Guideline to therapeutic drug monitoring

2003 4 27

I. General Guidelines
1. Measure body weight and/or height for pharmacokinetic calculation.
2. Sampling time
The timing of blood samples in relation to dosage is critical for correct
interpretation of the serum concentration result.
a) Obtain the serum sample at steady-state (treatment with a constant dose over at
least 4 half-lives) during long-term therapy.
b) Peak concentration is drawn when the drug absorption and distribution phases
are complete.
c) Trough concentration is measured just prior to the next dose.
d) Measure serum concentration immediately in case of evidence of toxicity or
overdose, and also at recommended sampling time if the dosing time is known.
e) The diagnosis of intoxication or overdose should not be made on serum drug
concentration alone. Peak or casual serum drug concentration is not a reliable
criterion for the diagnosis of intoxication.
3. Therapeutic range
Range of drug concentrations associated with a high
degree of efficacy and a low risk of dose-related toxicity.
4. Except for cyclosporine and tacrolimus monitoringin which heparinized tube
should be used all blood samples should be drawn in Venoject PLAIN (silicone
coated) tube.
5. Sample drawn during intravenous infusion should be obtained ideally from the
opposite limb.
6. If samples are drawn from an IV linethe line must be thoroughly flushed before
obtaining a specimen for analysis.
II. Antibiotics
Aminoglycosides
1. Calculate aminoglycoside dose based on ideal body weight and adjust by renal
function and serum levels.
2. Sampling time
Peak1hr after the initiation of a 30min- to 1hr infusion 1hr post IM dose (IM
absorption is less predictable).
Trough just prior to the next dose.
3. Therapeutic rangeg/ml
Gentamicin Tobramycin Netilmicin Amikacin
Peak 4-10 4-10 4-10 20-30
Trough <2 <2 <2 < 10
* Peak should be at the higher end of the therapeutic range for critically ill patients
and those with pulmonary infection.
4. Obtain serum concentrations 3-4 doses following initiation or readjustment of
therapy.
5. Monitoring parameters: renal function, hydration status, 8th cranial nerve
function.
6. Factors affecting serum level: hydration status, renal function, fever, ascites.
Vancomycin see attached

III. Antiepileptics
Carbamazepine
1. Sampling time trough.
2. Therapeutic range 4-12g/ml.
3. Time to steady-state2-6 days.
4. Monitoring parameters CBCliver function.
5. Factors affecting serum level altered GI functionenzyme-inducerand
enzyme-inhibitor.
Ethosuximide
1. Sampling timetrough.
2. Therapeutic range 40-100g/ml.
3. Time to steady-state children: 6 daysadults12 days.
4. Factors affecting serum levelchange in body size and metabolism
hemodialysis.
Phenobarbital
1. Sampling timetrough.
2. Therapeutic range10-40mcg/ml.
3. Time to steady-state8-24 days.
4. Factors affecting serum levelenzyme-inducerenzyme-
inhibitorhemodialysis.
Phenytoin
1. Sampling time
POtrough.
IV 2-4hr after dose.
2. Therapeutic range10-20g/ml.
3. Time to steady-state 5-30+ days.
4. Monitoring parameters albumin levelliver functionrenal function.
5. Factors affecting serum levelproduct formulationadministration route (IM,
NG feeding)hypoalbuminemiarenal failurealtered GI functionenzyme-
inducer, enzyme-inhibitor protein binding displacer.
6. In hypoalbuminemia patientthe serum concentration that would have been
observed with a normal albumin concentration should be determined by the
following equation:
Cpnormal binding = Cpobserved / {(0.9) [Albumin Levelobserved/4.4]+0.1}
7. In renal failure patientthe serum concentration that would have been observed
with a normal renal function should be determined by the following equation
Cpnormal binding = Cpobserved / {(0.48)(0.9) [Albumin Levelobserved/4.4]+0.1}
Valproic Acid
1. Sampling time trough.
2. Therapeutic range 50-100g/ml.
3. Time to steady-state2-3 days.
4. Monitoring parameters liver function albumin level.
5. Factors affecting serum levelhypoalbuminemia enzyme-inducerprotein
binding displacer.
IV. Methotrexate (MTX)
1. Sampling time 24 48 72 hrs after starting high dose MTX. Time when
concentration >0.1M should not exceed 48 hours.
2. Target serum level< 0.05M.
3. Leucovorin rescue for 12-72 hours or until MTX concentration < 0.05- 0.1M
48hr MTX conc. Leucovorin dose
> 10 M 1000 mg/m2 q2-3h IV
> 1 M 2
50 -100 mg/ m q4h
or 150 mg/m2 q4-6h IV
> 0.1 M 10-50 mg/m2 q6h
IV or PO
4. Monitoring parametersCBC renal functionurine pH (>6.5).
5. Factors affecting serum levelascites or pleural effusions intestinal
obstructionrenal insufficiencyliver function impairment.

V. Theophylline
1. Salt factors 100mg aminophylline is equivalent to 80-84mg theophylline.
2. Sampling time
IV-peak 30min post loading dose (30min infusion) or 4-6hr post beginning
continuous infusion.
IV-steady state > 12-24hr after beginning continuous infusion.
PO peak2hr post rapid release.
4-6hr post "Phyllocontin".
8-12hr post "Uniphyllin".
PO troughprior to next-dose.
3. Therapeutic range
Asthma 10-20g/ml.
Neonatal apnea5-10g/ml.
4. Time to steady-stateAdults & children 1-2 daysNeonates3-5 days.
5. Factors affecting theophylline clearance
1) Age
2) Disease Factors
Smoking history 1.6
Congestive heart failure 0.4
Acute pulmonary edema 0.5
Acute viral illness 0.5
Hepatic cirrhosis 0.5
Severe obstructive pulmonary 0.8
 Obesity IBW

VI. Digoxin
1. Sampling time To avoid assay interference fasting morning sample is
preferredor at least 6hr after dose.
2. Therapeutic range 0.8-2.0 ng/ml for patients with sinus rhythm more liberal
for patients with atrial fibrillation (may exceed 3 ng/ml).*
3. Time to steady-state
Normal 7-14 days.
End-stage renal disease 15-20+ days.
4. Monitoring parameters electrolytes, renal function, ECG.
5. Factors affecting serum level renal impairment cardiac disease thyroid
dysfunction drug interaction product formulation.
6. Factors influencing the response to digoxin hypokalemiametabolic
alkalosishypercalcemia hypomagnesemia underlying cardiac
diseasesthyroid function.
7. Drugs increase drug concentration quinidineverapamil
spironolactoneamiodarone adrenocorticosteroids.
* Digoxin serum levels may vary widelyclinical responsesigns and symptoms
of toxicity should be monitored primarily.

VII. Lithium
1. Sampling time just before the first morning dose of lithium and at least 12 hrs
after the last evening dose.
2. Therapeutic range
Maintenance 0.6-0.8 mEq/L (mmol/L).
Acute episodes 0.8-1.2 mEq/L (not to exceed 1.5mEq/L)
3. Monitoring parametersrenal function urine osmolalityCBCthyroid
functionECG CNS side effect

VIII. Cyclosporine
1. Please use heparinized tube for sampling as whole blood concentration is adopted.
2. Sampling time
Peakat least 2 to 3 hrs after the discontinuation of an infusion.
Troughjust before or within 1hr of the next scheduled dose.
3. Therapeutic rangedepending on the organs of transplantation and the degree of
rejection.
Fluorescence polarization immunoassay (monoclonalwhole blood)150-400
 ng/ml.
4. Monitoring parameters renal functioncholesterol and lipoprotein
levelselectrolytes.