Beruflich Dokumente
Kultur Dokumente
Dialysis of Drugs
Curtis A. Johnson, PharmD CKD Insights, LLC Verona, Wisconsin and Professor (Emeritus) of Pharmacy and Medicine University of Wisconsin-Madison Madison, Wisconsin
DISCLAIMERThese Dialysis of Drugs guidelines are offered as a general summary of information for pharmacists and other medical professionals. Inappropriate administration of drugs may involve serious medical risks to the patient that can only be identied by medical professionals. Depending on the circumstances, the risks can be serious and can include severe injury, including death. These guidelines cannot identify medical risks specic to an individual patient or recommend patient treatment. These guidelines are not to be used as a substitute for professional training. The absence of typographical errors is not guaranteed. Use of these guidelines indicates acknowledgment that neither CKD Insights, LLC. nor Genzyme will be responsible for any loss or injury, including death, sustained in connection with or as a result of the use of these guidelines. Readers should consult the complete information available in the package insert for each agent indicated before prescribing medications. Guides such as this one can only draw from information available as of the date of publication. Neither CKD Insights, LLC. nor Genzyme is under any obligation to update information contained herein. Future medical advances or product information may affect or change the information provided. Pharmacists and other medical professionals using these guidelines are responsible for monitoring ongoing medical advances relating to dialysis. Copyright 2009, CKD Insights, LLC. Printed in the U.S.A. All rights reserved. This material may not be published, rewritten or redistributed.
2 SEE DISCLAIMER REGARDING USE OF THIS GUIDE
I PREFACE
Preface
Drug removal during dialysis is frequently of interest to those caring for patients receiving hemodialysis or peritoneal dialysis. The extent of drug dialyzability determines whether supplemental dosing is necessary during or following dialysis. The accompanying table is a reference regarding the effect of either form of dialysis on drug clearance. This table should be used as a general guideline. The drugs included in the table are parent drugs. In some cases, these drugs are converted to pharmacologically active or toxic metabolites for which little dialysis information is known. Therefore, for a few drugs, a primary metabolite is also included in the table. When available, serum drug measurements may be appropriate for dosing individual patients. In all cases, patients should be monitored for clinical efcacy and toxicity.
Molecular Weight
Dialysis is dependent upon the use of a dialytic membrane: either a synthetic membrane with xed pore size, as in hemodialysis, or a naturally occurring peritoneal membrane, as in peritoneal dialysis. The movement of drugs or other solutes is largely determined by the size of these molecules in relation to the pore size of the membrane. As a general rule, smaller molecular weight substances will pass through the membrane more easily than larger molecular weight substances. A common assumption is that pore size of the peritoneal membrane is somewhat larger than that of the hemodialysis membrane. This would explain the observation that larger molecular weight substances appear to cross the peritoneal membrane to a greater extent than the hemodialysis membrane.
Protein Binding
Another important factor determining drug dialyzability is the concentration gradient of unbound (free) drug across the dialysis membrane. Drugs with a high degree of protein binding will have a low plasma concentration of unbound drug available for dialysis. Uremia may have an effect on protein binding for some drugs. Through mechanisms not completely understood, protein binding may decrease in uremic serum. Should this change in binding be substantial, increased dialyzability of free drug may occur.
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Because the primary binding proteins for most drugs (albumin, 1-acid glycoprotein) are of large molecular size, the drug-protein complex is often unable to cross the dialysis membrane, especially the hemodialysis membrane. Since the peritoneal membrane does permit the passage of some proteins, there may be some limited drug-protein removal with peritoneal dialysis. Increased protein concentrations often occur in peritoneal efuent during episodes of peritonitis.
I PREFACE
Volume of Distribution
A drug with a large volume of distribution is distributed widely throughout tissues and is present in relatively small amounts in the blood. Factors that contribute to a large volume of distribution include a high degree of lipid solubility and low plasma protein binding. Drugs with a large volume of distribution are likely to be dialyzed minimally.
Water Solubility
The dialysate used for either hemodialysis or peritoneal dialysis is an aqueous solution. In general, drugs with high water solubility will be dialyzed to a greater extent than those with high lipid solubility. Highly lipid-soluble drugs tend to be distributed throughout tissues, and therefore only a small fraction of the drug is present in plasma and accessible for dialysis.
Plasma Clearance
The inherent metabolic clearancethe sum of renal and nonrenal clearanceis often termed the plasma clearance of a drug. In dialysis patients, renal clearance is largely replaced by dialysis clearance. If nonrenal clearance is large compared to renal clearance, the contribution of dialysis to total drug removal is low. However, if renal (dialysis) clearance increases plasma clearance by 30% or more, dialysis clearance is considered to be clinically important.
Dialysis Membrane
As mentioned previously, the characteristics of the dialysis membrane determine to a large extent the dialysis of drugs. Pore size, surface area, and geometry are the primary determinants of the performance of a given membrane. The technology of hemodialysis has evolved, and new membranes have been introduced for clinical use. Interpretation of published literature should be tempered with the understanding that newer hemodialysis membranes may have different drug dialysis characteristics. Little can be done to alter the characteristics of the peritoneal membrane.
