InteractionsGuide Index Page

Case Analysis Toolclose

Enter Each Substance:

Analysis Search Terms:

MedicineWorks.com

TM

Health Resources Unlimited, Inc.

Devil's Claw

Botanical Name: Harpagophytum procumbens , DC ex Meissner.
Pharmacopoeial Name: Harpagophyti radix.
Common Names: Devil’s claw, grapple plant, Cape grapple plant.

herb description

Family

Pedaliaceae.

Parts Used

Secondary roots (tuber).

Common Forms

Dried: Cut/powdered secondary root, containing not less than 1.2% harpagoside.

Tincture, Fluid Extract, Hydroethanolic extracts 1:2, 1:3, 1:5 in 25% ethanol.

Standardized Extract: Tablets or capsules, standardized 6:1 to 9:1 on 8.5% harpagoside. (WS 1531, Schwabe GmbH) or 1.5:1 to 2.5:1 standardized at 2.5% harpagoside (Doloteffin, Ardeypharm GmbH).

interactions review

Strategic Considerations

Devil's claw, a South African native, has been used in Western Europe for chronic arthritic conditions for several decades. The root tubers are bitter, containing iridoid glycosides, principally harpagoside. ¹ The bitter nature of the remedy, suggested by Weiss ² as comparable to gentian, led the German Commission E to approve its use for dyspepsia and loss of appetite. ³ In practice, however, it is only used for atonic digestion secondary to or associated with a primary arthritic condition. The European Scientific Cooperative on Phytotherapy (ESCOP) indications are for low back pain and osteoarthritis. ^4,5There is positive clinical trial evidence as well as pharmacological support for the use of the herb in painful, chronic arthritic conditions. Most of the trials to date have been German or French and recently reviewed. ^6-8Neither of the European therapeutic monographs notes any interactions between devil's claw and pharmaceutical drugs.

Pharmacologically, devil's claw has three principal areas of action: anti-inflammatory and analgesic, antiarrhythmic and hypotensive, and bitter tonic. Data regarding mechanism of the anti-inflammatory action has been conflicting, with initial studies suggesting a nonecosanoid mechanism because animal models of inflammation did not respond to the extract, although some direct effect on lipoxygenase and cyclooxygenase (COX) pathways was noted. ^9-11More recent studies suggest that there may be a downregulation of inducible COX-2 and inducible nitric oxide synthase (iNOS), as well as a similar effect on tumor necrosis factor alpha (TNF-α) transcription, probably resulting from upstream effects on activating protein-1 (AP-1). ^12-15This is consistent with the efficacy of the herb as a chronic, rather than acute, anti-inflammatory and analgesic agent operating through different pathways than the nonsteroidal anti-inflammatory drug (NSAID)–type direct effects on arachidonic acid metabolism. ¹⁶ Parallels with other botanical derivatives exist, and evidence is emerging for modulation of nuclear factor kappa B (NF-κB), ¹⁷ as well as the metalloproteinase TIMP-2. ¹⁸ Mechanism aside, clinical trials on the anti-inflammatory effects of devil's claw have revealed useful data relating to coadministration with several different NSAIDs and in clinical populations with chronic arthritic complaints using long-term NSAID therapy for management. This is a primary area for integrative use of the herb.

The cardiovascular effects of devil's claw have not been studied in humans, although studies of ex vivo Langendorff preparations (rabbit heart) and live rats strongly suggest the potential for protection against arrhythmias, including those induced by digoxin, together with a biphasic dose-response on heart rate. ^19-21Interestingly, harpagoside did not reproduce the electrophysiological effects of whole-plant extract. The same researchers noted a hypotensive reaction to the extract in normotensive rats, but only with intraperitoneal administration of high doses. Further studies on this aspect of the herb's pharmacology have not been published, and devil's claw clearly is a complex remedy that is not fully understood. Traditional South African indications include seizures, and some scientific corroboration of this has been found in a murine model. ²² Meanwhile, monitoring heart rate and blood pressure in patients with either preexisting hypotension or disturbances of rate or rhythm during early stages of administration of the herb may be prudent.

