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2000
Volume 25, Issue 9
  • ISSN: 1389-2002
  • E-ISSN: 1875-5453

Abstract

Background

The US FDA has approved paxlovid, a combination of nirmatrelvir and ritonavir, as the first oral treatment for the management of mild-to-moderate COVID-19 patients.

Objective

The purpose of this review article is to explore the clinical data that is currently available regarding the drug-drug interactions (DDIs) of paxlovid with various medications.

Methods

Keywords, such as drug interactions, paxlovid, ritonavir, nirmatrelvir, pharmacokinetic interactions, CYP3A, and P-glycoprotein, were used to search online databases, including LitCOVID, Scopus, Embase, EBSCO host, Google Scholar, ScienceDirect, Cochrane Library, and reference lists.

Results

Paxlovid interacted with a variety of medications due to strong inhibition of CYP3A4 and P-gp transporter protein by ritonavir and the dual function of nirmatrelvir as a substrate and inhibitor of CYP3A enzymes and P-gp transporter protein. Numerous case reports and other studies determined that the risk of toxicities of several drugs, including anticoagulants (warfarin, rivaroxaban), calcium channel blockers (nifedipine, manidipine, verapamil), statins (atorvastatin), immunosuppressants (tacrolimus), antiarrhythmics (amiodarone), antipsychotics (clozapine, quetiapine), and ranolazine have been enhanced by the concomitant administration of paxlovid.

Conclusion

Adverse effects of paxlovid from DDIs can range from less-than-ideal therapeutic responses to potentially fatal toxicities. Effective management requires close observation, adjustments to dosage, and assessment of substitute treatments. Collaboration between pharmacists and other medical professionals is necessary to guarantee effective and safe treatment outcomes of paxlovid therapy.

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References

  1. Al-QahtaniA.A. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Emergence, history, basic and clinical aspects.Saudi J. Biol. Sci.202027102531253810.1016/j.sjbs.2020.04.03332336927
     [Google Scholar]
  2. WHO Coronavirus (COVID-19) Dashboard. https://covid19.who.int/
  3. MaideenN.M. Recent updates in the pharmacological management of COVID-19.Lett. Appl. Nano.BioSci.2021119691980
     [Google Scholar]
  4. MaideenN.M.P. Adjuvant therapies of COVID-19: A literature review.Coronaviruses2021210e17082119056210.2174/2666796702666210121144902
     [Google Scholar]
  5. BalasubramanianR. MaideenN.M.P. MuthusamyS. RamanathanS. Jahir HussainM.H. Role of supplements in the management of COVID-19: A comprehensive review.Infect. Disord. Drug Targets2023235e10032321454410.2174/187152652366623031009464636896901
     [Google Scholar]
  6. Emergency Preparedness/Drugs. Coronavirus (COVID-19). https://www.fda.gov/drugs/emergency-preparedness-drugs/coronavirus-covid-19-drugs
  7. United States Food and Drug Administration Press Announcements.2023 https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-antiviral-treatment-covid-19-adults
  8. HashemianS.M.R. SheidaA. TaghizadiehM. MemarM.Y. HamblinM.R. Bannazadeh BaghiH. Sadri NahandJ. AsemiZ. MirzaeiH. Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?.Biomed. Pharmacother.202316211436710.1016/j.biopha.2023.11436737018987
     [Google Scholar]
  9. BegeM. BorbásA. The design, synthesis and mechanism of action of Paxlovid, a protease inhibitor drug combination for the treatment of COVID-19.Pharmaceutics202416221710.3390/pharmaceutics1602021738399271
     [Google Scholar]
  10. Navitha ReddyG. JogvanshiA. NaikwadiS. SontiR. Nirmatrelvir and ritonavir combination: An antiviral therapy for COVID-19.Expert Rev. Anti Infect. Ther.202321994395510.1080/14787210.2023.224163837525997
