Cancer patients are often prescribed more than one drug and the need to elucidate potential harmful interactions between different drugs becomes vital. Drug-drug interaction (DDI) can be sorted into two broad categories, pharmacokinetic (PK) and pharmacokinetic (PD).
Briefly put, PK refers to two drugs that share some metabolism pathways, causing alterations in drug absorption, distribution, metabolism, or excretion. PD refers to when a drug enhances its effects in the presence of other drugs.
Three major classes of drugs are routinely administered for venous thromboembolism (VTE) treatment:
- Low-molecular-weight heparin (LMHW)
- Direct-acting oral anticoagulants (DOAC)
- Vitamin K agonists (VKA) 
LMWH has been the gold standard treatment for VTE for decades for its superior efficacy to VKA. Extensive studies on LMWH revealed low DDI with DOAC or VKA, minimal gastrointestinal (GI) absorption, and well-characterized bleeding risks .
On the other hand, DOACs are easy to use and carry a low risk of major bleeding. Although, the use of both LMHW and DOAC should be cautioned in patients with renal complications/fluctuations or at extremes of weight (<50 kg or >150 kg) .
Even if these drugs have relatively low bleeding risks when taken separately, taken in combination with other drugs can increase the risk of bleeding.
For example, the combination of anticoagulant drugs with antidepressants or selective serotonin reuptake inhibitors (SSRI) that exhibit a high affinity to the serotonin transporter may result in an increased risk of bleeding .
Concerning PK, the goldilocks rule is to avoid supra or sub-therapeutic drug levels during therapeutic anticoagulation.
Taking Rivaroxaban as a DOAC example, a fine balance exists between induction or inhibition of drug metabolism. For instance, phenytoin or carbamazepine induce cytochrome p450 isoenzymes, meaning that the rivaroxaban metabolism is increased, enhancing the risk for VTE recurrence [2-4].
On the other hand, inhibitors of cytochrome p450 like cobicistat increase the plasma levels of rivaroxaban, increasing the risk for more severe bleeding [3, 4]. Unfortunately, this is not true for all DOACs since their excretion method differs, changing their PK profile.
For instance, Rivaroxaban is primarily excreted by a P-glycoprotein (P-gp), and inhibitors or inducers of P-gp, like Ritonavir or Rifampicin, can increase or decrease plasma levels of Rivaroxaban, respectively [3, 4].
It remains important to note that the effect of an inhibitor on drugs starts and disappears rather quickly during co-medication, while the effect of inducers is usually delayed due to the new formation of new proteins, producing a long-lasting effect [3, 4].
During the ICTHIC webinar, “Long-term treatment & DDI implications in the management of CAT,” Dr. Hans-Peter Lipp shares some highlights on the impact of DDI on cancer patients.
You can watch Lipp’s lecture in the video below and the full webinar recording here.
- Song AB, Rosovsky RP, Connors JM, Al-Samkari H. Direct oral anticoagulants for treatment and prevention of venous thromboembolism in cancer patients. Vasc Health Risk Manag. 2019;15:175-186. Published 2019 Jun 21. doi:10.2147/VHRM.S132556
- Vranckx P, Valgimigli M, Heidbuchel H. The Significance of Drug-Drug and Drug-Food Interactions of Oral Anticoagulation. Arrhythm Electrophysiol Rev. 2018;7(1):55-61. doi:10.15420/aer.2017.50.1
- Del Re M, Fogli S, Derosa L, et al. The role of drug-drug interactions in prostate cancer treatment: Focus on abiraterone acetate/prednisone and enzalutamide. Cancer Treat Rev. 2017;55:71-82. doi:10.1016/j.ctrv.2017.03.001
- Mueck W, Kubitza D, Becka M. Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. Br J Clin Pharmacol. 2013;76(3):455-466. doi:10.1111/bcp.12075