Therapeutic drug monitoring (TDM) measures drug concentrations in patients' blood to optimize dosages. TDM is indicated for drugs with narrow therapeutic windows or variability. Common drugs monitored include aminoglycosides, antiepileptics, lithium, and digoxin. Interpretation of results considers compliance, interactions, and pharmacokinetics. TDM is underused in Tanzania due to lack of awareness, resources, and expertise, though it can improve outcomes and safety. The take-home message is that TDM ensures therapy effectiveness and safety by avoiding under- or overdosing.

1. THERAPEUTIC DRUG
MONITORING OF INDIVIDUAL
DRUGS
PRESENTER: Dr. Paul Patrick Mwasapi
(MMEDM Anesthesiology)
HD/MUH/T.655/2017
FACILITATOR: DR TOSI MICHAEL.

2. Overview
• Definitions
• Goals/needs of TDM
• Indications for TDM Article
• Classes and examples of drugs need TDM
• Interpretation of TDM results
• Overview of TDM in Tanzania
• Shortcoming of TDM in Tanzania
• Summary
• Take home message
• References

3. Objectives
• To understand and acknowledge the role
of TDM in clinical applications and
patients’ safety.
• To know the common drugs and
indications of TDM in our daily practice.
• To have an overview of TDM in Tanzania
• To understand the shortcomings of TDM in
Tanzania and their possible solutions.

4. 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.
• The aim of TDM is to help a clinician make a
therapeutic decision.

5. • TDM refers to the individualization of drug
dosage by maintaining plasma or blood drug
concentrations within a targeted therapeutic
range or window.
why??

6. Diagram 1. Therapeutic window

7. • The basis of TDM is on the assumption that
there is a definable relationship between dose
and plasma or blood drug concentration, and
between concentration and therapeutic
effects.

8. Characteristics of a drug for TDM
??Do all drug requires TDM??
NO!!
• In pharmacotherapy many medications are
used without monitoring of blood levels, as
their dosage can generally be varied
according to the clinical response that a
patient gets to that substance.
• In a small group of drugs, this is impossible,
as insufficient levels will lead to under
treatment or resistance, and excessive levels
can lead to toxicity and tissue damage.

9. Indications for therapeutic drug monitoring
may include
1. Drugs with Narrow therapeutic ranges.
2. Drugs with marked pharmacokinetic
variability.
3. Medications for which target
concentrations are difficult to monitor.
4. Drugs known to cause severe adverse
effects.

10. 5. There are potential patient compliance
or Adherence problems.
6.The drug dose cannot be optimized by clinical
observations alone.
7.For experimental purposes, to determine a
relationship between plasma drug
concentration and the pharmacological effect
(PD).
8.To determine PK properties of a Drug ie.
Volume of Distribution and Clearance of a drug.

11. Drugs not Suitable for TDM
• Drug that are used to treat a disease of
which their clinical end point can be easly
monitored e.g. BP, HR, Blood glucose,
Blood cholesterol
• Drugs whose serum con do not correlate
with therapeutic or toxic effects.
• Drugs with less complicated PK
• Drugs with Wide therapeutic index.

12. GOALs of TDM
• The goal of TDM is to use appropriate
concentrations of difficult-to-manage
medications to optimize clinical
outcomes in patients in various clinical
situations.
• Improvement of clinical effectiveness of a
drug by TDM can lead to decrease in cost
of medical care by preventing occurrences
of adverse effects.

13. INDICATIONS FOR REQUESTING
DRUG PLASMA CONCENTRATIONS
• Monitoring compliance/Adherence
• Individualizing therapy i.e. during dosage
changes
• Diagnosing undertreatment
• Avoiding toxicity
• Monitoring and detecting drug interactions
• Guiding withdrawal of therapy
• Detection of Drug abuse.

