# Pharmacogenomics and Therapeutic Drug Monitoring

> Pharmacogenomics and therapeutic drug monitoring for NEET-PG Medicine: HLA-B*1502, TPMT, G6PD and CYP2C19 testing, and drugs needing level monitoring.

- Canonical URL: https://prepelephant.com/topics/neet-pg/medicine/pharmacogenomics-and-therapeutic-drug-monitoring
- Exam / course: NEET-PG · Subject: Medicine
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-14
- Last updated: 2026-10-14
- Reference basis: Goodman and Gilman's The Pharmacological Basis of Therapeutics; CPIC Guidelines
- How to cite: "Pharmacogenomics and Therapeutic Drug Monitoring", PrepElephant, https://prepelephant.com/topics/neet-pg/medicine/pharmacogenomics-and-therapeutic-drug-monitoring

## Direct answer

Pharmacogenomics uses a patient's genotype to predict drug response and toxicity, while therapeutic drug monitoring measures drug concentrations to individualise dosing. Tests such as HLA-B*1502 before carbamazepine, TPMT before thiopurines and G6PD before primaquine prevent serious toxicity. Level monitoring is reserved for narrow therapeutic index drugs such as lithium, digoxin, phenytoin and vancomycin.

## What you must remember

- **Allele screening:** HLA-B*1502 is strongly linked to carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis, mainly in people of Asian ancestry, so testing precedes the first dose. HLA-B*5801 is similarly linked to allopurinol severe skin reactions.
- **TPMT and NUDT15:** deficiency raises thiopurine toxicity, so azathioprine and mercaptopurine doses are reduced or changed according to genotype.
- **G6PD deficiency:** oxidant drugs such as primaquine, dapsone, rasburicase and sulfonamides can cause haemolysis, so status is checked first.
- **CYP2C19:** poor metabolisers activate clopidogrel poorly, so an alternative P2Y12 inhibitor may be considered.
- **CYP2D6:** ultrarapid metabolisers convert codeine to high morphine levels, which is why codeine is restricted in children.
- **Narrow therapeutic index:** lithium, digoxin, phenytoin, valproate, vancomycin, aminoglycosides, tacrolimus and theophylline need level monitoring.
- **Timing:** levels are drawn at steady state, about five half-lives after a dose change, since earlier samples mislead.

## Choosing the right test before the first dose

A 30-year-old woman of Asian ancestry with epilepsy is due to start carbamazepine. The question is which genetic or level-based test belongs before the drug and which belongs after it.

| Gene or test | Drug | Action |
|---|---|---|
| HLA-B*1502 | Carbamazepine | Test before starting; choose an alternative if positive |
| HLA-B*5801 | Allopurinol | Test where the allele is common; alternatives if positive |
| TPMT | Azathioprine, mercaptopurine | Reduce dose or change drug when deficient |
| G6PD | Primaquine, dapsone | Avoid oxidant drugs in deficiency |
| CYP2C19 | Clopidogrel | Consider an alternative P2Y12 inhibitor in poor metabolisers |
| Drug level | Lithium, digoxin, phenytoin, vancomycin | Trough at steady state against an indication target |

Genetic tests are done once and applied before the first dose, while level monitoring is repeated and follows the patient over time. Both are needed for some drugs, such as thiopurines given with TPMT results and later clinical monitoring. Ordering also depends on ancestry, because the same allele is common in some populations and rare in others.

## Where the exam tries to catch you

Pharmacogenomics questions test whether the test is done before or after the drug, and which drug the gene governs.

- **Trap:** starting primaquine without a G6PD check. **Correct:** G6PD deficiency causes haemolysis with primaquine, so the test must come first.
- **Trap:** adding carbamazepine in a patient of Asian ancestry without testing. **Correct:** HLA-B*1502 testing is advised first, since the allele carries high risk of severe skin reactions.
- **Trap:** reading a lithium level drawn too early after a dose change. **Correct:** levels are interpreted at steady state, so the timing of the sample matters as much as its value.

## Frequently asked questions

### Which genetic test is done before starting carbamazepine?

HLA-B*1502 testing is done before starting carbamazepine, particularly in patients of Asian ancestry. A positive result indicates high risk of Stevens-Johnson syndrome or toxic epidermal necrolysis, so an alternative drug is usually chosen.

### Why is TPMT testing done before azathioprine?

TPMT testing identifies patients with reduced activity of the enzyme that inactivates thiopurines. Deficiency leads to high levels of active metabolites and severe myelosuppression, so doses are reduced or altered after the genotype is known.

### Which drugs need therapeutic drug monitoring in routine practice?

Lithium, digoxin, phenytoin, valproate, vancomycin, aminoglycosides, tacrolimus and theophylline need therapeutic drug monitoring because their therapeutic windows are narrow. Each is measured at steady state against a target set by its indication.

### What does CYP2C19 testing change in clinical practice?

CYP2C19 testing identifies poor metabolisers who activate clopidogrel poorly, so an alternative P2Y12 inhibitor may be considered. The same enzyme also handles some proton pump inhibitors, so their exposure varies with genotype.

### Why is G6PD testing needed before primaquine?

G6PD testing is needed before primaquine because deficient red cells are at risk of oxidant-induced haemolysis. Primaquine, dapsone, rasburicase and some sulfonamides are oxidant drugs that cause this, so G6PD status is checked first.