Herbal Medicines

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Herbal Medicines

• Sarah Fitt
• Pharmacist
• NZLTU

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Overview

• Interactions with prescribed medications
• Herbal medicines
• Traditional Chinese Herbal Medicines
• References/useful websites

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Drug Interactions

• All transplant recipients are pre-disposed to
  potential drug interactions which
• May affect levels of immunosuppression
• May increase side effects due to similar
  mechanisms of action and toxicities

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Drug-Drug Interactions

• 1) Drugs that affect kidney function when given
  together
• NSAIDS e.g. brufen, voltaren,
• amphotericin, aciclovir
• 2) Drugs that may affect absorption
• Absorption reduced by antacids so separate
  administration required

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3)Drugs that may affect metabolism - the way
the drug is broken down

• Large proportion of drugs and herbal remedies
  are metabolised in the liver via same system as
  Tacrolimus and Cyclosporin
• Therefore both prescribed medications and herbal
  medicines can interact with immunosuppression and
  
• other prescribed medications

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Inhibitors

• Some drugs called inhibitors decrease metabolism
  so need to ? drug levels of tacrolimus and
  cyclosporin e.g.
• Erythromycin (4fold increase in trough levels),
• Itraconazole (4fold)
• Diltiazem (4fold)
• Grapefruit juice (4 fold)

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Inhibitors

• Important to regularly monitor levels when drug
  is introduced and will need to decrease
  tacrolimus dose.
• When inhibitor is stopped, will need to
  increase tacrolimus dose to prevent rejection

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Inducers

• Other drugs called inducers increase metabolism
  and so need to ? drug levels of tacrolimus and
  cyclosporin e.g
• Phenytoin (50 reduction in trough level with ?
  phenytoin level)
• Rifampicin,
• St Johns wort

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Inducers

• Important to regularly monitor levels when
  inducer is introduced as will need to increase
  tacrolimus dose.
• When inducer is stopped, will need to reduce
  tacrolimus dose to prevent toxicity

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Other interactions

• Tacrolimus also may affect metabolism of other
  drugs e.g. warfarin,oral contraceptives.
• Also extensively bound to proteins so possible
  interactions with other drugs which bind to
  proteins e.g Brufen, Voltaren , warfarin and
  oral anti diabetic agents

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Drug Interactions

• Drugs that REDUCE blood levels
• (Increased dose of cyclosporin
• and tacrolimus required)
• Rifampicin
• Phenytoin
• St Johns Wort
• Prednisone
• Carbamazepine
• Phenobarbitone

• Drugs that INCREASE blood levels
• (Reduced dose of cyclosporin and tacrolimus
  required)
• Erythromycin, clarithromycin,
• (not azithromycin)
• Itraconazole , fluconazole, ketoconazole
• Grapefruit juice,
• Diltiazem,
• Verapamil

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Herbal medicines
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Herbal medicines

• Use of complementary therapies continues to
  increase world-wide. Estimated to be a global
  market of US 60billion
• Use of Traditional Chinese Herbal Medicines
  (TCMs) also on the increase with increasing
  Asian migration.

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Potential issues/problems with herbal medicines

• Many patients with chronic or incurable disease
  may feel that conventional medicines have failed
  them
• Easy to access, can be cheaper than conventional
  medicines with no GP or prescription costs
• Seen as safe and natural and able to be taken
  by general population

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Herbal medicines

• Internet provides lots of information on
  potential alternative therapies, but often
  unverified and written by manufacturers.
• Lack of medical regulation even if they claim
  medical benefits with no standards and lack of
  quality assurance
• e.g Pan Pharmaceuticals recall, May 2003

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Potential issues/problems with herbal medicines

• In many countries e.g. NZ, herbal medicines are
  classified as food supplements and thus are
  exempt from regulations, quality control and
  proof of efficacy that regulate pharmaceuticals

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Herbal medicines

• In early March, Medsafe withdrew three products
  made by Herbs Health
• Joint Plus capsules and S.E.N. Plus capsules
• Both contain frusemide and piroxicam
• Multistress capsules
• contains betamethasone steroid
• All at therapeutic doses

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Herbal medicines peri-operatively

• One US study showed that 32 of patients in an
  ambulatory surgery setting used herbal medicines
• However more than 70 of patients failed to
  disclose herbal medicine use during routine
  pre-operative assessment.
• Fear of prejudice, not real medicines, used for
  indication not related to surgery,
• Recommendation that all herbal medicines should
  be stopped 2-3 weeks prior to surgery

