Potential for Interactions Between Dietary Supplements and Prescription Medications a

Transcription

1 CLINICAL RESEARCH STUDY Potentil for Interctions Between Dietry Supplements nd Prescription Medictions Amit Sood, MD, MSc, Rich Sood, MD, b Frncis J. Brinker, ND, Rvneet Mnn, MBBS, c Lur L. Loehrer, Dietlind L. Whner-Roedler, MD, MSc Division of Generl Internl Medicine, Myo Clinic, Rochester, Minn; b Progrm in Integrtive Medicine, University of Arizon College of Medicine, Tucson; c Christin Medicl College, Ludhin, Punjb, Indi. ABSTRACT PURPOSE: The objective of this study ws to ssess the frequency of cliniclly significnt interctions cused by concurrent use of dietry supplements nd prescription mediction. METHODS: We conducted cross-sectionl, point-of-cre survey nd combined the findings with review of ptient medicl records. Ptients treted t Myo Clinic (Rochester, Minn) in 6 different specilty clinics were surveyed for their use of dietry supplements. Concurrent use of prescription medictions ws obtined from ptients medicl records. We used the Lexi-Interct online mediction nd dietry supplement interction nlysis progrm to ssess the potentil clinicl significnce of ech interction. RESULTS: We surveyed 1818 ptients; 1795 responded (overll response rte of 98.7%) nd 710 (39.6%) reported use of dietry supplements. In totl, 107 interctions with potentil clinicl significnce were identified. The 5 most common nturl products with potentil for interction (grlic, vlerin, kv, ginkgo, nd St John s wort) ccounted for 68% of the potentil cliniclly significnt interctions. The 4 most common clsses of prescription medictions with potentil for interction (ntithrombotic medictions, sedtives, ntidepressnt gents, nd ntidibetic gents) ccounted for 94% of the potentil cliniclly significnt interctions. No ptient ws hrmed seriously from ny interction. CONCLUSIONS: A smll number of prescription medictions nd dietry supplements ccounted for most of the interctions. The ctul potentil for hrm ws low Elsevier Inc. All rights reserved. The Americn Journl of Medicine (2008) 121, KEYWORDS: Adverse effects; Complementry medicine; Dietry supplements; Herbl products; Interctions; Mediction 3-6 Complementry nd lterntive medicine tretments re cse series or individul cse reports. The ctul potentil for used by more thn two-thirds of the US popultion, nd interction in lrge group of ptients is not well understood. 1 dietry supplements re some of the most populr tretments. This study ws designed to ssess the most common Most of these tretments re not regulted tightly by the UScliniclly significnt interctions mong ptients who concurrently use dietry supplements nd prescription medic- Food nd Drug Administrtion nd re vilble without prescription from physicin. Severl tretments hve the tions. The study involved point-of-cre survey of ptients potentil for dverse effects, including mediction interctions. treted in 6 different specilty clinics. The potentil for Dietry supplements typiclly hve multiple ctive phrmcologic constituents. Thus, the likelihood of interctions of interctions. interctions ws defined on the bsis of published evidence is incresed when compred with the likelihood of interctions between 2 prescription medictions. Currently, most 2 interctions involving dietry supplements re reported s PATIENTS AND METHODS Requests for reprints should be ddressed to Dietlind L. Whner- Roedler, MD, MSc, Division of Generl Internl Medicine, Myo Clinic, 200 First Street SW, Rochester, MN E-mil ddress: whnerroedler.dietlind@myo.edu Survey An 85-question survey ws designed to determine the use of complementry nd lterntive medicine therpies during the 6 months before the survey dte. Survey questions exmined use of 52 listed dietry supplements, nd text entry field /$ -see front mtter 2008 Elsevier Inc. All rights reserved. doi: /j.mjmed

2 208 The Americn Journl of Medicine, Vol 121, No 3, Mrch 2008 ws provided for ptients to document use of supplements not included in the survey. Detils of the survey hve been described previously. 