Apixaban: Drug interaction between apixaban and Selective Serotonin Reuptake Inhibitors (SNRI) and/or Serotonin and Noradrenaline Reuptake Inhibitors (SNRI) leading to increased risk of bleeding

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Apixaban (Eliquis®) is an oral anticoagulant indicated for prevention and treatment of venous thromboembolic events (VTE)1. Antidepressants belonging to the Selective Serotonin Reuptake Inhibitors (SSRI) and Serotonin Norepinephrine Reuptake Inhibitors (SNRI) may inhibit platelet aggregation by decreasing the uptake of serotonin by platelets2. The administration of SSRI and SNRI with oral anticoagulants such as apixaban increases the risk of bleeding by 2- to 3-fold.



The National Pharmaceutical Regulatory Agency (NPRA) has received information from the European Medicines Agency (EMA) on the drug interaction between apixaban and selective serotonin reuptake inhibitors (SSRI) and/or serotonin and noradrenaline reuptake inhibitors (SNRI), leading to increased risk of bleeding. 

Having considered the available evidence in EudraVigilance and in the literature, as well as the biological plausibility of the interaction, Pharmacovigilance Risk Assessment Committee (PRAC) has agreed to include the risk of this drug interaction in the product information of apixaban-containing medicinal products3.


Adverse Drug Reaction Reports:

NPRA has received a total of 62 ADR reports with 81 adverse events suspected to be related to apixaban. Majority of the adverse events (43.2%) are related to bleeding. However, no bleeding cases following the concomitant use of apixaban and SSRI or SNRI has been reported to NPRA up to present4

Globally, there is a total of 5,800 reports of apixaban which involved adverse events related to System Organ Class Vascular Disorders, such as haemorrhage. Of these, 163 reports (2.81%) reported co-administration of apixaban and SSRI or SNRI5.


Advice for Healthcare Professionals:

  • All healthcare professionals are advised to exercise caution if patients on apixaban are treated concomitantly with SSRIs or SNRIs.
  • Please report any adverse drug reactions suspected to be associated to apixaban use to NPRA.



  1. Eliquis® Malaysian Product Package Insert (Last revision date: April 2018).
  2. Horn, JR & Hansten, PD (2017). Oral Anticoagulants and NSAIDs, SSRIs, or SNRIs. Pharmacy Times .
  3. European Medicines Agency (2018). PRAC recommendations on signals-adopted at the 14-17 May 2018 PRAC Meeting. EMA/PRAC/287231/2018
  4. The Malaysian Adverse Drug Reaction Database, NPRA [Accessed: August 2018].
  5. World Health Organisation (WHO) Vigilyze Database [Accessed: August 2018].



This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, the NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.


National Pharmaceutical Regulatory Agency (NPRA)

Lot 36, Jalan Universiti (Jalan Prof Diraja Ungku Aziz), 46200 Petaling Jaya, Selangor, Malaysia.

  • Phone: +603-7883 5400




The Government of Malaysia and the National Pharmaceutical Regulatory Agency are not responsible for any loss or damage caused by the usage of any information obtained from this website.

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