Therapeutic Drug Monitoring

(TDM)
Buddhini Nayanathara
BPharm(UOR)
 Objectives

At the end of this lecture,

Student will be able to define,
• What is TDM
• Why we are doing TDM
• What are the drugs for TDM
• Indications of TDM
• Clinical applications of TDM
 Introduction
Therapeutic drug monitoring (TDM) is,

The clinical practice of measuring specific drugs at designated

intervals to maintain a constant concentration in a patient’s blood
stream, thereby optimizing individual dosage regimens
In other words, TDM refers to the individualization of drug
dosage by maintaining plasma or blood drug concentrations
within a targeted therapeutic range or window.

The goal of this process is to individualize therapeutic

regimens for optimal patient benefit
By combining knowledge of pharmaceutics, pharmacokinetics
and pharmacodynamics, TDM enables the assessment of the
efficacy and safety of a particular medication in a variety of
clinical settings.
 TDM in Simply…..

• In here we can check the plasma concentration of a drug in particular

time intervals

• Then we can identify whether that concentrations are within the safe
area or not (according to the therapeutic window of particular drug)

• Then we can adjust the dose according to that (on safe area)

• This is used for drugs with narrow therapeutic range

 TOXIC LEVEL

PLASMA DRUG CONCENTRATION MTC

THERAPEUTIC RANGE

MEC

SUB THERAPEUTIC LEVEL (Not reached to the therapeutic

outcomes)

TIME

MEC = Minimum Effective Concentration

MTC = Minimum Toxic Concentration
 Necessity of TDM

The science of Therapeutic Drug Monitoring grew out of the

recognition that:
• Certain drugs have a narrow therapeutic range
• In concentrations above the upper limit of the range, the drug
can be toxic
• In concentrations below the lower limit of the range, the drug
can be ineffective
• Not all patients have the same response at similar doses
 Criteria for TDM
• An appropriate analytical test for drug and active metabolites
must exist

• Drug should have a narrow therapeutic range

• Patents not showing adequate clinical response to a drug

despite being on adequate dose
There are several classes of drugs commonly monitored to
ensure correct blood concentration, including the following:

• Antiepileptics
Ex. Phenytoin, Valporic acid, etc.
• Antiarrythmics
Ex. Digitalis, Lignocaine, etc.
• Antibiotics
Ex. Gentamycin, Amikacin, Tobramycin
• Antineoplastics
Ex. Methotrexate
• Antimanics
Ex. Lithium
• Bronchodilators
Ex. Theophylline
• Immunosuppressives
Ex. Cyclosporine
 Indications for TDM
1. Drugs with a low therapeutic window:- will allow dose alterations to produce
optimal therapeutic effect or to avoid toxic effects. Ex: Lithium, phenytoin, and
digoxin

2. Drugs for which relationship between dose and plasma concentration is

unpredictable. Ex: Phenytoin

3. To evaluate compliance/ Non compliance of patient

4. Wide variation in the metabolism of drugs

5. For diagnosis of suspected toxicity & determining drug abuse

6. Drugs with steep dose response curve (small increase in dose
can result in a marked increase in desired/ undesired
response Ex: Theophylline)

7. When another drug alter the relationship between dose &

plasma concentration . Ex: plasma concentration of lithium is
increased by thiazide (Drug interaction)
8. Renal disease (Alter the relationship between dose and the
plasma concentration. Important in case of digoxin, lithium
and aminoglycoside antibiotics)
 TDM is unnecessary when:
1. Clinical outcome is unrelated either to dose or to plasma
concentration (That mean, TDM is unnecessary, when the
clinical outcome of a drug is not depended on the dose or
plasma concentration)

2. Dose need not be individualized

3. The pharmacological effect can be clinically quantified. (BP, HR,
Blood sugar, urine volume etc.)

4. Drugs with wide therapeutic range such as beta blockers and

calcium channel blockers
 Clinical Applications of TDM
• To confirm adequate serum concentrations where clinical
response is inadequate: TDM can be used to assess the
appropriateness of dosing regimen to maintain the minimum
concentration required to exhibit efficacy

• To avoid drug toxicity: maintaining a drug within the therapeutic

range can help to minimize the risk of toxicity
• To individualize dosing of some drug with an unpredictable
dose-response curve. Ex: Phenytoin

• To assess medication compliance

• To help predict a patients dose requirements

• To minimize the time period needed for dosage adjustment

• To identify poisons and to assess the severity of poisoning on an
emergency basis in a poisoned patient

• To assist dose adjustment in various disease states where

individual variations in drug ADME is important
 Basic Principles of TDM
1. Measurement of patient's serum or plasma drug
concentration taken at appropriate time after drug
administration

2. Knowledge of pharmacological and pharmacokinetic profiles

of the administered drugs
3. Knowledge of relevant patient’s profile like demographic
data, clinical status, laboratory and other clinical
investigations

4. Interpretation of Serum Drug Concentration (SDC) after

taking into consideration all of the above information and
individualizing drug regimen according to the clinical needs of
the patient
 Process of TDM
• Development of plasma profile in each patient

1. Administering a predetermined dose of drug

2. Collection of blood samples

3. Determination of blood samples

4. Plasma profile and pharmacokinetic model development:
- Clinical effect of drug
- Development of dosage regimen
- Diagnosis, dosage form selection, dosage regimen,
initiation of therapy

Evaluation of Clinical Response

 This is a multidisciplinary action

For that,

Physicians, Clinical pharmacists, Medical

Laboratory scientists, Nurses are involved
 Digoxin
Plasma Concentration Response

0.5 mcg/L No therapeutic effect

0.7 mcg/L Some increment in force of contraction of

heart
0.8 mcg/L Optimum therapeutic range

2-2.5 mcg/L Increase risk of toxicity although tolerated

in some patients
2.5 mcg/L Gastrointestinal, Cardiovascular and CNS
toxicity
 Theophylline
Plasma Concentration Response

5mg/L No bronchodilation

5-10 mg/L Some bronchodilation

10-20 mg/L Optimum bronchodilation, minimum

side effects
20-30 mg/L Increase incidence of nausea, vomiting
and cardiac arrhythmias
30 mg/L Cardiac arrhythmias and Seizures
 Lithium
Plasma Concentration Response

0.4 mmol/L Little therapeutic effect

0.4 to 1 mmol/L Optimum range for prophylaxis of mania

0.8 to 1.2 mmol/L Optimum range for acute mania

1.2 to 1.5 mmol/L Causes possible renal impairment

1.5 to 3 mmol/L Renal impairment, weakness, drowsiness,

thirst and diarrhea
3 to 5 mmol/L Confusion, convulsions, coma and death
 Phenytoin
Plasma Concentration Response

0.5mg/L No therapeutic effect

5-10 mg/L Some anti-convulsant action

10-20 mg/L Optimum concentration for convulsant

effect
20-30 mg/L Blurred vision

30 mg/L Ataxia, drowsiness, coma

 Summary
• TDM is the individualization of drug dosage by maintaining
plasma or blood drug concentrations within a targeted
therapeutic range or window
• This is applicable for safe use of drugs with narrow
therapeutic index Ex: Lithium, Digoxin, Phenytoin,
Theophylline, etc.
• TDM is used for reducing toxic effects of drugs, obtaining the
optimum therapeutic effect, individualizing of dosage and
increasing compliance
 Questions
1. Write a short note on Therapeutic Drug Monitoring

2. What are the indications for Therapeutic Drug Monitoring?

THANK YOU