     [Google Scholar]
  11. PakkirM.N. Pharmacokinetic and pharmacodynamic interactions of sulfonylurea antidiabetics.Eur. J. Med.201868396
     [Google Scholar]
  12. MaideenN.M.P. Tobacco smoking and its drug interactions with comedications involving CYP and UGT enzymes and nicotine.World J. Pharmacol.201982142510.5497/wjp.v8.i2.14
     [Google Scholar]
  13. MaideenN. Clinically important and pharmacologically relevant drug interactions with alcohol.AJBSR2019611710.5455/ajrms.20190602042343
     [Google Scholar]
  14. DaviesL.E. SpiersG. KingstonA. ToddA. AdamsonJ. HanrattyB. Adverse outcomes of polypharmacy in older people: Systematic review of reviews.J. Am. Med. Dir. Assoc.202021218118710.1016/j.jamda.2019.10.02231926797
     [Google Scholar]
  15. Pakkir MaideenN.M. ManavalanG. BalasubramanianK. Drug interactions of meglitinide antidiabetics involving CYP enzymes and OATP1B1 transporter.Ther. Adv. Endocrinol. Metab.20189825926810.1177/204201881876722030181852
     [Google Scholar]
  16. RasoolM.F. RehmanA. ImranI. AbbasS. ShahS. AbbasG. KhanI. ShakeelS. Ahmad HassaliM.A. HayatK. Risk factors associated with medication errors among patients suffering from chronic disorders.Front. Public Health2020853103810.3389/fpubh.2020.53103833330300
     [Google Scholar]
  17. Gonzaga de Andrade SantosT.N. Mendonça da Cruz MacieiraG. Cardoso Sodré AlvesB.M. OnozatoT. Cunha CardosoG. Ferreira NascimentoM.T. Saquete Martins-FilhoP.R. Pereira de LyraD.Jr Oliveira FilhoA.D. Prevalence of clinically manifested drug interactions in hospitalized patients: A systematic review and meta-analysis.PLoS One2020157e023535310.1371/journal.pone.023535332609783
     [Google Scholar]
  18. AksoyN. OzturkN. A meta-analysis assessing the prevalence of drug–drug interactions among hospitalized patients.Pharmacoepidemiol. Drug Saf.202332121319133010.1002/pds.569137705139
     [Google Scholar]
  19. FatundeO.A. BrownS.A. The role of CYP450 drug metabolism in precision cardio-oncology.Int. J. Mol. Sci.202021260410.3390/ijms2102060431963461
     [Google Scholar]
  20. KlyushovaL.S. PerepechaevaM.L. GrishanovaA.Y. The role of CYP3A in health and disease.Biomedicines20221011268610.3390/biomedicines1011268636359206
     [Google Scholar]
  21. Veiga-MatosJ. MoralesA.I. PrietoM. RemiãoF. SilvaR. Study models of drug–drug interactions involving P-Glycoprotein: The potential benefit of P-Glycoprotein modulation at the kidney and intestinal levels.Molecules20232822753210.3390/molecules2822753238005253
     [Google Scholar]
  22. PatelK.A. BhattM.H. HiraniR.V. PatelV.A. PatelV.N. ShahG.B. ChorawalaM.R. Assessment of potential drug–drug interactions among outpatients in a tertiary care hospital: Focusing on the role of P-glycoprotein and CYP3A4 (retrospective observational study).Heliyon2022811e1127810.1016/j.heliyon.2022.e1127836387483
     [Google Scholar]
  23. GerhartJ. CoxD.S. SinghR.S.P. ChanP.L.S. RaoR. AllenR. ShiH. MastersJ.C. DamleB. A comprehensive review of the clinical pharmacokinetics, pharmacodynamics, and drug interactions of Nirmatrelvir/Ritonavir.Clin. Pharmacokinet.2024631274210.1007/s40262‑023‑01339‑y38177893
     [Google Scholar]
  24. PAXLOVID. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf
  25. AzanzaJ.R. MensaJ. González del CastilloJ. Linares RufoM. MoleroJ.M. Madero ValleN. BarberánJ. Interactions listed in the Paxlovid fact sheet, classified according to risks, pharmacological groups, and consequences.Rev. Esp. Quimioter.202235435736110.37201/req/054.202235822605
     [Google Scholar]
  26. VazquezS.R. Drug-drug interactions in an era of multiple anticoagulants: A focus on clinically relevant drug interactions.Blood2018132212230223910.1182/blood‑2018‑06‑84874730463993
