Editors: Susla, Gregory M.; Suffredini, Anthony F.; McAreavey, Dorothea; Solomon, Michael A.; Hoffman, William D.; Nyquist, Paul; Ognibene, Frederick P.; Shelhamer, James H.; Masur, Henry
Title: Handbook of Critical Care Drug Therapy, 3rd Edition
> Table of Contents > Chapter 13 - Drug Monitoring
Chapter 13
Drug Monitoring

TABLE 13.1. Serum Drug Concentrations—Therapeutic Ranges
Drug Usual Therapeutic Range Time to Steady State with Normal Organ Function Usual Time Sampling
Antibiotics
Amikacin Multiple daily dose:
Peak: 20–40 mg/L
Trough: <10 mg/L
High dose extended interval:
Peak: not recommended
Trough: 0 mg/L
5–35 h Peak: 30–60 minutes after a 30-min infusion
Trough: Just before next dose

Trough: Just before next dose
Chloramphenicol Peak: 10–25 mg/L
Trough: 5–10 mg/L
12–24 h Peak: 30–90 min after a 30-min infusion
Trough: Just before next dose
Gentamicin Multiple daily dose:
Peak: 4–10 mg/L
Trough: <2 mg/L
High dose extended interval:
Peak: not recommended
Trough: 0 mg/L
5–35 h Peak: 30–60 min after a 30-min infusion
Trough: Just before next dose
Trough: Just before next dose
Streptomycin Peak: 40–50 mg/L
Trough: <5 mg/L
10–500 h Peak: 30–60 min after a 30-min infusion
Trough: Just before next dose
Sulfonamides (sulfamethoxazole, sulfadiazine, co-trimoxazole) Peak: <150 mg/L 24–48 h Peak: 2 h after 1-h infusion
Trough: Not applicable
Tobramycin Multiple daily dose:
Peak: 4–10 mg/L
Trough: <2 mg/L
5–35 h Peak: 30–60 min after a 30-min infusion
Trough: Just before next dose
Vancomycin Peak: 20–40 mg/L
Trough: <10 mg/L
24–36 h Peak: 1 h after 1-h infusion
Trough: Just before next dose
Antiarrhythmics
Amiodarone 0.5–2 mg/L Weeks to months Trough: Just before next dose
Digoxin 0.5–2 ng/ml 7–10 d Peak: 8–12 h after dose
Trough: Just before next dose
Digitoxin 20–35 ng/ml 25–70 d Peak: 4–12 h after dose
Trough: Just before next dose
Disopyramide 2–5 mg/L 24–48 h Trough: Just before next dose
Flecainide 0.2–1.0 mg/L 70–100 h Trough: Just before next dose
Lidocaine 1.5–5 mg/L 30–90 min after loading dose, 5–10 h without loading dose Anytime during a continuous infusion
Mexiletine 0.5–2 mg/L 48–72 h Trough: Just before next dose
Procainamide/ NAPA Procainamide: 4–10 mg/L
NAPA: 10–20 mg/L
Procainamide: 12–24 h
NAPA: 24–48 h
IV: 30 min after IV loading dose or anytime during continuous infusion
PO: Trough: Just before next dose
Quinidine 2.5–5 mg/L 30–36 h Trough: Just before next dose
Anticonvulsants
Carbamazepine 4–12 mg/L >14 d Trough: Just before next dose
Fosphenytoin Total: 10–20 mg/L (measured as phenytoin)
Free: 1–2 mg/L
8–50 d
Variable depending on daily dose
Peak: IV: 2 h after dose
IM: 4 h after dose
Trough: just before next dose
Pentobarbital 20–50 mg/L 75–110 h IV: Peak: Immediately after loading dose or anytime during a continuous infusion
Phenobarbital 15–40 mg/L 10–25 d Trough: Just before next dose
Phenytoin Total: 10–20 mg/L
Free: 1–2 mg/L
8–50 d
Variable depending on daily dose
IV: 2–4 h after dose
PO: 3–9 h after administration of phenytoin capsules
Primidone Primidone: 5–12 mg/L
Phenobarbital: 15–40 mg/L
Primidone: 72–170 h
Phenobarbital: 10–25 d
Trough: Just before next dose
Specimens should be assayed for primidone and phenobarbital
Valproic acid 50–100 mg/L 48–72 h Trough: Just before next dose
Bronchodilators
Theophylline 10–20 mg/L 48 h IV: Prior to IV bolus dose, 30 min after end of bolus dose or anytime during continuous infusion
PO: Peak: 2 h after rapid release product, 4 h after sustained release product
Trough: Just before next dose
Immunosuppressants
Cyclosporine Kidney:
<3 mo: Whole blood: HPLC, M-RIA, M-FPIA: 150–250 ng/ml
>3 mo: Whole blood: HPLC, M-RIA, M-FPIA: 100–200 ng/ml
Liver:
Whole blood: HPLC, M-RIA, P-FPIA: 200–300 ng/ml
Heart:
Whole blood: HPLC, M-RIA: 150–300 ng/ml
Bone marrow:
Serum/plasma: HPLC, M-RIA, P-FPIA: 150–300 ng/ml
36–170 h IV/PO: Trough: Just before next dose
Tacrolimus Plasma: 0.1–5 µg/L
Whole blood: 5–20 µg/L
60–190 h IV: Anytime during infusion
PO: Trough: Just before next dose
Preferred assay is MEIA
HPLC, high performance liquid chromatography; IM, intramuscular; IV, intravenous; MEIA, microparticulate enzyme immunoassay; M-FPIA, monoclonal fluorescence polarization immunoassay; M-RIA, monoclonal radioimmunoassay; P-FPIA, polyclonal fluorescence polarization immunoassay; PO, by mouth; NAPA, N-acetylprocainamide
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TABLE 13.2. Selected Drug Interactions
Primary Drug Interacting Drug/Mechanism Effect Management
Adenosine Theophylline/Inhibits the hemodynamic effects of adenosine Decreases the antiarrhythmic effectiveness of adenosine May require increased adenosine doses to control arrhythmia
Dipyridamole/Decreased adenosine metabolism Potentiates the pharmacologic effect of adenosine Reduce the dose of adenosine for the treatment of arrhythmias or for diagnostic tests
