Herb-Drug Interactions: Devil’s claw
Harpagophytum procumbens (Burch.) DC. (Pedaliaceae)
Synonym(s) and related species
Grapple plant, Harpagophytum, Wood spider. Harpagophytum burchellii Decne.
Devil’s Claw (British Pharmacopoeia 2009); Devil’s Claw Dry Extract (British Ph 2009, European Ph 2008); Devil’s Claw Root (European Ph, 6th ed., 2008 and Supplements 6.1, 6.2, 6.3 and 6.4).
Devil’s claw is usually standardised to the content of the iridoid glycoside, harpagoside. Other iridoid glycosides include harpagide and procumbide, and other constituents include diterpenes, the phenolic glycosides 6-acetylacteoside and 2,6-diacetylacteoside, flavonoids (including kaemp-ferol), triterpenes and harpagoquinone.
Use and indications
The dried secondary root tuber is used as a stomachic and bitter tonic, and for inflammatory disorders including arthritis, gout, myalgia, fibrositis, lumbago and rheumatic disease.
In vitro, a Devil’s claw extract moderately inhibited the activity of the cytochrome P450 isoenzymes, CYP2C8, CYP2C9, CYP2C19, and CYP3A4. Devil’s claw had the greatest effect on CYP2C9, but this was still, at best, a modest effect. For information on the pharmacokinetics of individual flavonoids present in Devil’s claw, see under flavonoids.
Limited evidence is available. Devil’s claw does not appear to affect blood pressure, and its theoretical interaction with drugs with antiplatelet effects seems unlikely to be of practical relevance; however, it may increase the anticoagulant effects of drugs such as warfarin.
For information on the interactions of individual flavonoids present in Devil’s claw, see under flavonoids.
Devil’s claw + Antihypertensives
Devil’s claw does not appear to affect blood pressure and is therefore unlikely to interact with antihypertensives to a clinically relevant extent, although further study is needed to confirm this.
In a randomised, placebo-controlled, 4-week study, a Devil’s claw extract was studied for the possible treatment of low back pain in 109 patients. One patient had an episode of tachycardia while on holiday, and stopped taking the herbal medicine. When he returned from holiday, Devil’s claw was restarted and was well tolerated. It was suggested that this adverse event was due to the change in climate rather than the medication. Furthermore, in the study, there was no significant change in systolic and diastolic blood pressure or heart rate between the beginning and the end of the study, and between Devil’s claw and placebo recipients. The Devil’s claw extract used in this study was given at a dose of 800 mg three times daily, equivalent to a daily dose of 50 mg of harpagoside.
Crude methanolic extracts of Devil’s claw, and isolated harpagoside, showed a significant and dose-dependent, protective action towards ventricular arrhythmias in rat hearts. In other animal studies, high doses of Devil’s claw have caused a reduction in blood pressure.
No mechanism established.
Importance and management
Clinical evidence is limited to one study that was not specifically designed to assess interactions. However, the available data suggest that Devil’s claw, used in standard doses, is unlikely to affect treatment with conventional antihypertensives, although this ideally needs confirmation in hypertensive patients. The reduction in blood pressure found in animal studies seems unlikely to be clinically relevant, due to the high doses used. Too little is known to be able to make any clinical recommendations regarding the potential anti-arrhythmic effect of Devil’s claw.
Devil’s claw + Antiplatelet drugs and NSAIDs
The interaction between Devil’s claw and antiplatelet drugs and NSAIDs is based on a prediction only.
Evidence, mechanism, importance and management
One licensed preparation for Devil’s claw suggests that there is a theoretical increased risk of bleeding if Devil’s claw is given with drugs that inhibit platelet aggregation, such as antiplatelet drugs and NSAIDs. The exact basis for this recommendation is unclear and another subsequently licensed preparation does not carry this warning. A case report suggests that Devil’s claw may interact with warfarin, see below, but this seems most likely to be due to a metabolic effect rather than intrinsic antiplatelet properties. Devil’s claw appears to be contraindicated in peptic ulceration, and this could be taken to suggest that any antiplatelet effects that it may have could increase the risks of bleeding from an ulcer. However, some sources suggest that this contraindication is because of the bitter properties of Devil’s claw (implying that it may stimulate gastric secretions), and there are no documented cases of bleeding or ulceration with the use of Devil’s claw. This warning with antiplatelet drugs and NSAIDs therefore appears to represent tremendous caution and it seems unlikely that the theoretical prediction will be of clinical importance.
Devil’s claw + Food
No interactions found.
Devil’s claw + Herbal medicines
No interactions found.
Devil’s claw + Warfarin and related drugs
Devil’s claw may increase the effects of warfarin, and possibly other coumarins.
A case report from a 5-year toxicological study describes the development of purpura in a patient following the concurrent use of Devil’s claw and warfarin.
In an in vitro study, a Devil’s claw extract modestly inhibited the activity of the cytochrome P450 isoenzyme CYP2C9.
Limited in vitro evidence suggests that Devil’s claw may inhibit the cytochrome P450 isoenzyme CYP2C9. Although the metabolism of warfarin is complex, CYP2C9 plays a significant role. Therefore it is possible that Devil’s claw could inhibit the metabolism of warfarin, raising its levels and increasing its effect.
Importance and management
Evidence is limited to a case study, which reports minor adverse effects, and experimental data. An interaction seems possible, but it has not been conclusively demonstrated. Although only warfarin has been studied, all coumarins are metabolised by CYP2C9 to some extent, and therefore they also have the potential to be affected. The evidence is too sparse to make any firm recommendations, but it may be prudent to consider a possible interaction if a patient taking a coumarin develops otherwise unexplained bruising.