093/cid/ciac901
Sunagawa SW, Havens JP, Podany A, Walker B, Scarsi KK, Bares SH. Long‐acting cabotegravir/rilpivirine concentrations in combination with intravenous rifampin: a case report. Open Forum Infect Dis. 2023;10(12):ofad604. doi:10.1093/ofid/ofad604
Ford SL, Lou Y, Lewis N, et al. Effect of rifabutin on the pharmacokinetics of oral cabotegravir in healthy subjects. Antivir Ther. 2019;24(4):301‐308. doi:10.3851/IMP3306
Margolis DA, Brinson CC, Smith GHR, et al. Cabotegravir plus rilpivirine, once a day, after induction with cabotegravir plus nucleoside reverse transcriptase inhibitors in antiretroviral‐naive adults with HIV‐1 infection (LATTE): a randomised, phase 2b, dose‐ranging trial. Lancet Infect Dis. 2015;15(10):1145‐1155. doi:10.1016/S1473‐3099(15)00152‐8
FDA, CDER. Highlights of prescribing information x coadministration with drugs where significant decreases in cabotegravir. 2024. Available from: www.fda.gov/medwatch
Crauwels H, van Heeswijk R, Kestens D. The pharmacokinetic (PK) interaction between ketoconazole and TMC278, an investigational non‐nucleoside reverse transcriptase inhibitor (NNRTI). In: 17th International AIDS Conference, Mexico City, Mexico; 2008.
van Heeswijk R, Hoetelmans R, Kestens D. The effects of CYP3A4 modulation on the pharmacokinetics of TMC278, an investigational non‐nucleoside reverse transcriptase inhibitor (NNRTI). In: 7th International Workshop on Clinical Pharmacology, Lisbon, Portugal; 2006.
Bordet C, Garcia P, Salvo F, et al. Antipsychotics and risk of QT prolongation: a pharmacovigilance study. Psychopharmacology (Berl). 2023;240(1):199‐202. doi:10.1007/s00213‐022‐06293‐4
Funk KA, Bostwick JR. A comparison of the risk of QT prolongation among SSRIs. Ann Pharmacother. 2013;47(10):1330‐1341. doi:10.1177/1060028013501994
Giardina EGV, Bigger JT, Glassman AH, Perel JM, Kantor SJ. The electrocardiographic and antiarrhythmic effects of imipramine hydrochloride at therapeutic plasma concentrations. Circulation. 1979;60(5):1045‐1052. doi:10.1161/01.cir.60.5.1045
Wen J, Sawmiller D, Wheeldon B, Tan J. A review for lithium: pharmacokinetics, drug design, and toxicity. CNS Neurol Disord Drug Targets. 2019;18(10):769‐778. doi:10.2174/1871527318666191114095249
Zaccara G, Perucca E. Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs. Epileptic Disord. 2014;16(4):409‐431. doi:10.1684/epd.2014.0714
Ezzet F, Karbwang J. Population pharmacokinetics and therapeutic response of CGP 56697 (artemether + benflumetol) in malaria patients. Br J Clin Pharmacol. 1998;46(6):553‐561. doi:10.1046/j.1365‐2125.1998.00830.x
Lefèvre G, Bindschedler M, Ezzet F, Schaeffer N, Meyer I, Thomsen MS. Pharmacokinetic interaction trial between co‐artemether and mefloquine. Eur J Pharm Sci. 2000;10(2):141‐151. doi:10.1016/s0928‐0987(00)00060‐9
White NJ. Cardiotoxicity of antimalarial drugs. Lancet Infect Dis. 2007;7(8):549‐558. doi:10.1016/S1473‐3099(07)70187‐1
Funck‐Brentano C, Bacchieri A, Valentini G, et al. Effects of dihydroartemisinin‐piperaquine phosphate and artemether‐lumefantrine on QTc interval prolongation. Sci Rep. 2019;9(1):777. doi:10.1038/s41598‐018‐37112‐6
Nosten F, ter Kuile FO, Luxemburger C, et al. Cardiac effects of antimalarial treatment with halofantrine. Lancet. 1993;341(8852):1054‐1056. doi:10.1016/0140‐6736(93)92412‐m
Tittle V, Bull L, Boffito M, Nwokolo N. Pharmacokinetic and pharmacodynamic drug interactions between antiretrovirals and oral contraceptives. Clin Pharmacokinet. 2015;54(1):23‐34. doi:10.1007/s40262‐014‐0204‐8
