Grapefruit seems to be the buzz word now-a-days in the medical world. With evidence that it can cause serious drug-food interactions due to alterations in liver function, experts on both sides are eager to get information out about it. Citrus growers don't want people abandoning their product out of fears of a drug interaction and pharmacists, doctors and drug companies want the correct information out there so that medications are as safe an effective as possible.
How Does the Grapefruit Cause a Drug Interaction and Why Does that Matter?
Without getting too technical, the grapefruit inhibits a liver enzyme (CYP3A4) which is responsible for the breakdown of some medications. By disabling this enzyme, two potential interactions occur; some drugs are disabled by this enzyme and others are activated. For those that are disabled (the more common reaction) the drug stays in the body longer, which can result in overdosage, toxicity and an increased incidence of side effects. With drugs that are activated by the enzyme, they remain in their inactive form in the blood stream and therapeutic effects are never seen. Obviously either can be bad. Pomelos (an Asian ancestor to the grapefruit) and Seville oranges can also have this interaction with medications. Some medications also inhibit the CYP3A4 enzyme much more strongly than grapefruit, including ketoconazole and itraconozole, therefore the interactions mentioned apply even more to those medications.
What Drugs to Look Out For
Out of all the medications that interact with grapefruit, HMG-CoA Reductase Inhibitors (-statins), used to treat high cholesterol, have gotten the worst reputation out of it. Statins carry a small risk of rhabdomyolysis, a rare but serious side effect that results in widespread muscle death and can be deadly. The higher the dose, the higher the likelihood of such a reaction. Since statins are metabolized by the CYP3A4 enzyme, grapefruit juice increases their overall levels in the blood, resulting in a higher risk of rhabdomyolysis. But contrary to popular belief, most statins don't carry as high a risk as was originally advertised. Zocor (simvastatin) and Mevacor (lovastatin) are most likely to cause an issue. Lipitor (atorvastatin) and Pravachol (pravastatin) have the possibility also, but it is considered a negligible risk. Many pharmacists and doctors still prefer their patients to avoid grapefruit all together when taking the medication.
Many macrolide antibiotics have a slight risk of an interaction also. Erythromycin may prolong the QT-interval which can slow heart rate. When it is not metabolized by the CYP3A4 enzyme, this risk is increased and an increased risk of sudden death has occurred in patients who use grapefruit products. Buspar (buspirone), as well as several benzodiazepines which are commonly used to treat anxiety can cause similar interactions, as well as many Calcium Channel Blockers.
Anticonvulsants, like Tegretol or Carbatrol (carbamazepine) are only considered a minor risk of interaction, but because the therapeutic window of the medication in considered small, even a small inhibition of clearance can result in unwanted side effects and a risk of toxicity. Similarly, many immunosuppressants (commonly given after organ transplants or with certain autoimmune diseases) can be shifted out of their therapeutic window by grapefruit, causing toxicity, even with low interference.
A complete list of these types of interactions can be found here or in a PDF chart here. As you can see, there is some discrepancy between the two lists and this is largely the result of varying sources and interests.
As a speedy-reference to the major interactions, The Florida Department of Citrus has provided this Quick-Check Chart, which includes the major grapefruit-drug interactions. Talk to your pharmacist about posting a copy in the pharmacy for the benefit of you, your coworkers and your patients. Obviously it doesn't cover all the interactions, but it does note the major ones and may even give you an idea of other medications in the same class to look out for.
Transporter-based drug interactions are relatively minor and are easily resolved by separating the medication from the grapefruit juice by about two hours. The mechanism of this interaction is that the grapefruit juice and the affected medication use the same channels to cross through the intestines into the blood. Think of it like a ferry to an island. The grapefruit juice and the medications need to use the same ferry to get across, but the grapefruit juice gets priority. The result is decreased effectiveness of the medication due to decreased availability. The only medication that is significantly impacted by this interaction is the antihistamine Allegra (fexofenadine). In fact, with Allegra's recent OTC launch, the manufacturers of Zyrtec decided to make a big deal of this, with the implication that it was UNSAFE to take fexofenadine with grapefruit juice. This is not the case and Chattem was quick to make sure the public was aware of this.
References
Bonagua, Ellen. "Important Message from the Allegra Medical Director." Important Message from the Allegra Medical Director. Chattem, Inc., 2011. Web. 13 May 2011. <http://www.alertmarketing.com/email/JHCE/14575_Chattem(Allegra)PH_EQ/final.html>.