7,8 Briefly, point-of-cre survey ws dministered to 1818 ptients in 6 different specilty clinics t Myo Clinic (Rochester, Minn) from September 2002 through July The 6 specilty clinics were the Deprtments of Generl Internl Medicine, Oncology, nd Physicl Medicine; the Fibromylgi Clinic; the Preopertive Clinic; nd the Spine Center. These 6 specilties were chosen becuse of the high volume of ptients nd becuse the ptients in these specilties were more likely to use complementry nd lterntive medicine tretments. A study ssistnt ws vilble to nswer questions nd fcilitte survey completion. Dietry supplements were defined s products contining herbs or other botnicl components, mino cids, enzymes, orgn tissues, glndulr extrcts, or metbolites. Vitmins nd minerls were not included in this definition. Prescription medictions were defined s phrmcologic gents tht were vilble in the United Sttes only by prescription from physicin. Aspirin lso ws included in this definition. For the purpose of this study, we nlyzed the responses bout the use of 52 listed dietry supplements seprtely from the dditionl products listed by the ptients in the free text re. Informed consent ws obtined from ech ptient, nd the study ws pproved by the Myo Clinic Institutionl Review Bord. CLINICAL SIGNIFICANCE Use of Prescription Mediction Ptients t Myo Clinic hve single integrted medicl record tht is shred by ll helth cre providers, thus ensuring complete nd consistent dt bout the prescription mediction usge. The ptient medicl records were reviewed by 3 study investigtors (AS, RS, DLW-R) fter confirming reserch uthoriztion for ech ptient. We exmined concurrent use of prescription mediction during the 6-month period covered by the survey of dietry supplement usge. Medicl records lso were reviewed to determine whether ny ptient ws seriously hrmed s the result of n interction between the dietry supplement nd prescription mediction. Serious hrm ws defined s hospitliztion for ggrvtion of ny underlying medicl condition or for new medicl problem tht ws direct result of the interction. Electronic medicl informtion ws vilble for ll ptients who completed the survey. We collected bseline dt, which included ptient demogrphics, self-perceived stress level (scle, 1-5; 5 ws the highest level of stress), nd number of symptoms checked on the review of systems questionnire, stndrd prt of our electronic medicl record. An individul Use of dietry supplements is common in the US popultion. Despite high prevlence of potentil interctions between dietry supplements nd prescription medictions, the ctul potentil for hrm is low. A smll number of prescription medictions nd dietry supplements ccount for most potentil interctions. Antithrombotic medictions were most likely to interct with dietry supplements. cse report form ws creted for ech prticipnt. On the bsis of the prticipnts reported use of dietry supplements, ech report included the list of potentil dietry supplement mediction interctions. Potentil Mediction Interctions The informtion on the potentil interctions ws obtined by serching the MEDLINE dtbse (using PubMed), 9 the Nturl Medicines Comprehensive Dtbse, 10 nd published textbook. 11 Interctions from the Nturl Medicines Comprehensive Dtbse were included if published reference ws vilble. In the MEDLINE serches, we used generic nmes of the supplements s key serch terms. All clinicl trils, cse reports, nd cse series for ech product were reviewed to crete mster list of potentil mediction interctions. The potentil for interction between 2 dietry supplements ws not considered in this study becuse of the reltively limited evidence-bsed informtion bout these interctions. Clinicl Significnce of Interctions Clinicl significnce of individul interctions ws ssessed using the Lexi-Interct online mediction nd dietry supplement interction nlysis progrm, which provided upto-dte informtion. 12 The progrm provided summry of mediction interctions with n ssigned risk rting (rnge, A-D nd X). The risk rting nd its interprettion were s follows: A no known interction; B no ction needed (potentil for interction but of no clinicl significnce); C monitor therpy (potentil for interction tht my be of clinicl significnce nd needs monitoring); D consider therpy modifiction (potentil for interction tht my be of clinicl significnce nd needs close monitoring, chnge in therpy, or both); nd X void combintion. Dt Anlysis Differences in bseline chrcteristics between prticipnts who did nd did not report use of dietry supplements were compred using the chi-squred nd log-rnk tests. P vlues.05 were considered sttisticlly significnt. Sttisticl nlysis ws performed using the SAS softwre pckge, version (SAS Institute, Cry, NC). RESULTS Survey Response Rte The overll response rte to the survey ws 98.7% (1795/ 1818). Of the 1795 respondents, 710 ptients (39.6%) re-

