Essentials of TDM

1. THERAPEUTIC DRUG
MONITORING
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2. TDM refers to the measurement and interpretation
of principally blood or plasma drug concentration
measurements with the purpose of optimizing a
patient’s drug therapy and clinical outcome while
minimizing the risk of drug induced toxicity
Time
Plasmadrugconcentration
MSC
MEC
THERAPEUTIC RANGE
TOXIC LEVEL
SUB THERAPEUTIC LEVEL
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3. Therapeutic drug monitoring (TDM) refers to
the measurement of drug concentrations in
biological fluids with the purpose of optimising a
patient’s drug therapy.
During administration of a dosage regimen, the
concentration should be maintained within the
therapeutic window.
TDM refers to the tool utilised to individualise
dosage regimen by maintaining plasma or blood
drug concentrations within the therapeutic
range.
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4. CRITERIA OF DRUGS IN TDM
• Drug with narrow therapeutic index.
• Drug should exhibit non-linear kinetics.
• Should have a beneficial concentration
response relationship between the blood drug
conc. and pharmacological effects with respect
to both efficacy and toxicity.
• There should be no easily measurable
physiological parameter.
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5. INDICATIONS
1. Drugs which have narrow therapeutic index
2. Drugs for which small changes in the concentration of
the drug in plasma are likely to exhibit large changes
in drug response (should exhibit non-linear kinetics)
3. Drugs which exhibit poor and erratic absorption
4. Drugs which exhibit relatively wider inter-individual
variation in drug metabolism
5. Patient exhibiting the signs and symptoms of toxicity
(Theophylline intake and persistent nausea)
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6. 6. To minimize the risk of toxicity
7. To identify the poison and to determine the
severity
8. Drugs where signs of over dosage or under
dosage are difficult to distinguish.
9. Drugs which are administered in the presence
of gastrointestinal, hepatic or renal disease
10.When patients are receiving multiple drug
therapy
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7. CONDITIONS TO PERFORM TDM
• To assist the optimisation of drug therapy,
including minimising risks of serious drug
toxicity
• In the assessment of the appropriateness of dosing
for drugs used as prophylactic therapy.
• To identify a drug or substance which may be
contributing to the presentation of a medical
emergency.
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8. CLINICALAPPLICATIONS
• 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 conc. 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. Eg: Phenytoin
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9. • 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.
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10. EXAMPLES OF DRUGS INDICATED FOR
TDM
• Bronchodilators: Theophylline
• Antibiotics
– Aminoglycosides - Gentamicin, Amikacin
– Others - Vancomycin
• Immunosuppressants: Cyclosporine
• Anticancers: Methotrexate
• Antiepileptics: Phenobarbital, Phenytoin, Valproate
• Cardiac Drugs : Digoxin, Procainamide, Lidocaine
• Psychoactive Drugs: Lithium, TCA
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11. DIGOXIN
• Cardiac glycoside
• Given IV or orally
• Plasma concentration-response relationship:
Dose Effect
< 0.5μcg/L No clinical effect
0.7μcg/L Some positive inotropic and conduction blocking effects
0.8-2μcg/L Optimum therapeutic range
2-2.5μcg/L Increased risk of toxicity
>2.5μcg/L GI, CVS and CNS toxicity
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12. • Half life: 30-50 hrs
• Time to reach steady state concentration: 7-12 days
• Sample collection time: pre dose trough or atleast 6 hrs
post-dose
• Drug interactions:
o Plasma concentration may be elevated by Amiodarone,
Quinidine, Verapamil and Diltiazem
• Principle route of elimination: 50-75% renal
Therapeutic range depends on indication. Low serum
potassium level may potentiate toxicity despite a serum
digoxin concentration within the therapeutic range
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13. THEOPHYLLINE
• Therapeutic range: 10-20 mg/L
• Half life:
o Non smoker- 7-11 hrs
o Smoker- 3-5 hrs
• Time to reach steady state concentration: 24-36 hrs
• Sample collection time: pre dose trough
• Drug interactions:
o Plasma concentration may be elevated by Cimetidine, Diltiazem, Oral
Contraceptives, Erythromycin, Ciprofloxacin, Mexiletine and
Fluvoxamine.
o Decreased by Rifampicin, Phenobarbitone, Carbamazepine and by
smoking
• Principle route of elimination: hepatic metabolism
Increased plasma concentration is seen in hepatic insufficiency, CCF and
hypoxia.4/4/2018 13KIRSHA,

14. GENTAMICIN
• Therapeutic range: <0.5 mg/L
• Half life: 2-5 hrs
• Time to reach steady state concentration: <24 hrs
• Sample collection time: pre-dose trough
• Principle route of elimination: renal elimination
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15. PHENYTOIN
• Therapeutic range: 10-20 mg/L
• Half life: dose dependent (10-30 hrs)
• Time to reach steady state concentration: dose dependent (8-
21 hrs)
• Sample collection time: any time once steady state is achieved
• Drug interactions:
o Plasma concentration may be elevated by Cimetidine, Diltiazem,
Amiodarone, Azole Antifungals, Fluvoxamine, Isoniazid and
Fluoxetine.
o Decreased by Rifampicin
• Principle route of elimination: hepatic metabolism
Dose dependent elimination; small increase in dose can give rise to
disproportionate increases in plasma concentration.4/4/2018 15KIRSHA,

16. 4/4/2018 16KIRSHA,

17. ROLE OF PHARMACIST
1. Initial selection of drug regimen: decisions about drug choice, dosing,
dosing interval, route of administration and dosage form of drug
considering age, sex, weight, race, metabolism, renal function, plasma
albumin concentration, use of other drugs and laboratory results
2. Refinement and adjustment of the dosage regimen based on TDM
results and the patient’s clinical response
3. Assessment of possible causes for unexpected results, such as non-
compliance, bioavailability problems, medication errors, drug
interactions or pharmacogenetic variability
4. Dosage adjustment for patients on haemodialysis or peritoneal dialysis
5. Provision of poison information
6. Research activities
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18. REFERENCES
• A Textbook of Clinical Pharmacy Practice- G.Parthasarathi,
Karin Nyfort, Hansen, Milap C Nahata Pg.No.-325 to 339
• Clinical Pharmacy 2nd edition- H.P.Tipnis, Amrita Bajaj
Pg.No.-358 to 377
• Biopharmaceutics and Pharmacokinetics P.L. Madan Pg.No-
399 to 407
• Clinical Pharmacy and Therapeutics, 5th Edition- Roger Walker
and Cate Whittlesea Pg No-37 to 43
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