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13 23
Digoxin
08 2 ng/mL
42; in uremia, CHF
Copyright 2008 by The McGraw-Hill Companies, Inc Click here for terms of use
Appendix
CMDT 2008
Table 1 Therapeutic drug monitoring1 (continued)
Drug Ethosuximide Gentamicin Effective Concentrations 40 100 mg/L Peak: 4 8 mg/L; trough: < 2 mg/L 180 350 ng/mL Half-Life (hours) Child: 30 Adult: 50 2 5; in uremia (73 on dialysis) in renal dysfunction Dosage Adjustments Comments Levels used primarily to assess compliance Toxicity is rare and does not correlate well with plasma concentrations Draw peak specimen 30 minutes after end of infusion Draw trough just before next dose In uremic patients, carbenicillin may decrease gentamicin half-life from 46 hours to 22 hours Drug is highly protein-bound Patient-specific decrease in protein binding may invalidate quoted range of effective concentration in CHF, liver disease in renal dysfunction in renal dysfunction Levels increased with cimetidine therapy CNS toxicity common in the elderly Thiazides and loop diuretics may increase serum lithium levels 7-Hydroxymethotrexate cross-reacts 15% in immunoassay To minimize toxicity, leucovorin should be continued if methotrexate level is > 01 mcmol/L at 48 hours after start of therapy Methotrexate > 1 mcmol/L at > 48 hours requires an increase in leucovorin rescue therapy Drug is highly protein-bound Patient-specific decrease in protein binding may invalidate quoted range of effective concentration in liver disease Metabolized primarily by the hepatic microsomal enzyme system Many drug-drug interactions Metabolite cross-reacts 10% in immunoassay Metabolism is capacity-limited Increase dose cautiously when level approaches therapeutic range, since new steady-state level may be disproportionately higher Drug is very highly protein-bound; protein binding is decreased in uremia and hypoalbuminemia Phenobarbital cross-reacts 05% Metabolized to phenobarbital Primidone/phenobarbital ratio > 1:2 suggests poor compliance in renal dysfunction 30% of patients with plasma levels of 12 16 mcg/mL have ECG changes; 40% of patients with plasma levels of > 16 mcg/mL have severe toxicity Metabolite N-acetylprocainamide is active Effective concentration is lower in chronic liver disease and nephrosis, where binding is decreased Sirolimus is an immunosuppressant used in combination with cyclosporine and corticosteroids for prophylaxis of organ rejection after kidney transplantation It has also been used in liver and heart transplantation Once the initial dose titration is complete, monitoring sirolimus trough concentrations weekly for the first month and every 2 weeks for the second month appears to be appropriate Tacrolimus is used for prophylaxis of organ rejection in adult patients undergoing liver or kidney transplantation and in pediatric patients undergoing liver transplantation It has also been used to prevent rejection in heart, small bowel, and allogeneic bone marrow transplant patients and to treat autoimmune diseases Antacid or sucralfate administration should be separated from tacrolimus by at least 2 hr (continued )
Imipramine
10 16
Lidocaine
1 5 mg/L
18; in uremia, CHF; in cirrhosis 22; in uremia 84; in uremia
Lithium Methotrexate
07 15 mmol/L
Nortriptyline
50 140 ng/mL
18 44
Phenobarbital Phenytoin
10 40 mg/L 10 20 mg/L; 5 10 mg/L in uremia, hypoalbuminemia
86; in cirrhosis Dose-dependent
Primidone
5 10 mg/L
Procainamide
4 8 mg/L
3; in uremia
Quinidine Salicylate Sirolimus
1 4 mg/L 150 300 mg/L Trough: 4 12 ng/ mL when used in combination with cyclosporine A; 12 20 ng/mL if used alone Trough: 5 20 ng/ mL
7; in CHF; in liver disease Dose-dependent 62
in liver disease, CHF in liver dysfunction and with drugs affecting CYP3A4 activity
Tacrolimus
87 113
in liver dysfunction and with drugs affecting CYP3A4 activity
CMDT 2008
Appendix
Table 1 Therapeutic drug monitoring1 (continued)
Drug Theophylline Effective Concentrations 5 20 mg/L Half-Life (hours) 9 Dosage Adjustments in CHF, cirrhosis, and with cimetidine Comments Caffeine cross-reacts 10% Elimination is increased 15 2 times in smokers 1,3-Dimethyl uric acid metabolite increased in uremia and, because of cross-reactivity, may cause an apparent slight increase in serum theophylline Tobramycin, kanamycin, and amikacin may cross-react in immunoassay 95% protein-bound Decreased binding in uremia and cirrhosis in renal dysfunction Toxicity in uremic patients leads to irreversible deafness Keep peak level < 30 40 mg/L to avoid toxicity
Tobramycin
Peak: 5 10 mg/ L; trough: < 2 mg/L 55 100 mg/L Trough: 5 15 mg/L
2 3; in uremia 13 19 6; in uremia
in renal dysfunction
Valproic acid Vancomycin
Use red-topped tube (not marbled) for therapeutic drug monitoring In general, the specimen should be drawn just before the next dose (trough) , unchanged; , increase(d); , decrease(d); HPLC, high performance liquid chromatography; CHF, congestive heart failure; CNS, central nervous system; ECG, electrocardiogram Modified, with permission, from Nicoll D et al: Pocket Guide to Diagnostic Tests, 5th ed McGraw-Hill, 2008
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