Amikacin | Conventional dosing: Peak: 20–30 mg/L; trough: < 10 mg/L | 2–3; ↑ in uremia | ↓ in kidney dysfunction | Concomitant kanamycin or tobramycin therapy may give falsely elevated amikacin results by immunoassay. |
| High dose once daily: Peak: 60 mg/L; trough: < 5 mg/L |
| Amitriptyline | 95–250 ng/mL | 9–25 | No dosage adjustments provided in manufacturer’s labeling | Drug is highly protein-bound. Patient-specific decrease in protein binding may invalidate quoted therapeutic reference interval for effective concentration. Use with caution in patients with kidney or liver dysfunction. |
| Panic: ≥ 500 ng/mL |
| Carbamazepine | 4–12 mg/L | 10–15 | ↓ (75% of dose) in severe kidney dysfunction; use with caution in liver dysfunction | Induces its own metabolism. Metabolite 10,11-epoxide exhibits 13% cross-reactivity by immunoassay. Adverse reactions: skin reactions, myelosuppression. |
| Cyclosporine | 100–300 mcg/L (ng/mL) whole blood | 6–12 | ↓ in kidney or liver dysfunction | Cyclosporine is lipid-soluble (20% bound to leukocytes; 40% to erythrocytes; 40% in plasma, highly bound to lipoproteins); the binding is temperature-dependent in vitro and concentration-dependent in vivo. HPLC and LC-tandem mass spectrometry methods are highly specific for parent drug and considered as the gold standard assays. Monoclonal fluorescence polarization immunoassay (FPIA) and monoclonal chemiluminescence immunoassay also measure cyclosporine reliably; polyclonal immunoassays are less specific due to cross-reaction with drug metabolites. Anticonvulsants and rifampin increase its metabolism. Erythromycin, ketoconazole, and calcium channel blockers decrease its metabolism. The main adverse reaction is concentration-related nephrotoxicity. |
| Desipramine | 100–250 ng/mL | 13–23 | No dosage adjustments provided in manufacturer’s labeling | Drug is highly protein-bound. Patient-specific decrease in protein binding may invalidate quoted therapeutic reference interval for effective concentration. |
| Panic: ≥ 500 ng/mL |
| Digoxin | HF: 0.5–0.9 mcg/L Atrial fibrillation: 0.5–2 mcg/L | 36–42; ↑ in uremia, HF | ↓ in kidney dysfunction, HF, hypothyroidism ↑ in hyperthyroidism | Bioavailability of digoxin tablets is 50–90%. Specimen must not be drawn within 4 hours of an intravenous dose or 6 hours of an oral dose. Dialysis does not remove a significant amount. Hypokalemia potentiates toxicity. Digitalis toxicity is a clinical and not a laboratory diagnosis. Digibind (digoxin-specific antibody) therapy of digoxin overdose can interfere with measurement of digoxin levels depending on the digoxin assay. Elimination reduced by amiodarone, quinidine, and verapamil. |
| Ethosuximide | 40–100 mg/L | Child: 30–40 Adult: 50–60 | No dosage adjustments provided in manufacturer’s labeling | Levels used primarily to assess clinical response and compliance. Toxicity is rare and does not correlate well with plasma concentrations. Use with extreme caution in patients with kidney or liver dysfunction. |
| Gentamicin | Conventional dosing: Peak: 4–8 mg/L; trough: < 2 mg/L | 2–3; ↑ in uremia (7.3 during dialysis) | ↓ in kidney dysfunction | Draw peak specimen (conventional dosing) 30 minutes after end of 30- to 60-min infusion. Draw trough just before next dose. In uremic patients, some penicillins (eg, carbenicillin, ticarcillin, piperacillin) may decrease gentamicin half-life from 46 hours to 22 hours, posing a risk of reduced antibacterial efficacy. The main adverse reactions are CNS, otic, and kidney toxicities. |
| High dose once daily: Peak: 20 mg/L; trough: undetectable |
| Imipramine | 180–350 ng/mL | 10–16 | No dosage adjustments provided in manufacturer’s labeling | Drug is highly protein-bound. Patient-specific decrease in protein binding may invalidate quoted therapeutic reference interval for effective concentration. |
| Panic: ≥ 500 ng/mL |
| Lidocaine | 1–5 mg/L | 1–2; ↔ in uremia, HF; ↑ in cirrhosis | ↓ in HF, liver dysfunction | Levels increased with cimetidine therapy. CNS toxicity common in the elderly. |
| Panic: ≥ 7.0 mg/L |
| Lithium | 0.5–1.2 mmol/L | 10–35; ↑ in uremia | ↓ in kidney dysfunction | Thiazides and loop diuretics may increase serum lithium levels. |