Nicotine/Increases the hemodynamic and AV nodal blocking effects of adenosine Potentiates the pharmacologic effect of adenosine Cigarette smokers or users of nicotine gum or patches should be monitored for a greater hemodynamic response to adenosine. Reduced adenosine doses may be required in these patients
Aminoglycosides Neuromuscular blocking agents/Prevent release of acetylcholine at neuromuscular junction Prolonged paralysis Monitor neuromuscular function with train-of-four stimulation
Antipseudomonal penicillins/ Inactivate aminoglycosides in vitro and in vivo Reduced aminoglycoside levels Send specimens for aminoglycoside level determination to lab for immediate assay
Inactivate aminoglycosides in vivo in patients with severe renal dysfunction
Amiodarone Cholestyramine/Increased amiodarone elimination Decreased amiodarone level Monitor amiodarone level, adjust amiodarone dose accordingly
Cimetidine/Decreased amiodarone metabolism Increased amiodarone level Monitor amiodarone level, adjust amiodarone dose accordingly
Cyclosporine/Decreased cyclosporine metabolism Increased cyclosporine level Monitor cyclosporine level, adjust cyclosporine dose accordingly
Digoxin/Decreased digoxin clearance Increased digoxin level Monitor digoxin level, adjust digoxin dose accordingly
Phenytoin/Decreased phenytoin metabolism
Increased amiodarone metabolism
Increased phenytoin level
Decreased amiodarone level
Monitor phenytoin and amiodarone levels, adjust doses accordingly
Warfarin/Altered protein binding and decreased metabolism Increased anticoagulant effect Monitor PT/INR, adjust warfarin dose accordingly
Anticoagulants Amiodarone/Altered warfarin protein binding and decreased warfarin metabolism Increased anticoagulant effect Monitor PT/INR, adjust warfarin dose accordingly
Barbiturates/Increased warfarin metabolism Decreased anticoagulant effect Monitor PT/INR, adjust warfarin dose accordingly
Cholestyramine/Decreased warfarin absorption Decreased anticoagulant effect Separate doses
Erythromycins (clarithro-, erythro-)/Decreased warfarin metabolism Increased anticoagulant effect Monitor PT/INR, adjust warfarin dose accordingly
Consider alternative antibiotic
Cimetidine/Decreased warfarin clearance Increased anticoagulant effect Monitor PT/INR, adjust warfarin dose accordingly
Ciprofloxacin/Decreased warfarin metabolism Increased anticoagulant effect Monitor PT/INR, adjust warfarin dose accordingly
Consider alternative antibiotic
Fluconazole, itraconazole, ketoconazole/Decreased warfarin metabolism Increased anticoagulant effect Monitor PT/INR, adjust warfarin dose accordingly
NSAIDS/Decreased platelet aggregation Increased bleeding Monitor for signs and symptoms of bleeding
Metronidazole/Decreased warfarin metabolism Increased anticoagulant effect Monitor PT/INR, adjust warfarin dose accordingly
Consider alternative antibiotic
Propafenone/Decreased warfarin metabolism Increased anticoagulant effect Monitor PT/INR, adjust warfarin dose accordingly
Rifampin/increased warfarin metabolism Decreased anticoagulant effect Monitor PT/INR, adjust warfarin dose accordingly
Salicylates/Decreased platelet aggregation Increased bleeding Monitor for signs and symptoms of bleeding
Sulfonamides/Altered warfarin protein binding Increased anticoagulant effect Monitor PT/INR, adjust warfarin dose accordingly
Consider alternative antibiotic
Proton Pump Inhibitors Warfarin Increased anticoagulant effect Monitor PT/INR, adjust warfarin dose accordingly
Phenytoin Increased phenytoin level Monitor phenytoin level, adjust phenytoin dose accordingly
Linezolid Adrenergic agents (i.e., dopamine, epinephrine) Increased adrenergic response Reduce and titrate adrenergic dose as needed to achieve desired response
Serotonergic agents (i.e., fluoxetine, paroxetine, sertraline, etc.) Increased risk for developing serotonin syndrome Avoid combination; use alternative antibiotic if possible
Ciprofloxacin Foscarnet/Decreased seizure threshold Increased risk of seizures Monitor for seizure activity
Adjust dose of each agent for degree of renal insufficiency
Mexiletine/Decreased mexiletine metabolism Increased mexiletine level Monitor mexiletine level, adjust mexiletine dose accordingly
Phenytoin/Decreased phenytoin metabolism Increased phenytoin level Monitor phenytoin level, adjust phenytoin dose accordingly
Theophylline/Decreased theophylline metabolism Increased theophylline level Monitor theophylline level, adjust theophylline dose accordingly
Warfarin/Decreased warfarin metabolism Increased anticoagulant effect Monitor PT/INR, adjust warfarin dose accordingly
Consider alternative antibiotic
Levofloxacin Warfarin/Decreased warfarin metabolism Increased anticoagulant effect Monitor PT/INR, adjust warfarin dose accordingly
