Αρχική World News Pharmacokinetic and Pharmacodynamic Interactions Between Anticancer and Antiviral Drugs

Pharmacokinetic and Pharmacodynamic Interactions Between Anticancer and Antiviral Drugs

In an article published on 10 June 2020 in the European Journal of Cancer, a group of French investigators led by Paul Gougis of the Department of pharmacology, Hôpital Pitié-Salpêtrière in Paris, France summarised classes of immunosuppressive anticancer drugs. Furthermore, they provided a summary of pharmacokinetic and pharmacodynamic interactions between anticancer drugs and some of antiviral drugs that are currently tested against COVID-19. The context is very relevant in the era of COVID-19, as more safety data is needed to support decisions for treatment of symptomatic COVID-19 patients with anticancer drugs.

The authors wrote that the patients treated for haematological malignancies and solid tumours have a four times higher risk of hospitalisation due to influenza infection, and a ten times higher risk of death. This could be due to their age, comorbidities, lymphopenia, or the immunosuppression caused by anticancer drugs.

They emphasised that safety data are lacking, and it might not be safe to treat symptomatic COVID-19 patients with immunosuppressive anticancer drugs which increase infections. Anticancer drugs that increase either neutropenia or infections are cytotoxic chemotherapy, proteasome inhibitors, histone deacetylase inhibitors, anti-CD20 therapy, PI3K-AKT-mTOR pathway inhibitors, BCR-ABL inhibitors, FLT3 inhibitors, MEK inhibitors, JAK inhibitors, BTK inhibitors, CDK4-6 inhibitors, PARP inhibitors, and multikinase inhibitors.

In particular, the authors underlined that it is not clear yet, if in case of COVID-19, anticancer treatments should be stopped. And it is also not known, if the treatment is interrupted, what is a safe time to resume it. Therefore, it is difficult at present time to decide on prescription of antiviral drugs concomitantly with non-immunosuppressive anticancer therapy.

Comparing the situation with antiretroviral drugs for treatment of HIV, the authors underlined that anticancer drugs and antiviral drugs have a narrow therapeutic index and pharmacological interactions are possible.

Pharmacokinetic-and-Pharmacodynamic-Interactions-Between-Anticancer-and-Antiviral-Drugs

Panel A: Classes of immunosuppressive anticancer drugs. Panel B: Summary of pharmacokinetic and pharmacodynamics interactions between non-immunosuppressive anticancer drugs and some of the drugs currently tested for COVID-19 treatment.

*Tamoxifen is a prodrug and the reported effect is on the active metabolite endoxifen CQ: chloroquine; GnRH: gonadotrophin-releasing hormone; HCQ: hydroxychloroquine; Id: cytochrome inducer; Ih: cytochrome inhibitor; Lopinavir/r: lopinavir/ritonavir association (KALETRA®); S: substrate

© Reprinted with permission from Elsevier

They wrote that some of them are substrates or interact with CYP3A4. As an example they stated enzalutamide which is a non-steroidal antiandrogen for the treatment of prostate cancer. In particular, it is both a CYP3A4 substrate and inducer. Ritonavir is a pharmacokinetic booster of lopinavir investigated in the treatment of COVID-19. Ritonavir is a substrate and a potent CYP3A4 inhibitor. Therefore, enzalutamide and ritonavir could interfere in terms of metabolism, decreasing or increasing each other’s clearance, and cause severe side effects or be responsible for decreased efficacy.

Favipiravir is also investigated for the treatment of COVID-19. It is a CYP2C8 inhibitor, and may increase anticancer drugs that are metabolised through this pathway, in particular dabrafenib and enzalutamide. Furthermore, dabrafenib and enzalutamide are CYP3A4 inducers and could significantly decrease hydroxychloroquine concentration during the first week of wash-out.

In terms of pharmacodynamic interactions, prolongation of QT interval is of particular clinical importance. Hydroxychloroquine and azithromycin prolong QT interval. Concomitant use of anticancer drugs that prolong QT interval could lead to Torsade-de-Pointes and consequently be fatal. The authors warned that electrocardiographic monitoring should be implemented to monitor duration of QT interval during such combination therapy.

Anticancer drugs could also potentiate nephrotoxicity and hepatotoxicity of antiviral drugs.

Reference

Gougis P, Fenioux C, Funck-Brentano C, et al. Anticancer drugs and COVID-19 antiviral treatments in cancer patients: what can we safely use? European Journal of Cancer, Published online 10 June 2020. DOI: https://doi.org/10.1016/j.ejca.2020.05.027.

