Although uncommon for herbal supplements pre- pared in the United States, herbal supplements from Asia and Indian Ayurvedic medicine may be contami- nated with Western drugs. In this case, drug overdose may occur in an unsuspecting person taking such herbal supplements because the presence of such Western drugs is not disclosed in package inserts. Some Chinese herbal supplements intended for diabetic patients may be contaminated with hypoglycemic agents, and taking such products may cause severe hypoglycemia. This topic was discussed previously.
However, Asian herbal supplements intended to treat other symptoms may also be contaminated with Western drugs. In one report, the authors analyzed 2069 samples of traditional Chinese medicines collected from eight hospitals in Taiwan, and in 618 samples (23.7%) they found undeclared Western pharmaceuti- cals, most commonly caffeine, acetaminophen, indome- tacin, hydrochlorothiazide, and prednisolone [90,91].
Most of these herbal supplements were used to allevi- ate pain, inflammation, or symptoms of arthritis.
Pharmaceuticals such as acetaminophen, indometacin, and prednisolone can achieve these therapeutic effects.
However, contaminated herbal supplements can also cause severe drug overdoses due to adulteration of the supplement with a drug.
CASE REPORT A 33-year-old female with an 8-year history of epilepsy was managed with valproate, carba- mazepine, and phenobarbital but was never prescribed phenytoin. One month before admission, she started
consuming three proprietary Chinese medicines in addition to her prescription medicines. She followed instructions for taking Chinese medicines for almost 1 month and then became comatose and was admitted to the hospital. Serum drug level assays on the second day of admission surprisingly showed a toxic phenytoin level of 48.5μg/mL (therapeutic range, 10 20μg/mL).
She was treated conservatively, and after 10 days her clinical signs of phenytoin toxicity disappeared and she did not suffer any neurological damage. Analyses of three Chinese proprietary medicines showed the pres- ence of 41 mg of phenytoin in jue dian shen ying wan (orange capsule), whereas the other two Chinese medi- cines were adulterated with carbamazepine and valpro- ate. The patient consumed six orange capsules for almost 1 month, causing her severe phenytoin toxicity.
Unfortunately, the manufacturer’s information stated that these preparations only contained Chinese medi- cines for controlling epilepsy[92].
Savaliya et al. [93] reported that Indian Ayurvedic medicines may be contaminated with both steroidal and nonsteroidal anti-inflammatory drugs. Dexamethasone and diclofenac were detected in 10 Ayurvedic products out of 58 preparations analyzed. In addition, piroxicam was detected in 1 product, and dexamethasone alone was detected in 1 product. Many Indian Ayurvedic med- icines are also contaminated with heavy metals such as lead, arsenic, or mercury either due to the manufactur- ing process or because the heavy metal (known as bhas- ma in Sanskrit) is a component of Ayurvedic medicine.
CASE REPORT A 58-year-old female from India who was residing in the United States presented to the emergency department with a 10-day history of pro- gressively worsening postprandial lower abdominal pain and nausea accompanied by vomiting. She was healthy but suffered from well-controlled non-insulin- dependent diabetes mellitus and hypertension. On admission, her physical exam was unremarkable except for abdominal tenderness in the lower quadrants.
