It is an important topic in Clinical Pharmacy.

1. Therapeutic Drug Monitoring
◻ Define
◻ Describe clinical applications
◻ List factors that affect serum drug concentrations
and which should be considered when interpreting
TDM results
◻ Role of Pharmacist in TDM
◻ Limitations of TDM

2. TDM:
Refers to measurement of drug concentrations in
biological fluids with the purpose of optimizing a
patient’s drug therapy.

3. NEED FOR THE TDM
◻ It is used to assist the optimization of drug therapy,
including minimizing the risk of serious drug toxicity
and the assessment of the appropriateness of dosing
for drugs used as prophylactic therapy. ( e.g.
kidney diseases: dialyzable or non-
dialyzable drugs)
◻ To identify a drug or substance which may be
contributing to the presentation of Medical
Emergency. (e.g. overdose of CNS drugs,

4. ◻ Why bother with measuring the
concentrations of medications?
⬜ TDM is the collection and measurement
of prescribed medications.
⬜ TDM is not necessary for most
medications because there is a good
correlation between the dosage and its
therapeutic effects

5. ⬜ For other drugs, there is a poor
relationship between dosage and
therapeutic effects. TDM is useful for
these drugs.
⬜ For TDM the term therapeutic range is
used to define the drug concentrations
where a desirable effect of the drug is
obtained.

6. ⬜ Drug concentrations outside the
therapeutic range do not provide clinical
benefit. It may even be harmful.
⬜ Drug concentrations above the
therapeutic range can have toxic or
other adverse effects that outweigh
the benefits of the drug.

7. Therapeutic Drug Monitoring
◻ Define
◻ Describe clinical applications
◻ List factors that affect serum drug concentrations
and which should be considered when interpreting
TDM results
◻ Role of Pharmacist in TDM
◻ Limitations of TDM

8. The Decision
1. The decision regarding the appropriateness of
TDM is based on a range of
considerations.
1. To confirm adequate serum
concentrations where clinical
response is inadequate.
For some drugs a minimum serum concentration
is needed to ensure efficacy TDM can be used to
assess the appropriateness of dosing regimen to

9. The Decision
3. To minimize time period for
dosage adjustment.
Empirical adjustment of dose would take a
long time.
4. To assist in dosage adjustment in
various disease states where
individual variations in drug
ADME may be important.
e.g. With severe renal disease (Cyclosporine)

10. The Decision
5. To individualize dosing for some
drugs with an unpredictable dose
– response curve.
e.g. Phenytoin (non linear pharmacokinetics)
6. To avoid drug toxicity.
Maintenance of serum drug concentration in
the therapeutic range. E.g. Aminoglycosides

11. The Decision
7. To identify poisons and to assess
the severity of poisoning on an
emergency basis.
e.g. Effectiveness of antidotes and the excretion of
poisons in body fluids can be monitored.
heavy metal poisoning antidotes e.g. dimercaprol

12. ◻ General Reasons for TDM
⬜ Drugs may be toxic at certain
concentrations and must be closely
monitored.
⬜ Patients may be non – compliant ( don’t
follow instructions ).
⬜ There may be a close difference
between therapeutic ranges and toxic
levels.

13. ⬜ Changes in the patient’s physiological
condition may alter plasma drug
concentrations ( liver or renal activity ).
⬜ Interactions between other drugs
⬜ Individual physiological differences
between patients may affect drug
utilization.

