Pharmacological Interactions of Nintedanib and Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis in Times of COVID-19 Pandemic

López-Matencio, José M. Serra; Gómez, Manuel; Vicente-Rabaneda, Esther F.; Ancochea, Julio; Castañeda, Santos

doi:10.3390/ph14080819

Cited by 19 publications

(34 citation statements)

References 65 publications

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“…The incidence rate of pulmonary fibrosis can be estimated at 2–6% after moderate COVID-19 [ 15 ]. By virtue of their pleiotropic anti-inflammatory and antifibrotic actions and their favorable profile in terms of clinically relevant pharmacokinetic interactions when used in combination [ 16 ], nintedanib and pirfenidone have become the primary drug candidate in this setting, with several ongoing trials to assess their risk/benefit profile in COVID-19. However, different concerns might hamper the effective use of these drugs: their side effects partially overlap the symptoms of COVID-19 (e.g., diarrhea, fatigue, loss of appetite), thus hampering early diagnosis and worsening clinical manifestation.…”

Section: Discussionmentioning

confidence: 99%

Liver Injury with Nintedanib: A Pharmacovigilance–Pharmacokinetic Appraisal

et al. 2022

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Drug-induced liver injury (DILI) with nintedanib has emerged as an adverse event of special interest in premarketing clinical trials. We characterized DILI with nintedanib in the real world and explored the underlying pharmacological basis. First, we assessed serious hepatic events reported to the Food and Drug Administration’s Adverse Event Reporting System by combining the disproportionality approach [reporting odds ratio (ROR) with 95% confidence interval (CI)] with individual case assessment. Demographic and clinical features were inspected (seriousness, onset, discontinuation, dechallenge/rechallenge, concomitant drugs) to implement an ad hoc causality assessment scoring system. Second, we appraised physiochemical and pharmacokinetic parameters possibly predictive of DILI occurrence. Significant disproportionality was found for nintedanib as compared to pirfenidone (N = 91; ROR = 4.77; 95% CI = 3.15–7.39). Asian population, low body weight (59 kg), and rapid DILI onset (13.5 days) emerged as clinical features. Hospitalization and discontinuation were found in a significant proportion of cases (32% and 36%, respectively). In 24% of the cases, at least two potentially hepatotoxic drugs (statins, proton pump inhibitors, antibiotics) were recorded. Causality was at least possible in 92.3% of the cases. High lipophilicity and predicted in silico inhibition of liver transporters emerged as potential pharmacokinetic features supporting the biological plausibility. Although causality cannot be demonstrated, clinicians should consider early monitoring and medication review on a case-by-case basis.

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Section: Discussionmentioning

confidence: 99%

Liver Injury with Nintedanib: A Pharmacovigilance–Pharmacokinetic Appraisal

et al. 2022

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“…However, little information is available about their drug-drug interactions, which is important mainly in polymedicated patients [42].…”

Section: Discussionmentioning

confidence: 99%

Rural treatment of COVID-19 patients with pirfenidone, nitazoxanide and colchicine. Case series

Esquivel

Calderón

Carrillo

et al. 2022

Monaldi Arch Chest Dis

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Combined treatments against SARS-CoV-2 are emerging and some have taken into account the post-COVID-19 fibrosis. The aim of this survey was to report the experience of treating COVID-19 patients with pirfenidone, nitazoxanide (NTZ) and colchicine. It was a case series report of COVID-19 patients treated from December 2020 to March 2021, in a rural health center located in the State of Mexico, Mexico. 23 patients were included (mean age 44.5 ± 17.1 years), 12 women (mean age 45.9 ± 17.9 years) and 11 men (mean age 43 ± 16.9 years) with four deaths (17.39%). The evolution time was of 17.3 ± 6.7 days being the main symptoms fever (82.6%), myalgia (69.6%) and cough (65.2%). The main comorbidities were overweight/obesity 18 (78.26%), type 2 diabetes mellitus (T2DM) 4 (17.39%), Chronic obstructive pulmonary disease (COPD) 5 (21.73%) and systemic hypertension 2 (8.69%). Two patients were intubated and both died; in these cases, they refused to take NTZ until after three days the medical doctor had prescribed it for the first time. It can be concluded that implementing a mixed treatment with pirfenidone, NTZ and colchicine could improve the survival rate in ambulatory patients of low socioeconomic status.

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“…In these patients, one should consider the drug interactions before starting the management. Metabolism of antifibrotics and anticoagulants is strongly influenced by cytochrome P450 3A4 (CYP3A4) and CYP1A2 [8,9]. Antifungal azoles like itraconazole, and voriconazole which is the treatment of choice in CCPA are inhibitors of CYP3A4, and CYP1A2 which may lead to decreased metabolism of antifibrotics and anticoagulants causing increased side effects [9].…”

Section: Discussionmentioning

confidence: 99%

Aspergilloma in Non-tuberculous Cavities in the Lung: Not to Get Startled

Pavirala¹,

Rao²,

Sahu³

et al. 2022

Cureus

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Aspergillus which is normally found as a colonizer in healthy individuals can manifest in various forms in patients with diseased lung or immunocompromised status. Aspergilloma is one such manifestation whereby the fungus makes its way into preexisting cavities in the lung, the most common underlying etiology being old tuberculous cavities, especially in countries with high TB prevalence. However, we hereby report two cases of Aspergillus infestation as aspergilloma in cavities because of extremely rare causes, namely pulmonary thromboembolism and idiopathic pulmonary fibrosis, respectively.

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Pharmacological Interactions of Nintedanib and Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis in Times of COVID-19 Pandemic

Cited by 19 publications

References 65 publications

Liver Injury with Nintedanib: A Pharmacovigilance–Pharmacokinetic Appraisal

Liver Injury with Nintedanib: A Pharmacovigilance–Pharmacokinetic Appraisal

Rural treatment of COVID-19 patients with pirfenidone, nitazoxanide and colchicine. Case series

Aspergilloma in Non-tuberculous Cavities in the Lung: Not to Get Startled

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