Laboratory tests indicated a normochromic normocytic anemia with hemoglobin of 7.7 g/dL, hematocrit of 22.6%, and mean corpuscular volume (MCV) of 87 fL with normal iron status. A computed tomography scan of the abdomen and pelvis showed no specific abnor- malities and the patient was discharged; however, she returned to the hospital 5 days later with worsening abdominal pain, nausea, and bilious vomiting. Physical exam was remarkable for diffuse abdominal tenderness and pale conjunctivae. The laboratory evaluation was notable for anemia with hemoglobin of 8.8 g/dL, hematocrit of 23.5%, MCV of 87 fL, and corrected retic- ulocyte count of 7%. The patient was admitted, and review of her peripheral blood smear demonstrated normochromic, normocytic anemia with extensive TABLE 7.5 Other Clinically Significant Drug Herb Interactions
Herb Interacting Drugs Effect
Ginkgo biloba Aspirin, ibuprofen Bleeding
Omeprazole Reduced plasma level Ritonavir Reduced plasma level
Trazodone Coma
Phenytoin, valproic acid Reduced concentration
Garlic Saquinavir Reduced effect
Chlorpropamide Hypoglycemia
Ibuprofen Bleeding
Ginseng Phenelzine Insomnia, headache,
irritability Kava Alprazolam, paroxetine Lethargic state
Levodopa Reduced effect
89
ADULTERATION OF HERBAL SUPPLEMENTS WITH WESTERN DRUGS
coarse basophilic stippling of the erythrocytes. Her heavy metal screening tests showed an elevated blood lead level of 102μg/dL (normal, ,10μg/dL). Zinc pro- toporphyrin was subsequently found to be elevated at 912μg/dL (normal, ,35μg/dL). Her diagnosis was severe lead poisoning. At that point, the patient dis- closed that she had been taking an Indian Ayurvedic medicine called Jambrulin obtained from Unjha phar- macy through a family member in India. She had been taking two pills daily over a period of 5 or 6 weeks in an effort to enhance control of her diabetes. She stopped taking the medication approximately 2 weeks prior to admission because of the abdominal pain. The patient was instructed not to take Jambrulin and received dimercaptosuccinic acid, an oral lead chelator, at a dose of 10 mg/kg three times a day for 5 days fol- lowed by 10 mg/kg twice a day for 2 weeks. At the end of chelation therapy, her blood lead level was signifi- cantly decreased to 46μg/dL and her symptoms were resolved. When Ayurvedic medicine pills were tested, they showed approximately 21.5 mg of lead per pill.
The pills were also sent to the Connecticut Department of Public Health Adult Blood Lead Epidemiology and Surveillance Program and Public Health Laboratory and were found to contain approximately 3.5% lead by weight or 35,000μg/g[94].
Heavy metals and pesticides are also frequently present as contaminants in commonly prescribed raw Chinese herbal medicines. Harris et al. [95] reported that out of 334 samples representing 126 different Chinese herbal medicines analyzed, all 334 samples contained at least one heavy metal (lead, arsenic, chro- mium, mercury, or cadmium), whereas 115 samples (34%) had detectable levels of all five heavy metals tested. In addition, 42 different pesticides were detected in 108 samples (36.7%). It is also possible that poisoning after consuming raw herbal supplement may occur due to mistaken identity of the plant. Linet al.[96]reported an outbreak of foxglove leaf poisoning when nine peo- ple mistakenly drank tea prepared from foxglove leaves instead of drinking tea made from comfrey leaves because comfrey leaves resemble foxglove leaves.
Significant cardiac toxicity developed in three indivi- duals, and digoxin concentrations varied from 4.4 to 135.9 ng/mL in these nine individuals. Patients were also treated with Digibind, and all patients recovered.
CONCLUSIONS
The popularity of herbal remedies among the gen- eral population is on the rise, and such practice also increases the risk of herbal supplement-induced liver damage, other organ damage, as well as drug herb interactions. Because of the perception that herbal
supplements are safe, the majority of people do not disclose their use of herbal supplements to their health care professionals. Mehta et al.[97]reported that over- all, only 33% of herbal and dietary supplement users reported disclosing their use of herbal supplements to their conventional health care providers. Therefore, the clinical laboratory may play an important role in help- ing clinicians to identify a potential drug herb interac- tion. For example, abnormal liver function tests in a healthy individual during a routine physical examina- tion may indicate use of kava or other herbal supple- ments known to cause liver damage. In addition, an elevated cholesterol level in a patient taking statin, which controlled his or her cholesterol level in the past, may be indicative of lower efficacy of the statin drug due to its lower serum levels secondary to a drug herb interaction. Similarly, hypoglycemia in a patient receiving a hypoglycemic agent may also be related to a drug herb interaction. If during routine drug monitoring, the observed drug level is signifi- cantly lower than the previous measurements and if noncompliance can be ruled out, it may be an indica- tion of a potential drug herb interaction. The most probable cause is use of St. John’s wort, and on discon- tinuation of St. John’s wort, the drug level usually returns to pre-herbal supplement use levels within 2 weeks. Similarly, observing an unusual INR during routine monitoring of a patient taking warfarin is also indicative of a potential interaction between warfarin and an herbal supplement[98].
In addition, many drugs that are not routinely mon- itored also interact with herbal supplements, and these herb drug interactions are more difficult to detect by laboratory test. Because of the serious consequences of treatment failure from drug herb interactions, trans- plant recipients, patients receiving HAART for AIDS treatment, as well as patients receiving warfarin or any related anticoagulants must refrain from using any herbal supplements.
References
[1] Calapai G. European legislation on herbal medicines: a look into the future. Drug Saf 2008;31:428 31.
