DISCLAIMER: This publication is intended for health care professionals. The information provided aims to update on medication safety issues and should not substitute 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 arising from the use of or reliance on this publication.

Overview of Product

Diosmin and hesperidin are flavonoid compounds of plant origin used to relieve symptoms associated with chronic venous insufficiency and haemorrhoidal disease.^1-3 In Malaysia, 22 diosmin-containing products are registered with the Drug Control Authority (DCA), all of which are oral fixed-dose combinations with hesperidin, available as over-the-counter (OTC) products.⁴

Overview of Safety Concern

Evidence from the scientific literature suggests that diosmin may interact with certain medications, including anticoagulants.¹ This interaction may elevate concentrations of anticoagulants in the blood, potentially enhancing their blood-thinning effects and increasing the risk of bleeding. Furthermore, studies have demonstrated that diosmin and hesperidin may independently exert blood-thinning effects.

Source of Safety Concern

The National Pharmaceutical Regulatory Agency (NPRA) received information from a Health Canada safety review regarding a possible increased risk of bleeding associated with the use of diosmin, whether used as a single ingredient or in combination with hesperidin.¹ This review was initiated following a Canadian case involving severe rectal bleeding in a patient who was taking a diosmin-containing product concomitantly with other medications, including an anticoagulant.^1,5 In total, Health Canada evaluated 19 reports of bleeding events associated with diosmin or diosmin-hesperidin combination products identified from the scientific literature, Canada Vigilance and World Health Organization (WHO) adverse reaction databases, with 4 cases assessed as possibly linked.¹

Background of the Safety Issue

In the index Canadian case, the event occurred after 2 days of diosmin use at the recommended dosage, and the patient’s condition improved shortly after discontinuation of the product.^1,5 However, the event was not medically verified and lacked laboratory data to confirm causality.⁵ Another reported case involved several years of diosmin use before the occurrence of spontaneous intraventricular haemorrhage.² Both patients were elderly and had concomitant use of anticoagulants.^2,5 These reports indicate that the time to onset may be variable and may be influenced by concomitant medicines or other patient-related factors. To mitigate this risk, Health Canada recommended updating product labels to advise consumers to consult a health care professional prior to product use if they are taking medications, including anticoagulants.¹

Local Adverse Drug Reaction Reports⁶

To date, the NPRA has received 99 reports involving 175 adverse events suspected to be related to diosmin-hesperidin-containing products. No reports of bleeding associated with the use of diosmin-hesperidin-containing products have been received.

Advice for Health Care Professionals

• Be aware of the increased risk of bleeding associated with the use of diosmin or diosmin-hesperidin combination products, particularly in patients taking medications that affect blood clotting, such as anticoagulants.
• Perform active medication reconciliation by routinely inquiring about the use of OTC health products or supplements in patients prescribed medications that affect blood clotting.
• Advise patients to seek medical attention if they experience signs or symptoms suggestive of bleeding, such as unexplained or prolonged bleeding, easy bruising, blood in the stool or black, tarry stools, or rectal bleeding.
• If suspected or significant bleeding occurs, evaluate the patient clinically and manage the bleeding as appropriate. Consider the patient’s concomitant medications and other potential causes of bleeding.
• Report all suspected adverse events related to the use of diosmin or diosmin-hesperidin combination products to the NPRA.

References

1. Health Canada. Summary Safety Review-Diosmin and Hesperidin-Assessing the Potential Increased Risk of Bleeding. Drug and Health Products Portal, Government of Canada. 2026 [cited 2026 May 13]. Available from: https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SSR1775582460008
2. Kumar RM, Van Gompel JJ, Bower R, Rabinstein AA. Spontaneous Intraventricular Hemorrhage Associated with Prolonged Diosmin Therapy. Neurocritical Care. 2011;14(3):438-440. Available from: https://doi.org/10.1007/s12028-011-9524-9
3. Asadi S, Mehrjerdi PZ, Fotouhi S, Askari VR, Rahimi VB. Diosmin and Its Aglycone form Diosmetin as Potential Therapeutics for Cardiovascular Diseases. Journal of Functional Foods. 2026;143:107383. Available from: https://doi.org/10.1016/j.jff.2026.107383
4. National Pharmaceutical Regulatory Agency (NPRA). QUEST3+ Product Search [Internet]. 2026 [cited 2026 Sep 29]. Available from: https://quest3plus.bpfk.gov.my/pmo2/index.php
5. Health Canada. Safety Brief: Diosmin or Diosmin in Combination with Hesperidin and the Increased Risk of Bleeding Health Product Info Watch [Internet]. 2026 May [cited 2026 Aug 26]; 2026(5): 2-4. Available from: https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/health-product-infowatch/may-2026.html#a2_1a
6. National Pharmaceutical Regulatory Agency (NPRA). The Malaysian National ADR Database (QUEST) [Internet]. 2026 [cited 2026 Jun 24]. Available from: https://www.npra.gov.my (access restricted)

Written by: Nafiza Mohd. Ismail

Reviewed/Edited by: Lim Sze Gee, Dr Rema Panickar, Noor'ain Shamsuddin, Norleen Mohamed Ali