Clinical Pharmacy · Short notes

Therapeutic Drug Monitoring: Short Notes & Cheat Sheet

Which drugs need TDM, target ranges, sampling times, and how to interpret a level in context.

Attempt Therapeutic Drug Monitoring MCQs

Short notes

Read these before you attempt the topic's MCQs.

Doing TDM properly

Most wrong TDM decisions come from a badly timed sample or from ignoring the patient's clinical state.

When TDM is useful

TDM measures drug concentrations to individualise dosing. It helps when a drug has a narrow therapeutic index, variable pharmacokinetics and a clear link between level and effect.
It also helps to check adherence, diagnose suspected toxicity and adjust doses in kidney or liver impairment.
Classic TDM drugs: digoxin, lithium, phenytoin, carbamazepine, valproate, theophylline, aminoglycosides, vancomycin, ciclosporin and tacrolimus.
Always interpret a level together with the patient's clinical state, not in isolation. Treat the patient, not the number.

Sampling

Levels are most meaningful at steady state, reached after about 4–5 half-lives (sooner if a loading dose was given).
A trough level is taken just before the next dose. A peak level is taken after distribution is complete.
Digoxin must be sampled at least 6 hours after a dose, because earlier levels reflect incomplete distribution and overestimate its effect.
Lithium is sampled 12 hours after the last dose.
Aminoglycoside peaks are drawn about 30 minutes after a 30-minute infusion ends; with once-daily dosing, a trough or a timed level with a nomogram is used.

Interpreting levels

Phenytoin is highly protein-bound. In low albumin the total level underestimates the active free drug, so correct it: corrected level = measured ÷ (0.2 × albumin in g/dL + 0.1).
Phenytoin's saturable metabolism means small dose increases can raise levels a lot.
Digoxin toxicity can occur at 'normal' levels if the patient has hypokalaemia, hypomagnesaemia or hypercalcaemia.
Vancomycin is increasingly dosed to an AUC of 400–600 mg·h/L rather than a trough alone.

Cheat sheet

High-yield facts in one place. Cover the right-hand column and test yourself.

Usual target ranges

Drug	Range (sample time)
Digoxin	0.5–2 ng/mL; 0.5–0.9 in heart failure (≥ 6 h post-dose)
Lithium	0.6–1.0 mmol/L maintenance, up to 1.2 acute (12 h)
Phenytoin	10–20 mg/L total (trough)
Carbamazepine	4–12 mg/L (trough)
Valproate	50–100 mg/L (trough)
Theophylline	10–20 mg/L (5–15 often used)
Gentamicin (conventional)	Peak 5–10, trough < 2 mg/L
Gentamicin (once daily)	Trough < 1 mg/L
Vancomycin	Trough 10–20 mg/L or AUC 400–600
Tacrolimus	Trough about 5–15 ng/mL (varies by transplant)

Level high? Check these first

Question	Why
Was the sample timed correctly?	Early digoxin samples are falsely high
Is it steady state?	Needs 4–5 half-lives
Kidney function changed?	Lithium, digoxin, aminoglycosides, vancomycin
New interacting drug?	Enzyme inhibitors, NSAIDs, diuretics
Albumin low?	Free phenytoin higher than total suggests

Memory aids

Digoxin needs Six hours: Sample digoxin at least 6 hours after the dose, after distribution.
Lithium at Twelve: Lithium levels are taken 12 hours after the last dose.

Exam traps

A digoxin level taken 2 hours after a dose is falsely high and should not be used to reduce the dose.
A 'normal' total phenytoin level can hide toxicity in a patient with low albumin.
Steady state takes 4–5 half-lives regardless of dose size; a loading dose only gets you there faster.
Once-daily aminoglycoside dosing relies on the post-antibiotic effect and a low trough to reduce toxicity.

Revised? Now test yourself.

Attempt the Therapeutic Drug Monitoring MCQs while the notes are fresh. Anything you get wrong is saved to your incorrect list for the next revision round.