[2] Moss K, Boon H, Ballantyne P, Kachan N. New Canadian natu- ral health product regulations: a qualitative study on how CAM practitioners perceive they will be impacted. BMC Complement Altern Med 2006;10(6):18.
[3] Mahady GB. Global harmonization of herbal health claims.
J Nutr 2001;131:1120S 3S.
[4] Kelly JP, Kaufman DW, Kelley K, Rosenberg L, et al. Recent trends in use of herbal and other natural products. Arch Intern Med 2005;165:281 6.
[5] Jha V. Herbal medicines and chronic kidney disease.
Nephrology 2010;15:10 17.
[6] Bent S. Herbal medicine in the United States: review of efficacy, safety and regulation. J Gen Intern Med 2008;23:854 9.
[7] Egan B, Hodgkins C, Shepherd R, Timotijevic L, et al. An over- view of consumer’s attitudes and beliefs about food supple- ments. Food Funct 2011;2:747 52.
[8] Jamieson DD, Duffield PH, Cheng D, Duffield AM. Composition of central nervous system activity of the aqueous and lipid extract of kava (Piper methysticum). Arch Int Pharmacodyn 1989;301:66 80.
[9] Scherer J. Kava-Kava extract in anxiety disorders: an outpatient observational study. Adv Ther 1998;15:261 9.
[10] Li XZ, Ramzan I. Role of Ethanol in Kava Hepatotoxicity Phytother Res 2010;24:475 80.
[11] Teschke R, Sarris J, Schwetzer I. Kava hepatotoxicity in tradi- tional and modern use: the presumed pacific kava paradox hypothesis revisited. Br J Clin Pharmacol 2012;73:170 4.
[12] Rowe A, Zhang LY, Ramzan I. Toxicokinetics of kava. Adv Pharmacol Sci 2011;326724 (open access journal).
[13] Escher M, Desmeules J. Hepatitis associated with kava, a herbal remedy. Br Med J 2001;322:139.
[14] Jappe U, Frankle I, Reinhold D, Gollnick HP. Sebotrophic drug reaction resulting from kava-kava extract therapy; A new entity?. J Am Acad Dermatol 1998;38:104 6.
[15] Almedi JC, Grimsley EW. Coma from the health food store:
interaction between kava and alprazolam. Ann Intern Med 1996;125:940 1.
[16] Christl SU, Seifert A, Seeler D. Toxic hepatitis after consump- tion of traditional kava preparation. J Travel Med 2009;16:55 6.
[17] Cow PJ, Connelly NJ, Hill RL, Crowley P, et al. Fatal fulminant hepatic liver failure induced by a natural therapy containing kava. Med J Aust 2003;178:442 3.
[18] Yeong ML, Swinburn B, Kennedy M, Nicholson G. Hepatic veno-occlusive disease associated with comfrey ingestion.
J Gastroenterol Hepatol 1990;5:211 14.
[19] Roulet M, Laurini R, Rivier L, Calame A. Hepatic veno- occlusive disease in newborn infant of a woman drinking herbal tea. J Pediatr 1988;112:433 6.
[20] Seeff LB. Herbal hepatotoxicity. Clin Liver Dis 2007;11:577 96.
[21] Kouzi SA, McMurtry RJ, Nelson SD. Hepatotoxicity of german- der (Teucrium chamaedrysL) and one of its constituent neoclero- dane diterpenes teucrin a in the mouse. Chem Res Toxicol 1994;7:850 6.
[22] Zhou SF, Xue CC, Yu XQ, Wang G. Metabolic activation of herbal and dietary constituents and its clinical and toxicological implications: an update. Curr Drug Metab 2007;8:526 53.
[23] Laliberte L, Villeneuve JP. Hepatitis after use of germander, a herbal remedy. Can Med Assoc J 1996;154:1689 92.
[24] Sheikh NM, Philen RM, Love LA. Chaparral associated hepato- toxicity. Arch Intern Med 1997;157:913 19.
[25] Nisbet BC, O’Connor RE. Black cohosh induced hepatitis. Del Med J 2007;79:441 4.
[26] Anderson IB, Mullen WH, Meeker JE, Khojasteh-Bakht SC, et al. Pennyroyal toxicity: measurement of toxic metabolites levels in two cases and review of literature. Ann Intern Med 1996;124:726 34.
[27] Favreau JT, Ryu ML, Braunstein G, Orshansky G, et al. Severe hepatotoxicity associated with use of dietary supplement. Ann Intern Med 2002;136:590 5.