14. ◻ Other factors that affect drug
concentrations
⬜ Routes of administration
■Intravenous – Parentally ( IV )
■Intramuscular injection ( IM )
■Subcutaneous injection
■Orally
■Rectal suppository
■Inhalation

15. ❑Absorption
■Absorption thru the GI tract is affected
by GI pH, and hepatic uptake.
⬜ Distribution
■Drugs may diffuse into different tissues
depending on characteristics of the
drug
■Lipid and water solubility

16. ⬜ Plasma proteins and other binding
substances
■Most drugs bind to a variety of plasma
proteins, but only the free ( unbound )
form has therapeutic activity.
■Total drug concentration may be within
therapeutic range, but the free ( active
form ) may be outside the therapeutic
range.
■Variations in plasma proteins
( pregnancy, inflammation, cancers,
renal disease ) may alter plasma drug

17. ⬜ Elimination
■Rate at which drugs are eliminated
from the body alters the plasma
concentration.
■The liver and kidney regulate excretion
of most drugs.
■“First Pass Elimination” : Liver
converts drugs to water soluble forms
for excretion
■Diseases of the liver and kidney
influence drug concentrations.
■Half – Life : Time for drug

18. ⬜ Pharmokinetics
■Correlation between dosage and
plasma drug concentrations.
■Most drugs are administered in multiple
doses over a period of time.
■Plasma drug concentrations oscillate
between a peak ( upper ) and trough
( lower ) concentrations during these
doses.
■Both the peak and trough drug levels
should be within the therapeutic range.

19. Biological sample
◻ Blood Sample : at Steady state
◻ Approx after 5 half lives
◻ Collected at the end of dosage interval and
before Next Dose : Trough Sample
◻ Sample collection: Venous blood
◻ If administration of drug and drawing of the
sample is at the same time then collect the
sample from the distant site.

20. Biological sample
◻ Drugs having longer half lives (mr than
24hrs) : once the distribution phase is over.
e.g. Digoxin: 24 hrs after the last dose.
◻ Drugs having short half life: predose
e.g. Morphine

22. Biological sample
◻ Collect 30 mins after completion of IV dose
◻ Collect 30 - 60 mins after IM injection
◻ Collect 60 mins after oral dose

23. Therapeutic Drug Monitoring
◻ Define
◻ Describe clinical applications
◻ List factors that affect serum drug concentrations
and which should be considered when interpreting
TDM results
◻ Role of Pharmacist in TDM
◻ Limitations of TDM

24. Factors affecting Serum Drug Concentration
◻ Patient demographics:
▪ Age, Sex, Body weight, Ethnicity
▪ Ethnicity : Renally & Hepatically cleared
drugs
e.g. Isoniazid
◻ Dosage regimen:
▪ Sample collection should be done after
achieving steady state level
◻ Sampling time:
▪ Short half lives: Predose (Morphine)
▪ Long Half lives: After the distribution phase is
achieved (Digoxin)

25. Factors affecting Serum Drug Concentration
◻ Patient compliance:
▪ When increase in the dose is required in
case of inadequate clinical effect (Serum
Calcium : Tablet shelcal)
◻ Individual capacity to distribute/
metabolize/ excrete drug:
▪ Dosage adjustment is required in case renal
impairment for the dose of drugs like digoxin,
aminoglycosides who are excreted by
kidneys.

26. Factors affecting Serum Drug Concentration
◻ Altered protein binding:
▪ In conditions such as Malnutrition or
Neuropathy the concentration of plasma
proteins is reduced.
▪ E.g. Phenytoin binds with albumin, so if
plasma albumin levels decreases then the
concentration of unbound (free) phenytoin
will increase leading to toxicity

27. Factors affecting Serum Drug Concentration
◻ Drug Interactions:
▪ E.g. Serum Digoxin level may increase if
given along with amiodarone, verapamil
without reducing the dose.
▪ Serum concentration of some hepaticallly
cleared drugs may be affected by drugs who
can either inhibit or induce hepatic
cytochrome P450 isoenzyme.
▪ Calcium channel blockers and calcium
supplements administered together

28. Factors affecting Serum Drug Concentration
◻ Pathological Factors:
▪ Co-morbidities should taken into
consideration.
▪ Vomiting, Inflammatory Bowel Disease,
Diarrhea will affect the serum drug
concentration.
▪ Patient suffering from Hepatic cirrhosis and
Tuberculosis: if normal doses of Rifampicin
and Isoniazid can lead to elevated levels of
these drugs increases the risk of
hepatotoxicity.
▪ Malabsorption leads to decreased serum

29. Factors affecting Serum Drug Concentration
◻ Alcohol and Tobacco Use:
▪ Alcohol: Hepatic microsomal enzyme
induction
increased clearance and decreased
serum concentrations of hepatically cleared
drugs such as Phenytoin.
▪ Cigarette Smoking Increases
hepatic clearance of Theophylline.
▪ Abruptly stoppage of smoking leads to
abnormally high levels of Theophylline.

