Therapeutic drug monitoring (TDM) involves measuring specific drug levels in a patient's bloodstream to maintain concentrations within a therapeutic range. TDM aims to optimize dosage regimens for individual patients. It is used to individualize therapy during initial treatment or dosage changes, monitor compliance, diagnose undertreatment, avoid toxicity from drug interactions, and guide withdrawal of therapy. TDM is most useful for drugs with narrow therapeutic windows where plasma concentrations are directly correlated with pharmacological or toxic effects.

1. Therapeutic Drug Monitoring
(TDM)

2. What is TDM??
• Therapeutic drug monitoring (TDM) is the clinical practice of
measuring specific drugs at designated intervals to maintain a
constant concentration in a patient’s bloodstream, thereby optimizing
individual dosage regimens
• TDM refers to the individualization of drug dosage by maintaining
plasma or blood drug concentrations within a targeted therapeutic
range or window
• Therapeutic drug monitoring is the measurement of specific drugs
and their metabolites at timed intervals to maintain a relatively
constant concentration of the medication in the blood.

3. • TDM involves the measurement of
drug concentrations in biological
fluid and the interpretation of
those concentrations.
• TDM is the clinical assessment of a
drug's pharmacokinetic properties.
• Interpretation requires knowledge
of the pharmacokinetics, sampling
time, drug history and the patient's
clinical condition
Therapeutic
Drug
Monitoring
Interpretation
Therapeutic
Drug
Measurement
What is TDM??

4. Why TDM??.... The Indication
1. Individualizing therapy
a. during early therapy
b. during dosage changes
2. Monitoring compliance
3. Diagnosing undertreatment
4. Avoiding toxicity
5. Monitoring and detecting drug interactions
6. Guiding withdrawal of therapy

5. Individualizing therapy
• during early therapy
• when the drug is being used as prophylaxis, it is impossible to monitor a response.
Thus, the physician can select a dosage that will produce a certain target plasma
concentration.
• Eg: In case of lithium in preventing manic-depressive attacks, to phenytoin in
preventing fits after neurosurgery or trauma, and to cyclosporine in preventing
transplant rejection.
• In all cases, plasma concentration measurements obtained and scrutinized during the
early treatment stages enable the physician to avoid toxic plasma concentrations.
• it is most important for those with narrow therapeutic ranges such as lithium,
cyclosporine, and aminoglycoside antibiotics
• during dosage changes
• If the dosage regimen must be altered for any reason at a later stage of treatment,
for example, in patients with renal failure, measuring plasma concentrations again
may be helpful

6. Monitoring compliance
• a low plasma concentrations reflects either poor recent compliance
or undertreatment.
• Poor compliance is implicated if the patient is prescribed a dose that
is unlikely to be associated with a measured low concentration or if a
previous measurement suggested that the plasma concentration
should be higher for the given dose

7. Diagnosing undertreatment
• Undertreatment of an established condition may be concluded if a
poor clinical response is observed
• When a loading dose of oral amiodarone is required in a patient
receiving digoxin, the digoxin dosage should first be reduced, and
digoxin therapy should be adjusted based on any signs and symptoms
of digoxin toxicity. This approach also applies to theophylline when
erythromycin is added to the regimen. Conversely, measuring the
whole blood cyclosporine concentration will help to avoid
undertreatment if rifampicin is added.

8. Avoiding toxicity
• drug toxicity can be diagnosed clinically.
• For example,
• it is relatively easy to recognize acute phenytoin toxicity, and measuring the
plasma concentration may be helpful in adjusting the dosage subsequently.
• digoxin toxicity may mimic certain symptoms of heart disease, and measuring
the plasma concentration in cases in which toxicity is suspected may be
helpful in confirming the diagnosis
• nephrotoxicity of aminoglycoside antibiotics is difficult to distinguish clinically
from that caused by a severe generalized infection. Thus, measuring
aminoglycoside plasma concentrations may help to distinguish between
toxicity and infection

9. Monitoring and detecting drug
interactions
• If the potential for a drug interaction is suspected, then measurement
of the plasma concentration may guide subsequent changes in
dosage.
• For example, when giving a thiazide diuretic to a patient taking
lithium, measuring the plasma lithium concentrations is helpful to
avoid drug interaction and toxicity

10. Guiding withdrawal of therapy
• Therapeutic drug monitoring for methadone in addiction recovery
patients is crucial for safety and success in recovery.
• Monitoring drug concentration levels through blood sampling ensures
patients adhere to the prescribed methadone usage to avoid
addiction or withdrawal complications and other related hazards

11. Therapeutic Range
• The therapeutic range
or therapeutic window
is the concentration
range of drug in plasma
where the drug has
been shown to be
efficacious without
causing toxic effect in
patient.

12. TDM will be useful if the following criteria are
met:
1) the drug in question has a narrow therapeutic range
2) A low toxic: therapeutic ratio
3) a direct relationship exists between the drug or drug metabolite
levels in plasma and the pharmacological or toxic effects
4) the therapeutic effect can not be readily assessed by the clinical
observation
5) large individual variability in steady state plasma concentration exits
at any given dose
6) appropriate analytic techniques are available to determine the drug
and metabolite levels.

13. TDM is unnecessary when
1) Clinical outcome is unrelated either to dose or to plasma
concentration
2) dosage need not be individualized
3) the pharmacological effects can be clinically quantified
4) when concentration effect relationship remains unestablished
5) drugs with wide therapeutic range such as beta blockers and
calcium channel blockers.