[28] SungHee Kole A, Jones HD, Christensen R, Gladstein J. A case of Kombucha tea toxicity. J Intensive care med 2009;24:205 7.
[29] Whiting PW, Clouston A, Kerlin P. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust 2002;177:440 3.
[30] Jorge OA, Jorge AD. Hepatotoxicity associated with the inges- tion of Centella Asiatica. Rev Esp Enferm Dig 2005;97:115 24.
[31] Vanhaelen M, Vanhaelen-Fastre R, Nut P, et al. Rapidly pro- gressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herb. Lancer 1993;341:387 91.
[32] Chang CH, wand YM, Yang AH, Chiang SS. Rapidly progres- sive intestinal renal fibrosis associated with Chinese herbal medicines. Am J Nephrol 2001;21:441 8.
[33] Gold LS, Slone TH. Aristolochic acid, an herbal carcinogen sold on the web after FDA alert. N Engl J Med 2003;349:1576 7.
[34] Kong PI, Chiu YW, Kuo MC, Chen Sc, et al. Aristolochic acid nephropathy due to herbal drug intake manifested differently as Fanconi’s syndrome and end stage renal failure in a 7-year follow up. Clin Nephrol 2008;70:537 41.
[35] Jellin J, Gregory P, Batz F , et al. Pharmacist’s letter/prescriber’s letter. Natural medicines comprehensive database. 4th edition Stockton, CA: Therapeutic Research Faculty; 2002.
[36] Blowey DL. Nephrotoxicity of over the counter analgesics, nat- ural medicines, and illicit drugs. Adolesc Med 2005;16:31 43.
[37] Myhre MJ. Herbal remedies, nephropathies and renal disease.
Nephron Nurs J 2000;27:473 8.
[38] Chau W, Ross R, Li JY, Yong TY, et al. Nephropathy associated with use of a Chinese herbal product containing aristolochic acid. Med J Aust 2011;194:367 8.
[39] Shaohua Z, Ananda S, Ruxia Y, Liang R, et al. Fatal renal fail- ure due to Chinese herb “GuanMu Tong” (Aristolochia manshur- iensis): autopsy finding and review of literature. Forensic Sci Int 2010;199:e5 7.
[40] Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care 2003;26:1277 94.
[41] Serraclara A, Hawkins F, Perez C, Dominguez E, et al.
Hypoglycemic action of an oral fig leaf decoction in type 1 dia- betic patients. Diabetic Res Clin Pract 1998;39:19 22.
[42] Karch AM, Jarch FE. The herb garden: remember to ask your patients all about preparations. Am J Nurs 1999;99:12.
[43] Sobieraj DM, Freyer CW. Probable hypoglycemic adverse drug reaction associated with prickly pear cactus, glipizide, and met- formin in a patient with type 2 diabetes. Ann Pharmacother 2010;44:1334 7.
[44] Ching CK, Lam YH, Chan AY, Mak TW. Adulteration of herbal antidiabetic products with undeclared pharmaceuticals: a case series in Hong Kong. Br J Clin Pharmacol 2011;73:795 800.
[45] Goudie AM, Kaye JM. Contaminated medication precipitating hypoglycemia. Med J Aust 2001;175:256 7.
[46] Harada T, Ohtaki E, Misu K, Sumiyoshi T, et al. Congestive heart failure cause by digitalis toxicity in an elderly man taking licorice containing Chinese herbal medicine. Cardiology 2002;98:218.
[47] Lin SH, Yang SS, Chau T, Halperin ML. An usual cause of hypokalemia paralysis: chronic licorice ingestion. Am J Med Sci 2003;325:153 6.
[48] Meltem AC, Figen C, Nalan MA, Mahir K, et al. A hypokalemic muscular weakness after licorice ingestion: a case report. Cases J 2009;17(2):8053.
[49] Knobel U, Modarres G, Schneemann M, Schmid C. Gitelman’s syndrome with persistent hypokalemia—Don’t forget licorice, alcohol, lemon juice, iced tea and salt depletion: a case report.
J Med Case Reports 2011;14:312.
[50] Teas J, Pino S, Critchley A, Braverman LE. Variability of iodine content in common commercially available edible seaweed.
Thyroid 2004;14:836 41.
[51] Mussig K, Thamer C, Bares R, Lipp HP, et al. Iodine induced thyrotoxicosis after ingestion of kelp containing tea. J Gen Intern Med 2006;21:C11 14.