14. Article
TITLE
Measuring adherence to antiretroviral therapy
in children and adolescents in western Kenya
AUTHORS
Rachel C Vreeman, Winstone M Nyandiko, Hai
Liu, Et Al
PUBLISH
Journal of International AIDS Society 2014

15. METHODOLOGY
Study Design: A prospective cohort study
involving 200 HIV-infected children, ≤14 years
of age and on ART and their caregivers.
Adherence was reported using caregiver report,
plasma drug concentrations and Medication
Event Monitoring Systems (MEMS®).
Objective: To compare multiple measures of
adherence and investigate factors associated
with adherence among HIV-infected children in
western Kenya.

16. RESULTS:
• Caregiver-reported missed doses to clinicians
at routine clinic visits suggested the highest
rates of adherence (97% reported no missed
doses) while Mean adherence by Medication
Event Monitoring system MEMS® was 87% .
• 14% of children on NVP and 27% on EFV
had sub-therapeutic drug levels, whereas
59% of children on NVP and 23% on EFV
had supra-therapeutic drug levels.

17. CONCLUSION:
• Adherence based on self report was high
compared to what was observed with TDM.
• Despite high rates of adherence by caregiver
report, missed and late doses, treatment
interruptions of more than 48 hours and sub-
therapeutic drug levels were common

18. TDM Testing Techniques
• HPLC – High Pressure Liquid Chromatography
• GC/MS – Gas chromatography Mass
Spectrometry
• LC/MS – Liquid chromatography Mass
Spectrometry
• RIA – Radioimmunometric assays
• PETINIA – Particle enhanced Turbidimetric
Inhibition Immunoassays.
• EMIT – Enzyme multiplied Immunoassay
Technique

19. Samples of TDM
• Plasma or Serum: Commonly used
• Whole Blood: Cyclosporine, Tacrolimus
• Urine: Benzodiazepine
• Sweat: Cocaine & Heroine
• Saliva: Marijuana, Cocaine, Alcohol, lithium
• Breath: Alcohol
• Hair: Heroin,Cocaine

20. COMMONLY MONITORED
DRUGS
1. Aminoglycosides e.g. gentamycin, amikacin,
tobramycin
2. Antiarrthymics e.g. amiodarone, lidocaine,
Quinidine, procainamide
3. Antiepileptic e.g. carbamazepine, ethosuximide,
phenobarbitone, phenytoin, valproivc acid.
4. Antidepressant e.g. amitryptilline, imipramine
5. Antipsychotics e.g. haloperidol, lithium
6. Others e.g. digoxin, salicylates, theophilline,
cyclosporin, vancomycin.

21. Aminoglycosides
Ex. Gentamicin
Has a low TI and also produce Dose related
side effect
• Bactericidal activity is linked to peak
concentration.
– Desired profile: High peak
• Toxicity (ototoxicity and nephrotoxicity)
related to total drug exposure
– Desired profile: Low trough

22. Therefore traditionally Peak and trough
concentration are monitored.
Targets For IV gentamicin
• Peak Concentration (30-60min post dose) =5-
10mg/l
• Trough Concentration (before next dose) <2 mg/l

23. Antiepileptic
Ex Phenytoin
An antiepileptic with
Narrow therapeutic window
High protein bound >drug-drug interaction,
drug disease interaction
Non Linear pharmacokinetic.
Long Half life i.e. >2weeks

24. • Approximately 90% of Phenytoin is bound to
albumin Thus doses should be corrected
according to albumin levels.
Target Concentration: 10mg/L
Therapeutic range: 10-20mg/L
Side effects: >20mg/L Nystagmus, >30mg/L
Ataxia, >40mg/L Decreased mentation
>100mg/L Death

25. Bronchodilator
Ex. Theophylline
A bronchodilator with narrow therapeutic index
and wide unpredictable variability in clearance.
Toxicity: Tachyarrhythmia, vomiting,
convulsions
PK:
90% Eliminated by liver 10% unchanged
eliminated by kidney (reverse ratio in neonate)