30. Factors affecting Serum Drug Concentration
◻Medication or Sampling Errors:
▪Prescription Errors: 0.1 g but misread as 1g
▪Blood drawn from the another patient.
▪Sample collected at wrong time.
▪Medications were administered to another
patient.

31. Factors affecting Serum Drug Concentration
◻ Laboratory Errors:
▪ In case of suspect of laboratory error, then
laboratory should be informed about the
same and test must repeated.
▪ E.g. Pus cells in urine report are very high
but patient is not showing any symptoms of
fever, chills, burning sensation while passage
of urine, etc., then chances of UTI are very
less. Report should be repeated.

32. Analytical Methods Used in TDM
◻ Chromatographic Method
◻ Enzyme Linked Immunosorbent
Immunoassay(ELISA)
◻ Enzyme Multiplies Immunotechnique (EMIT)
◻ Fluorescence Polarization Immunoassay
(FPIA)
◻ Radio-Immunoassay (RIA)
◻ One Step Dry Chemistry

33. Clinical Interpretation
1. Time of drug sampling with respect to the
last dose (predose or after the
distribution phase is achieved)
1. Duration of treatment with present dose
(days)
1. Dosing schedule (b.i.d., t.i.d. or o.d.)
1. Age and Gender of the patient

34. Clinical Interpretation
5.Concomitant medications (antihypertensives,
oral hypoglycemics, etc )
5.Disease status
5.Objective/Reason of monitoring, such as,
lack of effect, toxicity or as routine
procedure.

35. Therapeutic Drug Monitoring
◻ Define
◻ Describe clinical applications
◻ List factors that affect serum drug concentrations
and which should be considered when interpreting
TDM results
◻ Role of Pharmacist in TDM
◻ Limitations of TDM

36. Role of the pharmacist
1. Initial Selection of Drug Regimen: is
based on
▪ Dose, Dosing interval, route of
administration, dosage form of the drug
▪ Demographic Details of patients like
Age, Sex, Body weight, Race
▪ Disease Status of patients like Metabolism
Status, Renal Function, Plasma Albumin

37. Role of the pharmacist
2. Refinement and adjustment of the
dosage regimen:
▪ Important for Patient’s clinical response.
▪ E.g. in case of impaired renal function the
dose of digoxin should be reduced to avoid
toxicity.

38. Role of the pharmacist
3. Assessment for possible causes of
unusual results:
▪ The reasons could be Non-compliance,
Bioavailability problems, Medication errors,
Sampling errors

39. Role of the pharmacist
4. Assessment of dosage adjustments:
▪ In case of Hemodialysis, dialysable and
non-dialysable drugs must be considred
5. Management of acute drug
intoxication:
▪ E.g. Morphine or Barbiturate poisoning
6. Research activities:
▪ Assessment of cost-benefit aspects of TDM.

41. Therapeutic Drug Monitoring
◻ Define
◻ Describe clinical applications
◻ List factors that affect serum drug concentrations
and which should be considered when interpreting
TDM results
◻ Role of Pharmacist in TDM
◻ Limitations of TDM

42. TDM in India
◻ Clinical Pharmacology departments
◻ Private Medical Labs
◻ Factors which influence TDM in India :
◻ Cost is very high; people from lower
socioeconomic class cannot afford
◻ Alternative Medical systems: Ayurveda,
Homeopathy, Unani
◻ Malnutrition : People from lower socioeconomic
class

