Contents

Search

grapefruit

Pharmacokinetics: 1) inhibits cyt P450 3A4 & P-glycoprotein in the GI tract 2) hepatic cyt P450 3A4 not affected [7] 3) may take 3 days for cyt P450 3A4 enzyme activity to recover Adverse effects: - high citrus fruit consumption (orange juice & grapefruit) associated with increased risk for cutaneous melanoma (RR=1.36) [10]* * association possibly due to psoralen in citrus fruits; psoralen has photocarcinogenic properties in animals [10] Drug interactions: -> grapefruit inhibits cyt P450 3A4, thus inhibits metabolism of: a) HMG CoA reductase inhibitors: 1] atorvastatin (up to 25% increase) 2] lovastatin (up to 300% or more increase) 3] simvistatin (up to 300% or more increase) 4] pravastatin (Pravachol) & fluvastatin (Lescol) are NOT metabolized by cyt P450 3A4, thus are unaffected by consumption of grapefruit b) Ca+2 channel blockers - amlodipine - diltiazem - felodipine - nicardipine - nifedipine - nimodipine - nislodipine - verapamil c) benzodiazepines - diazepam - midazolam - quazepam - triazolam d) antiretroviral agents - amprenavir (probably not significant) - saquinavir - indinavir e) immunosuppressants - cyclosporine - sirolimus - tacrolimus f) anticonvulsants - carbamzepine - phenytoin g) antiarrythic agents - amiodarone - carvediolol - digoxin - quinidine h) antibiotics - clarithromycin - erythromycin - telithromycin (no effect) - itraconazole i) antineoplastic agents - etoposide j) ARBs - losartan k) antipsychotics - haloperidol l) antidepressants - buspirone - clomipramine - fluvoxamine - sertaline m) endocrine agents - estrogens - methylprednisolone - progesterone n) antihistamines - fexofenadine o) caffeine p) cisapride q) methdone r) scopalamine s) sildenafil t) theophylline u) cilostazol v) warfarin Mechanism of action: 1) inhibits CYP3A4 & P-glycoprotein in the GI tract [5] - irreversible inhibition of CYP3A4 - 48-72 hours to replenish CYP3A4 in the GI tract [8] 2) increases absorption of pharmaceuticals metabolized by cyt P450 3A4 3) one 8 oz glass of grapefruit juice or 1 grapefruit can cause significant drug interactions [5] 4) may reduce insulin levels & promote weight reduction by diminishing appetite [6]

Interactions

drug interactions

Related

cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

General

fruit

References

  1. Kaiser Permanente Northern California Regional Memo, 12/99
  2. http://www.powernetdesign.com/grapefrut/
  3. Prescriber's Letter 6(10):55, Oct, 1999
  4. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  5. Prescriber's Letter 9(9):54, Sept, 2002
  6. CBS Healthwatch from Netscape (Feb 9, 2004) research from Fujioka K. Scripps Metabolic Research Center, Scripps Clinic cited
  7. Prescriber's Letter 14(2): 2007 Potentional drug interactions with grapefruit Detail-Document#: 230204 (subscription needed) http://www.prescribersletter.com
  8. Prescriber's Letter 18(3): 2011 CHART: Potential Drug Interactions with Grapefruit Detail-Document#: 270307 (subscription needed) http://www.prescribersletter.com
  9. Prescriber's Letter 20(1): 2013 CHART: Potential Drug Interactions with Grapefruit COMMENTARY: OATP Fruit Juice Drug Interactions Detail-Document#: 290121 (subscription needed) http://www.prescribersletter.com
  10. Wu S, Han J, Feskanich D et al Citrus Consumption and Risk of Cutaneous Malignant Melanoma. JCO published online on June 29, 2015 PMID: 26124488 http://jco.ascopubs.org/content/early/2015/06/24/JCO.2014.57.4111.abstract - Berwick M Dietary Advice for Melanoma: Not Ready for Prime Time. JCO published online on June 29, 2015 PMID: 26124491 http://jco.ascopubs.org/content/early/2015/06/24/JCO.2015.61.8116.full