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Common herbal medicines

• All are readily available in NZ

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Common herbal medicines

• St. Johns Wort
• Anti-depressant
• Side effects - dry mouth, nausea, constipation,
  fatigue
• Drug interactions !
• Tacrolimus
• Can halve blood concentration of Tacrolimus
• Long half life - up to 5 days

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Common herbal medicines

• Echinacea - Natures antibiotic
• Used to treat abscesses, burns, eczema and
  respiratory infections
• Immunostimulant - may reduce effectiveness of
  immunosuppression
• Long term use associated with poor wound healing
  and opportunistic infections and liver problems

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Common herbal medicines

• Garlic
• Beneficial cardio-vascular agent -
  anti-platelet, anti-bacterial and anti
  hyperlipidaemic effects
• Side effects - stomach upsets, sweating,
  heartburn,
• Can increase the effects of warfarin and NSAIDS

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Common herbal medicines

• Ginseng
• Used to treat stress, fatigue, frequent colds
• Now standardised formulations in Europe under
  medicine regulation
• Can cause hypoglycaemia, hypertension, insomnia
  and headaches
• Decreases warfarin concentrations - risk of
  bleeding
• May reduce effectiveness of immunosuppression

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Common herbal medicines

• Kava
• Anxiolytic for stress
• Additive sedation with benzodiazepines
• Number of cases of acute liver failure leading to
  liver transplantation

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Table of potential herb-drug interactions
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Traditional Chinese Medicines (TCMs)
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Traditional Chinese Medicines (TCMs)

• In 1999 annual sales in States - US4 billion
• Conventional medicines often derived from TCMs
• Ephedrine from ma huang
• Idarubicn from dang gui lu hui
• Taxol from bark of Pacific yew

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TCMs

• No standardisation in formulae or quantities
• Adverse effects and interactions can be related
  to constituents themselves or contaminants
• Many TCMs appear to be metabolised in the liver
  and can affect liver function

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TCMs

• Known contaminants - mercury, lead, arsenic and
  copper
• Niu Huang Jie Du Pian - found to contain arsenic
• Product called Fufang luhui jiaonang was found to
  contain 11.7 mercury

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TCMs

• Undeclared conventional agents
• Anti diabetes remedies contained oral
  hypoglycaemics
• Many eczema creams contained steroids
• Remedies for joint pain contained steroids e.g
  dexamethasone and pain-killers
• e.g. Pil Ajaib Cap Emas, contains dexamethasone
  and indomethacin

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TCMs

• Wei Ge Wang
• Contains sildenafil and very similar packaging to
  Viagra

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TCMs

• Manup capsules
• May contain tadalafil (Cialis)

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Accidental substitution
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Hepatotoxic TCMS

• Shubao
• Slimming capsule containing nitrosfenfluramine,
  very similar to fenfluramine. Many other slimming
  products contain similar ingredients
• Hundreds of adverse effects reported in Japan -
  4 deaths

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TCMs

• Many reported interactions between TCMs and
  conventional medicines
• Danshen and dong quai potentiate anticoagulant
  effect of warfarin, of particular concern when
  also on NSAIDs
• -Liu Shen and digoxin- ventricular extrasystoles

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Summary

• Due to increasing use of alternative therapies,
  and readily accessible information, there is a
  important need for transplant patients
• to be aware of potential risks associated with
  self-medicating herbal remedies including
  traditional Chinese Herbal remedies.

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Useful websites

• www.nccam.nih.gov
• www.mayoclinic.com
• www.medicines.mhra.gov.uk
• www.herbmed.org
• www.consumerlab.com
• www.cam.org.nz

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Useful References

• Herbal products for Liver Disease - A therapeutic
  challenge for the New Millennium - Schuppan et
  al, Hepatology 30 (4) 1099-1103
• Barone - Transplantation, 71 (2) 239-241
• Herbal Medicines and Perioperative Care - Ang-Lee
  et al, JAMA 286 (2) 208-216
• Drug Interactions between Herbal and prescription
  medicines- E Williamson, Drug Safety 26 (15)
  1075-1092
• Drug Interactions with St Johns Wort - Mannel,
  Drug Safety 2004 27 (11) 773-797
• Interactions of Herbs with Cytochrome P450 -Zhou
  et al, Drug Metabolism Reviews 35 (1) 35-98
• Interaction between Modern and Chinese Medicinal
  Drugs A General Review - Cheng et al, Am Jour
  Chinese Med 31 (2) 163-169
• Chinese Proprietary Medicine in Singapore -Koh at
  al, Drug Safety 23 (5) 351-362