Therapeutic Drug Monitoring in Adults at NUH

The aim of TDM is to provide information that assists in achieving rapid, optimum treatment. In general, routine measurements are not required (exceptions: lithium, ciclosporin,
IV aminophylline and some antibiotics – see below), but rather taken to resolve a specific clinical problem, e.g. inadequate response, signs of toxicity.

Appropriate and documented specimen collection time is vital When taking a level, the following must be considered to avoid misleading results:

1. For dosage adjustment guidance, sampling at ‘steady-state’ is essential (unless confirming toxicity) and thus at least four elimination half-lives must have elapsed since the
last change of maintenance dose.
2. Samples must be taken at an appropriate time during a dose interval.
Interpretation of most results is made in relation to the therapeutic range but clinical decisions should not be based on drug concentrations alone. The range is only a guideline
derived from a normal population and some patients will respond or exhibit toxicity outside the expected ranges. Concentrations can be affected by factors such as age, drug
interactions, protein binding and drug metabolism. Also, liver and/or renal impairment may reduce clearance and increase the risk of toxicity, especially after a dose increase.

The following provides a guide to the most requested drug assays provided by the Department of Clinical Pathology. Drugs analysed daily at City & QMC are: lithium, digoxin,
theophylline, carbamazepine, phenytoin, gentamicin, vancomycin and tobramycin. Ciclosporin and tacrolimus are analysed at City Campus every weekday; to arrange analysis
on Saturday contact the City Campus duty biochemist on ext 59729 or bleep 7796. Lamotrigine and clozapine are analysed at QMC Campus 1-2 times per week. If results for
any drug are required urgently please telephone the laboratory first: QMC Campus 64932, City Campus 54436, out of hours bleep via switchboard.

Drug Therapeutic range Number of days Optimum sampling time Common signs and Type of sample
before steady state symptoms of toxicity required
Aminophylline Nausea, vomiting, tachycardia, 5mL serum (not
10 - 20mg/L 1 Sampling time not critical
Infusion anorexia, arrhythmias SST)
8 after first dose Nausea, vomiting, dizziness, 5mL serum (not
Carbamazepine 4 - 12mg/L Trough measurement before a dose
4 after a dose change visual disturbances SST)
12 hours after evening dose (for once daily Tremor, ataxia, dysarthria,
Lithium 0.4 - 1.2 mmol/L 5 nystagmus 5mL SST
dosing; otherwise, please discuss)
For renal transplant patients, use pre-dose See data sheets/BNF
Contact lab. Varies (trough) or 2 hour post dose Note, many drug interactions
Ciclosporin 4 5mL EDTA
with indication measurements (label clearly). For all other
oral uses, take trough level. IV anytime.
Drowsiness, lethargy, areflexia, 5mL serum (not
Clozapine 350-1000mg/L 2 Trough measurement before a dose coma, confusion, hallucinations SST)
At least 6 hours after oral dose. A trough Anorexia, vomiting, diarrhoea, 5mL serum (not
Digoxin 0.8 – 2.0µg/L 5
measurement before a dose is preferred visual disturbances SST)
Nystagmus, ataxia, impaired 5mL serum (not
Lamotrigine 2-15mg/L 5 Trough measurement before a dose
consciousness SST)
PO: Sampling time not critical due to slow Ataxia, slurred speech, 5mL serum (not
Phenytoin 10 - 20mg/L 7
absorption time. IV: trough measurement nystagmus, blurred vision SST)
5 - 15 µg/L + refer to See data sheets/BNF
Tacrolimus 4 Trough measurement before a dose 5mL EDTA
local guidance Note, many drug interactions
Theophylline Nausea, vomiting, tachycardia, 5mL serum (not
10 - 20mg/L 2 Trough measurement before a dose
Tablets anorexia, arrhythmias SST)

