Science to Practice
Latest highlights on drug safety and efficacy

18.6.2025

Nirmatrelvir/ritonavir, NMV/r (PAXLOVID™) is first oral antiviral for COVID-19. However, it poses significant risks for drug interactions, particularly for patients on immunosuppressive therapy such as tacrolimus. Ritonavir strongly inhibits CYP3A4 and P-glycoprotein, leading to dangerous increases in the levels of several co-administered drugs (1,2,3).

A real-world study from London found that nearly 90% of patients treated with NMV/r had potential drug-drug interactions, and 8% had to forgo treatment due to risk, and 53% required management. Alarmingly, more than half of the cases requiring intervention lacked documented guidance in EHR (4).

Up to 90% of patients treated with NMV/r face potential drug interactions – and over half of those requiring intervention lacked documented guidance in EHRs.

Numerous case reports have highlighted severe tacrolimus toxicity in transplant recipients treated with NMV/r. Based on this, clinical recommendations advise a substantial dose reduction or treatment interruption to maintain therapeutic whole blood levels if ritonavir is co-administered with tacrolimus. This adjustment should be guided by an experienced physician, in settings where daily tacrolimus monitoring is feasible (5,6,7,8,9,10).

Ultimately, NMV/r treatment requires individualized medication management and close monitoring—particularly in immunocompromised patients. Clinical pharmacology support is essential to ensure safety, avoid toxicity, and provide effective care in complex therapeutic situations.

For comprehensive insights into drug-drug interactions and adverse drug reactions, explore our databases Inxbase and Riskbase.

News produced by Medbase Medical Team

References

1. Stoiber A, Gray G, Sailer G, Huf W, Tonna A. Frequency, type and severity of drug-related problems and pharmacist interventions in Paxlovid® prescribing: a descriptive analysis. Int J Clin Pharm. 2025 Apr;47(2):471-476. PMID: 39708268
2. Mozaffari E, Chandak A, Ustianowski A, Rivera CG, Ahuja N, Jiang H, Berry M, Okulicz JF, Amin AN. Prevalence of Potential Drug Interactions With Direct-Acting Antivirals for COVID-19 Among Hospitalized Patients. Clin Ther. 2024 Oct;46(10):778-784. PMID: 39244489
3. Gerhart J, Cox DS, Singh RSP, Chan PLS, Rao R, Allen R, Shi H, Masters JC, Damle B. A Comprehensive Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Drug Interactions of Nirmatrelvir/Ritonavir. Clin Pharmacokinet. 2024 Jan;63(1):27-42. PMID: 38177893
4. Bukhari S, Hughes S, Mughal N, Moore LSP, Davies G, Vargas Zhang A, Ng M, Karagozlu Z, Boffito M. Nirmatrelvir/ritonavir: real world drug-drug interaction management experience. Expert Rev Anti Infect Ther. 2024 Sep;22(9):781-783. PMID: 39109469
5. Sabo AN, Cunat S, Kemmel V. Delayed Drug-Drug Interaction Between Antiviral Drugs and Tacrolimus in a Pancreatic Islet Transplant Recipient with SARS-CoV-2 Pneumonia-A Case Study. Ther Drug Monit. 2025 Feb 3; PMID: 39898493
6. Lipsitz J, Chowdary AR, Tsai P, Quigley R. Paxlovid-induced tacrolimus toxicity in a 16-year-old male with steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2025 Feb 25; PMID: 39998631
7. Schneider J, Wobser R, Kühn W, Wagner D, Tanriver Y, Walz G. Nirmatrelvir/ritonavir treatment in SARS-CoV-2 positive kidney transplant recipients – a case series with four patients. BMC Nephrol. 2023 Apr 15;24(1):99 PMID: 37061677
8. Lemaitre F, Budde K, Van Gelder T, Bergan S, Lawson R, Noceti O, Venkataramanan R, Elens L, Moes DJAR, Hesselink DA, Pawinski T, Johnson-Davis KL, De Winter BCM, Pattanaik S, Brunet M, Masuda S, Langman LJ. Therapeutic Drug Monitoring and Dosage Adjustments of Immunosuppressive Drugs When Combined With Nirmatrelvir/Ritonavir in Patients With COVID-19. Ther Drug Monit. 2023 Apr 1;45(2):191-199 PMID: 35944126
9. Dewey KW, Yen B, Lazo J, Seijo L, Jariwala R, Shah RJ, Quan D, Carpenter B, Paul Singer J, Breen K, Hays S, Florez R. Nirmatrelvir/ritonavir Use With Tacrolimus in Lung Transplant Recipients: A Single-center Case Series. Transplantation. 2023 May 1;107(5):1200-1205 PMID: 3652555          
10. Giguère P, Deschenes MJ, Loon MV, Hoar S, Fairhead T, Pazhekattu R, Knoll G, Karpinski J, Parikh N, McDougall J, McGuinty M, Hiremath S. Management and Outcome of COVID-19 Infection Using Nirmatrelvir/Ritonavir in Kidney Transplant Patients. Clin J Am Soc Nephrol. 2023 Apr 26;18(7):913-9 PMID: 37099447.