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COMPLEMENTARY AND ALTERNATIVE MEDICINE USE
IN THE TRANSPLANT PATIENT

Rochelle M Gellatly, BSc Pharm, ACPR, PharmD
The Alfred Hospital, Melbourne, Victoria, Australia

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rochelle gellatlyComplementary and alternative medicine (CAM) can be defined as a "group of diverse medical and health care systems, practices, and products that are not generally considered part of conventional medicine."1 This definition encompasses natural health products (NHPs), including herbal medicines, vitamins and minerals, mind and body medicine and manipulative and body-based practices.1

The use of CAM is increasing in the general population, and continues to rise. The prevalence of CAM usage reported in the literature ranges between 9-65%.2 The prevalence remains high when focusing on the use of NHPs alone. A survey conducted by Health Canada revealed that 71% of Canadians have used a NHP, with 38% using a NHP on a daily basis.3 Results from the United States show that 17.7% of adults use a NHP.1

Several studies exist that explore the use of CAM in solid organ transplant recipients.4,5,6 These studies suggest that while the use of NHPs is high, most preparations are taken without medical consultation and awareness of their toxicities or drug interactions were low. Therefore, knowledge of patient use and the potential effects on transplant recipients is prudent.

There is little research on the use of NHPs in combination with immunosuppressant medications. As a result, various NHPs are considered contraindicated or to be used with caution due to theoretical drug-disease and drug-drug interactions. Drug-disease interactions occur when the NHP used stimulates the immune system, putting the patient at risk of rejection. NHPs may also contribute to the long term complications of immunosuppressive therapies, such as hypertension and diabetes. Drug-drug interactions can occur when the metabolic enzyme cytochrome P-450 (CYP450) 3A4 or the drug efflux pump, P-glycoprotein (P-GP), are affected.7,8 This has important implications on both calcineurin inhibitors and mammalian target of rapamycin (mTOR) inhibitors, which are cornerstones in immunosuppressive therapy. Table 1 highlights common agents used by patients and the recommendations for use in a transplant population. This is not an exhaustive list, and readers are encouraged to consult evidence-based resources for further information.

Several case reports of adverse events with NHPs in transplant patients exist in the literature. Acute rejection requiring hospitalization has been reported in two heart transplant recipients after taking St. John's wort (SJW).9 Other case reports document acute rejection episodes while taking SJW, and therefore this therapy should be considered contraindicated in transplant recipients.10,11 There are no published case reports involving SJW and mTOR inhibitors, however this combination should be avoided. Severe acute rejection has also been reported in a renal transplant patient after taking alfalfa and black cohosh therapy for post-menopausal symptoms, despite maintaining therapeutic cyclosporine levels.12

It is important to document a history of all NHPs used by transplant patients. Consider questioning the patient on the use of NHPs if a sudden change in drug levels is seen. For those patients who wish to use NHPs, health care providers should encourage open disclosure of therapies. Useful resources for reviewing NHPs and their potential effects on transplant patients include the Natural Medicines Comprehensive Database and Herbs and Natural Supplements: An evidence-based guide.13,14 Resources for both health professionals and patients include the NCCAM website and CAMline.1,15 Various countries now have regulation and licensing requirements for NHPs, and therefore, encouraging patients to purchase safe therapies from registered brands is important.16,17

NHPs are commonly used in transplant patients and their effects need to be considered when used in conjunction with immunosuppressants and other associated therapies. Health professionals are encouraged to promote an open dialogue with their patients regarding the use of NHPs to ensure safe and effective therapies are utilized.


Table 1: Commonly used NHPs13,14


NHP

Common Indications

Warnings/Serious Adverse Effects

Astragalus

Immunostimulant for treatment of viral infections

Contraindicated in patients on immunosuppressants

Black Cohosh

Menopausal symptoms, premenstrual discomfort and dysmenorrhea

Hepatotoxicity; Rejection in renal transplant recipient13

Echinacea

Menopausal symptoms, premenstrual discomfort and dysmenorrhea

Hepatotoxicity; Rejection in renal transplant recipient13

Garlic

Hypertension and hyperlipidemia

May increase bleeding or clotting time; May interact with warfarin and antiplatelet drugs; May induce CYP450 3A4, therefore avoid use with CNIs and mTOR inhibitors

Ginger

Nausea and vomiting

Theoretical interaction with warfarin and antiplatelet drugs increasing bleeding; May increase insulin levels, causing additive effect with OHGs.

