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Wadie Najm, MD, MEd Retrieved September 29, 2011, from Does it Effect the Older Adult.

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Presentation on theme: "Wadie Najm, MD, MEd Retrieved September 29, 2011, from Does it Effect the Older Adult."— Presentation transcript:

1 Wadie Najm, MD, MEd Retrieved September 29, 2011, from http://opinion- Does it Effect the Older Adult UC Irvine- Geriatric Division Supported by a Reynolds Grant

2 Medication use by older adults Dietary Supplements – Regulations Quality Assurance How to Choose a Dietary Supplement Drug-herb interactions Resources 2UC Irvine - Reynolds Grant

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8 Passed by unanimous consent of House and Senate Signed into law by President Bill Clinton Amended the Food Drug & Cosmetic Act Recognized a new category of regulated productsDietary Supplements(DS) Treats DS in many respect as food (i.e. does not require premarket approval) 8UC Irvine - Reynolds Grant

9 9 Definition: A product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients Vitamins Minerals Herbs or other botanicals Amino acids Concentrate, metabolite, constituent, extract or combination of above listed ingredients UC Irvine - Reynolds Grant

10 Manufacturer responsible for safety evaluation FDA has burden of proving DS is unsafe once product is marketed Label must include: Name of each ingredient Quantity of each ingredient Total weight of all ingredient if a blend Identity of part of plant derived from Term Dietary Supplement Must contain nutritional labeling information 10UC Irvine - Reynolds Grant

11 DSHEA authorized use of FDA approved Health claims on label Describe the connection between a nutrient or food substance and a disease or health- related condition Statements may be included on the label that give the manufacturers description of the role of the D/S Must be accompanied by disclaimer This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease 11UC Irvine - Reynolds Grant

12 Requires proper controls to ensure that DS are processed in a consistent manner and meet quality standards. cGMP apply to all domestic and foreign companies involved in the US market Requires that DS are manufactured consistently as to identity, purity, strength and composition. Staggered 3 year phase for small business; effective June 2008 for large companies. 12UC Irvine - Reynolds Grant

13 U.S.P. notation! GMP or cGMP notation! Consumer Lab seal! Consider manufacturer / distributor Look at brand used in studies reporting positive outcome. 13UC Irvine - Reynolds Grant

14 14 FDA. (2010). TaintedDietarySupplements_1210. [pdf]. Retrieved September 29, 2011 from:

15 FDA has identified an emerging trend where several over-the-counter products, frequently represented as dietary supplements, contain hidden active ingredients that could be harmful List of Supplements: ements_cder 15UC Irvine - Reynolds Grant

16 Major delinquents: Weight loss supplements 70 + reports of contamination (2010) Sibutramine (Meredia®) Erectile function/Sexual enhancement 80 + reports of contamination (2010) Sildenafil (Viagra®), Tadalafil (Cialis®) Body building supplements 80 + reports of contamination (2010) Anabolic steroids or steroid analogs 16UC Irvine - Reynolds Grant

17 Usually > 1 active ingredient per supplement Variation in potency by season, region, etc. Lack of clinical trials Lack of full understanding of pharmacology of herbs Presence of multiple ingredients not yet characterized. Formulations using concentrated plant extracts Use of multiple supplements at one time 17UC Irvine - Reynolds Grant

18 18UC Irvine - Reynolds Grant HerbalGram. 2011

19 UC Irvine - Reynolds Grant19 HerbalGram. 2011

20 20 UC Irvine - Reynolds Grant Ann Intern Med. 2002;136:596-603

21 Ginkgo Evaluation of Memory (GEM) Study cohort 82.5% used at least 1 dietary supplement, with 54.5% using 3+. The overall mean number of prescription drugs was 3.5 ± 2.7 and dietary supplements were and 3.4 ± 3.0 83% of prescription drug users also used dietary supplements, and 90% of supplement users also used prescription drugs UC Irvine - Reynolds Grant 21 JAGS 57:1197–1205, 2009 UC Irvine-Reynolds Grant

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24 Look for available quality clinical research (Efficacy) Check for long tradition of use (Safety) Check that active ingredient(s) are identified Review mechanism of action determined Verify that Supplement is commercially available from a reliable source Ingredients and potency documented Quality assurance documented with seal of approval 24UC Irvine - Reynolds Grant

25 Two types of interactions exist: Pharmacokinetic: herb–drug interactions are caused by one drug interfering with the elimination, metabolism, or absorption of another drug; Pharmacodynamic: Herb/supplement interaction due to pharmacological properties similar or opposite to conventional medications. UC Irvine - Reynolds Grant 25

