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Cardiac toxicity associated with pharmacokinetic drug–drug interaction between crizotinib and sofosbuvir/velpatasvir: a case report
  • +9
  • Anthia Monribot,
  • Olivier Huillard,
  • Nihel Khoudour,
  • Laure-Hélène Préta,
  • Benoit Blanchet,
  • Laure Cabanes,
  • Rui Batista,
  • Nicolas Pallet,
  • Laurent Chouchana,
  • François Goldwasser,
  • Philippe Sogni,
  • Audrey Thomas-Schoemann
Anthia Monribot
Cochin Hospital, AP-HP, University of Paris

Corresponding Author:anthia.monribot@aphp.fr

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Olivier Huillard
Cochin Hospital, AP-HP, Université de Paris
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Nihel Khoudour
Cochin Hospital, AP-HP; CARPEM, Paris, France
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Laure-Hélène Préta
Cochin Hospital, AP-HP, University of Paris
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Benoit Blanchet
Cochin Hospital, AP-HP; CARPEM, Paris, France
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Laure Cabanes
Cochin Hospital, AP-HP, University of Paris
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Rui Batista
Cochin Hospital, AP-HP, University of Paris
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Nicolas Pallet
Hôpital Européen Georges Pompidou, AP-HP, University of Paris Descartes, INSERM U.1147
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Laurent Chouchana
Cochin Hospital, AP-HP, University of Paris,
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François Goldwasser
Cochin Hospital, AP-HP, Université de Paris
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Philippe Sogni
Cochin Hospital, AP-HP, Paris, France; University of Paris Descartes, Sorbonne Paris Cité
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Audrey Thomas-Schoemann
Cochin Hospital, AP-HP, Université de Paris
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Abstract

This case report describes of a pharmacokinetic drug–drug interaction between crizotinib, a tyrosine kinase inhibitor, and sofosbuvir/velpatasvir, a direct-acting antiviral drug, leading to cardiac toxicity. A 75-year-old man, with no cardiovascular history but a diagnosis of metastatic non-small cell lung cancer with MET exon-14 deletion and hepatitis C virus infection genotype 1A, received both crizotinib and sofosbuvir/velpatasvir. Crizotinib was well tolerated, but 1 week after sofosbuvir/velpatasvir initiation, the patient experienced bilateral lower-limb edema and class III NYHA dyspnea. We assumed that increased exposure to crizotinib could account for this cardiac toxicity. Drug causality was probable according to the Naranjo scale. We hypothesized a reciprocal interaction between crizotinib and velpatasvir, mediated by both cytochrome 3A4 (CYP3A4) and P-glycoprotein (P-gp). Clinicians should be aware of the risk of drug–drug interactions between direct-acting antiviral agents that inhibit CYP3A4 (glecaprevir) and/or P-gp (voxilaprevir) and anticancer tyrosine kinase inhibitors that are mostly CYP3A4 and/or P-gp substrates (gefitinib, afatinib, erlotinib, crizotinib, ceritinib, lorlatinib, brigatinib, capmatinib etc.).
05 Jul 2022Submitted to British Journal of Clinical Pharmacology
13 Jul 2022Submission Checks Completed
13 Jul 2022Assigned to Editor
25 Jul 2022Reviewer(s) Assigned
30 Aug 2022Review(s) Completed, Editorial Evaluation Pending
11 Sep 2022Editorial Decision: Revise Major
09 Nov 20221st Revision Received
10 Nov 2022Assigned to Editor
10 Nov 2022Submission Checks Completed
10 Nov 2022Review(s) Completed, Editorial Evaluation Pending
21 Nov 2022Reviewer(s) Assigned
03 Dec 2022Editorial Decision: Revise Minor
30 Dec 20222nd Revision Received
02 Jan 2023Assigned to Editor
02 Jan 2023Submission Checks Completed
02 Jan 2023Review(s) Completed, Editorial Evaluation Pending
14 Jan 2023Editorial Decision: Accept