Consider alternative antibiotic
Cyclosporine Anticonvulsants (phenytoin, phenobarbital, carbamazepine)/Increased cyclosporine metabolism Decreased cyclosporine level Monitor cyclosporine level, adjust cyclosporine dose accordingly
Diltiazem/Decreased cyclosporine metabolism Increased cyclosporine level Monitor cyclosporine level, adjust cyclosporine dose accordingly
Consider an alternative calcium channel blocker
Rifampin/Increased cyclosporine metabolism Decreased cyclosporine level Monitor cyclosporine level, adjust cyclosporine dose accordingly
Ketoconazole, fluconazole, itraconazole/Decreased cyclosporine metabolism Increased cyclosporine level Monitor cyclosporine level, adjust cyclosporine dose accordingly
Erythromycin, clarithromycin/ Decreased cyclosporine metabolism Increased cyclosporine level Monitor cyclosporine level, adjust cyclosporine dose accordingly
Aminoglycosides/ Increased nephrotoxicity Decreased renal function Monitor renal function
Amphotericin B/Increased nephrotoxicity Decreased renal function Monitor renal function
Metoclopramide, cisapride/Increased cyclosporine absorption Increased cyclosporine level Monitor cyclosporine level, adjust cyclosporine dose accordingly
Octreotide/Decreased cyclosporine absorption Decreased cyclosporine level Monitor cyclosporine level, adjust cyclosporine dose accordingly
Cimetidine, famotidine, omeprazole/Decreased cyclosporine metabolism Increased cyclosporine level Monitor cyclosporine level, adjust cyclosporine dose accordingly
Digoxin Amiodarone/Decreased elimination Increased digoxin level Monitor digoxin level, adjust digoxin dose accordingly
Diuretics/Increased potassium excretion Increased potential for digoxin toxicity Monitor potassium level
Consider the need for potassium supplements or potassium sparing diuretics
Propafenone/Decreased volume of distribution and nonrenal clearance Increased digoxin level Monitor digoxin level, adjust digoxin dose accordingly
Quinidine/Decreased binding and elimination Increased digoxin level Monitor digoxin level, adjust digoxin dose accordingly
Verapamil/Decreased digoxin elimination Increased digoxin level Monitor digoxin level, adjust digoxin dose accordingly
Heparin Nitroglycerin/Altered heparin clearance Decreased anticoagulant effect Monitor PTT, adjust heparin infusion accordingly
Meperidine Monoamine oxidase inhibitors (phenelzine, tranylcypromine)/ Block the reuptake of serotonin Increased agitation, blood pressure, heart rate, temperature, development of seizures Avoid drug combination
Consider an alternative analgesic
Phenytoin Cimetidine/Decreased phenytoin metabolism Increased phenytoin level Monitor phenytoin level, adjust phenytoin dose accordingly
Fluconazole/Decreased phenytoin metabolism Increased phenytoin level Monitor phenytoin level, adjust phenytoin dose accordingly
Potassium-sparing diuretics/ (amiloride, spironolactone, triamterene) Potassium supplements/Increased potassium intake
Angiotensin converting enzyme inhibitors/Decrease potassium elimination
Salt substitutes/Increase potassium intake
Theophylline/Increased theophylline metabolism
Increased potassium level
Increased potassium level
Increased potassium level
Decreased theophylline level
Monitor potassium level
Review medication profile
Monitor potassium level
Review medication profile
Monitor potassium level
Review medication profile
Monitor theophylline level, adjust theophylline dose accordingly
Tacrolimus Aluminum hydroxide/Impaired tacrolimus absorption Decreased tacrolimus level Monitor tacrolimus level, adjust tacrolimus dose accordingly
Dexamethasone/ Increased tacrolimus metabolism Decreased tacrolimus level Monitor tacrolimus level, adjust tacrolimus dose accordingly
Erythromycin/Decreased tacrolimus metabolism Increased tacrolimus level Monitor tacrolimus level, adjust tacrolimus dose accordingly
Fluconazole, itraconazole, ketoconazole/ Decreased tacrolimus metabolism Increased tacrolimus level Monitor tacrolimus level, adjust tacrolimus dose accordingly
Magnesium oxide/pH mediated tacrolimus degradation Decreased tacrolimus level Monitor tacrolimus level, adjust tacrolimus dose accordingly
Rifampin/Increased tacrolimus metabolism Decreased tacrolimus level Monitor tacrolimus level, adjust tacrolimus dose accordingly
Sodium bicarbonate/pH mediated tacrolimus degradation Decreased tacrolimus level Monitor tacrolimus level, adjust tacrolimus dose accordingly
Theophylline See Table 4.6
AV, atrioventricular; INR, international normalized ratio; NSAIDS, nonsteroid anti-inflammatory drug; PT, prothrombin time; PTT, partial prothrombin time
For a complete review of HIV/AIDS drug interactions (see: Piscitelli SC, Flexner C, Minor JR, et al. Drug interactions in patients infected with human immunodeficiency virus. Clin Inf Dis 1996;23:685–93.)