26 Induction of hepatic and intestinal drug- metabolism enzyme (Cytochrome P450 {CYP450}): important for Phase I drug metabolism. Induction of drug transporters (intestines, liver, kidney) i.e. P-glycoprotein, plays important role: Absorption Distribution Excretion 26UC Irvine - Reynolds Grant

27 Over 80 dietary supplements have some effect on a Cytochrome (CYP) enzyme, The potential to interact with drugs metabolized by these enzymes is high. The majority of the research is based on laboratory work (in vitro or in animals). The clinical significance of these remains questionable. UC Irvine - Reynolds Grant27

28 Role of CYP450 system is the metabolism and detoxification of endogenous compounds after they have been ingested. CYP 450 is found in high concentrations in the liver and small intestine. Comprehensive list of drug interaction: Indiana University Prescribers letter: &pt=3&fpt=28&dd=-1&pb=PL&s=PL 28UC Irvine - Reynolds Grant

29 29UC Irvine - Reynolds Grant DrugPlasmaConcDrugPlasmaConc

30 Used commonly alone or in combination with other supplements. Indications: Depression; anxiety; stress; insomnia Efficacy: good scientific evidence for mild to moderate depression. Standardized ingredient: Hyperforin; Hypericin Other phytochemicals are present. 30UC Irvine - Reynolds Grant

31 SJW is a complex mixture of over 24 constituents: flavonols, flavonol glycosides, biflavones, naphthodianthrones, acylphloroglucinols, and phenylpropanes Hyperforin is believed to be the major constituent responsible for its antidepressant activity, as it inhibits the reuptake of neurotransmitters in synapses Proposed action: inhibits 5-HT, NE, DA uptake; GABA receptor ligand; 31UC Irvine - Reynolds Grant

32 In vitro studies have demonstrated that SJW extract is a potent inducer of CYP3A4 and 2B6, and the responsible component was hyperforin. Based on in vitro, in vivo animal and human studies, SJW interacted with CYPs in two ways: induction of CYP and modulation (inhibition or stimulation) of enzyme activity, which may be the underlying mechanism for the observed SJW– drug interactions. 32UC Irvine - Reynolds Grant Proc Natl Acad Sci U S A.Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7500-2.

33 33UC Irvine - Reynolds Grant Comparison of pre-supplementation and post-supplementation phenotypic ratios for CYP3A4. (A= St Johns wort (SJW); B = garlic oil); Clin Pharmacol Ther 2002;72:276-87

34 34UC Irvine - Reynolds Grant Apparent sex-related difference in St Johns wort (SJW)–mediated CYP3A4 induction. Differences in pre-supplementation and post- supplementation) were significantly greater for female subjects. Clin Pharmacol Ther 2002;72:276-87

35 UC Irvine - Reynolds Grant35 Transplantation.Transplantation. 2001 Jan 27;71(2):239-41. 1)Drug interaction between St. John's wort and cyclosporine. Barone GW, et al. Ann Pharmacother. 2000 Sep;34(9):1013-6. 2)herb-drug interactions in renal transplant patients.. Nowack R, Nephrology 2008 Jun;13(4):337-47. 3)Interaction of Hypericum perforatum (St. John's wort) with cyclosporin A metabolism in a patient after liver transplantation. Karliova M, et al. J Hepatol. 2000 Nov;33(5):853-5.

36 Grapefruit has the potential to interact with numerous drugs. A number of organic compounds, identified as furanocoumarin derivatives, interfere with the hepatic and intestinal CYP3A4. Other bioactive compounds interfere with P- glycoprotein and organic anion transporting polypeptides (OATPs) either increasing or decreasing bioavailability of a number of drugs. UC Irvine - Reynolds Grant36 Clin Pharmacol Ther. 2007 May;81(5):631-3

37 37 UC Irvine - Reynolds Grant Concomitant ingestion of grapefruit juice and fexofenadine reduced fexofenadine area under curve (AUC)0–8 h by 52%; Grapefruit juice ingested 4 h before drug had no effect.

38 38 UC Irvine - Reynolds Grant NYTimes, March 20, 2006

39 39UC Irvine - Reynolds Grant Br J Clin Pharmacol 2010;70(5);645–655

40 Approximately 60 -80% of levothyroxine is absorbed after oral administration. This absorption occurs within the first 3 h of ingestion and is localized mainly in the jejunum and ileum. Absorption of levothyroxine is maximal when the stomach is empty 40UC Irvine - Reynolds Grant

41 Levothyroxine plus chromium picolinate 1000 mcg; decreases levothyroxine levels by 17% Calcium binds levothyroxine in the GI tract; variably reduces absorption Levothyroxine taken with coffee decreases levothyroxine levels by 27% to 36%. John-Kalarickal J, et al. Thyroid 2007;17:763-5. Benvega S, et al. Thyroid 2008;18:293-301. 41UC Irvine - Reynolds Grant