Effects on Drug Metabolism and Bioavailability

The bitter tonic aspects of the herb suggest that a potential for stimulation of hepatobiliary activity, but studies of the generic effect of bitters on drug metabolism and detoxification systems are unavailable, and pharmacokinetic interactions with devil's claw have not been reported to date. A single in vitro screening study of the effect of the herb on a mixture of human recombinant drug–metabolizing enzymes derived from baculovirus-infected insect cells suggested a potential inhibition of cytochrome P450 (CYP450) by devil's claw extracts. ²³

herb-drug interactions

Nonsteroidal Anti-Inflammatory Drugs and Related Antiarthritic Medications

Nonsteroidal anti-inflammatory drugs (NSAIDs):COX-1 inhibitors: Diclofenac (Cataflam, Voltaren), combination drug: diclofenac and misoprostol (Arthrotec), diflunisal (Dolobid), etodolac (Lodine), fenoprofen (Dalfon), furbiprofen (Ansaid), ibuprofen (Advil, Excedrin IB, Motrin, Motrin IB, Nuprin, Pedia Care Fever Drops, Provel, Rufen); combination drug: hydrocodone and ibuprofen (Reprexain, Vicoprofen), indomethacin (indometacin; Indocin, Indocin-SR), ketoprofen (Orudis, Oruvail), ketorolac (Acular ophthalmic, Toradol), meclofenamate (Meclomen), mefenamic acid (Ponstel), meloxicam (Mobic), nabumetone (Relafen), naproxen (Aleve, Anaprox, Naprosyn), oxaprozin (Daypro), piroxicam (Feldene), salsalate (salicylic acid; Amigesic, Disalcid, Marthritic, Mono Gesic, Salflex, Salsitab), sulindac (Clinoril), tolmetin (Tolectin). COX-2 inhibitors: Celecoxib (Celebrex). Acetylsalicylic acid:acetosal, acetyl salicylic acid, ASA, salicylsalicylic acid; Arthritis Foundation Pain Reliever, Ascriptin, Aspergum, Asprimox, Bayer Aspirin, Bayer Buffered Aspirin, Bayer Low Adult Strength, Bufferin, Buffex, Cama Arthritis Pain Reliever, Easprin, Ecotrin, Ecotrin Low Adult Strength, Empirin, Extra Strength Adprin-B, Extra Strength Bayer Enteric 500 Aspirin, Extra Strength Bayer Plus, Halfprin 81, Heartline, Regular Strength Bayer Enteric 500 Aspirin, St. Joseph Adult Chewable Aspirin, ZORprin; combination drugs: ASA and caffeine (Anacin); ASA, caffeine, and propoxyphene (Darvon Compound); ASA and carisoprodol (Soma Compound); ASA, codeine, and carisoprodol (Soma Compound with Codeine); ASA and codeine (Empirin with Codeine); ASA, codeine, butalbital, and caffeine (Fiorinal); ASA and extended-release dipyridamole (Aggrenox, Asasantin).

	Beneficial or Supportive Interaction, Not Requiring Professional Management
	Prevention or Reduction of Drug Adverse Effect

Probability: 1. Certain
Evidence Base:

Emerging

Effect and Mechanism of Action

Additive pharmacodynamic anti-inflammatory effect enables reduced drug dose and reduction in drug adverse effects for a range of NSAIDs.

