Update on drug interactions with non-vitamin-K-antagonist oral anticoagulants for stroke prevention in elderly patients

ABSTRACT

Introduction: We update the knowledge, since the last review in 2017, about drug–drug interactions (DDI) of non-vitamin-K-antagonist oral anticoagulants (NOAC) in patients ≥75 years.

Areas covered: The literature was searched for: ‘dabigatran,’ ‘rivaroxaban,’ ‘edoxaban,’ or ‘apixaban’ and drugs, affecting platelet function, CYP3A4-, CYP2C9-, or P-Gp-activity. Pharmacodynamic DDI of NOAC with drugs affecting platelet function like nonsteroidal anti-inflammatory drugs and antiplatelet agents occur most frequently. Pharmacokinetic DDI with NOAC were found for 37 of 117 drugs. Reports about DDI with NOAC were found for 51% of P-gp-affecting, 38% for CYP2C9-affecting and 27% for CYP3A4-affecting drugs. Reports about DDI of cardiovascular drugs with NOAC were the most prevalent, followed by anti-infective and nervous system drugs. NOAC plasma levels were measured in retrospective and cohort studies and were associated with concomitant medication. Reports about DDI of NOAC were found in 71 patients ≥75 years.

Expert opinion: The knowledge about DDI of NOAC in elderly patients is very limited. Studies should be carried out to investigate the role of drugs potentially interacting with NOAC, which until now have not been investigated. When studying DDI of NOAC, care should be taken to include elderly patients with impaired renal function and patients on polymedication.

KEYWORDS:

• Anticoagulation
• atrial fibrillation
• venous thromboembolism
• geriatrics
• drug–drug interaction

Article highlights

• Pharmacodynamic drug–drug interactions (DDI) of non-vitamin-K-antagonist oral anticoagulants (NOAC) with drugs affecting platelet function like nonsteroidal anti-inflammatory drugs (NSAID) and antiplatelet agents occur most frequently.

• Pharmacokinetic DDI with NOAC were found for 37 of 117 drugs. Reports about DDI with NOAC were found for 51% of P-gp-affecting, 38% for CYP2C9-affecting, and 27% for CYP3A4-affecting drugs. Reports about DDI of NOAC were found in 71 patients ≥75 years.

• Reports about DDI of cardiovascular drugs with NOAC were most prevalent, followed by anti-infective and nervous system drugs.

• Independent research, carried out by academic institutions, health-care providers, or public health bodies, and not by NOAC manufacturers, is urgently needed.

• Studies should be carried out to investigate DDI, including those that are used to treat COVD-19 infections, potentially interacting with NOAC, with special consideration for elderly patients with impaired renal function and patients on polymedication.

Declaration of interest

The author(s) have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.