I PREFACE
Special Considerations
HIGH PERMEABILITY DIALYSIS
Much of the information contained in this guide has been obtained from studies conducted under conditions of standard hemodialysis that employed conventional dialysis membranes. Changes in dialysis technology have led to more permeable dialysis membranes and the opportunity to employ higher blood and dialysate ow rates. These new technologies are often referred to as high permeability, high-efciency, and high-ux dialysis. The United States Food and Drug Administration has classied high permeability dialysis membranes as those whose in vitro ultraltration coefcient (KUf) is greater than 8 mL/hour/mm Hg. Commonly included in this group of dialysis membranes are polysulfone, polyacrylonitrile, and high-efciency cuprammonium rayon dialyzers. Changes in dialysis membranes and changes in blood and dialysis ow rates may have clinically important effects on drug removal through the membrane. There are an increasing number of studies that examine the effects of high permeability dialysis on drug dialyzability. Results of these studies conrm predictions that drug removal from plasma is often enhanced as compared with more traditional dialysis membranes. Studies with high permeability dialysis also demonstrate that removal of drug from plasma often exceeds the transfer of drug from tissues to plasma. As a result, a rebound of plasma drug concentrations
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following the conclusion of dialysis may occur as blood-tissue drug equilibration occurs. Patients receiving high permeability dialysis may require more drug compared with those receiving standard hemodialysis. Due to the many technical and physiological variables, individualized therapeutic drug monitoring may be necessary. The reader is referred to the primary literature for further details.
I SPECIAL CONSIDERATIONS
drugs contained in plasma. Unfortunately, few in vivo studies have been published, and very few drugs have been studied pharmacokinetically in intensive care patients. Therefore, many guidelines for drug dosing during CRRT are extrapolated from experiences with chronic hemodialysis or from theoretical considerations based upon general principles of drug removal derived from the physicochemical characteristics of the drug and the CRRT technique employed. Molecular weight of a drug has been an important determinant of drug dialyzability in conventional hemodialysis. This drug characteristic becomes less important during CRRT because of the use of highux hemolters that permit passage of larger molecules up to 5000 Da. As is true with conventional hemodialysis, drugs with a large volume of distribution are unlikely to be removed to a great extent during CRRT. Most of the body stores of such drugs are outside the vascular compartment and not accessible to the hemolter for removal. Similarly, drugs that are highly bound to plasma proteins are not subject to signicant removal during CRRT because the molecular weight of drug-protein complexes usually hinders passage of the complex across the lter. The fraction of unbound drug may change during renal failure, however, thus altering the likelihood of drug removal. If the unbound fraction increases, more drug clearance may occur. If the unbound fraction becomes less, there is likely to be less drug removal during CRRT.
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A useful tool to predict the likelihood of a drug to cross the hemolter membrane is the sieving coefcient. This term is dened as the ratio of drug concentration in the ultraltrate to the prelter plasma water concentration of the drug. If the sieving coefcient is close to 1.0, the drug has relatively free passage across the lter. The following table presents sieving coefcient data from in vitro and in vivo evaluations.
I SPECIAL CONSIDERATIONS
SIEVING COEFFICIENT
Drug Name Amikacin Amphotericin Ampicillin Cefotaxime Cefoxitin Ceftazidime Ceftriaxone Cefuroxime Clindamycin Digoxin Predicted Measured Condition Filter 0.95 0.88 in vivo PSa 0.10 0.40 in vivo PSa 0.80 0.69 in vivo PSa 0.62 0.51 in vivo PSa 0.30 0.30 in vitro PSa 0.90 0.90 in vivo PSa 0.10 0.71 in vivo PSa 0.66 0.59 in vivo PSa 0.40 0.98 in vivo PSa 0.80 0.96 in vivo PSa 0.35 in vitro PSa 0.18 in vitro PSb 1.21 in vitro AN69c 1.07 in vitro PAd 0.30 0.37 in vivo PSa
Erythromycin
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Drug Name Gentamicin Metronidazole Mezlocillin N-acetylprocainamide Nafcillin Oxacillin Phenobarbital Phenytoin
Predicted Measured Condition Filter 0.95 0.81 in vivo PSa 0.80 0.86 in vivo PSa 0.68 0.68 in vivo PSa 0.90 0.20 0.05 0.60 0.10 0.92 0.54 0.02 0.86 0.45 0.14 0.12 0.08 0.17 0.08 0.86 0.85 0.93 0.78 0.78 0.90 0.75 0.59 0.76 0.18 0.31 0.16 in vivo in vivo in vivo in vivo in vivo in vitro in vitro in vitro in vitro in vitro in vivo in vitro in vitro in vivo in vivo in vitro in vitro in vitro in vitro in vitro in vitro in vitro PSa PSa PSa PSa PSa PSa PSb AN69c PAd PSa PSa PSa AN69c PAd PSa PSa PSb AN69c PAd PSa AN69c PAd
Procainamide Theophylline
0.86 0.47
Tobramycin
0.95
Valproic acid
0.10
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I SPECIAL CONSIDERATIONS
Predicted Measured Condition Filter 0.90 0.76 in vivo PSa 0.60 in vitro PSa 0.71 in vitro PSb 0.64 in vitro AN69c 0.58 in vitro PAd
Amicon dialter (polysulfone) Renal System (polysulfone) c Hospal (AN69) d Gambro (polyamide)
b
The above table was published in the following article: Joy MS, Matzke, GR, Armstrong DK, Marx MA, Zarowitz BJ. A primer on continuous renal replacement therapy for critically ill patients. Ann Pharmacother. 1998;32:362-75. Reprinted with permission. Harvey Whitney Books Company. The specic CRRT technique employed will inuence the ultraltration rate and hence, the potential rate of drug removal. When CRRT relies solely on spontaneous blood ow without extracorporeal blood pumping, an ultraltration rate of 10-15 mL/min is anticipated. The addition of blood pumps and continuous dialysis may increase the ultraltration rate to 50 mL/min. Higher rates of ultraltration may lead to greater drug removal with a need for more frequent replacement doses. Drug removal can be determined by collection of the total volume of dialysate/ultraltrate and measurement of the concentration of drug in the efuent.