Greenblatt, MD, David. "Update on Drug Interactions with Grapefruit Juice: An Evidence-Based Review." Pharmacy Times CE. Pharmacy Times CE, Jan 2010. Web. 13 May 2011. <http://secure.pharmacytimes.com/lessons/201001-01.asp>.
"Patient Advice Label: Avoid Grapefruit." Total Pharmacy Supply. Web. 13 May 2011. <http://shop.tps-online.com/prodimg/400998.jpg>.
Zeratsky, R.D., L.D., Katherine. "Grapefruit Juice: Beware of Dangerous Medication Interactions." Mayo Clinic. Mayo Clinic, 06 Nov 2010. Web. 13 May 2011. <http://www.mayoclinic.com/health/food-and-nutrition/AN00413>.
Keep an eye out for another FDA update on Sunday. Until next time,
C. Samuels
Many macrolide antibiotics have a slight risk of an interaction also. Erythromycin may prolong the QT-interval which can slow heart rate. When it is not metabolized by the CYP3A4 enzyme, this risk is increased and an increased risk of sudden death has occurred in patients who use grapefruit products. Buspar (buspirone), as well as several benzodiazepines which are commonly used to treat anxiety can cause similar interactions, as well as many Calcium Channel Blockers.
Anticonvulsants, like Tegretol or Carbatrol (carbamazepine) are only considered a minor risk of interaction, but because the therapeutic window of the medication in considered small, even a small inhibition of clearance can result in unwanted side effects and a risk of toxicity. Similarly, many immunosuppressants (commonly given after organ transplants or with certain autoimmune diseases) can be shifted out of their therapeutic window by grapefruit, causing toxicity, even with low interference.
A complete list of these types of interactions can be found here or in a PDF chart here. As you can see, there is some discrepancy between the two lists and this is largely the result of varying sources and interests.
As a speedy-reference to the major interactions, The Florida Department of Citrus has provided this Quick-Check Chart, which includes the major grapefruit-drug interactions. Talk to your pharmacist about posting a copy in the pharmacy for the benefit of you, your coworkers and your patients. Obviously it doesn't cover all the interactions, but it does note the major ones and may even give you an idea of other medications in the same class to look out for.
Transporter-based drug interactions are relatively minor and are easily resolved by separating the medication from the grapefruit juice by about two hours. The mechanism of this interaction is that the grapefruit juice and the affected medication use the same channels to cross through the intestines into the blood. Think of it like a ferry to an island. The grapefruit juice and the medications need to use the same ferry to get across, but the grapefruit juice gets priority. The result is decreased effectiveness of the medication due to decreased availability. The only medication that is significantly impacted by this interaction is the antihistamine Allegra (fexofenadine). In fact, with Allegra's recent OTC launch, the manufacturers of Zyrtec decided to make a big deal of this, with the implication that it was UNSAFE to take fexofenadine with grapefruit juice. This is not the case and Chattem was quick to make sure the public was aware of this.
References
Bonagua, Ellen. "Important Message from the Allegra Medical Director." Important Message from the Allegra Medical Director. Chattem, Inc., 2011. Web. 13 May 2011. <http://www.alertmarketing.com/email/JHCE/14575_Chattem(Allegra)PH_EQ/final.html>.
Greenblatt, MD, David. "Update on Drug Interactions with Grapefruit Juice: An Evidence-Based Review." Pharmacy Times CE. Pharmacy Times CE, Jan 2010. Web. 13 May 2011. <http://secure.pharmacytimes.com/lessons/201001-01.asp>.
"Patient Advice Label: Avoid Grapefruit." Total Pharmacy Supply. Web. 13 May 2011. <http://shop.tps-online.com/prodimg/400998.jpg>.
Zeratsky, R.D., L.D., Katherine. "Grapefruit Juice: Beware of Dangerous Medication Interactions." Mayo Clinic. Mayo Clinic, 06 Nov 2010. Web. 13 May 2011. <http://www.mayoclinic.com/health/food-and-nutrition/AN00413>.
Keep an eye out for another FDA update on Sunday. Until next time,
C. Samuels
grapefruit gives an extraordinary number of medical advantages, high substance of vitamins, minerals, zinc, calcium, magnesium, biotin, and also strong antioxidants
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