[52] Shilo S, Hirsch HJ. Iodine induced hyperthyroidism in a patient with a normal thyroid gland. Postgrad Med J 1996;62:661 2.
[53] Sood A, Sood R, Brinker FJ, Mann R, et al. Potential for interac- tion between dietary supplements and prescription medica- tions. Am J Med 2008;121:207 11.
91
REFERENCES
[54] Yang XX, Hu ZP, Duan W, Zhu YZ, et al. Drug herb interac- tions: eliminating toxicity with hard drug design. Curr Pharmaceutical Design 2006;12:4649 64.
[55] Shi S, Klotz U. Drug interactions with herbal medicines. Clin Pharmacokinetic 2012;51:77 104.
[56] Viachojannis J, Cameron M, Churbasik WS. Drug interactions with St. John’s wort products. Pharmacol Res 2011;63:254 6.
[57] Izzo AA, Ernst E. Interaction between herbal medicines and prescribed drugs. Drugs 2009;69:1777 98.
[58] Ernst E. St.John’s wort supplements endanger the success of organ transplantation. Arch Surg 2002;137:316 19.
[59] Alscher DM, Klotz U. Drug interaction of herbal tea containing St. John’s wort with cyclosporine [letter]. Transpl Int 2003;16:543 4.
[60] Mai I, Bauer S, Perloff ES, Johne A, et al. Hyperforin content determines the magnitude of the St. John’s wort cyclosporine drug interaction. Clin Pharmacol 2004;76:330 40.
[61] Hebert MF, Park JM, Chen YL, Akhtar S, Larson AM. Effects of St John’s wort (Hypericum perforatum) on tacrolimus pharmaco- kinetics in healthy volunteers. Clin Pharmacol 2004;44:89 94.
[62] Mai I, Stormer E, Bauer S, Kruger H , et al. Impact of St. John’s wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients. Nephrol Dial Transplant 2003;18:819 22.
[63] Jiang X, Williams KM, Liauw WS, Ammit AJ, et al. Effect of St.
John’s wort and ginseng on the pharmacokinetics and pharma- codynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2004;57:592 9.
[64] Uygur Bayramicli O, Kalkay MN, Oskay Bozkaya E, Dogan Kose E, et al. St.John’s wort (Hypericum perforatum) and warfa- rin: dangerous liaisons. Turk J Gastroenterol 2011;22:115 [Letter to the editor].
[65] van den Bout-van den Beukel CJ, Koopmans PP, van der Ven AJ, De Smet PA, Burtger DM. Possible drug metabolism inter- actions of medicinal herbs with antiretroviral agents. Drug Metab Rev 2006;38:477 514.
[66] Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Fallon J.
Indinavir concentrations and St. John’s wort. Lancet 2000;355:547 8.
[67] de Maat MM, Hoetelmans RM, Math t RA, Van Gorp EC, et al.
Drug interaction between St. John’s wort and nevirapine. AIDS 2001;15:420 1.
[68] Johne A, Brockmoller J, Bauer S, Maurer A, et al.
Pharmacokinetic interaction of digoxin with an herbal extract from St John’s wort (Hypericum perforatum). Clin Pharmacol Ther 1999;66:338 45.
[69] Smith P. The influence of St. John’s wort on the pharmacokinet- ics and protein binding of imatinib mesylate. Pharmacotherapy 2004;24:1508 14.
[70] Mathijssen RH, Verweij J, de Bruijn P, Loos WJ, Sparreboom A.
Effects of St. John’s wort on irinotecan metabolism. J Natl Cancer Inst 2002;94:1247 9.
[71] Eich-Hochli D, Oppliger R, Golay KP, Baumann P, Eap CB.
Methadone maintenance treatment and St. John’s wort: a case study. Pharmacopsychiatry 2003;36:35 7.
[72] Murphy PA, Kern SE, Stanczyk FZ, Westhoff CL. Interaction of St. John’s wort with oral contraceptives: effects on the pharmacoki- netics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. Contraception 2005;71:4102 408.
[73] Wang LS, Zhou G, Zhu B, Wu J, et al. St.John’s wort induces both cytochrome P450 3A4 catalyzed sulfoxidation and 2 C19 dependent hydroxylation of omeprazole. Clin Pharmacol Ther 2004;75:191 7.
[74] Tannergren C, Engman H, Knutson L, Hedeland M, et al.