3 Sood et l Nturl Product Conventionl Mediction Interction 209 ported use of dietry supplements. These dt were reported previously. 7,8 Eleven ptients did not hve informtion bout the use of prescription medictions in their electronic medicl records, nd those ptients were excluded from the interction nlysis. Thus, the finl smple comprised 699 ptients. Of these, the medicl records of 185 (26.5%) showed use of dietry supplements. Bseline Comprisons The men ges were similr between prticipnts using dietry supplements nd prticipnts not using these products (Tble 1). Women were more likely to use dietry supplements thn men. Ptients using dietry supplements hd more symptoms on the review of systems thn ptients not tking these products. The men stress level ws sttisticlly different between the 2 groups (P.008), but the ctul difference of 0.1 ws not cliniclly meningful. The men number of prescription medictions per ptient ws not significntly different between the 2 groups (P.71). Potentil Mediction Interctions The most common dietry supplements with potentil for interction were grlic, vlerin, kv, ginkgo bilob, St John s wort, glucosmine, ginger, nd ginseng (Tble 2). The most common prescription mediction clsses with potentil for interction were ntithrombotic medictions, sedtives, ntidepressnt gents, nd ntidibetic gents (Tble 3). In totl, 369 potentil interctions were identified mong 236 ptients. Of these, 107 interctions were considered to hve potentil clinicl significnce (risk rting of C or D)(Tble 2). No potentil interctions resulted in serious hrm to ny ptient during the study period. DISCUSSION Principl Findings The present study showed tht pproximtely 2 of 5 surveyed ptients reported use of dietry supplements. In totl, 369 potentil interctions were identified mong 236 ptients. Of these interctions, only 107 (29%) hd potentil clinicl significnce. The 5 most commonly used dietry supplements with potentil for interction ccounted for 68% of ll possible interctions. The 4 most common prescription mediction clsses with potentil for interction ccounted for 94% of the possible interctions. No ptient hd serious hrm from the possible interctions during the study period (ie, no ptient ws hospitlized for n ggrvted underlying medicl condition or for new medicl problem tht ws cused by n interction). Use of dietry supplements ws documented in only 26% of the medicl records. Study Strengths nd Weknesses The study hd severl strengths, including lrge smple size, excellent response rte to the survey, inclusion of ptients from different specilty groups, nd vilbility of Tble 1 Chrcteristic Bseline Chrcteristics Use of Dietry Supplements* Yes (n 710) No (n 1085) P Vlue Age, yers.56 Men SD Medin (rnge) 58.5 (18-90) 59.0 (18-95) Sex, no. (%).003 Men (n 704) 248 (35) 456 (65) Women (n 1091) 462 (42) 629 (58) Specilty, no. (%) Generl internl 103 (33) 205 (67) medicine (n 308) Oncology 123 (40) 181 (60) (n 304) Physicl medicine 94 (32) 201 (68) (n 295) Fibromylgi 147 (51) 141 (49) Preopertive clinic 127 (42) 175 (58) (n 302) Spine center (n 298) 116 (39) 182 (61) Stress level.008 Men SD Medin (rnge) 3.0 (1-5) 3.0 (1-5) Symptoms, no..001 Men SD Medin (rnge) 9.0 (0-59) 7.0 (0-46) Prescription.71 medictions, no. Men SD Medin (rnge) 3.0 (0-18) 3.0 (0-22) *Excludes use of vitmins nd minerls. P vlues were clculted by compring mens only. Self-perceived stress level ws rted from 1 (low) through 5 (high). complete dt for most ptients. These strengths increse our confidence in the vlidity of the study results. Our study hd severl weknesses. First, like most surveys, ours did not eliminte the possibility of recll bis. Recll bis ws minimized, however, by providing the prticipnts with the nmes of ll commonly used products. Second, the medicl record informtion bout prescription mediction use my hve been incomplete or inccurte. To increse the ccurcy, we checked for documenttion from multiple cre providers t our institution nd from ptientprovided informtion tht ws scnned into the medicl records (ech ptient t Myo Clinic hs single integrted electronic medicl record). We lso were ble to obtin clinicl dt nd current list of medictions for 98.5% of our ptients (699 of 710), thus incresing the vlidity of our findings. Third, the existing informtion bout potentil interctions between dietry supplements nd prescription medictions ws incomplete. We relied primrily on the medicl literture to identify dverse interctions docu-