| Methotrexate | < 1.0 mcmol/L 48 hours post high-dose therapy, or according to protocol | 3–10 low dose; 8–15 high dose; ↑ in uremia | ↓ in kidney dysfunction | Therapeutic concentrations depend on the treatment protocol (low versus high dose) and time of specimen collection. 7-Hydroxymethotrexate cross-reacts 1.5% in immunoassay. To minimize toxicity, leucovorin should be continued if methotrexate level is > 0.1 mcmol/L at 48 hours after start of therapy. Methotrexate level > 1 mcmol/L at > 48 hours requires an increase in rescue therapy. In patients with methotrexate level > 1 mcmol/L and impaired kidney function, glucarpidase (intravenous injection) can be used as the rescue. |
| Nortriptyline | 50–140 ng/mL | 18–44 | ↓ in liver dysfunction | Drug is highly protein-bound. Patient-specific decrease in protein binding may invalidate quoted therapeutic reference interval for effective concentration. |
| Panic: ≥ 500 ng/mL |
| Phenobarbital | 10–40 mg/L | Child: 37–73 Adult: 53–140; ↑ in cirrhosis | ↓ in liver dysfunction | Metabolized primarily by the hepatic microsomal enzyme system. Many drug–drug interactions. |
| Phenytoin | 10–20 mg/L; 5–10 mg/L in uremia and severe hypoalbuminemia | Dose/concentration-dependent | No dosage adjustments provided in manufacturer’s labeling | Drug metabolite cross-reacts in immunoassays; the cross-reactivity may be of significance only in the presence of advanced chronic kidney disease. Metabolism is capacity-limited. Increase dose cautiously when level approaches therapeutic reference interval, since new steady-state level may be disproportionately higher. Drug is very highly protein-bound; protein binding is decreased in uremia and hypoalbuminemia. Monitoring free (unbound) drug level (pharmacologically active fraction, target range 0.5–2.0 mg/L) is recommended in severe kidney and liver dysfunction. |
| Panic: ≥ 35 mg/L |
| Sirolimus | Trough: 4–12 ng/mL when used in combination with cyclosporine A; 12–20 ng/mL if used alone | 57–63 | ↓ in liver dysfunction and with drugs inhibiting CYP3A4 activity | 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. When used in combination with cyclosporine, careful monitoring of kidney function is required. 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. The optimal time for specimen collection is 24 hours after the previous dose or 0.5 to 1 hours prior to the next dose (trough level). |
| Tacrolimus | Trough: 8–12 ng/mL | 8.7–11.3 | ↓ in liver dysfunction and with drugs inhibiting CYP3A4 activity | 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 stem cell transplantation patients and to treat autoimmune diseases. Antacid or sucralfate administration should be separated from tacrolimus by at least 2 hours. The optimal time for specimen collection is 12 hours after the previous dose or 0.5 to 1 hours prior to the next dose (trough level). |
| Theophylline | 5–15 mg/L | 4–9 | ↓ in HF, cirrhosis, and with cimetidine | Caffeine cross-reacts 10%. Elimination is increased 1.5–2 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. |
| Panic: ≥ 30 mg/L |
| Tobramycin | Conventional dosing: Peak: 5–10 mg/L; trough: < 2 mg/L | 2–3; ↑ in uremia | ↓ in kidney dysfunction | Tobramycin, kanamycin, and amikacin may cross-react in immunoassay. Some antibiotics may decrease tobramycin half-life in uremic patients, causing reduced antibacterial efficacy. |
| High dose once daily: Peak: 20 mg/L; trough: undetectable |
| Valproic acid (Valproate), total | 50–100 mg/L; 50–125 mg/L for bipolar disorder | Child: 6–8 Adult: 10–12 | Contraindicated in severe liver dysfunction | Significant fraction of the drug is protein-bound in vivo (concentration-dependent). Decreased binding in severe kidney disease and in liver dysfunction. Monitoring only total drug levels may be misleading. Monitoring with both total and free drug levels is preferred. Plasma concentrations show poor correlation with effect. |
| Panic: > 150 mg/L |
| Vancomycin | Trough: 10–20 mg/L | 4–7; ↑ in severe kidney dysfunction | ↓ in kidney dysfunction | Trough concentrations are recommended for monitoring vancomycin efficacy. Ototoxicity in uremic patients may lead to irreversible deafness. Monitoring serum levels to prevent ototoxicity in patients with normal kidney function receiving vancomycin monotherapy is not effective since this toxicity is rarely associated with monotherapy and does not correlate with serum levels. Data do not support using peak levels to monitor nephrotoxicity. Use trough levels. |
| Panic: ≥ 35 mg/L |