Therapeutic drug monitoring (TDM) involves measuring drug concentrations in blood to optimize drug efficacy and avoid toxicity. TDM is clinically important for drugs with a narrow therapeutic window, such as anticonvulsants, cardioactive drugs, theophylline, immunosuppressants, antidepressants, and some antibiotics. Altered pharmacokinetics in disease states can be identified through TDM, allowing dosage adjustments to properly manage patients and avoid adverse reactions. TDM is performed by collecting a blood sample at an appropriate time relative to drug dosing and measuring drug concentrations, which are interpreted based on the therapeutic range for that drug.

1. THERAPEUTIC DRUG
MONITORING
What ? Why ? When ? How?
Amit Kumar
Assistant professor
pharmacology

2. WHAT IS THERAPEUTIC
DRUG MONITORING ?

3. THERAPEUTIC DRUG MONITORING (TDM)
TDM is the manipulation of the dose of a drug using
plasma concentration as a guide to optimize its efficacy,
to avoid or identify toxicity and to detect or confirm
poor compliance.

4. THERAPEUTIC DRUG MONITORING …
• The range of drug concentrations most commonly
associated with optimal effect and an acceptable
incidence of toxicity - Therapeutic range
Therapeutic range is narrow for most drugs
- below range : drug not effective
- above range : drug toxic

5. Therapeutic Drug Monitoring
• 1960s: Development of Principles of TDM
• 1970s: Automation of Laboratory Methods
• 1980s: Widespread use of TDM in UK, USA, Europe
• 1980-1990: TDM started in India

6. PURPOSE OF TDM
• To confirm ‘effective’ concentrations
• To investigate unexpected lack of efficacy
• To avoid or anticipate toxic concentrations
• To check compliance

7. INDICATIONS
• Drugs with low safety margin
e.g. —digoxin, anticonvulsants, antiarrhythmics, theophylline,
aminoglycoside antibiotics, lithium, tricyclic antidepressants.
• Effect of drug not easy to measure.
• If individual variations are large. e.g.—antidepressants, lithium.
• Potentially toxic drugs used in the presence of renal failure.
e.g. —aminoglycoside antibiotics, vancomycin.
• In case of poisoning.
• In case of failure of response without any apparent reason,
e.g. —antimicrobials.

8. COMMON DRUGS IN TDM
 Antibacterial agents
- Aminoglycosides – Amikacin, gentamicin
- Others - Vancomycin
 Antiepileptic drugs
- Phenytoin, Phenobarbital, Carbamazepine, Valproic acid
 Immunosuppressive drugs - Cyclosporine, Tacrolimus
 Cardiac drugs - Digoxin Procainamide, lidocaine
 Psychoactive drugs - Lithium, TCA
 Bronchodilator – Theophylline
 Anticancer Drugs - Methotrexate

9. WHEN IS TDM NOT NECESSARY ???
• Drugs whose response is easily measurable,
e.g.— antihypertensives, hypoglycaemics, diuretics, oral anticoagulants,.
• Wide therapeutic range.
• Consistence pharmacokinetics .
• No Linear relationship between response and plasma conc.
• Drugs activated in the body. e.g.—levodopa.
• ‘Hit and run drugs’ (whose effect lasts much longer than the drug itself),
e.g.—reserpine, guanethidine, MAO inhibitors, omeprazole.
• Drugs with irreversible action, e.g.—organophosphate anticholinesterases,
phenoxybenzamine.

10. WHEN TO DO THERAPEUTIC
DRUG MONITORING ???

11. TIMING OF THE PLASMA SAMPLE
• Depends on the purpose of TDM
• When the purpose is dose adjustment: In case of long-acting drugs just prior to
the next dose
• for short-acting drugs sampling is done usually after 1–2 hours of oral/i.m.
dosing.
• In case of poisoning: Blood for drug level estimation should be taken at the
earliest to confirm the poisoning.
• c. For checking compliance to medication: Even random blood sampling can be
informative.

12. WHAT INFORMATION IS REQUIRED
FOR INTERPRETATION?
Before making dose adjustments, it is important to consider
 Time of sample in relation to last dose
 Duration of treatment with the current dose
 Dosing schedule
 Age, gender
 Other drug therapy
 Relevant disease

13. FACTORS AFFECTING INTERPRETATION
• Changes in Protein binding
• Active metabolites

14. FACTORS AFFECTING INTERPRETATION…
Changes in Protein binding:
 Assays - plasma or blood
 Measure bound & unbound drug
 Binding is changed by - disease states, displacement by
another drug or non-linearity in protein binding
- interpretation of total plasma or blood drug
concentrations must be modified
Eg:- Sodium valproate & salicylate show non-linear
binding in the therapeutic range making interpretation of
total drug concentrations difficult.

