Why Allegra May Not Work For You

Ever wonder why a certain medication may work great for a friend and do nothing for you? Interestingly, it could involve specific genes that transport 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 dissolves, goes through absorption, and then transports to the cells where it acts. Plus, it must stay inside of those target cells.

How the medication stays inside the cells – instead of being transported right back out of the cell – plays into genetics.

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

In the epithelial cells lining your intestines, the ABCB1 proteins involve the pumping of substances back into the intestinal lumen. So imagine taking an Allegra, it then dissolves, gets absorbed, and then part of that gets pumped back into the intestines to be eliminated.

Genetic variants in ABCB1 affect the amount staying in the cells vs the elimination. (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 drugs that treat cancer.


Genetic Variants:

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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 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

Members: Your genotype for rs1045642 is .

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

Members: Your genotype for rs1128503 is .

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.

Supplements:

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.


Related Articles and Genes:

Are you allergic to grass pollen? It may be genetic.
Allergies are usually due to a mix of genetic susceptibility and being exposed to certain triggering molecules. Several different gene variants have ties to an increased risk of grass pollen allergies.

Top 10 Genes to Check in Your Genetic Raw Data
These are 10 genes with important variants that can have a big impact on health. So check them out, cross them off your list if you don’t have them — and read the articles to learn more if you do carry the variant.



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. 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 the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.