Blair CS, Li S, Chau G, et al. Brief report: hormonal contraception use and cabotegravir pharmacokinetics in HIV‐uninfected women enrolled in HPTN 077. J Acquir Immune Defic Syndr. 2020;85(1):93‐97. doi:10.1097/QAI.0000000000002409
Trezza C, Ford SL, Gould E, et al. Lack of effect of oral cabotegravir on the pharmacokinetics of a levonorgestrel/ethinyl oestradiol‐containing oral contraceptive in healthy adult women. Br J Clin Pharmacol. 2017;83(7):1499‐1505. doi:10.1111/bcp.13236
Crauwels HM, van Heeswijk RP, Buelens A, Stevens M, Hoetelmans RM. Lack of an effect of rilpivirine on the pharmacokinetics of ethinylestradiol and norethindrone in healthy volunteers. Int J Clin Pharmacol Ther. 2014;52(2):118‐128. doi:10.5414/CP201943
Verfaillie S, Godinas L, Spriet I, Vos R, Verleden GM. Interaction between posaconazole and flucloxacillin in a lung transplant patient: decrease in plasma exposure of posaconazole and possible undertreatment of invasive aspergillosis: case report. BMC Pulm Med. 2022;22(1):110. doi:10.1186/s12890‐022‐01904‐4
Wortman JM, Leegwater E, Van Lammeren‐Venema D, Van Nieuwkoop C, Sobels A, Wilms EB. Drug–drug interaction: decreased posaconazole trough concentrations during concomitant flucloxacillin treatment. J Antimicrob Chemother. 2023;78(6):1471‐1475. doi:10.1093/jac/dkad107
Iversen DB, Dunvald ACD, Jespersen DM, et al. Flucloxacillin is a weak inducer of CYP3A4 in healthy adults and 3D spheroid of primary human hepatocytes. Clin Pharmacol Ther. 2023;114(2):434‐445. doi:10.1002/cpt.2959
Huwyler J, Wright M, Gutmann H, Drewe J. Induction of cytochrome P450 3A4 and P‐glycoprotein by the isoxazolyl‐penicillin antibiotic flucloxacillin. Curr Drug Metab. 2006;7(2):119‐126. doi:10.2174/138920006775541534
Akiyoshi T, Ito M, Murase S, et al. Mechanism‐based inhibition profiles of erythromycin and clarithromycin with cytochrome P450 3A4 genetic variants. Drug Metab Pharmacokinet. 2013;28(5):411‐415. doi:10.2133/dmpk.dmpk‐12‐rg‐134
Hancox JC, Hasnain M, Vieweg WVR, Gysel M, Baranchuk A, Methot M. Erythromycin, QTc interval prolongation, and torsade de pointes: case reports, major risk factors and illness severity. Ther Adv Infect Dis. 2014;2(2):47‐59. doi:10.1177/2049936114527744
Fiets R, Bos J, Donders A, et al. QTc prolongation during erythromycin used as prokinetic agent in ICU patients. Eur J Hosp Pharm. 2018;25(3):118‐122. doi:10.1136/ejhpharm‐2016‐001077
Briasoulis A, Agarwal V, Pierce WJ. QT prolongation and torsade de pointes induced by fluoroquinolones: infrequent side effects from commonly used medications. Cardiology. 2011;120(2):103‐110. doi:10.1159/000334441
Herzig K, Johnson DW. Marked elevation of blood cyclosporin and tacrolimus levels due to concurrent metronidazole therapy. Nephrol Dial Transplant. 1999;14(2):521‐523. doi:10.1093/ndt/14.2.521b
Wang JS, Backman JT, Kivistö KT, Neuvonen PJ. Effects of metronidazole on midazolam metabolism in vitro and in vivo. Eur J Clin Pharmacol. 2000;56(8):555‐559. doi:10.1007/s002280000201
Roedler R, Neuhauser MM, Penzak SR. Does metronidazole interact with CYP3A substrates by inhibiting their metabolism through this metabolic pathway? Or should other mechanisms be considered? Ann Pharmacother. 2007;41(4):653‐658. doi:10.1345/aph.1H401
Steegen K, Chandiwana N, Sokhela S, Venter WDF, Hans L. Impact of rilpivirine cross‐resistance on long‐acting cabotegravir‐rilpivirine in low and middle‐income countries. AIDS. 2023;37(6):1009‐1011. doi:10.1097/QAD.0000000000003505
Alexander SPH, Fabbro D, Kelly E, et al. The concise guide to PHARMACOLOGY 2023/24: enzymes. Br J Pharmacol. 2023;180(S2):S289‐S373. doi:10.1111/bph.16181