Research

Chrubasik et al. ^24-29 have conducted several trials with a proprietary extract of devil's claw (Doleteffin) in various arthritic conditions, comparing both drug versus herb and drug in combination with various NSAIDs, including the COX-2 inhibitor rofecoxib (Vioxx). The general conclusions of this (ongoing) series of controlled trials and qualitative investigations are (1) for acute exacerbations of chronic arthritic conditions, including low back pain, knee pain, and hip pain, devil's claw extract is associated with fewer adverse effects than NSAIDs; (2) coadministation allows a lower dose of NSAIDs (or of opioid rescue medications in trials where these were allowed); and (3) for longer periods of administration, devil's claw was associated with almost twice the incidence of pain-free outcomes than rofecoxib. This latter result was from a subsequent pilot study, which, although it lacked the statistical power to establish the result as significant due to sample size, was interesting because the trial dropouts were almost all in the NSAID group, resulting from adverse effects of the drug. ²⁶ In a qualitative study after coadministration of devil's claw with NSAIDs, the respondents were using a range of drugs that included aspirin, celecoxib, diclofenac, ibuprofen, indomethacin, ketoprofen, metazoal, naproxen, piroxicam, propyphenazon, and rofecoxib. This suggests that the effects observed in the controlled trials may be reasonably extrapolated to a number of anti-inflammatory drugs. In this connection, a 4-month trial compared diacerhein (an unrelated drug of the slow-acting drug for osteoarthritis–[SADOA] class) to devil's claw in 122 osteoarthritis patients. Diacerhein (a prodrug of the anthraquinone rhein, which is an interleukin-1 [IL-1] inhibitor), found fewer adverse effects and less rescue medication needed by the devil's claw group, although the degree of pain reduction was not significantly different. ³⁰ Lipopolysaccharide (LPS)–stimulated COX-2 (and iNOS) messenger ribonucleic acid (mRNA) increases were inhibited by harpagoside through blocking of NF-κB activation of LPS in a human hepatoma cell line model, although the detailed mechanism of inhibition has not been established. ¹⁷

Integrative Therapeutics, Clinical Concerns, and Adaptations

The NSAIDs, including selective COX-2 inhibitors, remain widely used for management of arthritic pain. The adverse effect profile of nonselective NSAIDs is a well-known problem, with gastropathies resulting in considerable expense for hospital care and responsible for about 17,000 deaths per year in the United States from major gastrointestinal bleeding. Emerging data also suggest that the COX-2 inhibitors are not as free from adverse effects as initially believed. ^31,32 Recently, it has become clear that if aspirin (including low dose, i.e., 80 mg/day) or any classic NSAIDs are combined with COX-2 inhibitors, the risk of bleeding is higher than for classic NSAIDs alone. On the economic cost side of the equation, standardized devil's claw and COX-2 inhibitors are probably equal in cost. At this stage, however, the use of devil's claw as adjunctive, or even where possible as an alternative, medication in acute exacerbations of long-standing arthritis should be actively considered. Given that the adverse effect profile of the herb is benign, coadministration may not require professional management because symptom relief is the determining factor for the patient.

theoretical, speculative, and preliminary interactions research, including overstated interactions claims