26. • Whenever possible establish drug levels
before administering IV and if in doubt do
not give a bolus loading dose.
• Therapeutic Range: 10-20mg/L

27. Antipsychotics
Ex. Lithium
Antipsychotic and a mood stabilizer with a
small TI, and dose related side effects
Targeted concentration: 1mmol/L
Toxicity: >1.5mmol/L Renal impairment.
3-5mmol/L Confusion, convulsion,
coma and Death

28. Others..
Ex. Digoxin
A cardiac glycoside used in treatment of heart
failure and atrial fibrillation.
• Small change in dose, may result in loss of
efficacy or serious adverse effects
• Toxicity: Vomiting, Insomnia, Hypokalemia
Target Range: 1-2µg/L
Optimum sampling time: Trough (pre-dose) or 6
hours post dose

29. DRUG Therapeutic range Toxicity
Antiepileptic drugs
PHENYTON 10-20mg/l >25mg/l
PHENOBARBITONE 10-30mg/l >35mg/l
Cardiovascular drugs
DIGOXIN <2.6nmol/l >4nmol/l
Anti psychotic drugs
LITHIUM 0.5-1.0mmol/l >1.5mmol/l
NORRIPTYLINE 200-600nmol/l >800nmol/l

30. INTERPRETATION OF TDM
RESULSTS
1.When Serum Concentrations are lower
than expected
Patient compliance.
Rapid elimination (Fast metabolizers)
Enlarged apparent volume of distribution.
Timing of Blood sample.
Blood interaction due to stimulation of
elimination or auto-induction.

31. 2. When serum concentration is Higher than
anticipated
Patient compliance
Rapid bioavailability
Smaller than anticipated Vd
Slow elimination
Poor renal or hepatic function.

32. 3. Serum concentration are correct but the
patient is not responding to therapy.
Altered receptor sensitivity e.g. tolerance
Drug interaction at the receptor site.
Changing hepatic blood flow

33. OVERVIEW OF TDM IN
TANZANIA
• There is essentially no use in clinical
practices in Tanzania.
• The little available information on TDM in
Tanzania is from few researches.
• The situation is the same in many developing
countries.

34. SHORTCOMINGS OF TDM SERVICES
IN TANZANIA SET UP
Hospital personnel are not aware of the
existence of TDM service.
Few clinical personnel with adequate
knowledge of TDM i.e. clinical
pharmacologists.
Physicians are not aware of the principles,
benefits, and the limitations of TDM service

35. …
No consultation when problems arise.
TDM is expensive.
Lack of research around TDM.
Lack of critical mass to operate TDM
services.

36. SUMMARY
• TDM is monitoring of plasma
concentration of drug for individualization
of dose in patients.
• Common Drug for TDM includes
aminoglycosides, anticonvulsants, Lithium
and Digoxin.
• TDM for Aminoglycosides i.e. involve
taking Peak and Trough concentration.
.

37. …
• Interpretation of TDM result is not merely a
comparison of blood concentration of a
drug and its therapeutic range but should
include other PK and PD parameters
• The uses of TDM in Tanzania are limited
due to lack of awareness, resources,
research and expertise.

38. Take home message
• TDM is essential in ensuring effectiveness of
the therapy and patient’s safety.
• With TDM you wont have to cross your fingers
and hope it works or crushing your head why
it didn’t. 

39. REFERENCES
• Kang J Et al Overview of TDM Korean J
Intern Med. 2009; 24: 1-10
• Holford NHG, Tett S. Therapeutic Drug
Monitoring. The strategy of target
concentration intervention. In: Speight T,
Holford NHG, editors. Avery’s Drug
Treatment.4th 1997. pp. 225–259.
• Diagram 1. Therapeutic window Adopted
from pharmcountry947.com/therapeutic-
dosage-nuzy.php (Accessed 10 Feb 2018)

40. • Vreeman RC Measuring adherence to
antiretroviral therapy in children and
adolescents in western Kenya J Int AIDS
Soc. 2014; 17(1): 19227