← Back to February 2018


WARNING: Do Not Combine


Jenny Au
Jennytau@gmail.com

Kirsten Diegel, RD, LDN, CNSC
Kdiegel1120@gmail.com
Temple University Hospital
Philadelphia, PA, USA



Managing immunosuppressant medications can be difficult, even for those with years of experience in the transplant field. Each patient can respond differently to medications for an assortment of reasons, and special considerations need to be made for a variety of factors, such as renal function. Immunosuppressant medications can be affected by other traditional drugs as well as nutrients and herbal supplements. The effect can be an increase or decrease in blood concentration of the medication depending on the drug, nutrient, and/or herbal supplement. For this reason, it is imperative that both pre- and post-transplant patients inform their healthcare providers of all medications and herbal supplements they are using. Below is a chart summarizing common herbal supplements and their effect on various medications used in a transplant recipient.

Herbal Supplement or Extract

Drug

Mechanism of Interaction / Therapeutic Consequence

Berberine

Cyclosporine

Inhibits CYP3A4 and intestinal P-gp / Increased bioavailability

Caffeine/high doses of chocolate

Methylphenidate
Sedative-hypnotics
Bronchodilators

Increase effect
Decrease effect
Increase chance of side effects like excitability, nervousness, and rapid heartbeat

Cannabidiol

Cyclosporine

Inhibits hepatic CYP3A4 / Increases bioavailability

Chamomile

Cyclosporine

Inhibits CYP3A4 / Increases bioavailability

Cranberry juice

Cyclosporine

Inhibits CYP3A4 / Increases bioavailability (speculative)

Echinacea

Cyclosporine

Possible inhibitor of CYP / Increases bioavailability (speculative)

Fish Oil

Cyclosporine

Inhibits CYP2C19, 2D6 and 34A / Increased bioavailability

Garlic

Anticoagulants &
aspirin

Unknown / Increased bleeding

Ginger

Cyclosporine
(oral only)

Reduces gastrointestinal motility / Decreases bioavailability

Gingko biloba

Anticoagulants &
aspirin

Inhabitation of platelet activating factor / Increased bleeding

Grapefruit juice, and other citrus fruits that contain furanocoumarins (limes, Seville oranges, tangelos

Cyclosporine

Felodipine Itraconazole

Increased bioavailability (oral only)/ Enhanced
immunosuppression or toxicity
Increased bioavailability / Possible hypotension
Decreased bioavailability / Fungal infection

Ginseng

Warfarin
MAO inhibitors

Decreased warfarin blood concentrations / Risk of thrombosis
Can cause headache, trouble sleeping, nervousness
and hyperactivity

Kava

Benzodiazepines

Additive sedation with benzodiazepines / Oversedation, possible coma

Liquorice

Cyclosporine
(oral only)
Diuretics and/or
antiarrythmic agents

Induced P-gp and CYP3A4 / Decreased bioavailability

Sodium retention and potassium depletion / Hypertension,
hypokalemia, and increased risk of arrhythmia

Mu huang

MAO Inhibitors
Antihypertension
Theophylline and/or
caffeine

Sympathomimetic interaction / Hypertensive crisis
Ephedrine alkaloids increase blood pressure / Hypertension
Enhanced CNS stimulant effect / Theophylline toxicity

Pomegranate juice

Cyclosporine

Inhibits intestinal CYP3A / Increased bioavailability

Quercetin

Cyclosporine
(oral only)

Induces CYP3A4 and intestinal P-gp / Decreased bioavailability

Reseveratrol

Cyclosporine

Inhibits CYP3A4 / Increases bioavailability

Scutellariae radix

Cyclosporine
(oral only)

Induces CYP3A4 and intestinal P-gp / Decreased bioavailability

Serenoa repens

Cyclosporine

Potent inhibitor of CYP3A4, 2D6, and 2C9 / Increases
bioavailability (speculative)

Spices/Condiments (pepper, fennel, dill, Asian ginseng, evening primrose, cat's claw, feverfew, frankincense)

Cyclosporine

Inhibits CYP3A4 / Increases bioavailability (speculative)

St John's wort

Cyclosporine

Digoxin
Indinavir, other
protease inhibitors
Theophylline

Antridepressants (SSRIs)

Reduced bioavailability and/or enhanced clearance / Reduced immunosuppression, possible organ rejection
Reduced bioavailability / CHF treatment failure
Reduced bioavailability / HIV treatment failure

Enhanced clearance / Sub-therapeutic theophylline concentrations
Inhibition of serotonin reuptake / Serotonism

Valerian

Barbiturates

Prolongs barbiturate sedation / Enhanced sedation

Wine (red)

Cyclosporine

Inhibits CYP3A4 / Increases bioavailability (speculative)

Herbal supplement intake can also have potentially life-threatening complications including increased risk of bleeding, sedating properties, and direct organ (renal, hepatic, and cardiac) toxicities.

Herbal Supplement Associated With Hepatotoxicity

Herbal Supplements that May Increase the Risk of Bleeding


  • Baikal skullcap
  • Chaparral
  • Pyrrolizidine
  • Germander
  • Greater celandine
  • Saw palmetto
  • Noni juice
  • Margosa oil
  • Aloe vera
  • Black cohosh
  • LipoKinetix
  • Astractylis gummifera
  • Impila
  • Mistletoe
  • Valerian
  • Senna
  • Pennyroyal
  • Kava
  • Liatris callilepis
  • Green tea extract
  • Cascara sagrada
  • OxyElite Pro
  • Chinese herbal medicines
    • Jin Bu Huan
    • Ma Huang
    • Dai-saiko-to
  • Hydroxycut
  • Herbalife supplements
  • Ayurvedic herbal products


  • High-dose fish oil
  • Garlic
  • Ginkgo biloba
  • Ginseng
  • Feverfew
  • Vitamin E
  • Ginger

Due to the fact that herbal supplements are found over-the-counter, many believe they are harmless and have no repercussions when used. However, as the previous tables show, not all supplements are benign, so it is best that healthcare teams are aware of their patients' comprehensive medication list. ■

Disclosure Statement: The authors have no conflicts of interest to disclose.


References:

  1. Barone G, Gurley B, Ketel B, et al. Herbal Supplements: A Potential for Drug Interactions in Transplant Recipients. Transplantation 2001;71:239-241
  2. Colombo D, Lunardon L, Bellia G. Cyclosporine and Herbal Supplement Interactions. Journal of Toxicology, 2014, 1-6. doi:10.1155/2014/145325
  3. Corey R and Rakela J. Complementary and Alternative Medicine: Risks and Special Considerations in Pretransplant and Posttransplant Patients. Nutrition in Clinical Practice, 2014;29;322-331
  4. Healy M. "Grapefruit not only food that can affect medication." USA Today. 20 Jan. 2013 Web. 26 Jan. 2018.
  5. Nowak R. Review Article: Cytochrome P450 enzyme and transport protein mediated herb-drug interactions in renal transplant patients: Grapefruit juice, St John's Wort - and beyond! Nephrology 2008;13:337-47



Share via:

links image    links image    links image    links image