An isolated case describes fatal intracerebral bleeding in a patienttaking Ginkgo biloba with ibuprofen,and another case describesprolonged bleeding and subdural haematomas in another patients taking Ginkgo biloba with rofecoxib. Studies involving diclofenac and flurbiprofen showed that Ginkgo biloba had no effect on pharmacokinetics of these drugs.
A case of fatal intracerebral bleeding has been reported in a 71-year-old patient taking a Ginkgo biloba supplement (Gingium) 4 weeks after he started to take ibuprofen 600mg daily (See reference number 1). A 69-year-old man taking a Ginkgo biloba supplement and rofecoxib had a subdural haematoma after a head injury,then recurrent small spontaneous haematomas. He was subsequently found to have a prolonged bleeding time, which returned to normal one week after stopping Ginkgo biloba supplement and rofecoxib, and remained normal after restarting low-dose rofecoxib (See reference number 2).
A placebo-controlled study in 11 healthy subjects who were given Ginkgo biloba leaf (Ginkgold) 120mg twice daily for three doses, followed by a single 100mg dose of flurbiprofen, found that pharmacokinetics of flurbiprofen were unchanged (See reference number 3).
A study in 12 healthy subjects who were given diclofenac 50mg twice daily for 14 days, with Ginkgo biloba extract (Ginkgold) 120mg twice daily on days 8 to 15, found no alteration in AUC or oral clearance of diclofenac (See reference number 4).
The reason for bleeding is not known, but Ginkgo biloba extract contains ginkgolide B, which is a potent inhibitor of platelet-activating factor that is needed for arachidonate-independent platelet aggregation. On their own,Ginkgo biloba supplements have been associated with prolonged bleeding times,(See reference number 5,6) left and bilateral subdural haematomas,(See reference number 5,7) a right parietal haematoma,(See reference number 8) post-laparoscopic cholecystectomy bleeding,(See reference number 9) and sub-arachnoid haemorrhage (See reference number 6). Ibuprofen is an inhibitor of platelet aggregation,but selective inhibitors of COX-2 such as rofecoxib have no effect on platelets and would not be expected to potentiate any bleeding effect of Ginkgo biloba.
The pharmacokinetic study involving diclofenac was designed to identify whether Ginkgo biloba exerted an inhibitory effect on cytochrome P450 isoenzyme CYP2C9, which is involved in metabolism of diclofenac. Although an indication that such an effect may occur was noted in studies in vitro using S-warfarin, in vivo study did not confirm that this interaction would be seen clinically (See reference number 4).
The evidence from these reports is too slim to forbid patients to take NSAIDs and Ginkgo biloba concurrently,but some do recommend caution (See reference number 10). Medical professionals should be aware of possibility of increased bleeding tendency with Ginkgo biloba, and report any suspected cases (See reference number 8). Consider also Antiplatelet drugs + Herbal medicines interaction.
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