Therapeutic Drug Monitoring
Therapeutic drug monitoring (TDM) is undertaken for drugs with a narrow therapeutic index, where there is only a small difference between the minimum effective concentrations and the minimum toxic concentrations in the blood. With such drugs, small increases in dose or in blood/plasma concentrations could lead to toxic effects.
Therapeutic Drug Monitoring (TDM) may therefore help to optimise therapy and avoid both sub-therapeutic and toxic plasma drug concentrations.
Always remember to treat the patient, not the level
Although plasma drug concentrations and the therapeutic interval are useful in evaluating drug therapy, they should not be the only criteria on which treatment is based. Full account must be taken of individual patient requirements and circumstances.
Timing is paramount
Drug concentrations in plasma or whole blood are only meaningful if the correct procedures are followed regarding the timing of specimens. It is very important to note the exact time the sample is taken and when each dose of the drug is given.
When a new drug is introduced, ‘steady state’ will not be achieved until four to five half-lives have elapsed after initiation of therapy or a change in dosage. Sampling before this time may not be beneficial; care needs to be taken with loading doses e.g. digoxin and phenytoin where misleading concentrations may occur in the early stages of treatment if the timing of specimens is wrong.
Interpretation of results
Concentrations can be affected by factors such as drug interactions, protein binding, drug metabolism and patient factors such as age, malabsorption and non-compliance. Also, liver and/or renal impairment may reduce clearance and increase the risk of toxicity, especially after a dose increase.
Ideal Body Weight
IBW for males (kg) = 50 + (2.3 x height in inches over 5 ft)
IBW for females (kg) = 45.5 + (2.3 x height in inches over 5 ft)
For Obese Patients- Adjusted Body Weight
Adjusted body weight (kg) = ideal body weight + 0.4 (actual body weight – ideal body weight)
|
Drug |
Therapeutic Range |
Time to steady state |
Optimum sampling time |
Major factors influencing serum levels |
Common signs and symptoms of toxicity |
|
Aminophylline |
10-20mg/L (lower levels e.g. 5-15mg/L may be effective) |
1-2 days |
IV - 18 hours after starting maintenance infusion Oral - pre -dose |
Increased by concurrent use with antibacterials (e.g. erythromycin, clarithromycin, Decreased in smokers, by drugs that induce hepatic metabolism (e.g. phenytoin, carbamazepine, rifampicin) |
Nausea , anorexia, vomiting, tachycardia, arrhythmias, agitation, convulsions |
|
Carbamazapine |
4-12mg/L |
1-2 weeks after initiation Up to 5 days after a dose change in a patient on established therapy |
Pre -dose 2 weeks on
|
Increased by concurrent use with Decreased by concurrent use with phenytoin, theophylline, rifampicin, St John’s wort |
Nausea, vomiting, dizziness, drowsiness, visual disturbances, ataxia, headache, nystagmus, hyponatraemia |
|
Digoxin |
0.5-2.0 (0.5-1micrograms/L (in heart failure)
|
7 days |
At least 6 hours after dose |
Increased by concurrent use with amiodarone |
Anorexia, headache, nausea, vomiting, diarrhoea, visual disturbances, arrhythmias. Risk of toxicity increased by electrolyte disturbances, e.g. hypercalcaemia, hypokalaemia, hypomagnesaemia |
|
Gentamicin (once daily dosing) |
<1mg/L |
10-15 hours with normal renal function |
Pre-dose |
Increased in renal impairment
|
Nephrotoxicity, ototoxicity (augmented by other ototoxic drugs i.e. intravenous furosemide) |
|
Lithium |
0.4 - 1.0
|
4-7 days |
12 hours |
Increased in renal impairment, by NSAIDs, diuretics (especially thiazides), ACEIs, ARBs Decreased by theophylline, calcitonin |
Nausea, vomiting, diarrhoea, blurred vision, polyuria, light headedness, muscle weakness, drowsiness, fine resting tremor increasing to coarse tremor, confusion, slurred speech, ataxia, dysarthria, nystagmus, restlessness, incontinence, hypernatraemia |
|
Phenytoin |
10-20mg/L |
7-10 days |
Pre- dose |
Increased in liver impairment and concurrent administration with diltiazem, clarithromycin, fluconazole, ketoconazole Decreased by theophylline, ciprofloxacin Affected by low albumin, enteral feeds (stop feed 2 hrs before and after dose) |
Ataxia, slurred speech, nystagmus, blurred vision, lethargy, confusion, hyperglycaemia
|
|
Theophylline |
10-20mg/L (lower levels e.g. 5-15mg/L may be effective)
|
up to 5 days |
5 days after starting oral treatment and at least 3 days after any dose adjustment. Take sample pre-dose for modified release preparations |
Increased by concurrent use with antibacterials (e.g. erythromycin, clarithromycin, ciprofloxacin), antifungals (e.g. fluconazole), in liver impairment, heart failure Decreased in smokers, by drugs that induce hepatic metabolism (e.g. phenytoin, carbamazepine, rifampicin) |
Nausea , anorexia, vomiting, tachycardia, arrhythmias, agitation, convulsions |
|
Vancomycin |
15-20mg/L |
20-35 hours |
Pre-dose |
Renal function |
Nephrotoxicity, ototoxicity |