Presentation for 19th December 01P

Therapeutic Drug Monitoring: 

Therapeutic Drug Monitoring Shaikh Hussam Lateef (Training Coordinator ) 1

Introduction: 

Introduction M onitoring of therapeutic drugs U sed to individualize dosage D rug concentrations can be maintained within a target range. 2

Which Drugs?: 

N arrow target range S ignificant pharmacokinetic variability C oncentration related therapeutic and adverse effects D esired therapeutic effect difficult to monitor Which Drugs? 3

Drugs commonly monitored: 

Drugs commonly monitored Drug Therapeutic range mg/L Digoxin 0.5 - 2.1 1 Amiodarone 1.0 - 2.5 Lignocaine 2.0 - 5.0 Quinidine 2.0 - 5.0 Flecainide 0.2 - 0.9 Mexilitine 0.5 - 2.5 Salicylate 150 - 300 Warfarin INR monitored as per condition Theophylline 10 - 20 Phenytoin 10 - 20 Carbamazepine 5.0 - 12 Sodium valproate 50 - 100 Phenobarbitone 15 - 40 Gentamicin , tobramycin , netilmicin trough <2 2 ; peak >5 Amikacin trough <5 2 ; peak >15 Vancomycin trough <10; peak 20 - 40 Lithium 0.6 - 1.2 3 (1) microgram/L (2) for 8-hourly dosing (3) mmol /L 4

Timing of the Plasma Sample “When to do it ?”: 

T he drug concentration changes during the dosing interval. T he least variable point in the dosing interval is just before the next dose is due. T his pre-dose or trough concentration is what is usually measured. D rugs with long half-lives such as phenobarbitone and amiodarone, samples can be collected at any point in the dosage interval. Timing of the Plasma Sample “When to do it ?” 5

Major sources of pharmacokinetic variability: 

C ompliance A ge - neonates, children, elderly P hysiology - pregnancy D isease - hepatic, renal, cardiovascular, respiratory D rug interactions E nvironmental influences on drug metabolism G enetic abnormalities of drug metabolism Major sources of pharmacokinetic variability 6

What Information is required for Interpretation?: 

What Information is required for Interpretation? Time of sample in relation to last dose Duration of treatment with the current dose Dosing schedule Age Other drug therapy Relevant disease states Reason for request e.g. lack of effect, routine monitoring, suspected toxicity 7

Example – Phenytoin : 

Example – Phenytoin Normal range: 10-20 mg/L 10% respond to level of 3 mg/L 50% to level of < 7 mg/L 90% to level of < 15mg/L Sample Timing > 3 days 8

Dose adjustment for low albumin levels: 

Dose adjustment for low albumin levels Normal PHT level = measured PHT level (0.2 x albumin) + 0.1 If the lab. Value comes out to be 6.5 , with an albumin level of 2.2, the actual PHT level will be: 9 12 mg / L

Dose Adjustment for concurrent Valproic acid : 

Dose Adjustment for concurrent Valproic acid Normal PHT level = measured PHT level + ( 0.01 x VPA level x Measured PHT level) PHT level measured = 6.5 VPA level = 55 Corrected PHT level = 10 10 mg / L

Monitoring of Vancomycin: 

Monitoring of Vancomycin Trough serum vancomycin concentrations are the most accurate and practical method for monitoring efficacy. Troughs should be obtained just prior to the next dose at steady-state conditions (just before the fourth dose). Minimum serum vancomycin trough concentrations should always be maintained above 10 mg/L to avoid development of resistance. Vancomycin serum trough concentrations of 15–20 mg/L are recommended to improve penetration, and improve clinical outcomes. 11

Dosing Regimen of Vancomycin: 

Dosing Regimen of Vancomycin Doses of 15–20 mg/kg (as actual body weight) given every 8–12 hr are recommended for most patients with normal renal function to achieve the suggested serum concentrations In seriously ill patients, a loading dose of 25–30 mg/kg (based on actual body weight) can be used to facilitate rapid attainment of target trough serum vancomycin concentration. Continuous infusion regimens are unlikely to substantially improve patient outcome when compared to intermittent dosing. 12

Case Report: 

Case Report Vancomycin given intravenously 1 gm Q12h for 7 days. At what time the levels should be taken. 13 Just before the next dose

Warfarin Case Report: 

Warfarin Case Report Consider an alternative method of anticoagulation Monitor INR frequently In the patient receiving intermittent tube feedings, administer warfarin between feedings In patients receiving continuous tube feedings, stop feedings 1 hour before and 1 hour after warfarin administration. Consider increasing the rate of feedings to avoid loss of calories 14 A patient on Enteral feed (high protein nutrition) receiving oral Warfarin 20 mg to achieve an INR = 3 for Mechanical prosthetic Valve replacement. Current INR = 1 . Other drugs in the profile have no interaction with warfarin. What should be the problem then? Warfarin-Nutrient Interaction

Warfarin Case Report: 

Administer warfarin consistently (ie, hold feedings for all doses) Do not add warfarin directly to the enteral nutrition Warfarin dose requirements may change if the enteral regimen is altered or if the oral diet is resumed If enteral feedings are initiated in a patient stable on warfarin, the warfarin dose may increase; and If warfarin is initiated in a patient currently receiving enteral nutrition, warfarin dosing may decrease upon resumption of oral diet 15 Warfarin Case Report

Conclusion: 

Conclusion The drug concentration is complementary to and not a substitute for clinical judgment so it is important to treat the individual patient and not the laboratory value. Drug concentrations may be used as surrogates for drug effects so therapeutic drug monitoring may assist with dose individualization. 16

Conclusion: 

Conclusion It can also be used to detect toxicity, so therapeutic drug monitoring can optimize patient management and improve clinical outcomes. Careful selection of drugs to be monitored should occur. Regular monitoring of many drugs is not required in a clinically stable patient. 17

References: 

References Birkett DJ. Therapeutic drug monitoring. Aust Prescr 1997;20:9-11. Chatterjee K. Congestive heart failure: what should be the initial therapy and why? Am J Cardiovasc Drugs 2002;2:1-6. Gross AS. Best practice in therapeutic drug monitoring. Br J Clin Pharmacol 1998;46:95-9. Begg EJ, Barclay ML, Duffull SB. A suggested approach to once-daily aminoglycoside dosing. Br J Clin Pharmacol 1995;39:605-9. eTG complete. Therapeutic Guidelines Ltd. 2007 Nov. 18

Slide 19: 

Thank You 19