42 42UC Irvine - Reynolds Grant Best Practice & Research Clinical Endocrinology & Metabolism 23 (2009) 781–792

43 Warfarin exerts its effect by interfering with the cyclic interconversion of vitamin K and its 2,3 epoxide (vitamin K1 epoxide). Treatment with warfarin results in the hepatic production of partially carboxylated & decarboxylated proteins with reduced anticoagulant activity. The anticoagulant effect of warfarin can be reversed by the intake of vitamin K1 (phytonadione) 43UC Irvine - Reynolds Grant Expert Opin. Drug Saf. (2006) 5(3):433-451

44 Factors that can contribute to variability: age, gender, ethnicity, vitamin K intake, Body weight, albumin level Other medication(s) UC Irvine - Reynolds Grant44 Expert Opin. Drug Saf. (2006)

45 Older adults are more likely to eat vegetables, therefore, have higher vitamin K intake. Vitamin K intake among adults > 55 years is estimated to range from 80 to 210 μg/day. UC Irvine - Reynolds Grant45 Expert Opin. Drug Saf. (2006) 5(3)

46 Absorption of warfarin may be inhibited by drugs that affect the bioavailability of warfarin, such as colestyramine or sucralfate. Warfarin also interacts with medications that are highly protein-bound (salsalate, sulfasalazine). Warfarin is inhibited by medications that induce cytochrome P450 liver enzymes (rifampin, carbamazepine) Warfarin is enhanced by medications that inhibit CYP liver enzymes (metronidazole, cimetidine). Pharmacodynamic interactions may occur with drugs that affect platelet function and aggregation, causing increased risk of bleeding (aspirin, clopidogrel, NSAIDs) UC Irvine - Reynolds Grant46 Expert Opin. Drug Saf. (2006) 5(3):433-451

47 Over 40 reports of interactions with warfarin (Coumadin) Glucosamine alone or in combination with chondroitin Most reports involved typical doses, Glucosamine 1500 mg/day and chondroitin 1200 mg/day Effect: bruising, bleeding {increased INR) Knudsen J et al., Pharmacotherapy 2008;28:540-8. 47UC Irvine - Reynolds Grant

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49 49UC Irvine - Reynolds Grant J Thromb Thrombolysis (2011) 31:326–343 Clinically significant drug interactions can occur when an interacting drug, food or herbal supplement is added during warfarin therapy, discontinued during warfarin treatment, or used intermittently during warfarin treatment.

50 UC Irvine - Reynolds Grant 50 Expert Opin. Drug Saf. (2006) 5(3)

51 UC Irvine - Reynolds Grant 51 Expert Opin. Drug Saf. (2006) 5(3)

52 UC Irvine - Reynolds Grant52

53 Bitter orange contains the stimulant synephrine QT-interval prolongation in case reports Combining with other QT-interval prolonging drugs increases risk of arrhythmia: Amiodarone Quinidine Sotalol Stimulants Several others Nasir JM, et al. Mayo Clin Proc 2004;79:1059-62. 53UC Irvine - Reynolds Grant

54 CaffeineEphedra UC Irvine - Reynolds Grant54 Guaraná Kola nut Yerba maté Green tea Black tea Cocoa Guaraná Kola nut Yerba maté Green tea Bitter orange Combinations

55 Medical history should include information about Herbal/Dietary supplements Consider Herbal – Drug interactions Physicians and patient must become better educated about the potential for interactions. Elderly people are subject to higher risk for Drug-Herb interactions 55UC Irvine - Reynolds Grant

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66 Herbal Supplements-Drug Interactions: Scientific and Regulatory Perspectives Y.W. Francis Lam, Shiew-Mei Huang, Stephen D. Hall (2006) Herbal Supplements: Efficacy, Toxicity, Interactions with Western Drugs, and Effects on Clinical Laboratory Tests. Amitava Dasgupta (2011) A-Z Guide to Drug-Herb-Vitamin Interactions Revised and Expanded 2nd Edition: Alan R. Gaby (2006) UC Irvine - Reynolds Grant66

67 Mandatory reporting for manufacturers Voluntary reporting for health professionals Report it to MedWatch Report using Natural Medicines Comprehensive Database: Natural Medicines Watch 67UC Irvine - Reynolds Grant

68 Tips for Older Dietary Supplement Users ion/ucm110493.htm My Dietary Supplements (MyDS) Mobile App (ODS) Zhou SF, et al. Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring. Ther Drug Monit. 2007 Dec;29(6):687-710. 68UC Irvine - Reynolds Grant

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