4 210 The Americn Journl of Medicine, Vol 121, No 3, Mrch 2008 Tble 2 Potentil Interctions of Dietry Supplements nd Prescription Medictions* Dietry Supplement Prescription Mediction Risk Ctegory C, No. of Ptients Risk Ctegory D, No. of Ptients Grlic Antipltelet gent 22 Wrfrin 3 Vlerin Sedtive 15 Kv Sedtive 7 Heptotoxic mediction 3 Ginkgo bilob Antipltelet gent 9 Wrfrin 1 St John s wort Antidepressnt gent 8 Trmdol 1 Orl contrceptive 1 Glucosmine Wrfrin 9 Ginger Antipltelet gent 7 Ginseng Antidibetic gent 6 Bilberry Antidibetic gent 3 Evening primrose oil Antipltelet gent 2 Feverfew Antipltelet gent 2 Tumeric Antipltelet gent 2 5-hydroxy-l-tryptophn Antidepressnt gent 2 Dong qui Antipltelet gent 1 Hwthorne Antihypertensive gent 1 Olive lef Antihypertensive gent 1 Pu d rco Antipltelet gent 1 *Excludes use of vitmins nd minerls. Potentil interctions in this ctegory my hve clinicl significnce. Ptients should be monitored. Potentil interctions in this ctegory my hve clinicl significnce. Ptients should be monitored closely or hve the therpy modified. mented in humns. However, these interctions my not lwys be direct effect of dietry supplement nd could be n effect of dulternts in the supplement (eg, hevy metls or pesticides), prescription medictions, or misidentified plnts Finlly, even though we surveyed ptients in 6 specilty clinics, the generlizbility of our study findings to the community setting might be limited. Comprison with Other Studies Use of dietry supplements is extremely common in the United Sttes. In the lrgest point-of-cre, popultion-bsed Tble 3 Prescription Medictions Tht Commonly Showed Cliniclly Significnt Interctions with Dietry Supplements* Mediction Clss No. of Ptients Antithrombotic mediction Wrfrin 13 Antipltelet gent 46 Sedtive 22 Antidepressnt gent 10 Antidibetic gent Insulin 3 Orl mediction 6 Other 7 *Excludes use of vitmins nd minerls. Antihypertensive gents, heptotoxic medictions, orl contrceptives, nd trmdol. survey to dte, of 31,044 surveyed ptients, 18.9% reported use of dietry supplements. 1 The higher proportion of 39.6% in our study likely resulted from combintion of referrl bis nd inclusion of ptients with medicl conditions such s cncer, fibromylgi, nd chronic pin, which incresed the likelihood of use of dietry supplements. In 1999, point-of-cre survey sked 458 vetern outptients bout their current use of dietry supplements. 18 Intke of prescription phrmceuticls ws identified through Veterns Administrtion phrmcy dtbse serch. A totl of 197 ptients reported using dietry supplements. The potentil for prescription mediction dietry supplement interction existed in 45% of these ptients (89/197). The higher estimte obtined in tht study likely is ttributble to the inclusion of vitmins nd minerls when considering possible interctions. The most common products with potentil for interction in tht study re mong the most likely products for interction in the present study (ie, grlic, ginseng, nd gingko bilob). Other studies hve documented concurrent use of herbl products nd prescription medictions. In ntionl survey conducted in the United Sttes, concurrent use of herbl remedies nd prescription medictions ws documented in 18.4% of prescription mediction users. 19 However, the potentil for interctions ws not ddressed. In British study involving 271 prticipnts older thn 50 yers, men of 5.91 supplements nd men of 2.26 prescription medictions were used concurrently. 20 However, specific evl-

5 Sood et l Nturl Product Conventionl Mediction Interction 211 ution of the potentil for interctions ws not reported. In smller survey of 76 ptients with cncer, 27% were reported to hve potentil for herbl products or vitmins 21 intercting with chemotherpeutic gents. In Cndin study of 195 ptients older thn 65 yers, 33 current users of 22 herbl medicines were identified. Among those ptients, 11 potentil herb-mediction interctions were identified in 9 ptients (27%). In Cndin study involving seniors with osteorthritis, 214 potentil interctions were identified. Of these, 30 were considered cliniclly significnt. Among ll prescription medictions, ntithrombotic gents re the best-described clss of medictions with 24,25 potentil for intercting with herbl products. In study involving serch of electronic dtbses, wrfrin ws the most common mediction documented to hve potentil 14 for interction with herbl products. Findings from the present study, which surveyed brod ptient popultion, confirmed tht ntithrombotic medictions indeed were the ones most likely to interct with dietry supplements. However, the ctul potentil for hrm in quntittive terms is unknown becuse well-designed studies to evlute dverse effects would be unethicl nd not fesible. Until further dt re vilble, ptients receiving ntithrombotic medictions generlly should be counseled to void dietry supplements known to interct with wrfrin or known