Therapeutic drug monitoring (Guidelines)

DRUG

TIME TO STEADY STATE

IDEAL SAMPLING TIME

TARGET RANGE

COMMENTS

CARBAMAZEPINE

2 to 3 weeks (initiation)

At least 2 to 4 weeks after dose change

Before dose (not critical)

4 to 12mg/L

Induces its own metabolism (peaks 3 weeks after initiation).

Check drug interactions especially with other antiepileptics and drugs with narrow therapeutic index.

Sampling is only useful if toxicity or poor compliance suspected. 

CICLOSPORIN

2 to 4 days

TROUGH (12 hours post-dose )

For renal transplant patients the levels are individualised according to patient risk – contact a Renal Consultant for advice.

Ulcerative colitis (short-term)

100 to 200 micrograms/L

Red EDTA tube to be sent to Blood Sciences for analysis on Tuesdays and Thursdays.

DIGOXIN

7 to 10 days (initiation and after dose change) This time is prolonged in renal impairment and can take up to 3 weeks.

Before dose or over 6 hours after dose

0·5 to 1 micrograms/L (Toxicity is more common at levels >2micrograms/L but may occur at lower levels.  When interpreting levels the clinical state of the patient, potassium level and thyroid function should be taken into consideration.)

Dose requirements are lower in renal impairment and the elderly.  Plasma digoxin levels should not be done routinely but are indicated: when toxicity is suspected, to assess lack of response ie suspected poor compliance, when an interacting medication is stopped or started or for patients with renal impairment (CrCl <20ml/min) where accumulation may result in toxicity.  For patients with CrCl<20ml/min a level should be taken within 7 days of initiation and at 3 weeks.  Levels should then be done periodically every 6 to 12 months or when there is a change to patient’s renal function or other reason to suspect toxicity.

GENTAMICIN

(See guidelines for dose selection criteria and assistance with therapeutic monitoring)

1 day (depends on renal function)

Use with caution in oliguric patients who are critically unwell.

For high-dose regimen

6 to 14 hours after start of infusion.

Use nomogram for timing of subsequent doses.

See nomogram on prescription chart or online gentamicin calculator

For all regimens dose interval depends on renal function, monitor more frequently if renal function changes or is unstable.

For high-dose regimen monitor once at initiation then every 2 or 3 days if renal function is stable. If renal function is unstable, monitor levels after every dose.

For guidance on gentamicin use in the treatment of infective endocarditis refer to ‘Policy for use of intravenous gentamicin as part of management of infective endocarditis in adults’.

LITHIUM

5 days (initiation and after dose change)

12 hours after dose

0·4 to 1 mmol/L (narrower range may be advised by psychiatrist)

Dose depends on renal function.

Check lithium level 4 to 7 days after initiation and 7 days after a dose change.

Monitor weekly until stabilised then every 3 months.

Monitor more regularly if renal function changes.

Monitor thyroid, calcium and renal function every 6 months. See CMO(2019)04: National guidance for monitoring Lithium. 

Check drug interactions.

Check lithium levels when interacting medication is started or stopped.

PHENYTOIN

2 to 3 weeks (initiation and after dose change)

Before dose (not critical)

10 to 20mg/L

Check phenytoin level 3 days after initiating treatment to confirm the patient’s metabolism is not remarkably different from the norm. 

Care with increase in dose – non-linear rise in level.

Care if hypoalbuminaemia, liver or renal failure. Check for drug interactions.

SIROLIMUS*

2 to 4 days

TROUGH (24 hours post-dose)

For renal transplant patients the levels are individualised according to patient risk – contact a Renal Consultant for advice.

Red EDTA tube to be sent to Blood Sciences for analysis on Fridays.

TACROLIMUS

2 to 4 days

TROUGH (12 or 24 hours post-dose depending on preparation prescribed)

For renal transplant patients the levels are individualised according to patient risk – contact a Renal Consultant for advice.

Red EDTA tube to be sent to Blood Sciences for analysis on a Monday, Wednesday and Friday.

TEICOPLANIN

3 to 5 days if loading dose given

TROUGH

20 to 30mg/L

For some deep seated infections, troughs up to 40mg/L may be required.

Troughs above 60mg/L associated with toxicity.

Loading dose is required to achieve steady state.

Serum levels sent to Bristol Laboratory on weekdays with turnaround time of 1 to 2 days.

TOBRAMYCIN

1 day (depends on renal function)

TROUGH (before dose)

PEAK (1 hour after end of infusion)

TROUGH less than 2mg/L

PEAK 6 to 10mg/L

Dose depends on renal function.

Monitor more frequently if renal function changes.

Alternative dosing regimens are used in patients with cystic fibrosis, seek advice from respiratory physicians.

THEOPHYLLINE

(aminophylline)

At least 5 days (initiation and after dose change)

or immediate if given IV (aminophylline) with a loading dose

Oral:

– 4 to 6 hours after dose (not critical)

Intravenous no loading:

– 4 to 8 hours after start of infusion

Intravenous with loading:

– 30 to 60 minutes

Conversion from IV to oral:

– over 24 hours after oral dose

10 to 20 mg/L

(serum levels of aminophylline are expressed as theophylline)

Some clinicians use low oral dose as there is evidence of therapeutic effect at levels as low as 5mg/L.

Aminophylline is theophylline in a formulation for intravenous administration.

Monitoring is more important for intravenous therapy or suspected toxic reaction.

Clearance altered by other drugs, smoking, hepatic dysfunction, cardiac disease and COPD, can be difficult to predict with any accuracy.

VALPROIC ACID

3 days

Pre-dose

50 to 100mg/L

Rarely useful.

Poor correlation between concentration and effect.

Sampling is only useful if toxicity or poor compliance suspected.

VANCOMYCIN

(See guidelines for dose selection criteria and therapeutic monitoring)

1 day if loading dose is given (depends on renal function)

TROUGH (before dose)

PEAK (2 hours after end of infusion)

TROUGH 10 to 20mg/L depending on advice from Microbiology

PEAK 18 to 26mg/L

Dose depends on renal function.

Monitor more frequently if renal function changes.

For deep-seated infections, troughs up to 20mg/L may be recommended by Microbiology.