Cardiovascular Drug Interactions With Nirmatrelvir/Ritonavir in Patients With COVID-19

Abraham, Sonu; Nohria, Anju; Neilan, Tomas G.; Asnani, Aarti; Saji, Anu Mariam; Shah, Jui; Lech, Tara; Grossman, Jason; Abraham, George M.; McQuillen, Daniel P.; Martín, David; Sax, Paul E.; Dani, Sourbha S.; Ganatra, Sarju

doi:10.1016/j.jacc.2022.08.800

Cited by 31 publications

(40 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2 The proposed decision-making algorithm is demonstrated in Figure 1. 3 In conclusion, for prevention of CV-DDIs, discontinuation or dose adjustment during the NMVr treatment and 3-5 days after completion of treatment in COVID-19 patients.…”

Section: Editorialmentioning

confidence: 97%

Covid-19-cardiovascular-disease patients treating with nirmatrelvir/ritonavir inducing cardiovasculardrug interactions

Cheepsattayakorn¹

2022

JLPRR

View full text Add to dashboard Cite

show abstract

Section: Editorialmentioning

confidence: 97%

Covid-19-cardiovascular-disease patients treating with nirmatrelvir/ritonavir inducing cardiovasculardrug interactions

Cheepsattayakorn¹

2022

JLPRR

View full text Add to dashboard Cite

show abstract

“…Therefore, co-administration of a CYP2C9 inducer and inhibitor could alter the drug clearance, plasma concentration and the resulting clinical efficacy [ 80 ]. Ritonavir, a pharmaceutical enhancer used in nirmatrelvir–ritonavir (NMVr or Paxlovid, manufactured by Pfizer), was claimed to be an inducer of CYP2C9 [ 81 , 82 ] as well as an inhibitor of CYP2C9 [ 83 ]. NMVr is used to treat symptomatic, non-hospitalised patients with COVID-19 who are at high risk of amplified severity, especially individuals with cardiovascular diseases [ 81 ].…”

Section: Drugs Used To Treat Covid-19mentioning

confidence: 99%

“…Ritonavir, a pharmaceutical enhancer used in nirmatrelvir–ritonavir (NMVr or Paxlovid, manufactured by Pfizer), was claimed to be an inducer of CYP2C9 [ 81 , 82 ] as well as an inhibitor of CYP2C9 [ 83 ]. NMVr is used to treat symptomatic, non-hospitalised patients with COVID-19 who are at high risk of amplified severity, especially individuals with cardiovascular diseases [ 81 ]. Drugs that are CYP3A4 inducers (e.g.…”

Section: Drugs Used To Treat Covid-19mentioning

confidence: 99%

“…Angiotensin-receptor blockers such as irbersartan, losartan and azilsartan, are metabolised by CYP2C9. Co-administration of these blood pressure lowering drugs with NMVr [ 81 ] can lead to hypotension, since NMVr induces CYP2C9 and thus enhances metabolism of these anti-hypertensives. Bosentan, a pulmonary hypertension drug, is also metabolised by CYP2C9.…”

Section: Drugs Used To Treat Covid-19mentioning

confidence: 99%

“…Bosentan, a pulmonary hypertension drug, is also metabolised by CYP2C9. Co-administration of bosentan with ritonavir was found to increase the concentration of bosentan by 48-fold, and therefore, concomitant use of bosentan and NMVr is contraindicated [ 81 ]. As a result, bosentan was recommended to be discontinued for at least 36 hours before administration of NMVr [ 108 ].…”

Section: Drugs Used To Treat Covid-19mentioning

confidence: 99%

See 2 more Smart Citations

Role of Cytochrome P450 2C9 in COVID-19 Treatment: Current Status and Future Directions

