Herb-drug interactionsOutlineLearning objectivesEvidence for herb-drug interactionsDrug Interaction ResolutionPK vs PD reviewPrevalence: Canadian seniorsPrevalence: Mayo ClinicSt. John’s wort (Hypericum perforatum)St John’s wortSt. John’s wort: PK interactionsSt. John’s wortClinical strategyWarfarin-herb interactionsSlide 15Warfarin and Chinese herbsWarfarin and “G” herbsWarfarin and lipid-based agentsGarlic (Allium sativum)Slide 20Herbs and diabetesHerbs and StatinsSlide 23GinkgoGinkgo and psychotropicsKava (Piper methysticum)Licorice (Glycyrrhiza glabra)Licorice: positive interactionHerbal laxativesOther potential interactionsOther possible interactionsSurgery and Dental ProceduresSlide 33Slide 34Dental procedures: herb side effectsClinical copingChecking for herb-drug interactionsHerb-drug Herb-drug interactionsinteractionsCharlotte Gyllenhaal, Ph.D.Charlotte Gyllenhaal, Ph.D.Department of Medicinal Chemistry and Department of Medicinal Chemistry and Pharmacognosy, Pharmacognosy, Block Center for Integrative Cancer TreatmentBlock Center for Integrative Cancer Treatment6-1870, [email protected], [email protected]►Evidence for herb-drug interactionsEvidence for herb-drug interactions►Pharmacokinetic (PK) versus pharmacodynamic Pharmacokinetic (PK) versus pharmacodynamic (PD) interactions(PD) interactions►St. John’s wortSt. John’s wort►WarfarinWarfarin►MiscellaneousMiscellaneous►Herb-drug interactions and surgical/dental Herb-drug interactions and surgical/dental proceduresprocedures►Use of computer databases for clinical questionsUse of computer databases for clinical questionsLearning objectivesLearning objectives►Distinguish between pharmacokinetic and Distinguish between pharmacokinetic and pharmacodynamic interactions.pharmacodynamic interactions.►Know the principal pharmacokinetic and Know the principal pharmacokinetic and pharmacodynamic interactions of St John’s Wort, i.e. pharmacodynamic interactions of St John’s Wort, i.e. induction of CYP450 3A4, and serotonin induction of CYP450 3A4, and serotonin syndrome/photosensitivitysyndrome/photosensitivity►Know the main reasons for herb-drug interactions with Know the main reasons for herb-drug interactions with warfarin, i.e. vitamin K activity; decreased GI absorption warfarin, i.e. vitamin K activity; decreased GI absorption or CYP450 2C9 metabolism; and herbs that decrease or CYP450 2C9 metabolism; and herbs that decrease platelet aggregation or thromboxane synthesis or have platelet aggregation or thromboxane synthesis or have coumarin content. coumarin content. ►Know the main reasons for caution with herbs and Know the main reasons for caution with herbs and surgery or dental procedures, i.e., herbal anticoagulants surgery or dental procedures, i.e., herbal anticoagulants (cause bleeding), sedative or stimulant herbs (modify (cause bleeding), sedative or stimulant herbs (modify anesthesia).anesthesia).►Know principles for clinical coping with herb-drug Know principles for clinical coping with herb-drug interactionsinteractionsEvidence for herb-drug Evidence for herb-drug interactionsinteractions►Case reportsCase reportsUnderreported? 70% “don’t ask-don’t tell”Underreported? 70% “don’t ask-don’t tell”►Lab studiesLab studiesDefine mechanismsDefine mechanisms►Recent interest in CYP450 inductionRecent interest in CYP450 induction►Not necessarily borne out in trials Not necessarily borne out in trials ►Human studies – interpret with cautionHuman studies – interpret with cautionTrials using probe drugsTrials using probe drugsMay be too short or expensiveMay be too short or expensiveMay be done on healthy population (not always)May be done on healthy population (not always)Genetic polymorphismsGenetic polymorphismsMultiple drug/herb users, elderly patientsMultiple drug/herb users, elderly patientsDe Smet, Br J Clin Pharm 2006; 63:258-67Drug Interaction ResolutionDrug Interaction Resolution►Require dosage adjustmentsRequire dosage adjustments►Temporary or complete elimination of Temporary or complete elimination of one or the other agent to avoid serious one or the other agent to avoid serious consequencesconsequences►Close monitoring of the subjectClose monitoring of the subject►Total change of drug therapyTotal change of drug therapyPK vs PD reviewPK vs PD review►PK: absorption, distribution, metabolism, PK: absorption, distribution, metabolism, eliminationeliminationCYP450, PgPCYP450, PgPAbsorption from GI tract (laxatives)Absorption from GI tract (laxatives)►PD: pharmacological functionPD: pharmacological functionAnticoagulant drugs plus anticoagulant herbsAnticoagulant drugs plus anticoagulant herbsSedative herbs plus anesthesiaSedative herbs plus anesthesia►NegativeNegativeMostMost►Positive or synergisticPositive or synergisticPossible PD or PKPossible PD or PKDecrease side effectsDecrease side effectsPrevalence: Canadian seniorsPrevalence: Canadian seniors►Canadian seniors with osteoarthritisCanadian seniors with osteoarthritisSurvey, n = 191. Average 2.8 prescriptions, 1.9 Survey, n = 191. Average 2.8 prescriptions, 1.9 self-care productsself-care products►Potential interactions detected using standard Potential interactions detected using standard databasesdatabases214 instances, 14% possible clinical significance214 instances, 14% possible clinical significance7 herbs/supplements, associated with 5 clinically 7 herbs/supplements, associated with 5 clinically insignificant interactionsinsignificant interactions1 recommendation to stop medications (dilatiazem 1 recommendation to stop medications (dilatiazem + atrorvastatin -> statin side effects intensified)+ atrorvastatin -> statin side effects intensified)Clinically significant interactions may be rare – but Clinically significant interactions may be rare – but thus easier to forget about and harder to monitor!thus easier to forget about and harder to monitor!Putnam, Can Fam Physician 2006; 52:340-45Prevalence: Mayo ClinicPrevalence: Mayo Clinic►6 specialty areas 6 specialty areas Survey of 1795 patients; 39.6% used supplementsSurvey of 1795 patients; 39.6% used supplements►Potential interactions detected using Lexi-Potential interactions detected using Lexi-Interact (available on PDA)Interact (available on PDA)107 interactions with potential clinical significance107 interactions