43. TDM in India
◻ Ethnic differences
◻ Variations in bioavailability

44. ◻ Classes of common therapeutic drugs
⬜ Cardioactives Heart
⬜ Anticonvulsants Seizures
( epilepsy )
⬜ Bronchodilators Asthma
⬜ Antibiotics Infection
⬜ Psychotropics Mood/Behavioral
disorders
⬜ Immunosuppresants Organ
transplants
⬜ Antineoplastics Cancer treatment

45. ◻ Cardioactive drugs ( heart medications )
⬜ Digoxin ( lanoxin )
■Strengthens cardiac contractions
■Good for CHF
■Therapeutic range : 0.5 - 2.0 ng / ml
■Toxic : > 3.0 ng / ml
■ Do not test within 8 – 10 hours of dosage

46. ◻ Cardioactive drugs ( heart medications )
⬜ Digoxin ( lanoxin )
■Overdoses are treated with “Digibind” ( anti
-digoxin drug )
■Digibind patients have elevated digoxin
because most techniques measure total
digoxin – not the free active form

47. ◻ Bronchodilators
⬜ Theophylline ( aminophylline )
■Pulmonary vasodilator
■Asthma treatment
■Therapeutic range : 10 - 20 ug / ml
◻ Psychotropics
⬜ Lithium ( Anti – depressant , mood
stabilizer )
⬜ Tricyclics ( Imipramine, desipramine,
amitriptyline )

48. ◻ Antibiotics
⬜Aminoglycosides ( Gentamycin,
Tobramycin )
■Inhibit protein synthesis of bacteria
■30S ribosomes are inhibited
■Given IV or IM ( poorly absorbed in GI
tract )
■Nephrotoxic - Trough levels must be
checked prior to dose

49. ◻ Trade names of common drugs
⬜ Acetaminophen Tylenol
⬜ Caffeine Vivarin
⬜ Carbamazepine Tegretol
⬜ Diazepam Valium
⬜ Lidocaine Xylocaine
⬜ Phenytoin Dilantin
⬜ Salicylate Aspirin

50. Potential for Error When Using TDM
◻ Assuming patient is at steady-state
◻ Assuming patient is actually taking the drug
as prescribed
◻ Assuming patient is receiving drug as
prescribed
◻ Not knowing when the drug concentration
was
measured in relation to dose administration
◻ Not considering drug interactions

51. ➢Antiepileptic Drug Monitoring Indications:
➢Soon after steady-state conditions are initially
expected
➢When the patient is seizure-free and experiencing
no adverse effects (determines therapeutic
concentration)
➢To determine the cause of relapse
➢Before and after any change in dose
➢Before and after introducing a drug that may
interact

52. ➢Whole plasma drug concentrations are most often
measured.
➢Unbound plasma concentrations may be requested
when a physician suspects that the patient’s protein
binding capacity for the drug may be altered due to
pregnancy, disease, malnutrition, or drug interaction.
Test Timing
Trough concentrations
Therapeutic Ranges
➢Carbamazepine (TEGRETOL) : 4 – 10 μg/mL
➢Phenytoin (DILANTIN): 10 – 20 μg/mL

53. Bronchodilators:
➢Chronic asthma
➢Test Timing: Trough concentrations
➢Therapeutic Range:
➢Caffeine: 1 – 30 μg/mL
➢Theophylline: 10 – 20 μg/mL

54. Several factors must be considered when
interpreting the results:
➢Patient’s liver function
➢Co-administered drugs
➢Smoker/non-smoker
➢Preparation used (pill or injectable)
➢Neonate or adult

55. 3 marks
1. Define Clinical Pharmacy and add a note on
Therapeutic Drug monitoring.
2. Describe Therapeutic Drug monitoring?
3. Define Therapeutic Drug monitoring. Enlist the
factors
affecting Therapeutic Drug Monitoring.
4.What do you mean by Therapeutic Drug
monitoring?

56. 1 marks
1. Define Therapeutic Drug monitoring.
2. Enlist the factors affecting Therapeutic Drug
Monitoring.
3.When to collect the samples for TDM based on
the half lives of drugs?