Therapeutic Drug Monitoring (TDM)

1. Therapeutic Drug Monitoring (TDM)

Fawzy Elbarbry, PhD, RPh, BCPS

2. Therapeutic Drug Monitoring

• Therapeutic drug monitoring (TDM) refers to adjustment
of drug doses based on measured plasma
concentrations to attain values within a therapeutic
range.
• Clinical pharmacists play a key role in ensuring safe and
effective administration of medications via performing
TDM of selected medications

3. TDM Decision-Making Process

4. When Should we Perform TDM?

• Good correlation between pharmacologic response and drug
concentrations
• Wide inter-patient variation
• Drug has narrow therapeutic index (range)
• Absence of good clinical markers of effect

5. Therapeutic Range

MTC= Minimum
toxic conc.
Therapeutic
Window
MEC= Minimum
effective conc.

6. Wide Therapeutic Range

MTC= Minimum
toxic conc.
Therapeutic
Window
MEC= Minimum
effective conc.

7. Narrow Therapeutic Range

Therapeutic
MTC= Minimum
toxic conc.
Window
MEC= Minimum
effective conc.

8. Narrow Therapeutic Range Drugs

Drug
Therapeutic Range
Digoxin
0.8-2.0 ng/ml
Gentamicin, tobramycin
5-10 mcg/ml (peak)
< 2 mcg/ml (trough)
Vancomycin
10-15 to 20 (trough)
Carbamazepine
4-12 mcg/ml
Phenobarbital
15-40 mcg/ml
Phenytoin
10-20 mcg/ml
Lithium
0.6-1.2 mEq/L
Valproic Acid
50-100 mcg/ml
Theophylline
10-20 mcg/ml

9. Patient variability: PK

10. Patient variability: PD

Published Therapeutic Range
Patient A
Subtherapeutic
Patient B
Therapeutic
Subtherapeutic
Toxic
Therapeutic
Toxic
Patient C
Subtherapeutic
Therapeutic
Toxic
Toxic
Patient D
Subtherapeutic
Therapeutic
0
25
50

11. Patient variability: Reasons

• Physiologic states that alter ADME:
– Age
– Genetic polymorphisms
– Pregnancy
• Disease/physiologic states that alter ADME:
– Organ dysfunction (hepatic and renal function)
– Genetic polymorphisms
– Variations in drug absorption (gastric motility)
• Drug interactions
• Variability can be Inter-patient, or Intra-patient.

12. Measuring Drugs Concentration:

Indications
1. Drugs used for prophylaxis
use of cyclosporine to prevent transplant rejection
2. Early diagnosis of toxicity
aminoglycoside-induced nephrotoxicity
3. Detection of drug Interactions
Addition of rifampicin to a cyclosporine regimen

13. Measuring Drugs Concentration:

Utilization
1. Time of sampling
Drug PK (e.g. distribution)
2. Biological Sample
Whole blood, plasma, serum, urine.
3. Measured drug moiety
Parent drug vs. metabolite,
Free vs. total

14. Measuring Drugs Concentration:

“Should I get a drug level for my patient?”
– Is the patient already responding appropriately to the drug
therapy?
– Is the patient having any toxicity from the drug therapy?
– Are the efficacy and toxicity of this drug better predicted by
measuring drug concentrations or evaluating clinical
response?
– How will obtaining a drug concentration change the clinical
management of the patient?
– What is the expected duration of therapy?
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15.

16.

17. Clinical Apps/Calculators

• https://globalrph.com/medical-calculatorsinternal-medicine/
• https://clincalc.com/

18.

Case 1
Patient: FG
Age: 89
Height: 160 cm
Weight: 49.2 Kg
Gender: F
[Cr]: 0.9 mg/dl
Indication: Pneumonia
Vancomycin Dose Per Pharmacy
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19.

Case 1: KEY: Hand Calculation
IBW = 52 kg
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IBW (males) = 50 kg + 2.3 kg for each inch over 5 feet in height
IBW (females) = 45.5 kg + 2.3 kg for each inch over 5 feet in height

20.

Case 1: KEY, Hand Calculation
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21.

Case 1: KEY, Hand Calculation
Loading Dose: 25-30 mg/kg
= 25-30 mg/kg X 49.2 kg ~ 1250-1500 mg, Infuse over 75-90 min
Final Recommendation:
Administer 1250 mg over 75 min now, followed by 750 mg Q24 hr. infused over 60 min
after 24 hr.
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22.

Case 1: KEY, Global RPh
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http://www.globalrph.com/aminoglycosides.htm

23.

Case 1: KEY, Global RPh
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24.

Case 1: KEY, ClinCal
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https://clincalc.com/Vancomycin/

25.

Case 1: KEY, ClinCal
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26. Learning Objectives

• Describe the different components of therapeutic drug
monitoring (TDM).
• List drug properties that make them candidates for TDM.
• Discuss factors to be considered when utilizing
measured drug concentration.
• Describe and list possible reasons for patient variability
within pharmacokinetics
• Distinguish the role of the pharmacist in providing
optimal patient care via performing clinical PK and TDM.
• Utilize Clinical Apps in drug therapy and monitoring