Citations

1.Boje K, Lechtenberg M, Nahrstedt A. New and known iridoid- and phenylethanoid glycosides from Harpagophytum procumbens and their in vitro inhibition of human leukocyte elastase. Planta Med 2003;69:820-825.View Abstract
2.Weiss R. Herbal Medicine. Meuss A, Translator. 6th ed. Beaconsfield, UK: Beaconsfield Publishers Ltd; 1988.
3.Blumenthal M, Busse W, Goldberg A et al. The Complete German Commission E Monographs. Austin, Texas: American Botanical Council: Integrative Medicine Communications; 1998.
4.ESCOP. Harpagophyti Radix. ESCOP Monographs: The Scientific Foundation for Herbal Medicinal Products. 2nd ed. Exeter, UK: European Scientific Cooperative on Phytotherapy and Thieme; 2003:233-240.
5.Chrubasik S. Addendum to the ESCOP monograph on Harpagophytum procumbens. Phytomedicine 2004; 11:691-695.View Abstract
6.Setty AR, Sigal LH. Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects. Semin Arthritis Rheum 2005;34:773-784.View Abstract
7.Gagnier JJ, Chrubasik S, Manheimer E. Harpgophytum procumbens for osteoarthritis and low back pain: a systematic review. BMC Complement Altern Med 2004;4:13.View Abstract
8.Gagnier J, Vantulder M, Berman B, Bombardier C. Herbal medicine for low back pain. Cochrane Database Syst Rev 2006:CD004504.
9.Fontaine J, Elchami AA, Vanhaelen M, Vanhaelen-Fastre R. [Biological analysis of Harpagophytum procumbens DC. II. Pharmacological analysis of the effects of harpagoside, harpagide and harpagogenine on the isolated guinea-pig ileum (author’s translation)]. J Pharm Belg 1981;36:321-324.View Abstract
10.Grahame R, Robinson BV. Devil’s claw (Harpagophytum procumbens): pharmacological and clinical studies. Ann Rheum Dis 1981;40:632.
11.Whitehouse LW, Znamirowska M, Paul CJ. Devil’s claw (Harpagophytum procumbens): no evidence for anti-inflammatory activity in the treatment of arthritic disease. Can Med Assoc J 1983;129:249-251.
12.Fiebich BL, Heinrich M, Hiller KO, Kammerer N. Inhibition of TNF-α synthesis in LPS-stimulated primary human monocytes by Harpagophytum extract SteiHap 69. Phytomedicine 2001;8:28-30.View Abstract
13.Loew D, Mollerfeld J, Schrodter A et al. Investigations on the pharmacokinetic properties of Harpagophytum extracts and their effects on eicosanoid biosynthesis in vitro and ex vivo. Clin Pharmacol Ther 2001;69:356-364.View Abstract
14.Jang MH, Lim S, Han SM et al. Harpagophytum procumbens suppresses lipopolysaccharide-stimulated expressions of cyclooxygenase-2 and inducible nitric oxide synthase in fibroblast cell line L929. J Pharmacol Sci 2003;93:367-371.View Abstract
15.Kundu JK, Mossanda KS, Na H-K, Surh Y-J. Inhibitory effects of the extracts of Sutherlandia frutescens (L.) R. Br. and Harpagophytum procumbens DC on phorbol ester-induced COX-2 expression in mouse skin: AP-1 and CREB as potential upstream targets. Cancer Lett 2005;218:21-31.View Abstract
16.Moussard C, Alber D, Toubin MM et al. A drug used in traditional medicine, Harpagophytum procumbens: no evidence for NSAID-like effect on whole blood eicosanoid production in human. Prostaglandins Leukot Essent Fatty Acids 1992;46:283-286.View Abstract
17.Huang TH-W, Tran VH, Duke RK et al. Harpagoside suppresses lipopolysaccharide-induced iNOS and COX-2 expression through inhibition of NF-κB activation. J Ethnopharmacol 2006;104:149-155.
18.Chrubasik JE, Lindhorst E, Neumann E et al. Potential molecular basis of the chondroprotective effect of Harpagophytum procumbens. Phytomedicine 2006;13:598-600.View Abstract
19.Circosta C, Occhiuto F, Ragusa S et al. A drug used in traditional medicine: Harpagophytum procumbens DC. II. Cardiovascular activity. J Ethnopharmacol 1984;11:259-274.View Abstract
20.Costa De Pasquale R, Busa G, Circosta C et al. A drug used in traditional medicine: Harpagophytum procumbens DC. III. Effects on hyperkinetic ventricular arrhythmias by reperfusion. J Ethnopharmacol 1985;13:193-199.View Abstract
21.Occhiuto F, Circosta C, Ragusa S et al. A drug used in traditional medicine: Harpagophytum procumbens DC. IV. Effects on some isolated muscle preparations. J Ethnopharmacol 1985;13:201-208.View Abstract
22.Mahomed IM, Ojewole JAO. Anticonvulsant activity of Harpagophytum procumbens DC [Pedaliaceae] secondary root aqueous extract in mice. Brain Res Bull 2006;69:57-62.
23.Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;18:2273-2281.View Abstract
24.Chrubasik S, Conradt C, Black A. The quality of clinical trials with Harpagophytum procumbens. Phytomedicine 2003;10:613-623.View Abstract
25.Chrubasik S, Junck H, Breitschwerdt H et al. Effectiveness of Harpagophytum extract WS 1531 in the treatment of exacerbation of low back pain: a randomized, placebo-controlled, double-blind study. Eur J Anaesthesiol 1999;16:118-129.View Abstract
26.Chrubasik S, Model A, Black A, Pollak S. A randomized double-blind pilot study comparing Doloteffin and Vioxx in the treatment of low back pain. Rheumatology (Oxford) 2003;42:141-148.View Abstract
27.Chrubasik S, Pollak S, Fiebich B. Harpagophytum extracts. Clin Pharmacol Ther 2002;71:104-105.View Abstract
28.Chrubasik S, Sporer F, Dillmann-Marschner R et al. Physicochemical properties of harpagoside and its in vitro release from Harpagophytum procumbens extract tablets. Phytomedicine 2000;6:469-473.View Abstract
29.Chrubasik S, Thanner J, Kunzel O et al. Comparison of outcome measures during treatment with the proprietary Harpagophytum extract doloteffin in patients with pain in the lower back, knee or hip. Phytomedicine 2002;9:181-194.
30.Chantre P, Cappelaere A, Leblan D et al. Efficacy and tolerance of Harpagophytum procumbens versus diacerhein in treatment of osteoarthritis. Phytomedicine 2000;7:177-183.View Abstract
31.Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 2001;286:954-959.View Abstract
32.Zhao SZ, Reynolds MW, Lejkowith J et al. A comparison of renal-related adverse drug reactions between rofecoxib and celecoxib, based on the World Health Organization/Uppsala Monitoring Centre safety database. Clin Ther 2001;23:1478-1491.
33.Shaw D, Leon C, Kolev S, Murray V. Traditional remedies and food supplements: a 5-year toxicological study (1991-1995). Drug Saf 1997;17:342-356.View Abstract
34.Fugh-Berman A, Ernst E. Herb-drug interactions: review and assessment of report reliability. Br J Clin Pharmacol 2001;52:587-595.View Abstract

