Why Allegra May Not Work For You

Ever wonder why a certain medication may work great for a friend and do nothing for you?  One reason could be your genes involved in transporting the medication into and out of your cells.

Let’s take fexofenadine (Allegra) for example.  You have watery eyes and a drippy nose during spring allergy season and take some Allegra to help with the symptoms. Once swallowed, that medication is dissolved, absorbed,  and then transported to the cells where it is going to act. Plus,  it has to stay inside of those target cells.

Staying inside the cells – instead of the medicine being transported right back out of the cell – is where genetics comes in to play here.

Certain medications and toxins are transported back out of cells by an ATP-binding cassette transporter protein encoded by the ABCB1 gene.

In the epithelial cells that line your intestines, the ABCB1 proteins are involved in pumping substances back into the intestinal lumen. So imagine if you take an Allegra, it dissolves, gets absorbed, and then part of that gets pumped back into the intestines to be eliminated.

Genetic variants in ABCB1 affect how much stays in the cells vs getting eliminated (through intestines, bile, urine). In general, it is a good thing for the body to get rid of a substance that it thinks might be toxic.

While an allergy medication not working well for you isn’t really a bid deal, the real problem comes when trying to keep chemotherapy drugs inside of cancer cells. Thus, this gene has been studied in depth for drug that treat cancer.


Genetic Variants:

ABCB1 gene (multidrug resistance protein, p-glycoprotein):
The genetic variant known as rs1045642 or C3435T has been extensively studied in regards to response to quite a few different drugs. Those who have the AA genotype (23andMe orientation) have less of an efflux (outward flow) of certain drugs — meaning that less of the drug is transported back out of the cell by the ABCB1 transporter. [ref]

Less of a drug transported out of the cell usually indicates a higher effectiveness of the drug for that individual. The variant, AA, is fairly common with about 25% of Caucasians carrying it (less frequent in Asian populations).

Check your genetic data for rs1045642 C3435T (23andMe v.4 only)

  • AA: reduced drug efflux (less of the drug is moved out of the cell), thus may have a better response to fexofenadine (Allegra), may need lower dosages of some drugs in comparison to those with GG [ref][ref]
  • AG: intermediate efflux
  • GG: greater efflux (out of the cell) for drugs and toxins, thus may need higher dosages of some drugs compared to those with AA genotype

Check your genetic data for rs1128503 C1236T (23andMe v4, v5; AncestryDNA):

  • G/G: reduced drug efflux (less of the drug moved out of the cell), thus may have a better response to fexofenadine[ref]
  • A/G: intermediate efflux
  • A/A: greater efflux out of the cell, may need higher dosages compared with people with the G/G genotype

Note that the two SNPs above, rs1045642 and rs1128503, are almost always inherited together. In some studies you may see one or the other rs id referred to. [ref]


Lifehacks:

If you carry one of the variants above, you may be wondering what you can do to increase the effectiveness of your allergy medicine during this pollen season.

A natural inhibitor of ABCB1 is piperine, a substance found in black pepper. Studies have shown that piperine increases the effectiveness of fexofenadine (Allegra) by about 2-fold. [ref] [ref]  Of course, check with your doctor if you have any questions about this or other medications.



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.