Complexity and clinical significance of drug–drug interactions (DDIs) in oncology: challenging issues in the care of patients regarding cancer-associated thrombosis (CAT)

Abstract

Cancer patients have an increased risk of developing venous thromboembolic events. Anticoagulation management includes prophylactic or therapeutic doses of low molecular weight heparins (LMWHs) or direct oral anticoagulants (DOACs). However, the management of thrombosis in patients with cancer is complex due to various individual and disease-related factors, including drug–drug interactions (DDIs). Furthermore, DDIs may impact both, cancer and venous thrombosis, treatment effectiveness and safety; their relevance is highlighted by the advances in cancer therapeutics. Given that these new oncology drugs are extensively used, more attention should be given to monitoring potential DDIs to minimize risks. Recognition of DDIs is of utmost importance in an era of rapid developments in cancer treatments and introduction of novel treatments and protocols. When managing cancer-associated thrombosis (CAT), the concomitant use of a DOAC and a moderate or strong modulator (inhibitor or inducer) of CYP3A4 or a P-glycoprotein (P-gp) is most likely to be associated with significant DDIs. Therefore, LMWHs remain the first-line option for the long-term management of CAT under these circumstances and physicians must consider utilizing LMWHs as first line. This review describes the risk of DDIs and their potential impact and outcomes in patients with cancer associated thrombosis (CAT) receiving anticoagulation. The DDIs explored include pharmacodynamics, pharmacokinetics, the breast cancer resistance protein (BCRP), and human plasma protein DDIs.

MecDDI: Clarified Drug–Drug Interaction Mechanism Facilitating Rational Drug Use and Potential Drug–Drug Interaction Prediction

“…The mechanisms underlying a particular DDI provide an effective way to identify and avoid its potential harm. − The explanation of the molecular mechanism for these DDIs provides a solid foundation for clinicians to deeply understand how DDI is developed and discover effective alternative therapies. − In this study, MecDDI is thus developed to clarify the mechanisms underlying >1,78,000 DDIs by explicit descriptions and graphic illustrations.…”

Direct oral anticoagulants in prevention and treatment of cancer-associated thrombosis

“…Kod bolesnika sa malignom bolešću postoji povećan rizik od razvoja tromboze povezane sa tumorom (cancer-associated thrombosis, CAT). Venski tromboembolizam (VTE) je dominantno zastupljen entitet kod CAT, a podrazumeva duboku vensku trombozu (DVT) i emboliju pluća (PE) [1][2][3][4][5] . Faktori rizika koji su u vezi sa većom incidencom VTE u ovoj populaciji bolesnika su primarna lokalizacija tumora, metastatska bolest, hematološki maligniteti, specifično lečenje (hemioterapija, hormonska terapija, operativno lečenje), ali i faktori koji se odnose i na opštu populaciju (starost, gojaznost, prisustvo komorbiditeta, imobilizacija) (Tabela 1) 1,[6][7][8][9][10] .…”

“…Adekvatna prevencija i lečenje CAT predstavlja izazov u kliničkoj praksi, uzimajući u obzir potencijalne interakcije između antikoagulantne terapije i hemioterapije i rizika od nastanka krvarenja 2,11 . U terapiji VTE primenjuju se niskomolekularni heparini (LMWH), direktni oralni antikoagulansi (DOAK) i antagonisti vitamina K (VKA) 1,4 .…”

“…S obzirom na eliminaciju DOAK putem bubrega i jetre, njihova primena je kontraindikovana kod bolesnika sa klirensom kreatinina manjim od 15 ml/min i hepatičnom insuficijencijom. DOAK prolaze placentalnu barijeru i njihova upotreba kod trudnica je kontraindikovana 2,11,15…”

“…Kao posledica izmenjenog vezivanja dva leka za isti transporter nastaje njihova kompeticija, što može rezultirati smanjenjem transporta jednog ili oba leka, na primer vezivanje za Pgp. Pored navedenog, mogu nastati interakcije usled vezivanja za proteine plazme ili izmenjene apsorpcije leka 2 .…”