9.2 Therapeutic Monitoring & Laboratory Interpretation
Key Takeaways
- Cockcroft-Gault creatinine clearance = (140 − age) × weight (× 0.85 for women) ÷ (72 × serum creatinine in mg/dL) — it remains the basis of most renal drug-dosing thresholds
- Draw trough levels immediately before the next dose; digoxin samples must be at least 6 hours post-dose and lithium 12 hours post-dose to be interpretable
- Key drug targets: digoxin 0.5–2.0 ng/mL, lithium 0.6–1.0 mmol/L, phenytoin 10–20 mg/L (correct for low albumin), vancomycin AUC/MIC 400–600, theophylline 10–20 mg/L
- Common renal dose triggers: metformin (stop if eGFR <30), DOACs, gabapentin and digoxin — check renal function before dispensing
- Potassium above 6.0 mmol/L, INR above 5, or digoxin toxicity symptoms are critical values requiring urgent action, documented communication and read-back
Reference Ranges a Pharmacist Must Interpret
The exam tests recognition of abnormal results and their medication implications, not just recall of numbers. Core ranges:
| Test | Typical reference / target | Pharmacist relevance |
|---|---|---|
| HbA1c (glycated haemoglobin) | Diabetes diagnosis ≥6.5%; glycaemic target often <7% (individualised) | Reflects ~3 months of glycaemic control; drives therapy escalation |
| Fasting lipid panel | Total cholesterol desirable <5.0 mmol/L; triglycerides <1.7 mmol/L; LDL goals are risk-based (e.g. <1.8 mmol/L in very-high-risk patients) | Statin monitoring and cardiovascular risk management |
| ALT / AST (liver enzymes) | Roughly <40 U/L (lab-dependent) | >3× upper limit of normal with symptoms triggers review of hepatotoxic drugs |
| TSH (thyroid-stimulating hormone) | ~0.4–4.0 mIU/L | Guides levothyroxine dose; recheck ~6 weeks after a dose change |
| INR (international normalised ratio) | Warfarin target 2.0–3.0 for most indications; 2.5–3.5 for mechanical mitral valves | Dose adjustment and bleeding-risk assessment |
| Serum potassium | 3.5–5.0 mmol/L | ACE inhibitors, ARBs, spironolactone raise it; diuretics lower it |
| Serum sodium | 135–145 mmol/L | SSRIs and diuretics can cause hyponatraemia, especially in older adults |
Therapeutic Drug Monitoring (TDM)
Trough samples are drawn immediately before the next dose; peak samples are drawn after distribution is complete. Levels are only meaningful at steady state (about five half-lives) unless toxicity is suspected.
Peak timing is drug-specific. For a conventional-dose aminoglycoside given as a 30-minute infusion, the peak is taken about 30 minutes after the infusion ends. For vancomycin under AUC-guided dosing, two levels (peak and trough) within the same interval allow Bayesian or first-order AUC estimation. Samples drawn before steady state must be interpreted with caution: they can only exclude gross overdose or confirm accumulation, never confirm that the maintenance regimen is correct. When a dose is changed, wait roughly five half-lives before re-sampling — longer in renal impairment, where half-lives of renally cleared drugs such as digoxin and gentamicin are substantially prolonged.