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TABLE 13.3. Dosage Adjustments in Renal and Hepatic Failure
Agent Adjustment in Renal Failure (CrCl: ml/min/1.73 M2)    
CrCl Dosage Adjustment in Hepatic Failure Comments
Acebutolol >50 100% of daily dose No change  
  25–49 Reduce daily dose by 50%    
  <25 Reduce daily dose by 75%    
Acyclovir (intravenous) >50
25–50
10–25
0–10
HD:
5 mg/kg q8h
5 mg/kg q12h
5 mg/kg q24h
2.5 mg/kg q24h
2.5 mg/kg q24h
No change  
Acyclovir (oral) 200 mg q4h (5 × /d) or 400 mg q12h No change  
  >10
0–10
800 mg q4h
>25
10–25
0–10
No change
200 mg q12h
(5 × /d)
No change
800 mg q8h
800 mg q12h
   
Alfentanil No change   Decrease  
Allopurinol 80
60
40
20
10
0
250 mg q24h
200 mg q24h
150 mg q24h
100 mg q24h
100 mg q48h
100 mg q72h
No change  
Alprazolam No change   Decrease  
Amantadine ≥80
60–79
40–59
30–39
20–29
10–19
100 mg bid
200 mg/100 mg alternating qod
100 mg qd
200 mg 2 × /week
100 mg 3 × /week
200 mg/100 mg alternating q7d
No change  
Amikacin >160
100–159
60–99
40–59
<40
HD:
q6–8h
q8–12h
q12–18h
q18–24h
q24–48h
Monitor serum level 1 h after HD, suppl. dose after HD as needed
No change Adjust dose based on serum concentrations and patient's clinical response; in critically ill patients, dosing intervals increased secondary to increased fluid accumulation and reduced renal function
Aminophylline No change   0.3 mg/kg/h Adjust dose based on serum concentrations and patient's clinical response
Amiodarone No change   Reduce dosage in severe liver disease Adjust dose based on serum concentrations and patient's clinical response
Amlodipine No change   2.5 mg/d to maximum 5 mg/d  
Amoxicillin 10–50 250–500 mg q6–12h No change  
  <10 250–500 mg q12–16h    
  HD: 250–500 mg q16–24h with an additional 250 mg dose after dialysis    
Amoxicillin-clavulanic acid >30
15–30
250–500 mg q8h
250–500 mg q12–18h
No change  
  5–15 250–500 mg q20–36h    
  <5 250–500 mg q48h    
  HD: Suppl. dose after HD    
Ampicillin (intravenous and oral) >50 0.25–2 g q4–6h No change  
  10–50 0.25–2 g q6–12h    
  <10 0.25–2 g q8–16h    
  HD: Suppl. dose after HD    
Ampicillin-sulbactam ≥30
15–29
5–14
HD:
1.5–3 g q6–8h
1.5–3 g q8–12h
1.5–3 g q24h
Suppl. dose after HD
No change  
Argatroban No change   Moderate liver disease: 0.5 µg/kg/min More than 4 h may be required for full reversal of full anticoagulant effects after stopping infusion
Atenolol 15–35 50 mg qd No change  
  <15 25 mg qd    
  HD: 25–50 mg after dialysis    
Azathioprine >10
<10
No change
May need to decrease
Use with caution; possible decrease in conversion to 6-mercaptopurine  
Aztreonam >30 0.5–1 g q8–12h No change  
  10–30 1–2 g initially, then 0.25–1 g q8–12h    
  <10 1–2 g initially, then 0.125–0.5 g q8–12h    
  HD: same as <10 ml/min with suppl. dose of 0.0625–0.250 g after HD    
Benazepril <30 or SCr >3 mg/dl: 5 mg qd to maximum 40 mg qd   No change In patients with a CrCl <30 ml/min, a loop diuretic is preferred to a thiazide diuretic
Betaxolol Severe renal impairment or HD: 5 mg qd to maximum 20 mg qd   No change  
Bivalirudin ≥60 No change No change  
  30–60 20% dose reduction    
  10–29 60% dose reduction    
  HD: 90% dose reduction    
Captopril 10–50 75% of usual dose q12–18h No change  
  <10 50% of usual dose q24h    
Carbamazepine No change   Decrease Adjust dose based on serum concentrations and patient's clinical response
Caspofungin No change   Moderate liver disease: 70 mg loading dose followed by 35 mg q24h No experience in severe liver disease
Cefadroxil >50 0.5–1 g q12h No change  
  25–50 0.5 g q12h    
  10–25 0.5 g q24h    
  <10 0.5 g q36h    
Cefazolin <55 1 g q6–8h No change  
  35–54 1 g q8–12h    
  11–34 0.5–1 g q12h    
  <10 0.5–1 g q24h    
  HD: Suppl. dose after HD    
Cefepime >60 0.5–2 g q12h No change  
  30–60 0.5–2 g q24h    
  11–29 0.5–1 g q24h    
  <10 0.25–0.5 g q24h    
  HD: Suppl. dose after HD    
Cefixime 21–60 300 mg qd No change  
  <20 200 mg qd    
  HD: Suppl. dose not required    
Cefotaxime >20
<20
HD:
1–2 g q4–12h
0.5–1 g q4–12h
0.5–2 g q24h with suppl. dose after HD
Possible adjustment in severe disease Partially metabolized to desacetyl-cefotaxime, which has partial activity
Cefoxitin >50 1–2 g q6–8h No change  
  30–50 1–2 g q8–12h    
  10–29 1–2 g q12–24h    
  5–9 0.5–1 g q12–24h    
  <5 0.5–1 g q24–48h    
  HD: 1–2 g after HD    
Cefpodoxime <30 100–200 mg q24h No change  
  HD: 100–200 mg 3 × /wk after dialysis    
Cefprozil <30 250 mg q24h No change  
  HD: 250 mg after dialysis    
Ceftazidime >50 1 g q8h No change  
  31–50 1 g q12h    
  16–30 1 g q24h    
  6–15 0.5 g q24h    
  <5 0.5 g q48h    
  HD: 1 g initially, then 1 g after HD    
Ceftibuten >50 400 mg qd    
  30–49 200 mg qd    
  5–29 100 mg qd    
  HD: 400 mg after HD    
Cefuroxime >20 0.75–1 g q8h No change  
  10–20 0.75 g q12h    
  <10 0.75 g q24h    
  HD: Suppl. dose after HD    
Cephalexin 11–40 0.5 g q8–12h No change  
  5–10 0.25 g q12h    
  <5 0.25 g q12–24h    
Chloramphenicol See Comments   See Comments Adjust dose based on serum concentrations and patient's clinical response
Chlorpromazine No change   Avoid or decrease due to increased cerebral sensitivity  
Cidofovir Increase in SCr ≥0.3–0.4 mg/dl above baseline: 3 mg/kg
Increase in SCr ≥0.5 mg/dl above baseline or urinary protein ≥3+: cidofovir must be discontinued