     [Google Scholar]
  27. VazquezS.R. WilsonA.S. WittD.M. Management of potential drug-drug interactions with nirmatrelvir-ritonavir and oral anticoagulants: A case series.J. Thromb. Thrombolysis202254458358610.1007/s11239‑022‑02707‑436253637
     [Google Scholar]
  28. MuseO. PatellR. LeeM. LechT. GuirguisM. DodgeL. ZwickerJ.I. Impact of Paxlovid on international normalized ratio among patients on chronic warfarin therapy.Blood2022140252757275910.1182/blood.202201743336240439
     [Google Scholar]
  29. WangZ. ChanE.C.Y. Physiologically-based pharmacokinetic modeling-guided dose management of oral anticoagulants when initiating nirmatrelvir/ritonavir (Paxlovid) for COVID-19 treatment.Clin. Pharmacol. Ther.2022112480380710.1002/cpt.268735712802
     [Google Scholar]
  30. RizkJ.G. LazoJ.G.Jr GuptaA. LavieC.J. EffronM.B. Proposal for a simple algorithmic approach to manage drug–drug interactions of oral anticoagulants with Nirmatrelvir/Ritonavir in COVID-19 outpatients.Semin. Thromb. Hemost.202349108508810.1055/s‑0042‑175002435738295
     [Google Scholar]
  31. MaideenN.M. Drug interactions of non-dihydropyridine calcium channel blockers involving CYP3A enzymes and P-gp transporter protein.Biointerface Res. Appl. Chem.20201046026603210.33263/BRIAC104.026032
     [Google Scholar]
  32. MaideenN.M. Drug interactions of Dihydropyridine calcium channel blockers (CCBs) involving CYP3A enzymes.Eur. J. Med.201972106113
     [Google Scholar]
  33. RauserM.S. McGraneI.R. A CYP3A4 drug-drug interaction between Nirmatrelvir/Ritonavir and Nifedipine leading to edema, oliguria, and acute kidney injury: A case report.Ann. Pharmacother.202357899199210.1177/1060028022114313136560849
     [Google Scholar]
  34. KepfingerJ. TagerD. SmithK. A case of Nifedipine overdose due to drug interaction with Paxlovid.Am. J. Respir. Crit. Care Med.2023207A3512
     [Google Scholar]
  35. SathapornN. KhwannimitB. WisaratapongT. WongpraphairotS. A rare cause of refractory vasodilatory shock due to calcium channel blocker toxicity from drug-drug interaction between Ritonavir-Boosted Nirmatrelvir (Paxlovid) And Manidipine.J. Health Sci. Med. Res. JHSMR2023416202396210.31584/jhsmr.2023962
     [Google Scholar]
  36. HaqueO.I. MaharS. HussainS. SloaneP. Pharmacokinetic interaction between verapamil and ritonavir-boosted nirmatrelvir: Implications for the management of COVID-19 in patients with hypertension.BMJ Case Rep.2023161e25267710.1136/bcr‑2022‑25267736639196
     [Google Scholar]
  37. BalasubramanianR. MaideenN.M.P. HMG-CoA reductase inhibitors (Statins) and their drug interactions involving CYP enzymes, P-glycoprotein and OATP transporters-an overview.Curr. Drug Metab.202122532834110.2174/18755453MTEz9MzEj533459228
     [Google Scholar]
  38. KhanS. FamaJ. Acute encephalopathy due to polypharmacy interactions with the use of paxlovid: A Case report.Cureus2023153e3653510.7759/cureus.3653537090279
     [Google Scholar]
  39. CulasR. NathS. NathS. Safely prescribing nirmatrelvir and ritonavir: Avoiding drug-drug interactions.JAMA Intern. Med.2023183436236310.1001/jamainternmed.2022.683436807493
     [Google Scholar]
  40. Titte RS. Herwig-UlfM-K. BruceK. Pharmacokinetic principles of immunosuppressive drugs.Am. J. Transplant.20055220721710.1111/j.1600‑6143.2005.00748.x15643980
     [Google Scholar]
  41. PrikisM. CameronA. Paxlovid (nirmatelvir/ritonavir) and tacrolimus drug-drug interaction in a kidney transplant patient with SARS-2-CoV infection: A case report.Transplant. Proc.20225461557156010.1016/j.transproceed.2022.04.01535599203
     [Google Scholar]