| Drug | Target range | Sampling notes |
|---|---|---|
| Digoxin | 0.5–2.0 ng/mL (heart failure target 0.5–0.9) | Sample ≥6 hours post-dose, ideally pre-dose; hypokalaemia, hypomagnesaemia, hypercalcaemia and renal impairment potentiate toxicity |
| Lithium | 0.6–1.0 mmol/L (maintenance) | 12-hour post-dose sample; toxicity >1.5 mmol/L; dehydration, NSAIDs, ACE inhibitors and thiazides raise levels |
| Phenytoin | 10–20 mg/L | Correct for hypoalbuminaemia: adjusted level = measured ÷ [(0.2 × albumin in g/dL) + 0.1]; saturable kinetics mean small dose increases can cause large level rises |
| Vancomycin | AUC₂₄/MIC 400–600 mg·h/L for serious MRSA infection | Trough 15–20 mg/L was the historical surrogate; AUC-guided dosing is now preferred |
| Gentamicin | Once-daily dosing: trough <1 mg/L; conventional dosing: peak 5–10 mg/L, trough <2 mg/L | High troughs signal accumulation and nephro-/ototoxicity risk |
| Theophylline | 10–20 mg/L | Narrow therapeutic index; levels rise with ciprofloxacin, erythromycin and cimetidine, and fall in smokers |
Interpreting Liver Enzyme Patterns
When reviewing liver function tests (LFTs), look at the pattern, not just the magnitude. A hepatocellular pattern (ALT/AST markedly raised, alkaline phosphatase relatively spared) points to hepatocyte injury and triggers review of hepatotoxic drugs such as paracetamol overdose, statins, isoniazid, or valproate. A cholestatic pattern (alkaline phosphatase and bilirubin predominating) suggests impaired bile flow, as with co-amoxiclav or anabolic steroids. A rise in ALT or AST beyond three times the upper limit of normal accompanied by symptoms (nausea, jaundice, dark urine) is a standard threshold for stopping or reviewing a suspect drug. Isolated, mild, asymptomatic transaminase rises on statins are common and usually do not require discontinuation.
Renal Function Assessment and Dose Triggers
The Cockcroft-Gault equation estimates creatinine clearance (CrCl):
CrCl (mL/min) = [(140 − age) × weight in kg × (0.85 if female)] ÷ (72 × serum creatinine in mg/dL)
Drug dosing references were historically validated against CrCl, whereas laboratories report eGFR (estimated glomerular filtration rate); be alert that the two can differ, especially at extremes of body weight. Classic renal dose-adjustment triggers:
- Metformin — contraindicated if eGFR <30 mL/min/1.73 m²; review risks and benefits at 30–45 (lactic acidosis risk).
- Direct oral anticoagulants (DOACs) — dabigatran is contraindicated at CrCl <30 mL/min; apixaban, rivaroxaban and edoxaban need dose reduction or avoidance at defined renal thresholds.
- Gabapentin — reduce dose and frequency as CrCl falls; accumulation causes sedation and myoclonus.
- Digoxin — reduce maintenance dose in renal impairment and monitor levels.
- Others frequently examined: enoxaparin (reduce at CrCl <30) and many renally cleared antibiotics.
Trends vs Single Values
A single result should be interpreted against the baseline and the trend, the timing of the sample, and the clinical picture. An HbA1c falling from 9% to 7.5% is progress even though it remains above target; a potassium creeping from 4.2 to 5.4 over three visits on spironolactone is more concerning than one isolated 5.2. Never act on a laboratory number alone when a repeat sample or clinical review would change the decision.
Critical Values Requiring Urgent Action
Recognise results that cannot wait for routine follow-up:
- Potassium >6.0 mmol/L (or <3.0 mmol/L) — risk of life-threatening arrhythmia; urgent medical assessment.
- INR >5 — high bleeding risk; withhold warfarin and refer urgently, immediately if any bleeding.
- Digoxin toxicity — nausea, vomiting, anorexia, blurred or yellow-tinted vision, confusion, or new arrhythmia, especially with a level >2.0 ng/mL: withhold and refer.
The pharmacist must document and communicate critical values promptly to the prescriber, using structured communication with read-back (the receiver repeats the value back to confirm accuracy), and record who was informed, when, and the response.
Using Cockcroft-Gault, estimate the creatinine clearance of a 70-year-old woman weighing 60 kg with a serum creatinine of 1.2 mg/dL.
When should a blood sample be drawn to interpret a digoxin level for routine monitoring?
A patient taking lisinopril and spironolactone has a laboratory result showing serum potassium of 6.4 mmol/L. What should the pharmacist do?