No change Contraindicated in patients with preexisting SCr >1.5 mg/dl, CrCl ≤55 ml/min or preexisting urine protein concentration ≥100 mg/dl
Cimetidine >30
<30
HD:
300 mg q6–8h
300 mg q12h
Suppl. dose after HD and q12h during interdialysis period
No change Dosage may be based on gastric acid secretory response; further dose reductions when hepatic impairment is also present
Ciprofloxacin (Intravenous) >30
5–29
200–400 mg q12h
200–400 mg q18–24h
No change  
Ciprofloxacin (Oral) 30–50
5–29
HD:
250–500 mg q12h
250–500 mg q18h
250–500 mg qd suppl. doses not required
No change In patients with severe infections and severe renal impairment, 750 mg PO q12–18h with careful monitoring
Clarithromycin <30 500 mg initially, then 250 mg qd-bid No change  
Clindamycin No change   Decrease dose in moderate to severe disease  
Codeine 10–50 Decrease dose by 25% Decrease  
  <10 Decrease dose by 50%    
Daptomycin ≥30 4 mg/kg q24h No change  
  <30 including HD and CAPD 4 mg/kg q48h    
Dexmedetomidine No change   Reduce  
Desirudin >60
≥31–60
<31
15 mg q12h
5 mg q12h
1.7 mg q12h
No change Moderate renal dysfunction: monitor aPTT and SCr at least daily; if aPTT is >2 × control 1; interrupt therapy until aPTT returns to <2 × control, 2; resume therapy at reduced dose guided by initial degree of aPTT abnormality
Severe renal dysfunction: monitor aPTT and SCr at least daily; If aPTT is >2 × control 1; interrupt therapy until aPTT returns to <2 × control, 2; consider additional dose reduction guided by initial degree of aPTT abnormality
Diazepam No change   Decrease Active metabolites contribute to effect; use agents without active metabolites
Didanosine HD: 25% of the usual qd dose No change  
Digoxin See Comments   No change Adjust dosage based on serum concentrations and patient's clinical response
Disopyramide (immediate release capsules) >40
30–40
15–30
<15
100 mg q6h
100 mg q8h
100 mg q12h
100 mg q24h
No change Adjust dosage based on serum concentrations and patient's clinical response
Divalproex No change   Decrease Adjust dosage based on serum concentrations and patient's clinical response
Dofetilide >60 500 µg bid No change  
  40–60 250 µg bid    
  20–<40 125 µg bid    
  <20 Contraindicated    
Doxacurium See Comments   No change Monitor paralysis with train-of-four nerve stimulation
Doxycycline No change   Decrease dosage in moderate disease  
Enalaprilat >30 1.25 mg q6h No change  
  <30 0.625 mg q6h    
Enoxaparin   Prophylactic doses    
  >30 40 mg q24h    
  <30 30 mg q24h No change Anti-Xa levels may be lower in critically ill patients receiving standard doses
    Treatment doses    
  >30 1 mg/kg bid    
  <30 1 mg/kg qd    
Eptifibatide ACS: SCr <2 mg/dl: bolus: 180 µg/kg followed by infusion of 2 µg/kg/min SCr 2–4 mg/dl: bolus: 180 µg/kg followed by infusion of 1 µg/kg/min
PCI: SCr <2 mg/dl: Bolus: 180 µg/kg followed by infusion of 2 µg/kg/min; a second 180 µg/kg bolus dose is administered 10 minutes after the first; SCr 2–4 mg/dl; bolus: 180 µg/kg followed by infusion of 1 µg/kg/min; a second 180 µg/kg bolus dose is administered 10 min after the first
  No change  
Ertapenem >30 1 g q24h No change  
  ≤10–30 500 mg q24h    
  HD: <6h before HD session 150 mg after HD    
  HD: ≥6h before HD session No supplemental dose    
Erythromycin No change   Decrease dosage in moderate to severe disease Increased incidence of reversible hearing loss in patients with renal insufficiency
Esomeprazole No change   Do not exceed 20 mg in patients with severe liver impairment  
Eszopiclone No change   1 mg at bedtime in patients with severe liver disease  
Ethambutol 70–100 15 mg/kg q24h No change  
  10–50 15 mg/kg q24–36h    
  <10 15 mg/kg q48h    
Famciclovir Herpes zoster (immunocompetent)   No change  
  >60 500 mg q8h    
  40–59 500 mg q12h    
  20–39 500 mg q24h    
  <20 500 mg q48h    
  HD: 250 mg after dialysis    
Famotidine >10 20 mg q12h No change  
  <10 20 mg q24h    
Flecainide <20 Decrease usual dose by 25–50% Decrease Initial dose in patients with renal impairment is 100 mg q12h
Dose adjustment should be made no faster than every 4 d
Adjust dose based on serum concentrations and patient's clinical response
Fluconazole >50
21–50
11–20
HD:
200–400 mg q24h
50% q24h
25% q24h
Usual dose after HD
No change Patients with impaired renal function should receive an initial loading dose of 50–400 mg followed by daily maintenance dose based on CrCl
Foscarnet Induction Doses   No change  
    Equal to 60 mg/kg/dose    
  ml/min/kg q8h    
  ≥1.6 60    
  1.5 57    
  1.4 53    
  1.3 49    
  1.2 46    
  1.1 42    
  1.0 39    
  0.9 35    
  0.8 32    
  0.7 28    
  0.6 25    
  0.5 21    
  0.4 18    
  Maintenance Doses      
    Equal to 90 mg/kg/dose    
  ml/min/kg q24h    
  ≥1.4 90    
  1.2–1.4 78    
  1.0–1.2 75    
  0.8–1.0 71    
  0.6–0.8 63    
  0.4–0.6 57    
    Equal to 120 mg/kg/dose    
  ml/min/kg q24h    
  ≥1.4 120    
  1.2–1.4 104    
  1.0–1.2 100    
  0.8–1.0 94    
  0.6–0.8 84    
  0.4–0.6 76    
Fosphenytoin No change   Decrease dosage in severe disease Adjust dosage based on unbound “free” phenytoin serum concentrations and patient's clinical response
Gabapentin >60 400 mg tid No change  
  30–60 300 mg bid    
  15–30 300 mg qd    