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Because of the multiple techniques employed in CRRT, the variability in individual patient circumstances, and the lack of in vivo data, the tables in this guide do not contain information on drug removal during CRRT. Once again, the reader is referred to the primary literature for assistance with the dosing of specic drugs.
PLASMAPHERESIS
Plasmapheresis is another special consideration in which drug removal from plasma may be of concern. This technique is used for the treatment of certain immunologic, infectious, and metabolic diseases, as well as for the removal of toxins that cannot be removed by hemodialysis or peritoneal dialysis. Plasmapheresis removes plasma from the patient with replacement by crystalloid or colloid solutions. Solutes such as drug molecules that are present in the plasma may be removed from the patient. Unfortunately, little is known about the specic pharmacokinetic effects of plasmapheresis. The procedure may be most likely to remove substances that are lipophilic, that are highly protein-bound, and that have a small volume of distribution. The reader is referred to reference 4.
SUMMARY
Drug dialyzability is determined by a complex interaction of many factors, including the characteristics of the drug and the technical aspects of the dialysis system. Published studies on drug dialyzability should specify the conditions that pertain during dialysis. Results
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from these studies should be applied with caution to other dialysis conditions.
Supplemental dosing is usually not required. As a general principle, usual methods of continuous ambulatory peritoneal dialysis (CAPD) provide relatively low drug clearances during any given dialysate exchange. However, cumulative drug removal may require dosage supplementation at appropriate intervals. Relatively little research has examined peritoneal drug clearance in PD techniques that utilize automated systems employing large volumes of short dwells at night, often accompanied by one or more longer daytime dwells (APD). Similarly, little data exists on the effects of tidal peritoneal dialysis on drug clearance. A few studies have conrmed that clearance of some drugs is increased by APD due to the increased drug concentration gradient between blood and dialysate. Increased drug dialyzability may occur with increased peritoneal dialysate ow rates or in the presence of peritonitis. A designation of U indicates that no dialysis studies have been published, but that the author of this guide has concluded that signicant drug removal during dialysis is unlikely based upon the physicochemical characteristics of the drug, which are primarily a high degree of protein binding, a large molecular weight, or a large volume of distribution. A designation of L indicates that no published data exist on the removal of the drug during high permeability dialysis. However, the author has extrapolated data from studies using conventional dialysis to conclude that signicant drug removal is likely to occur during high permeability dialysis. A designation of ND indicates that no data are available on drug dialyzability. In some cases, the literature reports the use of a high permeability, or
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high-ux, dialysis membrane, however the type of membrane is not specied. A designation of NS indicates membrane type is not specied.
Key
Yes Indicates that dialysis enhances plasma clearance by 30% or more. Supplemental dosing may be required or dosing after dialysis should be considered. No Indicates that dialysis does not have a clinically important effect on plasma clearance. Supplemental dosing is usually not required. U Indicates signicant drug removal is unlikely based on physicochemical characteristics of the drug such as protein binding, molecular size or volume of distribution L Indicates no published data exist, but information extrapolated from studies using conventional dialysis techniques suggests signicant drug removal is likely during high permeability dialysis ND Indicates there are no data on drug dialyzability with this type of dialysis NS Indicates the type of membrane was not specied * Removed with hemoperfusion Note: In these tables, conventional hemodialysis is dened as the use of a dialysis membrane whose in vitro coefcient of ultraltration (KUf) 8 mL/hour/mm Hg. Data also are placed in the conventional column if the literature does not specify the type of dialysis membrane employed. High permeability hemodialysis is dened as the use of a dialysis membrane whose KUf >8 mL/hour/mm Hg. In the tables, the KUf of the membrane(s) used is included in parentheses.