Gingko Biloba

Dementia

May increase bleeding or clotting time; May interact with warfarin and antiplatelet drugs; May effect CYP450 isoenzymes including 3A4, therefore avoid use with CNIs and mTOR inhibitors.

Ginseng

Improving well-being and managing stress

Diabetics should monitor for possible hypoglycemia; May enhance antiplatelet and anticoagulant effects of therapies; Avoid use in patients on immunosuppressants (Panax).

Kava

Sleep and reduce anxiety

Interacts with sedatives, alcohol, anesthetics, and analgesics. May effect CYP450 isoenzymes and P-GP pump therefore avoid use with CNIs and mTOR inhibitors.

Melatonin

Insomnia

May increase blood pressure, bleeding time, and insulin resistance; immunostimulant properties therefore avoid in those on immunosuppressants.

St. John's wort

Mild to moderate depression

Interacts with CNI and mTOR inhibitors, warfarin, theophylline, aminophylline, digoxin. Induces CYP3A4 thus lowering drug levels, therefore avoid use.


Disclosure Statement: The author has no conflicts of interest to disclose.

References:

  1. NCCAM 2011, What is Complementary and Alternative Medicine?, National Center for Complementary and Alternative Medicine, Maryland, accessed 18/6/12, http://nccam.nih.gov/health/whatiscam
  2. Ernst E. Prevalence of use of complementary/alternative medicine: a systematic review. Bulletin of the World Health Organization, 2000;78(2):252-7.
  3. Health Canada 2010, Charting A Course: Refining Canada's Approach to Regulating Natural Health Products, Ontario, accessed 18/6/12, http://www.hc-sc.gc.ca/ahc-asc/branch-dirgen/hpfb-dgpsa/blueprint-plan/chart-course_tracer-voie-eng.php.
  4. Foroncewicz B, Mucha K, Gryszkiewicz J, Florczak M, Mulka M, Chmura A, Szmidt J, Patkowski W, Paczek L. Dietary Supplements and Herbal Preparations in Renal and Liver Transplant Recipients. Transplant Proceed 2011;43:2935-7.
  5. Matthees BJ, Anantachoti P, Kreitzer MJ, Savik K, Hertz MI, Gross CR. Use of Complementary therapies, adherence and quality of life in lung transplant recipients. Heart Lung 2001;30:258-68.
  6. Hess S, De Geest S, Halter K, Dickenmann M, Denhaerynck K. Prevalence and correlates of selected alternative and complementary medicine in adult renal transplant patients. Clin Transplant 2009;23:56-62.
  7. Ogu CC, Maxa Jl. Drug interactions due to cytochrome P450. BUMC Proceedings 2000;13:421-3.
  8. Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmcokinet 2000;38:41-57.
  9. Ruschitzka F, Meier PJ, Turina M, Lüscher TF, Noll G. Acute heart transplant rejection due to Saint John's wort. Lancet 2000;355:548-549.
  10. Turton-Weeks SM, Barone GW, Gurley BJ, Ketel BL, Lightfoot ML, Abul-Ezz SR. St John's wort: a hidden risk for transplant patients. Prog Transplant 2001;11:116-20.
  11. Moschella C, Bertrand MS, Jaber L. Interaction between cyclosporine and Hypericum perforatum (St. John's wort) after organ transplantation Am J Kidney Dis 2001;38:1105-7.
  12. Light TD, Light. Acute Renal Transplant Rejection Possibly Related to Herbal Medications. Am Journ Transplant 2003;3:1608-9.
  13. Therapeutic Research Faculty 2012, Natural Medicines Comprehensive Database, California, accessed 24/6/2012, http://www.naturaldatabase.com.
  14. Braun L, Cohen M. (2010). Herbs and Natural Supplements: An evidence-based guide 3rd Edition. Australia: Elsevier.
  15. CAMline n.d. accessed 24/6/2012, http://www.camline.ca
  16. Health Canada 2012, About Natural Health Product Regulation in Canada, Ontario http://www.hc-sc.gc.ca/dhp-mps/prodnatur/about-apropos/index-eng.php.
  17. Therapeutics Goods Administration 2012, The regulation of complementary medicines in Australia - an overview, accessed 24/6/2012, http://www.tga.gov.au/industry/cm-basics-regulation-overview.htm.