St John’s wort can cause a moderate reduction in anticoagulant effects of phenprocoumon and warfarin
In a randomised, placebo-controlled crossover study in 10 healthy men,(See reference number 1)St John’s wort extract (LI 160, Lichtwer Pharma) 900mg daily for 11 days reduced AUC of a single 12mg dose of phenprocoumon by a modest 17.4%. There is also a case report of a 75-year-old woman taking phenprocoumon who had a reduced anticoagulant response (a rise in Quick value) 2 months after starting to take St John’s wort (See reference number 2).
In a randomised, crossover study in 12 healthy subjects, one tablet of St John’s wort three times daily for 3 weeks modestly decreased AUC of both R- and S-warfarin by about 25 % after a single 25mg dose of warfarin taken on day 14. In this study, brand of St John’s wort used was Bioglan tablets, each tablet containing an extract equivalent to 1 g of Hypericum perforatum flowering herb top containing 825 micrograms of hypericin and 12.5mg of hyperforin (See reference number 3).
The Swedish Medical Products Agency received 7 case reports over 1998 to 1999 period of patients stabilised on warfarin who showed decreased INRs when St John’s wort was added. Their INRs fell from normal therapeutic range of about 2 to 4 to about 1. The INRs of 4 of patients returned to their former values when St John’s wort was stopped (See reference number 4)
Uncertain, but it is suggested that St John’s wort increases metabolism and clearance of anticoagulants(See reference number 1,3,4) possibly by induction of cytochrome P450 isoenzymes. It affected both R– and S-warfarin (See reference number 3). Oral bioavailability was not altered (See reference number 3).
Information seems to be limited to these reports,but a modest pharmacokinetic interaction is established, which might be clinically important. It would be prudent to monitor INRs of patients taking phenprocoumon, warfarin or any other coumarin if they start taking St John’s wort, being alert for need to slightly raise anticoagulant dosage. However, note that advice of CSM in UK is that St John’s wort should not be used with warfarin. They note that degree of induction of warfarin metabolism is likely to vary because levels of active ingredients may vary between St John’s wort preparations. If a patient is already taking combination, they advise checking INR, stopping St John’s wort and then monitoring INR closely and adjusting anticoagulant dosage as necessary (See reference number 5).
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