In News:

Pharmacogenomics is increasingly being highlighted as a transformative approach in healthcare, enabling personalised drug prescriptions based on an individual’s genetic makeup and moving away from the traditional “one-size-fits-all” model of treatment.

What is Pharmacogenomics?

Pharmacogenomics is the study of how genetic variations influence an individual’s response to medicines. It combines pharmacology (study of drugs) with genomics (study of genes) to determine whether a drug will be effective, ineffective, or potentially harmful for a specific person. This approach replaces trial-and-error prescribing with precision medication.

Scientific Basis

• Genetic differences, especially in drug-metabolising enzymes such as the cytochrome P450 (CYP) family, significantly affect drug absorption, metabolism, and clearance.
• Nearly 75% of commonly prescribed drugs are metabolised by CYP enzymes.
• Variations create different metaboliser types:
  • Poor metabolisers → drug accumulation and toxicity
  • Ultrarapidmetabolisers → reduced drug efficacy
• Studies show that ~90% of individuals carry at least one actionable pharmacogenetic variant, making this clinically relevant at the population level.

Clinical Applications

• Cardiovascular Medicine:
  • Warfarin: Variants in CYP2C9 and VKORC1 explain ~50% of dose variability. Genotype-guided dosing reduces bleeding risk and stabilises therapy faster.
  • Clopidogrel: Loss-of-function variants in CYP2C19 reduce drug activation, increasing risk of stent thrombosis; guidelines now recommend alternative drugs for poor metabolisers.
• Psychiatry:Antidepressants and antipsychotics metabolised by CYP2D6/CYP2C19 show improved outcomes and fewer side effects with genetic-guided prescribing.
• Oncology:Screening for DPYD variants before using 5-fluorouracil prevents severe, life-threatening toxicity.
• Immunology & Neurology:Testing for HLA-B*57:01 (Abacavir) and HLA-B*15:02 (Carbamazepine) prevents fatal drug reactions such as Stevens–Johnson syndrome.

Economic Relevance

• Cost of genetic testing has declined sharply to USD 200–500 per panel.
• Pharmacogenomics is most cost-effective in chronic diseases requiring long-term medication.
• Preventing even a single serious adverse drug reaction can offset testing costs for multiple patients.
• Pre-emptive panel testing offers lifetime utility, guiding prescriptions for dozens of drugs.

Key Challenges

• Knowledge Gaps: Limited pharmacogenomics training among doctors and pharmacists.
• Infrastructure: Lack of electronic health record–based decision-support systems.
• Regulatory & Reimbursement Issues: Inconsistent insurance coverage and evolving regulatory guidance.
• Research Complexity: Millions of SNPs must be linked accurately to drug response, and drug development for small genetic subgroups can be costly.

Way Forward

• Promote pre-emptive genetic testing integrated with electronic health records.
• Strengthen medical education and clinical guidelines on pharmacogenomics.
• Expand digital clinical decision-support systems.
• Encourage public–private investment to lower costs and widen access.