  <15 300 mg qod    
  HD: 300–400 mg loading dose then    
    200–300 mg after dialysis    
Ganciclovir (Intravenous) Induction Dosage   No change  
  ≥70 5 mg/kg q12h    
  50–69 2.5 mg/kg q12h    
  25–49 2.5 mg/kg q24h    
  10–24 1.25 mg/kg q24h    
  HD: 1.25 mg/kg 3 × weekly after dialysis    
  Maintenance Dosage      
  ≥70 5 mg/kg q24h    
  50–69 2.5 mg/kg q24h    
  25–49 1.25 mg/kg q24h    
  10–24 0.625 mg/kg q24h    
  HD: 0.625 mg/kg 3 × weekly after dialysis    
Gatifloxacin ≥40 400 mg qd No change  
  <40 200 mg qd    
  HD: 200 mg qd    
Gemifloxacin >40 320 mg q24h No change  
  ≤40 160 mg q24h    
  HD or CAPD 160 mg q24h    
Gentamicin >160
100–159
60–99
40–59
<40
HD:
q6–8h
q8–12h
q12–18h
q18–24h
q24–48h
Monitor serum level 1 h after HD; supplemental dose after HD as needed
No change Adjust dosage based on serum concentrations and patient's clinical response; in critically ill patients dosing intervals are increased secondary to increased fluid accumulation and reduced renal function
Imipenem >71
41–70
21–40
6–20
HD:
125–500 mg q6–12h
125–500 mg q6–8h
125–250 mg q6–12h
125–250 mg q12h
Suppl. dose after HD and at 12 h intervals; patients with CrCl <5 ml/min/1.73M2 should not receive imipenem if HD not instituted within 48 h
No change See manufacturer's recommendations for dose adjustments based on severity of infection, weight, and renal function
Isoniazid No change   Decrease  
Labetalol No change   Decrease  
Lamivudine >50
30–49
15–29
5–14
<5
150 mg bid
150 mg qd
150 mg once, then 100 mg qd
150 mg once, then 50 mg qd
50 mg once, then 25 mg qd
No change  
Lansoprazole No change   Consider dosage in patients with severe liver disease  
Lepirudin >60
45–60
0.15 mg/kg/h
0.075 mg/kg/h
No change Maintain aPTT 1.5–2.5 times control
  30–44 0.045 mg/kg/h    
  15–29 0.0225 mg/kg/h    
  <15 Avoid or stop infusion    
Levofloxacin >50
20–49
10–19
HD
0.5–1 g q24h
0.5 g initially, then 0.25 g q24h
0.5 g initially, then 0.25 g q48h
0.5 g initially, then 0.25 g q48h
No change  
Lidocaine No change   Maintenance dose 2 mg/min or less Adjust dosage based on serum concentrations and patient's clinical response
Linezolid HD Reduce No change  
Lisinopril 10–30
<10
5 mg qd
2.5 mg qd
No change  
Lorazepam No change   No change  
Meperidine >50
10–50
q3–4h
q6h (25% decrease)
Decrease Should avoid in patients with CrCl <10 ml/min
Metabolite accumulates in renal failure and may produce seizures
Meropenem >50
26–50
10–25
<10
HD:
1 g q8h
1 g q12h
0.5 g q12h
0.5 g q24h
Unknown
No change  
Methadone >50
10–50
<10
q6h
q8h
q8–12h
Decrease Significant accumulation with repetitive dosing
Methyldopa >10
<10
0.25–1 g q6h
Decrease
Avoid  
Metoclopramide <40 50% of recommended dose No change  
Metoprolol No change   Decrease  
Metronidazole <10 500 mg q12h Decrease dosage in severe disease  
Midazolam Decrease   Decrease Active metabolites contribute to effect
Milrinone 50
40
30
20
10
5
0.43 µg/kg/min
0.38 µg/kg/min
0.33 µg/kg/min
0.28 µg/kg/min
0.23 µg/kg/min
0.2 µg/kg/min
No change  
Minoxidil See Comments   No change Patients with renal failure or those receiving dialysis may require approximately 1/3 less drug than in patients who are not receiving dialysis; in patients receiving dialysis, the dose should be administered after dialysis
Moexipril >40
<40
7.5–30 mg qd
3.75–15 mg qd
   
Mycophenolate <25 Avoid doses >1 g bid    
Nadolol >50
31–50
10–30
<10
q24h
q24–36h
q24–48h
q40–60h
No change  
Nafcillin No change   Decrease dosage in severe disease  
Nicardipine 20 mg PO tid with conventional capsules or 30 mg PO bid with sustained release capsules Severe liver failure: 20 mg PO bid with conventional release capsules In liver failure, oral bioavailability may increase by four-fold
Severe hepatic failure dosing should be reduced from tid to bid
Use with caution in patients with portal hypertension
Sustained-release capsules should be avoided in patients with hepatic failure
Nimodipine No change   30 mg PO q4h Blood pressure and heart rate should be monitored
Nitroprusside See Comments   No change Maintain thiocyanate concentration <10 mg/dL
Oxacillin No change   Decrease in severe disease  
Pancuronium See Comments   See Comments Active metabolite accumulates in renal failure
Monitor paralysis with train-of-four nerve stimulation
Penicillin >50
10–50
<10
HD:
2–4 MU q2–6h
1–2 MU q4–6h
0.5–1 MU q8–12h or
1–2 MU q12–18h
Suppl. dosage after HD
No change Maximum recommended dose in renal failure is 4–10 MU/24h
Patients with combined renal and liver disease may need further dosage reductions
Pentamidine >50
10–50
<10
4 mg/kg q24h
4 mg/kg q36h
4 mg/kg q48h
No change  
Pentobarbital No change   See Comments Adjust dosage based on serum concentrations and patient's clinical response
Phenobarbital No change   See Comments Adjust dosage based on serum concentrations and patient's clinical response
Phenytoin No change   Decrease dose in severe disease Adjust dosage based on unbound “free” phenytoin serum concentrations and patient's clinical response
Pindolol No change   Decrease  
Piperacillin >40
20–40
<20
HD:
2–4 g q4–6h
3–4 g q8h
3–4 g q12h
2 g q8h and 1 g after HD
No change  
Piperacillin-tazobactam >40
20–40
<20
HD:
3.375 g q6h
2.25 g q6h
2.25 g q8h
2.25 g q8h and 0.75 g after HD
No change  
