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Which Medications are Affected by Ethnic Variations in Genotypes?

By Dr Vivienne Miller, GP and Fellow, The Royal Australian College of General Practitioners

Research is ongoing into the ethnic differences in genotypes and how this may affect certain metabolic pathways. It is known that the CYP3A pathway shows genetic variation in people of different ethnic heritage, and that this can result in altered medication effects and side-effects. It is an advantage to both the doctor and patient to be aware of this possibility when prescribing. Below is a summary of some common medications and the information that needs to be considered when suggesting them for different groups in our multi-cultural society.

Tricyclic antidepressants – Approximately 8% of Caucasian people do not metabolise tricyclics well and are at risk of toxicity. When prescribing to this group, commence with a low dose and increase slowly to avoid significant side-effects.1

Codeine – Slow and rapid metabolism of codeine is due to genetic variations in the CYP2D6 pathway.   Southern European, Arabian and some Indigenous African people may metabolise codeine quickly, and may become drowsier faster, requiring much lower doses as they are at increased risk of respiratory depression.  Slower metabolisers  include Western European and other Indigenous African people.2  These individuals are more likely to complain that codeine is ineffective for pain relief.

Warfarin – Asian people may often have VCORC1 gene variants that result in the need for a much lower therapeutic dose of warfarin.1, 3 In contrast, Indigenous African people may need a higher dose to maintain therapeutic levels.1,3

ACE inhibitors – Indigenous African people do not respond as favourably as Caucasian people to this group of medications.3 They also have an increased risk of angio-oedema from this ACE inhibitors.

Beta-blockers – Indigenous African people have a reduced antihypertensive effect from this group of medications compared to Caucasian people.3

Rosuvastatin – Asian people may need a lower starting dose and reduced total dose to avoid side-effects.1

Carbamazepine – People with Chinese, Taiwanese, Indian, Malaysian and Thai ethnicity (not Japanese people) are at increased risk of Stevens-Johnson syndrome, due to the HLA-B*1502 gene.1

 

1. Yasuda SU, Zhang L,  Huang S-M. The Role of Ethnicity in Variability in Response to Drugs: Focus on Clinical Pharmacology Studies Nature Publishing Group
http://www.fda.gov/downloads/Drugs/ScienceResearch/…/UCM085502.pdf

2. Joel Iedema. Cautions with Codeine. Australian Prescriber, Vol 34, No5, Oct 2011/.
http://www.australianprescriber.com/magazine/34/5/133/5

3. Johnson, J. New Drugs and Technologies:  Ethnic Differences in Cardiovascular Drug Response; Potential Contribution of Pharmacogenetics Circulation 2008, 118: 1383-93
http://circ.ahajournals.org/content/118/13/1383.full