  42. Berar YanayN. BognerI. SakerK. TannousE. Paxlovid-Tacrolimus drug–drug interaction in a 23-year-old female kidney transplant patient with COVID-19.Clin. Drug Investig.202242869369510.1007/s40261‑022‑01180‑435816278
     [Google Scholar]
  43. YoungC. PapiroT. GreenbergJ.H. Elevated tacrolimus levels after treatment with nirmatrelvir/ritonavir (Paxlovid) for COVID-19 infection in a child with a kidney transplant.Pediatr. Nephrol.20233841387138810.1007/s00467‑022‑05712‑035982345
     [Google Scholar]
  44. StawiarskiK. AveryR. StroutS. UmapathiP. Risks of paxlovid in a heart transplant recipient.J. Heart Lung Transplant.2023421303210.1016/j.healun.2022.08.02936344373
     [Google Scholar]
  45. ZaarurL. PatelA. PasternakB. Drug interaction between Tacrolimus and Paxlovid (Nirmatrelvir/Ritonavir) in an adolescent with inflammatory bowel disease.JPGN Rep.202344e35210.1097/PG9.000000000000035238034448
     [Google Scholar]
  46. LuoW. HeY. WeiM.G. LuG.B. YiQ. Paxlovid–tacrolimus drug– drug interaction caused severe diarrhea that induced combined diabetic ketoacidosis and a hyperglycemic hyperosmolar state in a kidney transplant patient: A case report.J. Med. Case Rep.202317140610.1186/s13256‑023‑04135‑137742028
     [Google Scholar]
  47. SindelarM. McCabeD. CarrollE. Tacrolimus drug–drug interaction with Nirmatrelvir/Ritonavir (Paxlovid™) managed with phenytoin.J. Med. Toxicol.2023191454810.1007/s13181‑022‑00922‑236536192
     [Google Scholar]
  48. KwonE.J. YunG.A. ParkS. KimS. ChaeD.W. ParkH.S. LeeT. JeongJ.C. Treatment of acute tacrolimus toxicity with phenytoin after Paxlovid (nirmatrelvir/ritonavir) administration in a kidney transplant recipient.Kidney Res. Clin. Pract.202241676877010.23876/j.krcp.22.21836474331
     [Google Scholar]
  49. LindauerK.E. HamelA.G. Case report: Nirmatrelvir/Ritonavir and tacrolimus in a kidney transplant recipient with COVID-19.Am. Fam. Physician2022105656957035704835
     [Google Scholar]
  50. TsuzawaA. KatadaY. UmemuraK. SugimotoM. NishikawaA. SatoY. YoshidaY. KitadaN. YonezawaA. NakajimaD. DateH. TeradaT. A case report of a prolonged decrease in tacrolimus clearance due to co-administration of nirmatrelvir/ritonavir in a lung transplant recipient receiving itraconazole prophylaxis.J. Pharm. Health Care Sci.2023911210.1186/s40780‑023‑00280‑337004119
     [Google Scholar]
  51. LangeN.W. SalernoD.M. JenningsD.L. ChoeJ. HedvatJ. KovacD.B. ScheffertJ. ShertelT. RatnerL.E. BrownR.S.Jr PereiraM.R. Nirmatrelvir/ritonavir use: Managing clinically significant drug-drug interactions with transplant immunosuppressants.Am. J. Transplant.20222271925192610.1111/ajt.1695535015924
     [Google Scholar]
  52. RoseD.T. GandhiS.M. BedardR.A. MondyK.E. ChuA.L. GambleK.C. GeeA.T. KundraM.A. WilliamsA.L. LeeB.K. Supratherapeutic tacrolimus concentrations with nirmatrelvir/ritonavir in solid organ transplant recipients requiring hospitalization: A case series using rifampin for reversal.Open Forum Infect. Dis.202297ofac23810.1093/ofid/ofac23835854994
     [Google Scholar]
  53. WangA.X. KoffA. HaoD. TuznikN.M. HuangY. Effect of nirmatrelvir/ritonavir on calcineurin inhibitor levels: Early experience in four SARS-CoV-2 infected kidney transplant recipients.Am. J. Transplant.20222282117211910.1111/ajt.1699735158412
     [Google Scholar]
  54. XiaT. WangY. Coronavirus disease 2019 and transplantation: The combination of lopinavir/ritonavir and hydroxychloroquine is responsible for excessive tacrolimus trough level and unfavorable outcome.Am. J. Transplant.20202092630263110.1111/ajt.1599232400965
     [Google Scholar]