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Drug
Abacavir Abatacept Abciximab Acamprosate Acarbose Acebutolol (diacetolol) Acetaminophen Acetazolamide Acetohexamide Acetophenazine Acetylcysteine Acitretin Acrivastine Acyclovir Adalimumab Adefovir Adenosine Agalsidase alfa Agalsidase beta Albendazole Albumin Albuterol Aldesleukin Alefacept Alemtuzumab Alendronate Alfentanil Alfuzosin Alglucerase Aliskiren
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U U U ND ND Yes (NS) Yes (NS) U U U Yes (7.5) No (NS) ND Yes (NS) U Yes (NS) U No (7.5) U No (NS) U No (NS) ND ND U No (NS) U U U ND
No (40) U ND ND ND L L ND ND ND ND U ND L U ND ND No (10) U ND ND ND ND ND U ND ND U U ND
ND U U ND ND ND No No U U ND U ND No U ND U U U U U U ND ND U ND U U U ND
I CHART
Drug
Allopurinol Almotriptan Alosetron Alprazolam Alprostadil Alteplase Altretamine Alvimopan Amantadine Ambenonium Ambrisentan Amdinocillin Amifostine Amikacin Amiloride Aminocaproic acid Aminoglutethimide Aminosalicylic acid Amiodarone Amitriptyline Amlodipine Amoxapine Amoxicillin Amphetamine Amphotericin B Amphotericin B lipid complex Ampicillin Amprenavir Amrinone
Yes (NS) ND ND No (NS) U U ND ND No (NS) ND U No (NS) ND Yes (NS) ND Yes (NS) Yes (NS) Yes (NS) No (NS) No (NS) No (NS) U Yes (NS) ND No (NS) No (NS) Yes (NS) U U
ND ND ND U ND U ND ND No ND U No ND Yes ND Yes ND ND No No No U No ND No U No U No
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Drug
Amsacrine U Anagrelide ND Anakinra No (NS) Anastrozole ND Anidulafungin No (NS) Anisindione U Anisoylated plasminogen ND streptokinase activator complex Anistreplase U Antithymocyte globulin U (ATG) Apomorphine U Aprepitant No (NS) Aprotinin U Arbutamine ND Argatroban U Aripiprazole U Armodanil ND Arsenic trioxide No (NS) Articaine ND Ascorbic acid Yes (5.5) Asparaginase U Aspirin Yes (NS) Atazanavir U Atenolol Yes (NS) Atomoxetine U Atorvastatin No (NS) Atovaquone U Atracurium U
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U ND No ND ND U ND U U U U U ND ND U ND U ND Yes U Yes U No U U U U
I CHART
Drug
Atropine Auranon Azacitidine Azathioprine Azelastine Azithromycin Azlocillin Aztreonam Baclofen Balsalazide Basiliximab Benazepril (benazeprilat) Bendamustine Bendroumethiazide Benzphetamine Benzquinamide Benztropine Bepridil Beractant Betamethasone Betaxolol Bethanechol Bevacizumab Bexarotene Bezabrate Biapenem Bicalutamide Biperiden Bisoprolol
No (NS) No (NS) ND Yes (NS) U ND Yes (NS) Yes (NS) ND U U No (NS) U No (NS) ND U ND No (NS) U ND No (NS) ND U U No (NS) Yes (NS) U ND No (NS)
ND ND ND ND U No No No ND U U ND U U ND ND ND U U ND No ND U U No ND U ND ND
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Drug
Bivalirudin Bleomycin Bortezomib Bosentan Bretylium Bromfenac Bromocriptine Brompheniramine Budesonide Buomedil Bumetanide Bupivacaine Buprenorphine Bupropion Buspirone Busulfan Butalbital Butoconazole Butorphanol Cabergoline Caffeine Calcitonin Calcitriol Calfactant Candesartan Capecitabine Capreomycin Captopril Carbamazepine Carbenicillin
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Yes (NS) No (NS) ND U Yes (NS) No (NS) U ND U No (NS) U U U No (NS) No (NS) Yes (NS) ND U U ND ND U No (4.2-5.3) ND No (NS) ND Yes (NS) Yes (NS) No (NS) Yes (NS)
ND ND ND No (11.1) L ND ND ND U No (20) U U U No (10) ND Yes (8.1) ND U ND ND ND U No (31) ND No (8.1) ND L L Yes (22, 55) L
ND No ND U ND U U ND U U U U U No ND ND ND U U ND ND U U ND ND ND ND No No No
I CHART
Drug
Carbidopa/levodopa Carbinoxamine Carboplatin Carboprost Carisoprodol Carmustine Carprofen Carteolol Carumonam Carvedilol Caspofungin Cefaclor Cefadroxil Cefamandole Cefazolin Cefdinir Cefditoren Cefepime Cexime Cefmenoxime Cefmetazole Cefodizime Cefonicid Cefoperazone Ceforanide Cefotaxime Cefoxitin Cefpirome Cefpodoxime Cefprozil
ND/U ND Yes (NS) ND Yes (NS) No (NS) U ND Yes (NS) No (NS) No (NS) Yes (NS) Yes (NS) Yes (NS) Yes (6, 8) ND No (NS) Yes (NS) No (NS) Yes (NS) Yes (NS) No (NS) No (NS) No (NS) Yes (NS) Yes (NS) Yes (NS) Yes (NS) Yes (NS) Yes (NS)