15. FACTORS AFFECTING INTERPRETATION…
Active metabolites:
 Metabolites which may not be measured can contribute to
the therapeutic response
- Carbamazepine - Carbamazepine -10,11-epoxide
- Procainamide - N acetylprocainamide
- Primidone treatment is monitored by measuring the
concentration of the active metabolite Phenobarbitone,
But primidone itself and another metabolite,
phenylethylmalonamide are also active

16. HOW TO DO THERAPEUTIC
DRUG MONITORING ???

17. TDM PROCESS
Clinical pharmacologists, clinical pharmacists analytical
scientists, doctors and nurses
Doctors request TDM tests for specific patients according
to specific indications
Nurse is responsible for collecting the blood samples for
analysis

18. Performing TDM tests is mainly a responsibility of the
analytical scientist or technician
Clinical pharmacologist or pharmacist interprets
these results & converts them into useful information
and recommendations to the requested doctor

19. Regulatory Environment
1. Sample
prepared
3. Verify drug
analysis result
2.Performing
analysis
4. Sample
collected
3. Test
ordered
2. Test
selected
1. Clinical
question
P
R
E
A
N
A
L
Y
T
I
C
A
L
2. Clinical
answer
1.Reporting
result
Patient
Care
4. Effect on
patient care
3. Action
taken
P
O
S
T
A
N
A
L
Y
T
I
C
A
L

20. SAMPLE MATRICES
• Venous blood - Cyclosporine, tacrolimus, sirolimus, & everolimus -
• Saliva - Phenytoin, carbamazepine, theophylline, digoxin, & lithium
• Urine - anticonvulsant & psychoactive drugs
• Tears - valproic acid
• Bile - Penicillins, cephalosporins, aminoglycosides & cardiac glycosides
• Foetus Blood & Amniotic Fluid - Drugs that can affect the fetus
- Antibiotics, anticonvulsants & tranquillizers
• Breast Milk - Phenobarbital, theophylline, psychoactive drugs & drugs of abuse
might be detected

21. SAMPLE MATRICES…
• Cerebrospinal Fluid (Csf) :- Antibiotics that are used in CNS
infections, anticonvulsants, psychoactive drugs, & protease
inhibitors
• Hair
• Nails
• Sweat
• Feces

22. • REQUEST FORM OF TDM
Patient Name............................................. Date............................................... HN........................................................
Age.................................. Sex................................. Wt...................................... Ht.........................................................
Ward.............................................Ordered by....................................................... Phone No..........................................
DRUG LEVEL REQUESTED..................................................................................................................................................
REASON FOR REQUEST :
( ) Suspected toxicity ( ) Compliance
( ) Therapeutic confirmation ( ) Absence of therapeutic response
Please indicate when level is needed :
( ) within 24 h ( ) within 1-2 h ( ) stat ( ) others........................
TIME AND DATE OF LAST DOSE :
Date.................... Route : IV, IM, SC, PO, Others...........................
Time.................... Dose.......................... Freq..................................
THIS DRUG LEVEL IS FOR : SAMPLING TIME :
( ) Trough or predose level Date....................... Time.........................
( ) Peak level Date....................... Time........................
DOES THE PATIENT HAVE ORGAN-SYSTEM DAMAGE ?
( ) Renal ( ) Hepatic ( ) Cardiac ( ) GI ( ) Endocrine ( ) Others........................….
OTHER DRUG(S) PATIENT IS TAKING :.........................................................................................................……..
DRUG LEVEL & USUAL THERAPEUTIC RANGE............................................................................................…….
INTERPRETATION...............................................................................................................................................…...
.............................................................................................................................................................................…….
Date.......................... Technologist................................. Time............................…………..

23. The purpose of TDM is to
individualize the dosage to achieve
maximum efficacy of a drug and at the
same time minimize adverse drug
reactions
SUMMARY
TDM has
clinical importance for drugs with a narrow
therapeutic window, such as various
anticonvulsants, cardioactive drugs,
theophylline, immunosuppressants, tricyclic
antidepressants, antiretroviral drugs, certain
antibiotics, & neoplastic drugs.

24. Altered pharmacokinetic parameters
are observed for many drugs in
disease states including hepatic and
renal impairment, cardiovascular
disease, thyroid dysfunction, & cystic
fibrosis
Altered drug disposition
also occurs in pregnant
women.TDM helps to
identify such altered drug
disposition, & dosage
adjustment can be made
for proper management of
the patient to avoid
adverse reactions.
SUMMARY…