  55. SalernoD.M. JenningsD.L. LangeN.W. KovacD.B. ShertelT. ChenJ.K. HedvatJ. ScheffertJ. BrownR.S.Jr PereiraM.R. Early clinical experience with nirmatrelvir/ritonavir for the treatment of COVID-19 in solid organ transplant recipients.Am. J. Transplant.20222282083208810.1111/ajt.1702735278260
     [Google Scholar]
  56. FishbaneS. HirschJ.S. NairV. Special considerations for paxlovid treatment among transplant recipients with SARS-CoV-2 infection.Am. J. Kidney Dis.202279448048210.1053/j.ajkd.2022.01.00135032591
     [Google Scholar]
  57. HiremathS. BlakeP.G. YeungA. McGuintyM. ThomasD. IpJ. BrownP.A. PandesM. BurkeA. SohailQ.Z. ToK. BlackwellL. OliverM. JainA.K. ChaglaZ. CooperR. Early experience with modified dose nirmatrelvir/ritonavir in dialysis patients with coronavirus disease 2019.Clin. J. Am. Soc. Nephrol.202318448549010.2215/CJN.000000000000010736723285
     [Google Scholar]
  58. ToussiS.S. NeutelJ.M. NavarroJ. PrestonR.A. ShiH. KavetskaO. LaBadieR.R. BinksM. ChanP.L.S. DemersN. CorriganB. DamleB. Pharmacokinetics of oral Nirmatrelvir/Ritonavir, a protease inhibitor for treatment of COVID -19, in subjects with renal impairment.Clin. Pharmacol. Ther.2022112489290010.1002/cpt.268835712797
     [Google Scholar]
  59. LingscheidT. KinzigM. KrügerA. MüllerN. BölkeG. Tober-LauP. MünnF. KriedemannH. WitzenrathM. SanderL.E. SörgelF. KurthF. Pharmacokinetics of nirmatrelvir and ritonavir in COVID-19 patients with end-stage renal disease on intermittent hemodialysis.Antimicrob. Agents Chemother.20226611e01229-2210.1128/aac.01229‑2236286542
     [Google Scholar]
  60. HoertelN. BoulwareD.R. Sánchez-RicoM. BurgunA. LimosinF. Prevalence of contraindications to nirmatrelvir-ritonavir among hospitalized patients with COVID-19 at risk for progression to severe disease.JAMA Netw. Open2022511e224214010.1001/jamanetworkopen.2022.4214036378313
     [Google Scholar]
  61. BeldenK.A. YeagerS. SchulteJ. CantarinM.P.M. MossS. RoyerT. CoppockD. “Saving lives with nirmatrelvir/ritonavir one transplant patient at a time”.Transpl. Infect. Dis.2023252e1403710.1111/tid.1403736847419
     [Google Scholar]
  62. TangY. LiY. SongT. Optimizing the use of nirmatrelvir/ritonavir in solid organ transplant recipients with COVID-19: A review of immunosuppressant adjustment strategies.Front. Immunol.202314115034110.3389/fimmu.2023.115034137081880
     [Google Scholar]
  63. LoC.M. ChenW.H. TsaiM.Y. LuH.I. HsiaoY.H. ChenY. WuH.F. HuangK.T. WangY.H. Drug Interaction between Co-packaged Nirmatrelvir-ritonavir and Tacrolimus might cause Hyponatremia and Tacrolimus Intoxication in lung transplant recipients.J. Cardiothorac. Surg.202419113210.1186/s13019‑024‑02599‑w38491538
     [Google Scholar]
  64. TomidaT. ItoharaK. YamamotoK. KimuraT. FujitaK. UdaA. KitahiroY. YokoyamaN. HyodoY. OmuraT. YanoI. A model-based pharmacokinetic assessment of drug–drug interaction between tacrolimus and nirmatrelvir/ritonavir in a kidney transplant patient with COVID-19.Drug Metab. Pharmacokinet.20235310052910.1016/j.dmpk.2023.10052937924724
     [Google Scholar]
  65. CoyneM. AyeM. Tacrolimus toxicity in two renal transplant recipients treated with Nirmatrelvir/Ritonavir: A case series.Ann. Intern. Med. Clin. Cases202323e22112110.7326/aimcc.2022.1121
     [Google Scholar]
  66. ModiS. KahwashR. KisslingK. Case report: Tacrolimus toxicity in the setting of concurrent Paxlovid use in a heart-transplant recipient.Eur. Heart J. Case Rep.202375ytad19310.1093/ehjcr/ytad19337252201
     [Google Scholar]
  67. ThenR.F. Shahnaz ShahF.K. WCN23-0117 paxlovid (nirmatrelvir/ritonavir) and cyclosporin in a kidney transplant patient with covid-19 infection.Kidney Int. Rep.202383S456S45710.1016/j.ekir.2023.02.1024
     [Google Scholar]
  68. MichaelS. HeilbronnerR. LloydC.M. LevitinH.W. HeilbronnerR.N. Paxlovid-induced tacrolimus toxicity in the treatment of COVID-19: A case report.Cureus2023152e3548910.7759/cureus.3548936999105
