Overview

Postpartum haemorrhage (PPH) is referred to as the loss of 500 ml of blood or more during the first 24 hours following delivery.¹ The prevalence rate of PPH is approximately 5% of all women giving birth worldwide.

Background

The National Pharmaceutical Regulatory Agency (NPRA) received information from the European Medicines Agency (EMA) and United Kingdom Medicines and Healthcare products Regulatory Agency (UK MHRA) on the association of certain antidepressant medicines with the risk of PPH.^2,3

Both reviews concluded that data from several observational studies suggested an increase in risk of postpartum bleeding with the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) during the month before delivery.^2,3 It is also concluded that this risk may also apply to vortioxetine, an atypical antidepressant drug. 

Adverse Drug Reaction (ADR) Reports

To date, NPRA has received a total of 841 reports with 1,580 adverse events suspected to be related to citalopram, desvenlafaxine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine and vortioxetine.⁴ Adverse reactions related to bleeding events such as bruise, cerebral haemorrhage, epistaxis, gastrointestinal haemorrhage, gingival bleeding, haemorrhoidal bleeding, decreased platelet count and thrombocytopenia have been reported. However, no event of PPH has been reported to NPRA.

Advice for Healthcare Professionals

• Note that the use of certain antidepressants in pregnant patients during the last month prior to giving birth may increase the risk of postpartum haemorrhage.
• Always consider the benefits and risks of antidepressant use in pregnant women as well as the risks of untreated depression during pregnancy.
• Counsel pregnant patients on the use of antidepressants including the risks, particularly in women at later stages of pregnancy.
• Consider the patient’s risk factors for bleeding or thrombotic events when treating the patient with antidepressants.
• Be vigilant of the risks identified and continue anticoagulant treatment in women who are at high risk of thrombotic events.
• Please report all suspected adverse events associated with antidepressants to the NPRA.

 References:

1. World Health Organization. WHO recommendations Uterotonics for the prevention of postpartum haemorrhage. Geneva: World Health Organization [Internet]. 2018 [Cited 2021 February 9]. Available from https://apps.who.int/iris/bitstream/handle/10665/277276/9789241550420-eng.pdf?ua=1
2. European Medicines Agency (EMA). PRAC recommendations on signals: Adopted at the 28 September-1 October 2020 PRAC meeting [Internet]. 2020 October 26 [Cited 2020 October 27]. EMA/PRAC/513083/2020.
3. Medicines and Healthcare products Regulatory Agency (MHRA). Drug Safety Update: SSRI/SNRI antidepressant medicines: small increased risk of postpartum haemorrhage when used in the month before delivery [Internet]. 2021 January 7 [Cited 2021 January 11]. Available from https://www.gov.uk/drug-safety-update/ssri-slash-snri-antidepressant-medicines-small-increased-risk-of-postpartum-haemorrhage-when-used-in-the-month-before-delivery.
4. National Pharmaceutical Regulatory Agency. The Malaysian National ADR Database [Internet]. 2021 [Cited 2021 February 5]. Available from https://www.npra.gov.my.

NPRA has completed a review of this safety issue and a directive [Ruj. Kami: NPRA.600-1/9/13 (33)] has been issued for registration holders of products containing antidepressants (citalopram, desvenlafaxine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine and vortioxetine) to update the local package inserts with this new safety information.

DISCLAIMER

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.