St. John’s wort decreases the bioavailability of R and S- verapamil through induction of the first pass metabolism. Clin Pharmacol Ther 2004;5:298 309.
[75] Xu H, Williams KM, Liauw WS, Murray M, et al. Effects of St. John’s wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide. Br J Pharmacol 2008;153:1579 86.
[76] Sugimoto K, Ohmori M, Tsuruoka S, Nishiki K, et al. Different effect of St. John’s wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther 2001;70:518 24.
[77] Gordon RY, Becker DJ, Rader DJ. Reduced efficacy of rosuvas- tatin by St. John’s wort [letter to the editor]. Am J Med 2009;122:e1 2.
[78] Singh YN. Potential for interaction of kava and St. John’s wort with drugs. J Ethnopharmacol 2005;100:108 13.
[79] Dannawi M. Possible serotonin syndrome after combination of buspirone and St. John’s wort. J Psychopharmacol 2002;16:401.
[80] Gordon JB. SSRIs and St. John’s wort: possible toxicity. Am Fam Physician 1998;57:950 3.
[81] Heck AM, DeWitt BA, Lukes AL. Potential interaction between alternative therapies. Am J Health Syst Pharm 2000;57:1221 7.
[82] Lambert JP, Cormier A. Potential interaction between warfarin and boldo-fenugreek. Pharmacotherapy 2002;21:509 12.
[83] Tam LS, Chan Tym Leung WK, Critchley JA. Warfarin interac- tion with Chinese traditional medicines: danshen and methyl salicylate medicated oil. Aust NZ J Med 1995;25:238.
[84] Yu CM, Chan JC, Sanderson JE. Chinese herbs and warfarin potentiation by danshen. J Intern Med 1997;25:337 9.
[85] Lee NJ, Fermo JD. Warfarin and royal jelly interaction.
Pharmacotherapy 2006;26:583 6.
[86] Shalansky S, Lynd L, Richardson K, Ingaszewski A, et al. Risk of warfarin related bleeding events and supra therapeutic inter- national normalized ratios associated with complementary and alternative medicines: a longitudinal study. Pharmacotherapy 2007;27:1237 47.
[87] Chan HT, So LT, Li SW, Siu CW. Effect of herbal consumption on time in therapeutic range of warfarin therapy in patients with atrial fibrillation. J Cardiovasc Pharmacol 2011;58:87 90.
[88] Hamann GI, Campbell JD, George CM. Warfarin cranberry interaction. Ann Pharmacother 2011;45:e17.
[89] Izzo AA. Interactions between herbs and conventional drugs:
overview of clinical data. Med Princ Pract 2012;21:404 28.
[90] Huang WF, Wen KC, Hsiao ML. Adulteration by synthetic ther- apeutic substances of traditional Chinese medicine in Taiwan.
J Clin Pharmacol 1997;37:344 50.
[91] Vanderstricht BI, Parvasis OE, Vanhaelen-Fastre RJ. Remedies may contain cocktail of active drugs. Br Med J 1994;308:1162.
[92] Lau KK, Lai CK, Chan AYW. Phenytoin poisoning after using Chinese proprietary medicines. Hum Exp Toxicol 2000;19:385 6.
[93] Savaliyaa AA, Prasad B, Raijada DK, Singh S. Detection and characterization of synthetic steroidal and non-steroidal antiin- flammatory drugs in Indian Ayurvedic/herbal products using LC-MS/TOF. Drug Test Anal 2009;1:372 81.
[94] Gunturu KS, Nagarajan P, McPhedran P, Goodman TR, et al.
Ayurvedic herbal medicine and lead poisoning. J Hematol Oncol 2011;20(4):51.
[95] Harris ES, Cao S, Littlefield BA, Craycroft JA, et al. Heavy metal and pesticides content in commonly prescribed individ- ual raw Chinese herbal medicines. Sci Total Environ 2011;409:4297 305.
[96] Lin CC, Yang CC, Phua DH, Deng JF, et al. An outbreak of fox- glove leaf poisoning. J Chin Med Assoc 2010;73:97 100.
[97] Mehta DH, Gardiner PM, Phillips RS, McCarthy EP. Herbal and dietary supplement disclosure to health care providers by individual with chronic conditions. J Altern Complement Med 2008;14:1263 9.
[98] Dasgupta A, Bernard DW. Complementary and alternative medicines: effects on clinical laboratory tests. Arch Pathol Lab Med 2006;130:521 8.