     [Google Scholar]
  69. MaynardR.D. BatesP. Korpi-SteinerN. Monitoring tacrolimus toxicity following Paxlovid administration in a liver transplant patient.Pract. Lab. Med.202336e0032210.1016/j.plabm.2023.e0032237649541
     [Google Scholar]
  70. Guzmán CorderoC. Saez-Torres de VicenteM. Management of nirmatrelvir/ritonavir and tacrolimus interaction in kidney transplant recipients infected by COVID-19: A three-case series.Eur. J. Hosp. Pharm. Sci. Pract.202431217517710.1136/ejhpharm‑2022‑00354436535689
     [Google Scholar]
  71. LiuY. LiuY. CaiC. HuiF. ZhangY. WangB. WangX. ZhangY. SongX. HeL. YangH. Effect of Paxlovid on Tacrolimus concentration in perioperative kidney transplant patients infected with COVID-19: A case report.Transplant. Proc.20235581822182510.1016/j.transproceed.2023.07.00737558545
     [Google Scholar]
  72. ShahA. NasrullahA. ButtM.A. YoungM. Paxlovid with caution: Novel case of Paxlovid-induced tacrolimus toxicity in a cardiac transplant patient.Eur. J. Case Rep. Intern. Med.2022991110.12890/2022_00352836299835
     [Google Scholar]
  73. FredrickS. WiseB. BowmanL. DeWolfeD. TaylorJ. MelaragnoJ. Impact of Nirmatrelvir-Ritonavir on tacrolimus concentrations.Am. J. Transplant.2022787788
     [Google Scholar]
  74. CorderoC.G. de VicenteM.S.T. Elevated tacrolimus blood concentration due to the interaction with Nirmatrelvir/Ritonavir During COVID-19 treatment: A case report.Transplant. Proc.20235581826182810.1016/j.transproceed.2023.03.00137037726
     [Google Scholar]
  75. ZaarurL. PatelA. PasternakB. Drug interaction between Paxlovid and Tacrolimus in an adolescent with inflammatory bowel disease.Gastroenterology20231644S1510.1053/j.gastro.2023.03.03638034448
     [Google Scholar]
  76. DeweyK.W. YenB. LazoJ. SeijoL. JariwalaR. ShahR.J. QuanD. CarpenterB. Paul SingerJ. BreenK. HaysS. FlorezR. Nirmatrelvir/ritonavir use with tacrolimus in lung transplant recipients: A single-center case series.Transplantation202310751200120510.1097/TP.000000000000439436525555
     [Google Scholar]
  77. BellmannR. SmuszkiewiczP. Pharmacokinetics of antifungal drugs: Practical implications for optimized treatment of patients.Infection201745673777910.1007/s15010‑017‑1042‑z28702763
     [Google Scholar]
  78. CoxD.S. Van EyckL. PawlakS. BeckermanB. LinnC. GinmanK. Thay ChaY. LaBadieR.R. ShiH. DamleB. Effects of itraconazole and carbamazepine on the pharmacokinetics of nirmatrelvir/ritonavir in healthy adults.Br. J. Clin. Pharmacol.20238992867287610.1111/bcp.1578837184075
     [Google Scholar]
  79. WangP. XingH. ZhangX. YangJ. Complexity interactions between Nirmatrelvir/Ritonavir and Voriconazole in patients with coronavirus disease 2019.Clin. Infect. Dis.202376122209221010.1093/cid/ciad15936942525
     [Google Scholar]
  80. KoniecznyK. DorianP. Clinically important drug–drug interactions between antiarrhythmic drugs and anticoagulants.J. Innov. Card. Rhythm Manag.20191033552355910.19102/icrm.2019.10030432494414
     [Google Scholar]
  81. SluijtersA. LemaitreF. BelkhirL. BolandL. HaufroidV. De GreefJ. A case report of safe Coadministration of amiodarone with short-term treatment Nirmatrelvir-ritonavir.Clin. Pharmacol. Ther.2023113476876910.1002/cpt.280536544259
     [Google Scholar]
  82. AbrahamS. NohriaA. NeilanT.G. AsnaniA. SajiA.M. ShahJ. LechT. GrossmanJ. AbrahamG.M. McQuillenD.P. MartinD.T. SaxP.E. DaniS.S. GanatraS. Cardiovascular drug interactions with nirmatrelvir/ritonavir in patients with COVID-19: JACC review topic of the week.J. Am. Coll. Cardiol.202280201912192410.1016/j.jacc.2022.08.80036243540
     [Google Scholar]