The information presented in InteractionsGuide™ is provided for healthcare professionals and members of the general public seeking information on healthcare options for educational and reference purposes only. The data is based on published scientific studies, clinical experience, and established usage, with selected sources cited as available for each topic. In considering the information provided healthcare professionals are advised to apply their educational training, clinical experience, and a reasonable standard of care.

InteractionsGuide™ is not intended to provide users with information on the treatment of specific medical conditions outside of the context of the relationship with their healthcare provider. The therapeutic options contained in InteractionsGuide™ will not be appropriate for all individuals nor will the therapeutic outcomes suggested necessarily occur in all individuals. Further, different individuals with the same symptoms or diagnosis often require differing treatments.

Users of InteractionsGuide™ who are not health care professionals are advised to consult their physician, appropriately-trained healthcare practitioner, and/or pharmacist before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using any supplements, herbs, remedies, dietary changes or other forms of self-care. Complete information about the effects of specific nutrients, herbs, dietary supplements and possible interactions between such substances and a prescription or over-the-counter medication should be confirmed with the prescribing physician, a pharmacist, or both. Health Resources Unlimited, Inc. does not recommend specific substances, therapies or practitioners.

Please review the Terms and Conditions and Licensing Agreement for further information and the terms and conditions governing your use of InteractionsGuide.com.

© 2008-2010 MedicineWorks.com, a division of Health Resources Unlimited, Inc., and its licensors. All rights reserved.
The Interactions logo and InteractionsGuide are trademarks of Health Resources Unlimited, Inc.
All other products and brands mentioned are trademarks or registered trademarks of their respective trademark owners.

User login