Prazosin 1 mg bid   No change Patients with chronic renal failure may require only small doses of the drug
Primidone No change   Decrease Avoid in severe liver disease
Adjust dosage based on serum concentrations and patient's clinical response
Procainamide Normal:
Mild:
Moderate:
Severe:
2.7 mg/kg/h
2.0 mg/kg/h
1.5 mg/kg/h
1.0 mg/kg/h
No change Adjust dosage based on serum concentrations and patient's clinical response
Propoxyphene Decrease   Decrease  
Propranolol No change   Decrease  
Quinidine No change   Decrease Adjust dosage based on serum concentrations and patient's clinical response
Quinapril >60
30–60
10–30
<10
10 mg qd
5 mg qd
2.5 mg qd
Insufficient data for recommendations
No change  
Ramipril <40 25% of normal dose No change  
Ranitidine >50
10–50
<10
50 mg IV q6–8h
75% of normal dose q24h
50% of normal dose q24h
No change  
Rifampin No change   Decrease Dosage should be decreased in patients with hepatic/biliary obstruction
Rimantadine <10 100 mg qd Severe liver failure: 100 mg qd  
Rocuronium No change   See Comments Hepatic disease extends clinical duration
Monitor paralysis with train-of-four nerve stimulation
Sotalol >60
30–59
10–30
<10
80 mg q12h
80 mg q24h
80 mg q36–48h
Individualize
No change Each incremental dosage increase should be made only after a given dosage has been repeated at least 5 or 6 times at the dosing interval appropriate for the degree of renal impairment
Stavudine Weight >60 kg      
  >50
26–50
10–25
40 mg q12h
20 mg q12h
20 mg q24h
   
  <10 or HD: Unknown    
  Weight <60 kg      
  >50
26–50
10–25
30 mg q12h
15 mg q12h
15 mg q24h
   
  <10 or HD: Unknown    
Streptomycin 50–80
10–50
<10
HD:
7.5 mg/kg q24h
7.5 mg/kg q24–72h
7.5 mg/kg q72–96h
50% to 75% of the initial loading dosage after dialysis
No change Therapy may begin with an initial 1 g loading dose
Adjust dosage based on serum levels and patient's clinical response
Tacrolimus See Comments   See Comments Adjust dosage based on serum levels and patient's clinical response
Tetracycline Reduce   Use with caution Doxycycline is the preferred agent in patients with renal failure
Thiopental No change   Decrease  
Ticarcillin-clavulanic acid >60
30–60
10–30
<10
HD:
3.1 g q4–6h
2 g q4h
2 g q8h
2 g q12h
3.1 g initially, then 2 g q12h with suppl. dosage after HD
No change Patients with CrCl <10 ml/min and hepatic dysfunction should receive 3.1 g initially, then 2 g q24h
Tigecycline No change   Severe liver disease: 100 mg initially, then 25 mg q12h No adjustment required in mild to moderate liver disease
Timolol Decrease   Decrease  
Tirofiban <30 1/2 the usual infusion rate No change  
Tobramycin >160
100–159
60–99
40–59
<40
HD:
q6–8h
q8–12h
q12–18h
q18–24h
q24–48h
Monitor serum level 1 h after HD, suppl. dosage after HD as needed
No change Adjust dosage based on serum levels and patient's clinical response
In critically ill patients, dosing intervals are increased secondary to increased fluid accumulation and reduced renal function
Torsemide Edema of chronic renal failure 10–20 mg IV/PO qd as a single dosage, doses may be doubled to maximum 200 mg/d Edema in patients with hepatic cirrhosis: 5–10 mg IV/PO qd as a single dosage, doses may be doubled to maximum 40 mg/d  
Tramadol >30
<30
50–100 mg q4–6h
50–100 mg q12h, not to exceed 200 mg/d
50 mg q12h  
Tranexamic acid SCr:
1.36–2.83
2.83–5.66
> 5.66
SCr:
1.36–2.83
2.83–5.66
>5.66
IV dose
10 mg/kg bid
10 mg/kg qd
10 mg/kg q48h or 5 mg/kg qd
Tablets
15 mg/kg bid
15 mg/kg qd
15 mg/kg q48h or 7.5 mg/kg qd
No change  
Trimethoprim- sulfamethoxazole >30
15–30
<15
Usual dose
50%
Avoid
Decrease Patients with CrCl ≤10 ml/min may receive 5 mg/kg TMP qd
Monitor serum concentrations; maintain peak sulfa level <150 mg/L
Valacyclovir Acute herpes zoster   No change The rate, but not extent, of conversion of valacyclovir to acyclovir may be reduced in patients with moderate to severe liver disease
  >50
30–49
10–29
<10
HD:
1 g q8h
1 g q12h
1 g q24h
0.5 g q24h
Suppl. dose after dialysis
   
Valganciclovir Induction   No change  
  ≥60
40–59
25–39
10–24
900 mg bid
450 mg bid
450 mg qd
450 mg qod
   
  Maintenance/ Prophylaxis   No change  
  ≥60
40–59
25–39
10–24
900 mg qd
450 mg qd
450 mg qod
450 mg twice weekly
   
Valproic acid No change   Decrease Adjust dosage based on serum concentrations and patient's clinical response
Vancomycin >50
30–50
<30
0.5–1g q12h
0.5–1g q24h
Per levels
No change Adjust dosage based on serum concentrations and patient's clinical response
Vecuronium See Comments   See Comments Active metabolite accumulates in renal failure
Monitor paralysis with train-of-four nerve stimulation
Verapamil No change   Decrease  
Voriconazole No change   Decrease maintenance dose by 50% in patients with mild to moderate liver disease  
Warfarin No change   Decrease Monitor INR/PT
Zaleplon No change   Reduce dose to 5 mg hs Do not use in patients with severe liver disease
Zidovudine Severe renal impairment: 300–400 mg/d   Unknown  
  End-stage renal disease on dialysis: 100 mg PO q6–8h or 1 mg/kg IV q6–8h      
Zolpidem No change   5 mg qhs  
aPTT, activated partial thromboplastin time; CAPD; continuous ambulatory peritoneal dialysis; CrCl, creatinine clearance; HD, hemodialysis; INR, international normalized ratio; IV, intravenous; PO, by mouth; PT prothrombin time; TMP, trimethoprim; TMP-SMX, Trimethoprim-sulfamethoxazole.
