appendix 4:
Therapeutic drug level monitoring

• Suspected toxicity
• Lack of response
• To assess patient compliance
• To assess therapy following a change in dosage regimen
• A change in clinical state of the patient
• Potential drug interaction due to a change in other medications
• Where manifestations of toxicity and disease are similar

• Only clinically relevant tests should be performed; do not perform tests that cannot be interpreted or do not assist patient management. Random levels that do not conform to the timings indicated below are not clinically useful
• Blood samples should be collected only after the drug concentration has reached steady-state i.e. at least 4 half-lives at a constant dosing regimen. Levels close to steady state may be reached earlier if a loading dose has been administered. Drugs with long half-lives may be monitored before steady-state has been achieved to ensure patients with impaired metabolism or renal excretion are not at risk of developing toxicity at the initial dosage regimen
• To interpret a result, the details of the dosage regimen (dose and duration) must be known
• For patients suspected of symptoms of drug toxicity, the best time to take the blood specimen is when the symptoms are occurring
• A range of drug concentrations is usually targeted rather than a specific value as the effect of a drug at a known concentration may vary greatly between individuals

• ‘Peak’ levels refer to the highest blood concentration of a drug after administration
• ‘Trough’ levels refer to the lowest blood concentration of a drug after administration
• ‘Steady-state’ refers to the situation reached when the intake of a drug equals that of its removal from the body
• If there is a question as to whether an adequate dose of the drug is being achieved, it is usually best to obtain trough levels (rather than peak) as these are less influenced by absorption and distribution problems. However, for some drugs where toxicity is a concern (such as gentamicin), peak levels may be requested
• Trough levels are usually obtained at the end of the dosage interval i.e. immediately before the next dose is due to be given

Peak levels are usually obtained:

• Thirty minutes after an intravenous dose (if given by infusion, 30 minutes after the infusion has been stopped). Aminoglycoside antibiotics (vancomycin, gentamicin, tobramycin) given by bolus should have their levels checked 30 minutes post dose to avoid the distribution phase
• One hour after an intramuscular dose
• One to two hours after oral dosing
• Slow release drugs may not produce peak levels for several hours after ingestion