SST: Serum Separator Tube - gold top ; Serum (not SST) – red top tube ; EDTA - purple top
The following summarises optimum sampling times for antibiotics:
Drug/Dosing Optimum sampling time(s) Dose adjustments Target Range/Points to note Sample
Schedule Required
Weekdays only. Processed off-site, results available next day.
Usual dose is 15mg/kg/day in two
Ideal levels: Pre-dose (trough) <10mg/L Post-dose (peak)
Pre-dose (trough) level and post- divided doses. Advice on dosing and
>20mg/L
dose (peak) level one hour after dose adjustments in renal impairment
Amikacin Further monitoring is usually twice weekly pre-dose levels if no 5mL SST
administration. Samples should be and subsequent monitoring should be
dose change and normal renal function + urine output
taken after 24hrs. discussed with a medical microbiologist.
A medical microbiologist will give advice on dosage and the
need for further assays if abnormal results
Pre-dose (trough) level just before Patients with impaired renal function Ideal levels: Pre-dose (trough) <2mg/L (endocarditis <1mg/L)
Multiple Daily
the third or fourth dose and should have a loading dose, but Post-dose (peak) 5-10mg/L(endocarditis 3-5mg/L)
Dose 5mL SST
post-dose (peak) level one hour subsequent dosing and monitoring See antibiotic website for more advice if sub-therapeutic/toxic.
Regimen
after administration. should be discussed with a Further monitoring is usually twice weekly trough levels, if no
Gentamicin
microbiologist dose changes and normal renal function + urine output.
If patient is <65 yrs with good renal The ideal pre-dose (trough) level is <1.0mg/L. It is not
Once Daily function + urine output, give second necessary to do a post-dose level.
Gentamicin + Trough level 18-24 hours after the dose without awaiting result See antibiotic website for more advice if sub-therapeutic/toxic.
5mL SST
Tobramycin first dose If patient is >65 yrs or abnormal renal Further monitoring is usually twice weekly pre-dose (trough)
Dosing function await result and advice from levels if no dose-change and normal renal function + urine
medical microbiologist output.
Ideal levels: Pre-dose (trough) <2mg/L
Pre-dose (trough) level just before
Multiple Daily Advice on dosing and dose adjustments Post-dose (peak) 5-10mg/L
the third or fourth dose and
Dose in renal impairment and subsequent See antibiotic website for more advice if sub-therapeutic/toxic.
post-dose (peak) level one hour 5mL SST
Regimen monitoring should be discussed with a Further monitoring is usually twice weekly pre-dose levels if no
after administration.
Tobramycin medical microbiologist. dose changes and normal renal function +urine output.

Pre-dose (trough) level just before The standard target range is 10-15mg/L although microbiology
the third or fourth dose. A level The normal dose is 1g BD, adjust dose may advise a higher range (15-20mg/L) for less-susceptible
should be taken and the dose to 1g OD if patient is >65 yrs or has CrCl MRSA.
5mL SST
Vancomycin administered (unless severe renal of 20-50ml/min. For critical care patients See antibiotic website for more advice if sub-therapeutic/toxic.
impairment). Assay result should be use an alternative dosing regimen – see Further monitoring is usually twice weekly pre-dose (trough)
checked before the following dose the antibiotic website. levels if no dose changes and normal renal function + urine
is given. output.
Information needed on the request card: Time of last dose, dosage regimen and level taken (Pre/Post), indication for treatment, body weight and other antibiotics: see Antibiotics website for
more details.
• Teicoplanin and aciclovir, monitoring is not normally required, but can be monitored after discussion with microbiology in renal impairment or when treating severe infections.
• Monitoring for 5-flucytosine should be arranged with microbiology who will advise what levels are required.
• For streptomycin, levels should be arranged with microbiology and taken pre and (1 hour) post the fourth dose (sent by microbiology to reference laboratory).

For further information or advice on therapeutic drug monitoring, or how to manage toxic or sub-therapeutic levels, please contact:
Pharmacy, Medicines Information 64185 or 61200. Out of hours contact the On-call Pharmacist via switchboard Updated:
Microbiology, see guidance on antibiotic website Duty doctor 61163 Tim Hills/ Tony Hitch : Sept. 2011
Clinical Pathology, QMC 63087/61168, NCH 55591/55592. Out of hours please contact the On-call Clinical Biochemist via switchboard Update ratified DTC: Sept 2011
at either campus. Review date: Sept 2013