Drug
Cefroxadine Cefsulodin Ceftazidime Ceftibuten Ceftizoxime Ceftobiprole Ceftriaxone Cefuroxime Celecoxib Cephalexin Cephalothin Cephapirin Cephradine Certolizumab Cetirizine Cetrorelix Cetuximab Cevimeline Chloral hydrate Chlorambucil Chloramphenicol Chlordiazepoxide Chloroquine Chlorothiazide Chlorpheniramine Chlorpromazine Chlorpropamide Chlorprothixene Chlorthalidone Chlorzoxazone
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ND Yes (NS) Yes (NS) Yes (NS) Yes (NS) ND No (NS) Yes (NS) U Yes (NS) Yes (NS) Yes (NS) Yes (NS) U U ND U ND Yes (5.5) No (NS) Yes (NS) No (NS) No (NS) No (NS) Yes (NS) No (NS) No* (NS) U No (NS) ND
ND L L L L ND ND L ND L L L L U No (18.7-66.7) ND U ND L ND L ND ND ND L ND ND ND ND ND
I CHART
Drug
Cholecalciferol Cholestyramine Choriogonadotropin Ciclesonide Cidofovir Cilastatin Cilazapril Cilostazol Cimetidine Cinacalcet Cinoxacin Ciprooxacin Cisapride Cisatracurium Cisplatin Citalopram Cladribine Clarithromycin Clavulanic acid Clemastine Clevidipine Clinaoxacin Clindamycin Clodronate Clofarabine Clofazimine Clobrate Clomiphene Clomipramine Clonazepam
U U U U ND Yes (NS) Yes (NS) U No (NS) No (NS) No (NS) No (NS) No (NS) U No (NS) No (8) ND ND Yes (NS) ND U No (6.4) No (NS) ND ND No (NS) No (NS) ND U No (NS)
U U U U No ND ND U No No U No U U ND U ND ND Yes ND U ND No No ND No No ND U U
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Drug
Clonidine Clopidogrel Clorazepate Clotrimazole Cloxacillin Clozapine Codeine Colchicine Colesevalam Colestipol Colistin Conivaptan Cortisone Cromolyn sodium Cyanocobalamin Cyclacillin Cyclobenzaprine Cyclophosphamide Cycloserine Cyclosporine Cyproheptadine Cystadane Cysteamine Cytarabine Dabigatran Dacarbazine Daclizumab Dactinomycin Dalteparin Danaparoid
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No (NS) U No (NS) U No (NS) U No (NS) No (NS) U U No (NS) U No (NS) U No (NS) Yes (NS) U Yes (6.4) ND No (NS) ND ND ND ND ND ND U ND U ND
No U U U No U U No U U No U No U ND No U ND ND No ND ND No No ND ND U ND U ND
I CHART
Drug
Dantrolene Dapsone Daptomycin Darbepoetin alfa Darifenacin Darunavir Dasatinib Daunorubicin Decitabine Deferasirox Deferoxamine Deazacort Delavirdine Demeclocycline Denileukin Desipramine Desloratadine Desmopressin Desogestrel Desvenlafaxine Dexamethasone Dexchlorpheniramine Dexfenuramine Dexmedetomidine Dexmethylphenidate Dexrazoxane Dextroamphetamine Dezocine Diatrizoate Diazepam
ND Yes (NS) No (NS) U U U U ND ND U Yes (NS) No (NS) U ND U No (NS) No (NS) ND U No (NS) No (NS) Yes (NS) ND U ND ND ND ND L No (NS)
ND ND No U U U U ND ND U ND U U ND U No No ND U U No No ND U ND ND ND ND ND U
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Drug
Diazoxide Dibekacin Diclofenac Dicloxacillin Dicyclomine Didanosine Diethylpropion Diethylstilbesterol (fosfestrol) Diunisal Digitoxin Digoxin Digoxin immune Fab Dihydrocodeine Dihydroergotamine Diltiazem Dimenhydrinate Dimyristoyl lecithin Dinoprostone Diphenhydramine Diphenoxylate/ Atropine Dipyridamole Dirithromycin Disopyramide Disulram Divalproex Dobutamine Docetaxel Dofetilide
Yes (NS) Yes (NS) U No (NS) ND No (7.9) ND No (NS) No (NS) No (NS) No (NS) No (NS) ND ND No (NS) ND ND ND U ND U No (NS) No (NS) U No (NS) No (NS) No (NS) ND
L L ND ND ND No (40) ND ND ND ND ND U ND ND ND ND ND ND ND ND ND ND U U ND ND U ND
Yes ND U No ND No ND ND U No No No ND ND No ND ND ND U ND ND No U U No No U ND
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I CHART
Drug
Dolasetron Domperidone Donepezil Dopamine Doripenem Dornase alfa Doxacurium Doxapram Doxazosin Doxepin Doxercalciferol Doxorubicin Doxycycline Doxylamine Dronabinol Droperidol Drosperinone Drotrecogin alfa Duloxetine Dutasteride Eculizumab Edetate calcium (ETDA) Edrophonium Efalizumab Efavirenz Eletriptan Emtricitabine Enalapril (enalaprilat) Encainide
ND U U No (NS) Yes (NS) U No (NS) ND No (NS) No (NS) No (NS) No (NS) No (NS) ND U U U U U U U Yes (NS) ND U No (NS) ND Yes (NS) Yes (NS) No (NS)
ND U ND ND ND U ND ND ND ND U ND ND ND ND ND U U U U U L ND U ND ND ND L ND
ND U U U ND U U ND No No U ND No ND U U U U U U U Yes ND U No ND ND Yes ND
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Drug
Enfuvirtide Enoxacin Enoxaparin Entacapone Entecavir Enfuvirtide Ephedrine Epinephrine Epirubicin Eplerenone Epoetin alfa Epoprostenol Eprosartan Eptacog alfa Eptibatide Ergocalciferol Ergotamine Erlotinib Ertapenem Erythromycin Escitalopram Eslicarbazine Esmolol (ASL-8123) Esomeprazole Estazolam Estradiol Estramustine Estrogens, conjugated Estrone Estropipate
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No (NS) No (NS) No (NS) U No (NS) No (NS) ND ND ND No (7) No (NS) ND U U ND ND ND U Yes (NS) No (NS) ND Yes (NS) Yes (NS) U U No (NS) ND ND No (NS) ND
U No No U No U ND ND ND ND No ND U U ND ND ND U ND No ND ND Yes U U ND ND ND ND ND
I CHART
Drug
Eszopiclone Etanercept Ethacrynic acid Ethambutol Ethanolamine oleate Ethchlorvynol Ethinyl estradiol Ethionamide Ethosuximide Ethotoin Etidronate Etodolac Etonogestrel Etoposide Etoricoxib Etravirine Everolimus Exemestane Exenatide Ezetimibe Famciclovir (penciclovir) Famotidine Felbamate Felodipine Fenuramine Fenobrate Fenoldopam Fenoprofen Fentanyl
ND No (NS) No (NS) No (NS) ND No* (NS) U U Yes (NS) ND ND No (NS) ND No (NS) No (NS) U ND U ND U Yes (NS) No (NS) ND No (NS) ND No (NS) U No (NS) U
ND U U U ND No No U ND ND ND U ND No U U ND U ND U ND No ND U ND U No U ND
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Drug
Ferric gluconate Ferrous (iron) salts Ferumoxytol Fexofenadine Filgrastim Finasteride Flavoxate Flecainide Fleroxacin Floxuridine Fluconazole Flucytosine Fludarabine Fludrocortisone Flumazenil Fluorouracil/FBAL Fluoxetine Fluoxymesterone Fluphenazine Flurazepam Flurbiprofen Flutamide Fluticasone Fluvastatin Fluvoxamine Folic acid Follitropin alfa Follitropin beta Fomepizole Fondaparinux
32
No (NS) ND U ND No (NS) ND No (NS) ND No (NS) ND U ND ND ND No (NS) ND U No (8.1, 22) ND ND Yes (NS) L Yes (NS) L ND ND ND ND ND ND No (NS)/ND No (40)/Yes (40) No (NS) ND ND ND U ND No (NS) ND ND ND No (NS) ND U U No (NS) ND U No (NS) Yes (NS) L ND ND ND ND Yes (NS) L No (NS) ND
U U ND U U U ND U No ND Yes Yes ND ND ND ND No ND U U No U U U U ND ND ND ND U
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Drug
Fosamprenavir Fosaprepitant Foscarnet Fosfomycin Fosinopril (fosinoprilat) Fosphenytoin Frovatriptan Fulvestrant Furosemide Fusidic acid Gabapentin Gadobenate Gadobutrol Gadodiamide Gadolinium Gadopentetate Gadoteridol Gadoversetamide Gadoxetate Galantamine Gallium Gallopamil Galsulfase Ganciclovir Ganirelix Garenoxacin Gatioxacin Geftinib Gemcitabine Gembrozil
U No (NS) Yes (4.1) Yes (NS) No (NS) U ND U No (NS) No (NS) Yes (NS) ND Yes (5.5) Yes (NS) Yes (NS) Yes (NS) ND ND Yes (NS) ND ND U U Yes (NS) ND No (NS) ND U Yes (7) No (NS)
U U ND ND No U ND U U No ND ND ND No ND ND ND ND ND ND ND U U ND ND No ND U ND No
33
Drug
Gemioxacin Gemtuzumab Gentamicin Gestodene Glatiramer Gliclazide Glimepiride Glipizide Glucagon Glutethimide Glyburide Glycopyrrolate Gold sodium thiomalate Goserelin Granisetron Grepaoxacin Griseofulvin Guaifenesin Guanabenz Guanadrel Guanethidine Guanfacine Guanidine Halofantrine Haloperidol Heparin Hexobarbital Hirudin Hydralazine
34
No (NS) U Yes (NS) U ND U U U U No* (NS) No (NS) ND No (NS) ND ND ND ND ND U ND ND No (NS) ND ND No (NS) No (NS) No (NS) No (4.3-6.5) No (NS)
ND U Yes U ND U U U U No U ND U ND ND ND ND ND ND ND ND No ND ND No No U ND No
I CHART
Drug
Hydrochlorothiazide Hydrocodone Hydrocortisone Hydromorphone Hydroxychloroquine Hydroxyurea Hydroxyzine Ibandronate Ibritumomab Ibuprofen Ibutilide Idarubicin Idebenone Idursulfase Ifosfamide Iloprost Imatinib Imidapril (imidaprilat) Imiglucerase Imipenem Imipramine Immune globulin Indapamide Indinavir Indomethacin Iniximab Insulin Insulin aspart Insulin detemir Insulin glargine
No (NS) ND U ND ND No (NS) No (NS) ND U No (NS) ND U U U Yes (1.6) ND No (NS) No (NS) U Yes (NS) No (NS) U No (NS) U No (NS) U No (NS) U No (NS) U
U ND U ND ND U No ND U U ND U U U ND ND U U U Yes No U U ND U U No U ND U
35
Drug
Insulin glulisine U ND Insulin lispro U ND Interferons No (NS) Yes (20-33) Iobenguane No (NS) ND Iodipamide ND ND Iodixanol Yes (3.1, 4.2) L Iohexol Yes (NS) Yes (15.5) Iomeprol Yes (6.8) L Iopamidol Yes (4.8) L Iopromide Yes (5.5-6.8) Yes (8.1-62) Iotrolan Yes (NS) L Ioversol Yes (6.3) L Ioxaglic acid L Yes (15.5) Ioxilan Yes (NS) L Ioxitalamic acid ND ND Irbesartan No (NS) ND Irinotecan/ Yes/No (NS) ND SN-38 metabolite Iron dextran U No (8.1-10.1) Iron sucrose U No (11.1-55) Isocarboxazid ND ND Isoniazid No (NS) No (80) Isoproterenol ND ND Isosorbide dinitrate No (NS) ND Isosorbide mononitrate Yes (NS) L Isotretinoin U U Isradipine No (NS) ND Itraconazole No (NS) No (65) Ivermectin ND ND Ixabepilone ND ND
36
I CHART
Drug
Kanamycin Yes (NS) Ketamine No (NS) Ketoconazole No (NS) Ketoprofen U Ketorolac U Ketotifen ND Labetolol No (NS) Lactulose U Lamivudine No (NS) Lamotrigine No (NS) Lanreotide ND Lansoprazole No (NS) Lanthanum carbonate No (NS) Lapatinib U Laronidase U Leunomide No (NS) Lenalidomide Yes (NS) Lepirudin No (4.3-6.2) Letrozole ND Leucovorin ND Leuprolide ND Levamisole ND Levetiracetam Yes (NS) Levobupivacaine U Levocarnitine Yes (NS) Levocetirizine No (NS) Levodopa U Levooxacin U Levoleucovorin ND Levomethadyl U
Yes U No U U ND No U No U ND U U U U No ND ND ND ND ND ND ND U ND U U No ND U
37
Drug
Levonorgestrel Levorphanol Levosimendan Levothyroxine Lidocaine Lincomycin Linezolid Liothyronine Lisdexamfetamine Lisinopril Lithium Lomeoxacin Lomustine Loperamide Lopinavir Loracarbef Loratadine Lorazepam Losartan Lovastatin Loxapine L-tryptophan Lubiprostone Lumefantrine Mangafodipir Mannitol Maprotiline Maraviroc Mecamylamine Mecasermin
38
U ND No (6.4) U No (NS) No (NS) Yes (NS) ND ND Yes (NS) Yes (NS) No (NS) No (NS) ND U Yes (NS) No (NS) No (NS) No (NS) U ND U U ND ND Yes (NS) No (NS) ND ND ND
U ND U U U No ND ND ND ND Yes No U ND U ND No U No U ND ND U ND ND Yes U ND ND ND
I CHART
Drug
Mechlorethamine U U Meclofenamate U ND Medroxyprogesterone U U Mefenamic acid No (NS) ND Meoquine U ND Megestrol acetate ND ND Meloxicam No (NS) U Melphalan No (NS) ND Memantine ND ND Menadiol ND ND Menotropins ND ND Mepenzolate ND ND Meperidine/ No (NS)/ND No (8.1)/Yes (8.1) normeperidine Meprobamate Yes (NS) L Mercaptopurine Yes (NS) L Meropenem Yes (NS) L Mesalamine (5-ASA) Yes (5.5) ND Mesna ND ND Mesoridazine U ND Metaproterenol ND ND Metaxalone ND ND Metformin Yes (NS) L Methadone No (NS) ND Methaqualone No (NS) ND Methenamine ND ND Methicillin No (NS) ND Methimazole No (NS) ND Methocarbamol ND ND Methohexital U U
SEE DISCLAIMER REGARDING USE OF THIS GUIDE
U U U U U ND U ND ND ND ND ND U/ND Yes ND ND U ND U ND ND ND No No ND No No ND U
39
Drug
Methotrexate Methoxsalen Methoxypolyethylene glycol-epoetin beta Methscopolamine Methsuximide Methyldopa Methylergonovine Methylnaltrexone Methylphenidate Methylprednisolone Methysergide Metoclopramide Metolazone Metoprolol Metronidazole Mexiletine Mezlocillin Micafungin Miconazole Midazolam Midodrine (de-glymidodrine) Mifepristone Miglitol Miglustat Milrinone Minocycline Minoxidil Mirtazapine
Yes (NS) ND U ND ND Yes (NS) ND ND U Yes (NS) ND No (NS) No (NS) Yes (NS) Yes (NS) Yes (NS) Yes (NS) U No (NS) No (NS) ND U ND ND ND No (NS) Yes (NS) U
No ND U ND ND Yes ND ND U ND ND No U ND No No No U No U ND U ND ND ND No Yes U
40
I CHART
Drug
Misoprostol Mitomycin Mitotane Mitoxantrone Mivacurium Modanil Moexipril Molindone Montelukast Moricizine Moroctocog alfa Morphine Moxioxacin Muromonab-CD3 Mycophenolate (mycophenolic acid) Nabilone Nabumetone Nadolol Nadroparin Nafarelin Nafcillin Nalbuphine Nalidixic acid Nalmefene Naloxone Naltrexone Nandrolone Naproxen Naratriptan
U ND ND No ND ND ND U U U U No ND U No ND ND ND ND ND No ND U U ND ND ND U ND
41
Drug
Natalizumab Nateglinide/ M1 metabolite Nebivolol Nedocromil Nefazodone Nelarabine Nelnavir Neomycin Nesiritide Netilmicin Nevirapine Niacin Niacinamide Nicardipine Nicotine Nicotinic acid Nifedipine Nilotinib Nilutamide Nimodipine Nisoldipine Nitazoxanide Nitrendipine Nitrofurantoin Nitroglycerin Nitroprusside Nizatidine Nomifensine Nonacog alfa
42
U U/Yes (NS) U ND U U U Yes (NS) U Yes (NS) ND ND ND No (NS) ND ND No (NS) U ND No (NS) No (NS) U No (NS) Yes (NS) No (NS) Yes (NS) No (NS) ND U
I CHART
Drug
Norepinephrine Norethindrone Noroxacin Norgestimate Norgestrel Nortriptyline Nylidrin Nystatin Octreotide Ooxacin Olanzapine Olmesartan Olsalazine Omapatrilat Omega-3-acid ethyl esters Omeprazole Ondansetron Oprelvekin Orboban Orlistat Ornidazole Orphenadrine Oseltamivir Oxacillin Oxaliplatin Oxandrolone Oxaprozin Oxazepam Oxcarbazepine
ND ND No (NS) U ND No (NS) ND U Yes (NS) Yes (6.0) No (NS) U U No (NS) ND U U U Yes (NS) U Yes (NS) ND Yes (NS) No (NS) ND U No (NS) No (NS) ND
ND No U U ND No ND U ND No No U U ND ND U U U ND U No ND Yes No ND U U U ND