  83. JerlingM. Clinical pharmacokinetics of ranolazine.Clin. Pharmacokinet.200645546949110.2165/00003088‑200645050‑0000316640453
     [Google Scholar]
  84. CaseyB.III VernickR.C. BahekarA. PatelD. Ncogo AleneI. Ranolazine toxicity secondary to Paxlovid.Cureus2023154e3715337153311
     [Google Scholar]
  85. ShnayderN.A. AbdyrakhmanovaA.K. NasyrovaR.F. Oxidation of Antipsychotics.Encyclopedia20222297498910.3390/encyclopedia2020064
     [Google Scholar]
  86. LuM.L. LaneH.Y. Clinically significant interactions with antipsychotics.Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological AgentsSpringer2016397421
     [Google Scholar]
  87. LiuC.I. GohK.K. ChenC.H. Neutropenia after the coadministration of clozapine and nirmatrelvir-ritonavir in a patient with SARS-CoV-2 infection: A case report with a literature review.Front. Psychiatry202213109600610.3389/fpsyt.2022.109600636620672
     [Google Scholar]
  88. NasserN.G. WelshC. MitraA. SwanM. Serotonin syndrome precipitated by paxlovid initiation.Cureus2023158e4289837664331
     [Google Scholar]
  89. Pérez-MañáC. PapaseitE. FonsecaF. FarréA. TorrensM. FarréM. Drug interactions with new synthetic opioids.Front. Pharmacol.20189114510.3389/fphar.2018.0114530364252
     [Google Scholar]
  90. TrescotA.M. DattaS. LeeM. HansenH. Opioid pharmacology.Pain Physician20082s11Suppl.S133S15310.36076/ppj.2008/11/S13318443637
     [Google Scholar]
  91. AdmaneS. ClarkM. ReddyA. NarayananS. BrueraE. Safely prescribing opioids with Nirmatrelvir/Ritonavir-Case report and management recommendations.J. Pain Symptom Manage.2024671e99e10410.1016/j.jpainsymman.2023.09.02737797677
     [Google Scholar]
  92. ValdesJ. BoggsD.L. BoggsA.A. ReyJ.A. Clinically significant interactions with benzodiazepines.Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological AgentsSpringer2016471495
     [Google Scholar]
  93. GunjaN. The clinical and forensic toxicology of Z-drugs.J. Med. Toxicol.20139215516210.1007/s13181‑013‑0292‑023404347
     [Google Scholar]
  94. CoxD.S. RehmanM. KhanT. GinmanK. SalageanuJ. LaBadieR.R. WanK. DamleB. Effects of nirmatrelvir/ritonavir on midazolam and dabigatran pharmacokinetics in healthy participants.Br. J. Clin. Pharmacol.202389113352336310.1111/bcp.1583537354048
     [Google Scholar]
  95. PatsalosP.N. BerryD.J. BourgeoisB.F.D. CloydJ.C. GlauserT.A. JohannessenS.I. LeppikI.E. TomsonT. PeruccaE. Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on therapeutic strategies.Epilepsia20084971239127610.1111/j.1528‑1167.2008.01561.x18397299
     [Google Scholar]
  96. WanounouM. CaracoY. LevyR.H. BialerM. PeruccaE. Clinically relevant interactions between ritonavir-boosted nirmatrelvir and concomitant antiseizure medications: Implications for the management of COVID-19 in patients with epilepsy.Clin. Pharmacokinet.20226191219123610.1007/s40262‑022‑01152‑z35895276
     [Google Scholar]
  97. YalcinN. AllegaertK. COVID-19 and antiepileptic drugs: An approach to guide practices when nirmatrelvir/ritonavir is co-prescribed.Eur. J. Clin. Pharmacol.202278101697170110.1007/s00228‑022‑03370‑735930055
     [Google Scholar]
  98. MarzoliniC. KuritzkesD.R. MarraF. BoyleA. GibbonsS. FlexnerC. PozniakA. BoffitoM. WatersL. BurgerD. BackD.J. KhooS. Recommendations for the management of drug–drug interactions between the COVID-19 antiviral nirmatrelvir/ritonavir (Paxlovid) and comedications.Clin. Pharmacol. Ther.202211261191120010.1002/cpt.264635567754
     [Google Scholar]
  99. MikusG. FoersterK.I. TerstegenT. VogtC. SaidA. SchulzM. HaefeliW.E. Oral drugs against COVID-19.Dtsch. Arztebl. Int.20221191526326935302484
     [Google Scholar]
