Drug Monitoring



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













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.)





























TABLE 13.3. Dosage Adjustments in Renal and Hepatic Failure













































































































































































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Jun 16, 2016 | Posted by in CRITICAL CARE | Comments Off on Drug Monitoring

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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