Source

NEWSLETTER

Συμπληρώστε το email σας για να λαμβάνετε τις σημαντικότερες ειδήσεις από το ogkologos.com

Βρείτε μας

2,449ΥποστηρικτέςΚάντε Like
57ΑκόλουθοιΑκολουθήστε

Διαβαστε Επίσης

Καρκίνος και Κορωνοϊός (COVID-19) ΜΕΡΟΣ Α

Εάν είστε καρκινοπαθής, το ανοσοποιητικό σας σύστημα μπορεί να μην είναι τόσο ισχυρό όσο κανονικά, έτσι μπορεί να ανησυχείτε για τους κινδύνους που σχετίζονται...

ΠΑΓΚΟΣΜΙΑ ΗΜΕΡΑ ΚΑΡΚΙΝΟΥ

Η Παγκόσμια Ημέρα Κατά του Καρκίνου καθιερώθηκε με πρωτοβουλία της Διεθνούς Ένωσης κατά του Καρκίνου (UICC), που εκπροσωπεί 800 οργανώσεις σε 155 χώρες του...

ΕΞΕΛΙΞΕΙΣ ΣΤΗ ΘΕΡΑΠΕΙΑ ΤΟΥ ΜΗ-ΜΙΚΡΟΚΥΤΤΑΡΙΚΟΥ ΚΑΡΚΙΝΟΥ ΤΟΥ ΠΝΕΥΜΟΝΑ (ΜΜΚΠ)

ΕΞΕΛΙΞΕΙΣ ΣΤΗ ΘΕΡΑΠΕΙΑ ΤΟΥ ΜΗ-ΜΙΚΡΟΚΥΤΤΑΡΙΚΟΥ ΚΑΡΚΙΝΟΥ ΤΟΥ ΠΝΕΥΜΟΝΑ (ΜΜΚΠ) Γράφει ο Δρ Παπαδούρης Σάββας, Παθόλογος-Ογκολόγος   Ο ΜΜΚΠ βρίσκεται αναλογικά στο 80% και πλέον του συνολικού...

Διατρέχουν όντως οι καρκινοπαθείς μεγαλύτερο κίνδυνο λόγω κοροναϊού;

Σε πρακτικό επίπεδο, τα δεδομένα των σχετικών μελετών υποδηλώνουν ότι η χημειοθεραπεία ή οι άλλες αντι-νεοπλασματικές θεραπείες δεν αυξάνουν σημαντικά τον κίνδυνο θνησιμότητας από...

FDA: Η ακτινοβολία των smartphones δεν προκαλεί καρκίνο

Σε μια νέα έκθεσή της, η Υπηρεσία Τροφίμων και Φαρμάκων (FDA) των ΗΠΑ αναφέρει ότι επανεξέτασε τις σχετικές επιστημονικές έρευνες που δημοσιεύθηκαν τα τελευταία...

Νέα ανακάλυψη, νέα ελπίδα για τον καρκίνο

Ένα νεοανακαλυφθέν τμήμα του ανοσοποιητικού μας συστήματος θα μπορούσε να αξιοποιηθεί για την αντιμετώπιση όλων των ειδών καρκίνου, σύμφωνα με επιστήμονες του πανεπιστημίου Cardiff...
- Advertisment -

Ροή Ειδήσεων

Making Important Decisions During Cancer: A Survivor’s Story

Bethany Hart lives with her husband Kevin, sons, and 3 dogs in the suburbs of Indianapolis, Indiana. She is a survivor of small cell neuroendocrine cervical cancer....

Adjuvant Immunotherapy Approved for Some Patients with Lung Cancer

October 26, 2021, by NCI Staff Atezolizumab (Tecentriq) is approved as an additional treatment for some patients with stage II to IIIA (pictured) non-small cell...

Cure Probability Models for Evaluation of Patients with a Previous Cancer Diagnosis for Solid Organ Transplantation

Findings from a first study that applied a formal statistical framework to inform the evaluation of transplant candidates with a previous cancer diagnosis were...

Teacher Reads To Students One Day After Having Brain Surgery

Meucci - who had her surgery on a Wednesday - was going live from her intensive care unit hospital room that very next Thursday...

6 things you need to know about cervical screening

This article was originally published in 2017 during Cervical Screening Awareness Week. It has now been reviewed and updated. Cervical screening, also known as the...

EMA Recommends Granting a Marketing Authorisation for Sacituzumab Govitecan

On 14 October 2021, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting...