What is the interaction between Kisqali (ribociclib) and Non-Vitamin K Anticoagulant (NOAC)?

From the Guidelines

Kisqali (ribociclib) can be used with non-vitamin K antagonist oral anticoagulants (NOACs) but requires careful monitoring due to potential drug interactions, as it is a moderate CYP3A4 inhibitor that may increase NOAC plasma concentrations, potentially elevating bleeding risk. When prescribing these medications together, healthcare providers should be aware of the potential interactions and take necessary precautions. According to the 2018 European Heart Rhythm Association practical guide on the use of NOACs in patients with atrial fibrillation 1, the absorption, distribution, metabolism, and excretion of the different NOACs should be considered, as well as the potential interactions with accompanying drugs and comorbidities.

Some key points to consider when using Kisqali with NOACs include:

• The potential for increased NOAC plasma concentrations due to CYP3A4 inhibition by Kisqali, which may elevate bleeding risk
• The need for dose adjustments of the NOAC, typically reducing the NOAC dose by 25-50% depending on the specific agent used
• Regular monitoring of coagulation parameters and clinical assessment for bleeding signs
• Patient education about potential bleeding symptoms and instruction to report any unusual bruising or bleeding immediately

The interaction between Kisqali and NOACs occurs because Kisqali inhibits the metabolism of NOACs that are CYP3A4 substrates, such as rivaroxaban and apixaban, while edoxaban and dabigatran may be less affected 1. Alternative anticoagulation strategies could be considered in high-risk patients, but the benefits of continuing breast cancer treatment with Kisqali alongside necessary anticoagulation often outweigh the risks when properly managed. As noted in the 2018 EHRA Practical Guide on NOACs in AF 1, knowledge regarding interactions is expanding, and new information may modify existing recommendations, highlighting the need for ongoing monitoring and assessment.

From the Research

Kisqali and NOAC Interaction

• There is no direct evidence of interaction between Kisqali (ribociclib) and NOACs (novel oral anticoagulants) in the provided studies 2, 3, 4, 5, 6.
• Kisqali is a cyclin-dependent kinase 4/6 inhibitor used in the treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer 4, 6.
• NOACs, such as dabigatran and rivaroxaban, are used as alternatives to warfarin for anticoagulation therapy 2.
• A study on the effects of FXa-targeting DOACs (direct oral anticoagulants) on cancer progression found that rivaroxaban and dabigatran did not inhibit breast cancer growth and metastasis in orthotopic xenograft models 3.

Kisqali Mechanism and Efficacy

• Kisqali has been shown to significantly improve progression-free survival in patients with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer when used in combination with endocrine therapy 4, 6.
• The efficacy of Kisqali in early breast cancer has also been demonstrated, with a significant improvement in invasive disease-free survival when used in combination with a nonsteroidal aromatase inhibitor 5.

NOACs Mechanism and Considerations

• NOACs have more predictable pharmacodynamic and pharmacokinetic properties than warfarin, but may require dosage adjustments in renal impairment and are contraindicated in severe liver impairment 2.
• The use of NOACs may also be associated with a higher risk of bleeding, and there are no specific antidotes for treating NOAC-related over-anticoagulation 2.