Reports of warfarin-glucosamine interaction

In view of the popular use of complementary medicines locally, HSA would like to highlight to healthcare professionals the potential drug interaction between warfarin and glucosamine. Glucosamine is a health supplement available in a large variety of products and used for the symptomatic relief of osteoarthritis

Reports from Australia TGA and UK MHRA

The Australian Therapeutic Drugs Administration (TGA) has received 12 reports describing a possible interaction between warfarin and glucosamine². From the reports, it was found that patients previously stabilised on warfarin experienced changes in the International Normalised Ratio (INR) after they started taking glucosamine. In ten out of the 12 cases, the patients had an increase in the INR whilst a slight fall in INR was observed in the other two cases. The peak INR ranged from 4.1 to 12 in eight of the cases. It was observed that the INR change ranged from 4 to 20 days after commencing glucosamine and in one case, the INR rise occurred two days after the dose of glucosamine was increased. Most of the INR increases did not lead to any complications except for hyphaema in one patient and haemoptysis and petechiae in another patient.

The UK Medicines and Healthcare products Regulatory Agency (MHRA) has also received seven reports suggesting an interaction between glucosamine and warfarin². In those cases, patients on warfarin therapy who previously had a stable INR experienced an INR increase after they started taking glucosamine.

Reports from the WHO-ADR database

In a separate report from the World Health Organisation (WHO) Collaborating Centre for International Drug Monitoring, 22 spontaneous cases of suspected warfarin-glucosamine interaction originating from Australia, Canada, Denmark, Sweden, United Kingdom and the United States were filtered from the WHO-Adverse Drug Reaction database³. An increased effect of warfarin was documented in 21 patients and one case involved decreased effect of warfarin. Two of the 22 patients were concomitantly using chondroitin, another health supplement also for the relief of arthritic pain.

Among the 21 cases of elevated INR, the event resolved when glucosamine was discontinued in 17 cases. Eleven of the patients had been chronic users of warfarin before the increased effect was established. The onset of increased INR was detected within three weeks in eight patients and within one to six months in five patients. In nine cases, the event required medical attention, hospitalization or closer INR monitoring. Four cases required prolonged hospitalization and/or the antidote vitamin K to reverse the effects of warfarin. One patient had an increase in INR three days after switching from glucosamine hydrochloride 750mg to glucosamine sulfate 1g, which suggested a dose effect.

The mechanism of interaction between warfarin and glucosamine remains unclear. It has been postulated that there is a possible pharmacodynamic interaction between glucosamine(a chemical component of heparin) and warfarin^3. Animal studies have shown that glucosamine has an inhibitory action on platlets in vivo, by suppressing platlet agregation, ATP release and thromboxane A₂ production.⁴

Conclusions

The Pharmacovigilance Branch has not received any local reports of INR changes associated with warfarin-glucosamine interaction.

Healthcare professionals are advised to monitor INR closely and titrate warfarin doses accordingly in patients on warfarin treatment who are consuming or commencing glucosamine or other complementary and herbal medicines. The INR of patients should also be monitored when there is a change in the dosing of complementary medicines.

References:

1. Australian Adverse Drug Reaction Bulletin, Vol. 27, No.1, Feb 2008.

2. MHRA/CSM. Current Problems in Pharmacovigilance 2006; 31:8.

3. Drug Safety 2006: 29:911.

4. Inflamm Res. 2005 Dec; 54(12):493-9.