to hve n ntipltelet effect. Distinguishing between rel potentil for hrm nd purely specultive interction is importnt. Despite high prevlence of the potentil for interction, no serious dverse events such s hospitliztion or serious bleeding due to interctions were documented in ny of our ptients. Some interctions tht were included in the study could be considered specultive. However, it might be prudent to tke blnced but cutious pproch, even if some cusend-effect reltionships re not well estblished, nd prticulrly if the purported tretments re not proven to hve beneficil biologic effect. Furthermore, dietry supplements often re intended to be tken for long periods, nd given the high prevlence of their use, even smll potentil for hrm might hve public helth consequences. In summry, the present study showed tht smll number of prescription medictions nd dietry supplements ccounted for most potentil interctions. This informtion likely will help educte ptients nd physicins bout these potentil interctions. ACKNOWLEDGMENT Editing, proofreding, nd reference verifiction were provided by the Section of Scientific Publictions, Myo Clinic. References 1. Brnes PM, Powell-Griner E, McFnn K, Nhin RL. Complementry nd lterntive medicine use mong dults: United Sttes, Adv Dt. 2004;343: Izzo AA. Herb-drug interctions: n overview of the clinicl evidence. Fundm Clin Phrmcol. 2005;19: Willimson EM. Interctions between herbl nd conventionl medicines. Expert Opin Drug Sf. 2005;4: Izzo AA, Ernst E. Interctions between herbl medicines nd prescribed drugs: systemtic review. Drugs. 2001;61: Fugh-Bermn A. Herb-drug interctions. Lncet. 2000;355: [Errtum in: Lncet. 2000;355:1020]. 6. Hu Z, Yng X, Ho PC, et l. Herb-drug interctions: literture review. Drugs. 2005;65: Whner-Roedler DL, Elkin PL, Lee MC, et l. Complementry nd lterntive medicine: use by ptients seen in different specilty res in tertiry-cre centre. Evid Bsed Integr Med. 2004;1: Whner-Roedler DL, Elkin PL, Vincent A, et l. Use of complementry nd lterntive medicl therpies by ptients referred to fibromylgi tretment progrm t tertiry cre center. Myo Clin Proc. 2005;80: Entrez PubMed. Ntionl Center for Biotechnology Informtion. Avilble t: Accessed June Nturl Medicines Comprehensive Dtbse. Stockton, CA: Therpeutic Reserch Fculty, c Avilble t: nturldtbse.com. Accessed June Brinker FJ. Herb Contrindictions nd Drug Interctions: With Extensive Appendices Addressing Specific Conditions, Herb Effects, Criticl Medictions, nd Nutritionl Supplements, 3 rd edn. Sndy, OR: Eclectic Medicl Publictions; Lexi-Comp Online Hospitl/Institutionl Solutions. Lexi-Comp, Inc.; c2007. Avilble from: Accessed Februry Ko RJ. Adulternts in Asin ptent medicines. N Engl J Med. 1998; 339: Fugh-Bermn A, Ernst E. Herb-drug interctions: review nd ssessment of report relibility. Br J Clin Phrmcol. 2001;52: [Errtum in: Br J Clin Phrmcol. 2002;53:449P]. 15. Tyler VE. Product definition deficiencies in clinicl studies of herbl medicines. Sci Rev Altern Med. 2000;4: But PP. Herbl poisoning cused by dulternts or erroneous substitutes. J Trop Med Hyg. 1994;97: Gertner E, Mrshll PS, Filndrinos D, et l. Complictions resulting from the use of Chinese herbl medictions contining undeclred prescription drugs. Arthritis Rheum. 1995;38: Peng CC, Glssmn PA, Trilli LE, et l. Incidence nd severity of potentil drug-dietry supplement interctions in primry cre ptients: n explortory study of 2 outptient prctices. Arch Intern Med. 2004;164: Eisenberg DM, Dvis RB, Ettner SL, et l. Trends in lterntive medicine use in the United Sttes, : results of follow-up ntionl survey. JAMA. 1998;280: Cnter PH, Ernst E. Herbl supplement use by persons ged over 50 yers in Britin: frequently used herbs, concomitnt use of herbs, nutritionl supplements nd prescription drugs, rte of informing doctors nd potentil for negtive interctions. Drugs Aging. 2004;21: McCune JS, Htfield AJ, Blckburn AA, et l. Potentil of chemotherpy-herb interctions in dult cncer ptients. Support Cre Cncer. 2004;12: Dergl JM, Gold JL, Lxer DA, et l. Potentil interctions between herbl medicines nd conventionl drug therpies used by older dults ttending memory clinic. Drugs Aging. 2002;19: Putnm W, Lwson B, Fril D, et l. Potentil for drug interctions in seniors with osteorthritis. Cn Fm Physicin. 2006;52: Heck AM, DeWitt BA, Lukes AL. Potentil interctions between lterntive therpies nd wrfrin. Am J Helth Syst Phrm. 2000;57: Norred CL, Brinker F. Potentil cogultion effects of preopertive complementry nd lterntive medicines. Altern Ther Helth Med. 2001;7:58-67.