P.285

TABLE 13.4. Peritoneal Dialysis—Local Antibiotic Instillation
Drug Initial Systemic (IV) Dose Dialysate (mg/2L Bag) Concentration Comments
Aminoglycosides  
Amikacin 7.5 mg/kg 12–15 mg Monitor serum concentrations
Gentamicin 2 mg/kg 8–16 mg Monitor serum concentrations
Tobramycin 2 mg/kg 8–16 mg Monitor serum concentrations
Cephalosporins  
Cefazolin 0.5 g 250–500 mg  
Cefotaxime 2 g 500 mg  
Cefoxitin 1 g 200 mg  
Ceftazidime 1 g 250 mg  
Ceftriaxone 1 g 500 mg  
Penicillins  
Ampicillin-Sulbactam 1–2 g 100 mg  
Piperacillin 4 g 500 mg  
Ticarcillin 1–2 g 250 mg  
Quinolones  
Ciprofloxacin 400 mg 50 mg  
Other Antibiotics  
Aztreonam 1 g 500 mg  
Clindamycin 300 mg 300 mg  
Erythromycin 0.5–1 g 150 mg  
Imipenem 0.5–1 g 100–200 mg  
Trimethoprim/ sulfamethoxazole (TMP/SMX) 320/1,600 mg 80/400 mg  
Vancomycin 1 g 30–50 mg Monitor serum concentrations
Antifungal Agents  
Amphotericin B 0.5 mg/kg (see Table 10.3) 2–8 mg For serious infections, amphotericin B must be given IV
Fluconazole 150 mg IP qod Administer intraperitoneal dose qod
IP, intraperitoneal; IV, intravenous
P.286

TABLE 13.5. Hemofiltration Drug Removal
Drug CVVH CVVHD of CVVHDF
Acyclovir 5–7.5 mg/kg q24h 5–7.5 mg/kg q24h
Amikacin 7.5 mg/kg adjust dose based on serum levels 7.5 mg/kg adjust dose based on serum levels
Amphotericin B deoxycholate 0.4–1 mg/kg q24h 0.4–1 mg/kg q24h
Amphotericin B lipid complex 3–5 mg/kg q24h 3–5 mg/kg q24h
Amphotericin B liposomal 3–5 mg/kg q24h 3–5 mg/kg q24h
Ampicillin/sulbactam 3 g q12h 3 g q8h
Aztreonam 1–2 g q12h 2 g q12h
Cefazolin 1–2 g q12h 2 g q12h
Cefepime 1–2 g q12h 2 g q12h
Cefotaxime 1–2 g q12h 2 g q12h
Ceftazidime 1–2 g q12h 2 g q12h
Ceftriaxone 2 g q12–24h 2 g q12–24h
Cefuroxime 1.5 g initially, then 750 mg q24h NR
Ciprofloxacin 200 mg q12h 200–400 mg q12h
Clindamycin 600–900 mg q8h 600–900 mg q8h
Colistin 2.5 mg/kg q48h 2.5 mg/kg q48h
Daptomycin 4 or 6 mg/kg q48h 4 or 6 mg/kg q48h
Famotidine 10 mg q12h 10 mg q12h
Fluconazole 200–400 mg q24h 400–800 mg q24h
Ganciclovir NR 5 mg/kg q48h
Gentamicin 2.5–3 mg/kg adjust dose based on serum levels 2.5–3 mg/kg adjust dose based on serum levels
Imipenem-cilastatin 500 mg q8h 500 mg q6–8h
Levofloxacin 250–500 mg q24h 250–500 mg q24h
Linezolid 600 mg q12h 600 mg q12h
Meropenem 0.5–1 g q8–12h 1 g q8–12h
Moxifloxacin 400 mg q24h 400 mg q24h
Nafcillin 2 g q4–6h 2 g q4–6h
Oxacillin 2 g q4–6h 2 g q4–6h
Piperacillin 4 g q12h NR
Piperacillin/tazobactam 4.5 g q8h 4.5 g q8h
Ranitidine 50 mg q24h 50 mg q24h
Ticarcillin/clavulanate 2 g q6–8h 3.1 g q6h
Tobramycin 2.5–3 mg/kg adjust dose based on serum levels 2.5–3 mg/kg adjust dose based on serum levels
Vancomycin 1 g adjust dose based on serum levels 1 g adjust dose based on serum levels
Voriconazole 4 mg/kg PO q12h 4 mg/kg PO q12h
CVVH, continuous venovenous hemo filtration; CVVHD, continuous venovenous hemodialysis; CVVHDF, continuous veno-venous hemo diafiltration; NR, not recommended; PO, by mouth