Lim

Bishtawi

Lim

2023

Eur J Drug Metab Pharmacokinet

View full text Add to dashboard Cite

The major human liver drug metabolising cytochrome P450 (CYP) enzymes are downregulated during inflammation and infectious disease state, especially during coronavirus disease 2019 (COVID-19) infection. The influx of proinflammatory cytokines, known as a ‘cytokine storm’, during severe COVID-19 leads to the downregulation of CYPs and triggers new cytokine release, which further dampens CYP expression. Impaired drug metabolism, along with the inevitable co-administration of drugs or ‘combination therapy’ in patients with COVID-19 with various comorbidities, could cause drug–drug interactions, thus worsening the disease condition. Genetic variability or polymorphism in CYP2C9 across different ethnicities could contribute to COVID-19 susceptibility. A number of drugs used in patients with COVID-19 are inducers or inhibitors of, or are metabolised by, CYP2C9, and co-administration might cause pharmacokinetic and pharmacodynamic interactions. It is also worth mentioning that some of the COVID-19 drug interactions are due to altered activity of other CYPs including CYP3A4. Isoniazid/rifampin for COVID-19 and tuberculosis co-infection; lopinavir/ritonavir and cobicistat/remdesivir combination therapy; or multi-drug therapy including ivermectin, azithromycin, montelukast and acetylsalicylic acid, known as TNR4 therapy, all improved recovery in patients with COVID-19. However, a combination of CYP2C9 inducers, inhibitors or both, and plausibly different CYP isoforms could lead to treatment failure, hepatotoxicity or serious side effects including thromboembolism or bleeding, as observed in the combined use of azithromycin/warfarin. Further, herbs that are CYP2C9 inducers and inhibitors, showed anti-COVID-19 properties, and in silico predictions postulated that phytochemical compounds could inhibit SARS-CoV-2 virus particles. COVID-19 vaccines elicit immune responses that activate cytokine release, which in turn suppresses CYP expression that could be the source of compromised CYP2C9 drug metabolism and the subsequent drug–drug interaction. Future studies are recommended to determine CYP regulation in COVID-19, while recognising the involvement of CYP2C9 and possibly utilising CYP2C9 as a target gene to tackle the ever-mutating SARS-CoV-2.

show abstract

Clinical Risk and Outpatient Therapy Utilization for COVID-19 in the Medicare Population

Wilcock,

Kissler,

Mehrotra

et al. 2024

JAMA Health Forum

View full text Add to dashboard Cite

ImportanceMultiple therapies are available for outpatient treatment of COVID-19 that are highly effective at preventing hospitalization and mortality. Although racial and socioeconomic disparities in use of these therapies have been documented, limited evidence exists on what factors explain differences in use and the potential public health relevance of these differences.ObjectiveTo assess COVID-19 outpatient treatment utilization in the Medicare population and simulate the potential outcome of allocating treatment according to patient risk for severe COVID-19.Design, Setting, and ParticipantsThis cross-sectional study included patients enrolled in Medicare in 2022 across the US, identified with 100% Medicare fee-for-service claims.Main Outcomes and MeasuresThe primary outcome was any COVID-19 outpatient therapy utilization. Secondary outcomes included COVID-19 testing, ambulatory visits, and hospitalization. Differences in outcomes were estimated based on patient demographics, treatment contraindications, and a composite risk score for mortality after COVID-19 based on demographics and comorbidities. A simulation of reallocating COVID-19 treatment, particularly with nirmatrelvir, to those at high risk of severe disease was performed, and the potential COVID-19 hospitalizations and mortality outcomes were assessed.ResultsIn 2022, 6.0% of 20 026 910 beneficiaries received outpatient COVID-19 treatment, 40.5% of which had no associated COVID-19 diagnosis within 10 days. Patients with higher risk for severe disease received less outpatient treatment, such as 6.4% of those aged 65 to 69 years compared with 4.9% of those 90 years and older (adjusted odds ratio [aOR], 0.64 [95% CI, 0.62-0.65]) and 6.4% of White patients compared with 3.0% of Black patients (aOR, 0.56 [95% CI, 0.54-0.58]). In the highest COVID-19 severity risk quintile, 2.6% were hospitalized for COVID-19 and 4.9% received outpatient treatment, compared with 0.2% and 7.5% in the lowest quintile. These patterns were similar among patients with a documented COVID-19 diagnosis, those with no claims for vaccination, and patients who are insured with Medicare Advantage. Differences were not explained by variable COVID-19 testing, ambulatory visits, or treatment contraindications. Reallocation of 2022 outpatient COVID-19 treatment, particularly with nirmatrelvir, based on risk for severe COVID-19 would have averted 16 503 COVID-19 deaths (16.3%) in the sample.ConclusionIn this cross-sectional study, outpatient COVID-19 treatment was disproportionately accessed by beneficiaries at lower risk for severe infection, undermining its potential public health benefit. Undertreatment was not driven by lack of clinical access or treatment contraindications.

show abstract

Cardiovascular Drug Interactions With Nirmatrelvir/Ritonavir in Patients With COVID-19

Cited by 31 publications

References 41 publications

Covid-19-cardiovascular-disease patients treating with nirmatrelvir/ritonavir inducing cardiovasculardrug interactions

Covid-19-cardiovascular-disease patients treating with nirmatrelvir/ritonavir inducing cardiovasculardrug interactions

Role of Cytochrome P450 2C9 in COVID-19 Treatment: Current Status and Future Directions

Clinical Risk and Outpatient Therapy Utilization for COVID-19 in the Medicare Population

Contact Info

Product

Resources

About