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ukmla 2026

Therapeutic Drug Monitoring

Measurement of drug concentrations in blood to optimise efficacy and minimise toxicity — essential for narrow therapeutic index drugs where small changes in level cause significant clinical effects

Review date
reviewed 2026-04-05
Reading time
4 min read
Author
Dr Kola Tytler MBBS CertHE MBA MSt MRCGP
Clinical Pharmacologycommonchronic
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Condition details
Clinical Pharmacology
common
4 min read
reviewed 2026-04-05
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About This Page

This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.

Key points

  • TDM is indicated for drugs with narrow therapeutic index, significant toxicity, and unreliable dose-response relationship
  • Key drugs requiring TDM: gentamicin, vancomycin, lithium, digoxin, phenytoin, carbamazepine, theophylline, ciclosporin, tacrolimus
  • Sampling time is CRITICAL: trough (pre-dose) for most drugs; 12 hours post-dose for lithium; peak and trough for gentamicin (Hartford nomogram)
  • Gentamicin: once-daily (extended-interval) dosing is standard — monitor with Hartford nomogram or local protocol
  • Vancomycin: AUC/MIC-guided dosing is now preferred over simple trough monitoring

Overview

Therapeutic drug monitoring (TDM) involves measuring drug concentrations in blood (usually plasma or serum) to individualise dosing and maintain drug levels within a target range. TDM is most useful for drugs with a narrow therapeutic index (small margin between therapeutic and toxic concentrations), unpredictable pharmacokinetics, serious toxicity, and where clinical response is difficult to measure directly. The timing of blood sampling relative to the last dose is critical — incorrect timing leads to uninterpretable results. TDM is particularly important in patients with renal or hepatic impairment, extremes of age, and those on multiple interacting drugs.

Epidemiology

TDM is a routine part of clinical practice in hospital medicine, particularly in infectious diseases (aminoglycosides, vancomycin), psychiatry (lithium, clozapine), neurology (antiepileptics), and transplant medicine (ciclosporin, tacrolimus). Inappropriate drug levels are a significant cause of preventable ADRs and treatment failure. Approximately 30% of patients on narrow TI drugs experience subtherapeutic or supratherapeutic levels at some point.

Clinical Features

Symptoms
This topic covers a monitoring strategy rather than a clinical condition
Signs

Investigations

First-line
Drug level at correct sampling timeTiming is critical — see individual drug protocols below
Second-line
Renal and hepatic functionAdjust doses based on eGFR and LFTs — affects drug clearance

Management

BNF TDM guidance + local hospital protocols
1
Key drugs and their monitoring
  • Gentamicin: once-daily dosing (5–7 mg/kg) — check level at 6–14 hours post-dose, plot on Hartford nomogram. Trough <1 mg/L to avoid nephro/ototoxicity
  • Vancomycin: AUC/MIC target 400–600 (or trough 15–20 mg/L for serious infections in older protocols). Draw trough immediately before next dose
  • Lithium: 0.4–1.0 mmol/L. Take sample 12 HOURS post-dose. Monitor every 3–6 months when stable
  • Digoxin: 1.0–2.0 ng/mL. Take sample at least 6 HOURS post-dose (ideally immediately pre-dose)
  • Phenytoin: 10–20 mg/L (40–80 µmol/L). Non-linear (zero-order) kinetics — small dose increases can cause large level increases. Adjusted for albumin
  • Carbamazepine: 4–12 mg/L. Auto-induces its own metabolism — levels may fall after 2–4 weeks
  • Theophylline: 10–20 mg/L (55–110 µmol/L). Narrow TI — toxicity causes arrhythmias and seizures
  • Ciclosporin and tacrolimus: target ranges depend on organ transplanted and time post-transplant
2
When to check levels
  • At steady state (usually 4–5 half-lives after starting or dose change)
  • When toxicity is suspected
  • When efficacy is suboptimal despite adequate doses
  • After changes in renal/hepatic function
  • When interacting drugs are started or stopped

Complications

  • Toxicity from supratherapeutic levels: Nephrotoxicity (gentamicin), ototoxicity (aminoglycosides), seizures (theophylline, phenytoin)
  • Treatment failure from subtherapeutic levels: Infection breakthrough, seizure recurrence, transplant rejection
  • Incorrect sampling leading to wrong dose adjustment
UKMLA Exam Tips
  • 1Narrow therapeutic index drugs: Lithium, Digoxin, Phenytoin, Gentamicin, Theophylline, Carbamazepine, Vancomycin, Ciclosporin/Tacrolimus
  • 2Lithium: 12 hours post-dose. Digoxin: 6+ hours post-dose. Gentamicin: Hartford nomogram timing
  • 3Phenytoin has ZERO-ORDER kinetics — saturable metabolism means small dose changes cause disproportionate level increases
  • 4Phenytoin level must be corrected for low albumin: adjusted level = measured / (0.2 × albumin [g/L]/44 + 0.1)
  • 5Gentamicin causes nephrotoxicity and ototoxicity — monitor trough levels (<1 mg/L)
  • 6Carbamazepine auto-induces its own metabolism — levels fall after 2–4 weeks, may need dose increase
  • 7Always check timing of the sample — a correctly timed sample is essential for interpretation

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Clinical Pharmacology · Article 11 of 16