  100. MarzoliniC. KuritzkesD.R. MarraF. BoyleA. GibbonsS. FlexnerC. PozniakA. BoffitoM. WatersL. BurgerD. BackD. KhooS. Prescribing nirmatrelvir–ritonavir: How to recognize and manage drug–drug interactions.Ann. Intern. Med.2022175574474610.7326/M22‑028135226530
     [Google Scholar]
  101. Guy-AlfandaryS. ZhuratS. BerlinM. De HaanT. GuetaI. ShihmanterR. GolikA. BerkovitchM. EyalS. GoldsteinL.H. Managing potential drug interactions of Nirmatrelvir/Ritonavir in COVID-19 patients: A perspective from an Israeli cross-sector collaboration.Clin. Pharmacol. Ther.202211261156115810.1002/cpt.261035521643
     [Google Scholar]
  102. LemaitreF. GrégoireM. MonchaudC. BouchetS. Saint-SalviB. PolardE. BenaboudS. ChouchanaL. CracowskiJ-L. DriciM-D. GarraffoR. GuilhaumouR. Jonville-BeraA-P. MolimardM. MuretP. PeytavinG. RichardV. SolasC. French Pharmacovigilance Network (CRPV) ANRS-MIE AC-43 Clinical Pharmacology Committee, joint working group SFPT Therapeutic Drug Monitoring and Treatment Personalization group (STP-PT) of the French Society of Pharmacology and Therapeutics (SFPT) Management of drug-drug interactions with nirmatrelvir/ritonavir in patients treated for Covid-19: Guidelines from the French Society of Pharmacology and Therapeutics (SFPT).Therapie202277550952110.1016/j.therap.2022.03.00535618549
     [Google Scholar]
  103. RossS.B. Bortolussi-CourvalÉ. HanulaR. LeeT.C. Goodwin WilsonM. McDonaldE.G. Drug interactions with nirmatrelvir-ritonavir in older adults using multiple medications.JAMA Netw. Open202257e222018410.1001/jamanetworkopen.2022.2018435793089
     [Google Scholar]
  104. LemaitreF. BuddeK. Van GelderT. BerganS. LawsonR. NocetiO. VenkataramananR. ElensL. MoesD.J.A.R. HesselinkD.A. PawinskiT. Johnson-DavisK.L. De WinterB.C.M. PattanaikS. BrunetM. MasudaS. LangmanL.J. Therapeutic drug monitoring and dosage adjustments of immunosuppressive drugs when combined with nirmatrelvir/ritonavir in patients with COVID-19.Ther. Drug Monit.202345219119910.1097/FTD.000000000000101435944126
     [Google Scholar]
  105. LimS. TignanelliC.J. HoertelN. BoulwareD.R. UsherM.G. Prevalence of medical contraindications to nirmatrelvir/ritonavir in a cohort of hospitalized and nonhospitalized patients with COVID-19.Open Forum Infect. Dis.202298ofac38910.1093/ofid/ofac38936000003
     [Google Scholar]
  106. de OliveiraL.M. da Silva Dal PizzolT. Comment on “Tacrolimus drug-drug interaction with Nirmatrelvir/Ritonavir (Paxlovid™) managed with Phenytoin”.J. Med. Toxicol.202319330730810.1007/s13181‑023‑00936‑436988814
     [Google Scholar]
  107. GirardinF. ManuelO. MarzoliniC. BuclinT. Evaluating the risk of drug-drug interactions with pharmacokinetic boosters: The case of ritonavir-enhanced nirmatrelvir to prevent severe COVID-19.Clin. Microbiol. Infect.20222881044104610.1016/j.cmi.2022.03.03035358684
     [Google Scholar]
  108. ChangC.T. OngS.Y. LimX.J. ChewL.S. RajanP. Managing nirmatrelvir/ritonavir during COVID-19: Pharmacists’ experiences from the Perak state of Malaysia.J. Pharm. Policy Pract.20221517010.1186/s40545‑022‑00469‑136274169
     [Google Scholar]
/content/journals/cdm/10.2174/0113892002320326250123082112
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Pharmacokinetic Interactions of Paxlovid Involving CYP3A Enzymes and P-gp Transporter: An Overview of Clinical Data
Current Drug Metabolism 25, 639 (2024); https://doi.org/10.2174/0113892002320326250123082112
/content/journals/cdm/10.2174/0113892002320326250123082112
/content/journals/cdm/10.2174/0113892002320326250123082112
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  • Article Type:     Review Article
Keyword(s): CYP3A; Drug interactions; nirmatrelvir; P-glycoprotein; paxlovid; pharmacokinetic interactions; ritonavir

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