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Critical values for therapeutic drug levels.

The concept of critical values for drug levels was developed by Daniel M. Baer, MD, professor emeritus of laboratory medicine, Oregon Health Sciences University, Portland, OR, and first published in the April 1982 issue of MLO. This table is an expanded version of that publication revised by Diane M. Lyle, Pharm.D, BCPS, Critical Care Clinical Pharmacy Specialist, Portland VA Medical Center. Dr. Baer is a member of MLO's Editorial Board and editor of MLO's "Tips from the Clinical Experts" department.
Drug Therapeutic range Critical value

ANTIBIOTICS (Specimen collection depends on the dosing protocol
followed. Consult the hospital pharmacy.)

Gentamicin 4-10 mcg/mL peak > 2 mcg/mL trough
 < 2 mcg/ml trough
Tobramycin 4-10 mcg/mL peak > 2 mcg/mL trough
 < 2 mcg/mL trough
Amikacin 15-30 mcg/mL peak > 10 mcg/mL trough
 > 10 mcg/mL trough
Vancomycin 20-40 mcg/mL peak 60-80 mcg/mL peak
 5-15 mcg/mL trough

ANALGESICS (Specimen collection: For toxic ingestion, draw sample at any
time, noting times of ingestion and sample collection. Usually two
samples, several hours apart, acted to determine half-life.)

Acetaminophen 5-20 mcg/mL 150 mcg/mL
Salicylate 10-20 mg/dL >30 mg/dL

ANTIEPILEPTICS (Specimen collection: Trough, before next dose.
Subsequent samples should be drawn at same time in relation to drug
dosing.)

Carbamazepine* 4-12 mcg/mL >20 mcg/mL
Ethosuximide 40-100 mcg/mL >200 mcg/mL
Phenobarbitol 15-40 mcg/mL >60 mcg/mL
Phenytoin 10-20 mcg/mL >40 mcg/mL
Primidone 5-12 mcg/mL >24 mcg/mL
Valproic acid 50-100 mcg/mL >200 mcg/mL

*4-8 if patient is on multiple antiepileptic drugs

ANTIDEPRESSANTS

Lithium specimen collection: 12 hours after dose
Lithium (acute) 1.0-1.6 mEq/L >2.0 mEq/L
Lithium (chronic) 0.6-1.2 mEq/L

Specimen collection: Trough, before next dose
Amitriptyline 120-250 ng/mL* 400 ng/mL*
Imipramine 150-300 ng/mL 400 ng/mL
Nortriptyline 50-150 ng/mL 200 ng/mL
Protriptyline 75-250 ng/mL 400 ng/mL
Doxepin 110-250 ng/mL* 400 ng/mL*

*Parent drug plus demethylated metabolite

OTHER DRUGS

Cyclosporin 100-500 ng/mL
Tacrolimus 5-20 mcg/L trough >25 mcg/L
Theophylline 10-20 mcg/mL >25 mcg/mL
Digoxin 0.5-2.0 ng/mL 2.5 ng/mL

Drug Comment

ANTIBIOTICS (Specimen collection depends on the dosing protocol
followed. Consult the hospital pharmacy.)

Gentamicin These values correlate only with standard dosing, not
 pulse or single daily dosing.
Tobramycin Toxicity is related to trough concentrations and time
 spent at that concentration.
 Several methods for single daily dosing exist.
 Depending on the Method, timing of drawing levels and
 desired levels will vary.
Amikacin
Vancomycin Draw peak 2-3 hrs after infusion ends.
 Peak concentrations not correlated with clinical
 efficacy.
 Toxicity is correlated with very high levels (60-80
 mcg/mL) or duration of therapy.
 Draw trough immediately before next dose.

ANALGESICS (Specimen collection: For toxic ingestion, draw sample at any
time, noting times of ingestion and sample collection. Usually two
samples, several hours apart, acted to determine half-life.)

Acetaminophen To be measured 4 hours after the last dose.
Salicylate

ANTIEPILEPTICS (Specimen collection: Trough, before next dose.
Subsequent samples should be drawn at same time in relation to drug
dosing.)

Carbamazepine* Toxicity is usually clinically evident. Serious
 toxicity is likely at twice the upper therapeutic
 level.
Ethosuximide
Phenobarbitol
Phenytoin Toxicity may occur at lower concentrations in
 presence of low albumin.
Primidone
Valproic acid

*4-8 if patient is on multiple antiepileptic drugs

ANTIDEPRESSANTS

Lithium specimen collection: 12 hours after dose
Lithium (acute) Levels over 5 mEq/L are potentially lethal.
Lithium (chronic)

Specimen collection: Trough, before next dose
Amitriptyline Life-threatening cardiac toxicity or seizures are
 seen if concentration is over 1,000 ng/mL
Imipramine
Nortriptyline
Protriptyline
Doxepin

OTHER DRUGS

Cyclosporin High-performance liquid chromatography or monoclonal
 immunoassay using whole blood. Sampling at a few
 time points may provide more cost-effective
 monitoring. Levels will vary based on whether taken
 from whole blood, serum, or plasma. Refer to
 institution's method for pharmacokinetic monitoring.
Tacrolimus Whole blood samples
Theophylline Above this concentration, 75 percent of patients
 have toxic symptoms. Serious toxicity causes seizures
 that can be fatal. Draw sample at peak. Different
 theophylline timed release medications have peaks at
 different times. Medication package insert should be
 consulted. Serial measurements should be collected at
 the same time each day.
Digoxin Eighty-seven percent of patients with greater than 2
 ng/mL digoxin have toxic symptoms.

Proper interpretation of therapeutic drug concentrations requires that
the specimen be drawn at an appropriate time in relation to drug
administration.
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No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2004 Gale, Cengage Learning. All rights reserved.

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Publication:Medical Laboratory Observer
Article Type:Illustration
Geographic Code:1USA
Date:Aug 1, 2004
Words:744
Previous Article:Table of reference intervals.
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