Pharmacokinetic variability of anticoagulants in patients with cancer-associated thrombosis: Clinical consequences

Crit Rev Oncol Hematol. 2018 Sep:129:102-112. doi: 10.1016/j.critrevonc.2018.06.015. Epub 2018 Jul 9.

Abstract

The use of anticoagulants in patients with cancer is challenging as several co-morbidities modifying pharmacokinetic (PK) parameters and significant drug-drug interactions with concomitant anti-neoplastic therapies may lead to PK variability resulting in increased risk of thrombosis or bleeding. Data on the management of patients with cancer-associated thrombosis (CAT) in real life are scarce since patients with cancer presenting with significant comorbidities tend to be excluded from large trials. This review is mostly based on case-reports and pharmacokinetics in an attempt to provide oncologists, with relevant orientation based on our best knowledge to date. Overall, low-molecular-weight heparins (LMWH) are the preferred option for the long-term prophylaxis and treatment of CAT as their benefit-risk was shown superior to vitamin K antagonists (VKA). Direct oral anticoagulants (DOAC) may represent an alternative to LMWH provided that a favorable benefit-risk in patients with CAT is evidenced in the future. We recommend a systematic risk-assessment including body composition, multiple medication, and renal function. Moreover a systematic and early discussion between pharmacist and oncologist should optimize the benefit-risk ratio for each patient.

Keywords: Anticoagulants; Cancer-associated thrombosis; Drug-drug interactions; Pharmacokinetics; Risk assessment.

Publication types

  • Review

MeSH terms

  • Anticoagulants / pharmacokinetics*
  • Anticoagulants / therapeutic use*
  • Humans
  • Neoplasms / blood
  • Neoplasms / complications*
  • Neoplasms / therapy
  • Risk Assessment
  • Thrombosis / blood
  • Thrombosis / drug therapy*
  • Thrombosis / etiology
  • Tissue Distribution
  • Treatment Outcome

Substances

  • Anticoagulants