Ovid: Handbook of Critical Care Drug Therapy

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
Aminoglycosides	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
Proton Pump Inhibitors	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
Linezolid	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
Phenytoin	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)
Agent	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