43
Drug
Oxtriphylline Oxybutynin Oxycodone Oxymetholone Oxymorphone Paclitaxel Palifermin Paliperidone Palivizumab Palonosetron Pamidronate Pancuronium Panitumumab Pantoprazole Papaverine Para-aminosalicylate Paricalcitol Paromomycin Paroxetine Peoxacin Pegademase Pegaspargase Peglgrastim Peginterferon alfa-2a Peginterferon alfa-2b Pegvisomant Pemetrexed Pemoline Penbutolol
44
Yes (NS) ND ND ND ND No (NS) U ND U ND Yes (6.4) ND U No (5.1) U U No (5.5) ND No (NS) No (NS) U U U U U U ND Yes (NS) No (NS)
No ND ND ND ND No ND ND U ND ND ND U ND U U ND ND U No U U U U U U ND No No
I CHART
Drug
Penicillamine Penicillin Pentamidine Pentazocine Pentobarbital Pentosan polysulfate Pentostatin Pentoxifylline Perexane Perutren Pergolide Perindopril (perindoprilat) Perphenazine Phenacetin Phenazopyridine Phendimetrazine Phenelzine Phenobarbital Phenoxybenzamine Phentermine Phentolamine Phenylbutazone Phenytoin Phytonadione Pilocarpine Pimagedine (aminoguanidine) Pimozide Pinaverium
Yes (NS) Yes (NS) No (NS) Yes (NS) No (NS) ND ND U ND ND U Yes (NS) U ND ND ND ND Yes (NS) ND ND ND No (NS) No (NS) ND ND Yes (NS) ND U
ND No No ND U ND ND ND ND ND U ND U ND ND ND ND Yes ND ND ND U No ND ND ND ND U
45
Drug
Pindolol ND Pioglitazone U Piperacillin Yes (NS) Piroxicam U Pizotyline U Plicamycin ND Polyethylene glycol U Polythiazide No (NS) Poractant alfa ND Pormer No (NS) Posaconazole No (NS) Pralidoxime ND Pramipexole No (NS) Pramlintide ND Pravastatin No (5.3) Prazepam No (NS) Praziquantel No (NS) Prazosin No (NS) Prednisolone U Prednisone No (NS) Pregabalin Yes (NS) Primaquine No (NS) Primidone Yes (NS) Probenecid U Probucol No (NS) Procainamide/N-acetyl Yes (NS)/ procainamide (NAPA) Yes (NS) Procarbazine ND Prochlorperazine U Procyclidine ND
46
ND ND L ND U ND U ND ND U ND ND ND ND ND ND ND ND No (NS) ND L ND L U ND L/L ND ND ND
ND U No U U ND U No ND U ND ND U ND ND U ND No U No ND ND ND U No No/No ND U ND
I CHART
Drug
Progesterone Proguanil Promazine Promethazine Propafenone Propantheline Propofol Propoxyphene Propranolol Propylthiouracil Protriptyline Pseudoephedrine Pyrantel Pyrazinamide Pyridostigmine Pyridoxine Pyrilamine Pyrimethamine Quazepam Quetiapine Quinapril (quinaprilat) Quinidine Quinine Quinupristin/ dalfopristin Rabeprazole Raloxifene Raltegravir Raltitrexed Ramelteon
U No (NS) U No (NS) No (NS) ND U No (NS) No (NS) No (NS) No (NS) No (NS) ND Yes (NS) ND ND ND ND U ND No (NS) No* (NS) No (NS) ND U U ND ND ND
U ND U ND No ND U No No ND No U ND No ND ND ND ND U ND No No No No/No U U ND ND ND
47
Drug
Ramipril (ramiprilat) Ranibizumab Ranitidine Ranolazine Rapacuronium Rasagiline Rasburicase Recainam Remifentanil Repaglinide Reserpine Reteplase Reviparin Ribavirin Rifabutin Rifampin Rifapentine Rifaximin Rilmenidine Rilonacept Riluzole Rimantadine Risedronate Risperidone Ritodrine Ritonavir Rituximab Rivastigmine Rizatriptan Rocuronium
48
No (NS) U No (NS) ND ND ND U No (NS) U U No (NS) ND No (NS) No (NS) U No (NS) U U No (NS) U U No (NS) ND ND Yes (NS) U No (NS) ND ND ND
ND U No ND ND ND U U U U No ND U U U No U U U U U U ND ND Yes No U ND ND ND
I CHART
Drug
Ropinirole Ropivacaine Rosiglitazone Rosuvastatin Rotigotine Roxithromycin Ruboxistaurin Runamide Ruoxacin Sacrosidase Salsalate Sapropterin Saquinavir Sargramostim Secobarbital Secretin Selegiline Sermorelin Sertindole Sertraline Sevelamer Sevourane Sibutramine Sildenal Silodosin Silver Simethicone Simvastatin Sirolimus Sisomicin
U U No (NS) No (NS) U ND U No (NS) ND ND Yes (NS) ND U ND No (NS) ND ND ND No (NS) No (NS) U ND U U ND No (NS) U U U Yes (NS)
U U ND ND U ND U ND ND ND L ND No (40) ND ND ND ND ND ND ND U ND ND No (65) ND ND U ND U L
U U U U U No U U ND ND No ND U ND No ND ND ND ND U U ND U U ND U U U U ND
49
Drug
Sitagliptin Sitaxsentan Sodium oxybate Sodium polystyrene sulfonate Solifenacin Somatropin Sorafenib Sotalol Sparoxacin Spectinomycin Spirapril (spiraprilat) Spironolactone Stanozolol Stavudine Streptokinase Streptomycin Streptozocin Sucralfate Sufentanil Sulbactam Sulfadiazine Sulfadoxine Sulfamethoxazole Sulfapyridine Sulfasalazine Sulnpyrazone Sulsoxazole Sulindac Sumatriptan
50
No (NS) U ND U U No (NS) U Yes (NS) ND Yes (NS) U U ND Yes (NS) U Yes (NS) ND No (NS) U Yes (NS) ND ND Yes (NS) ND U No (NS) Yes (NS) No (NS) ND
ND U ND U U U U L ND L ND ND ND Yes (NS) U L ND ND ND L ND ND L ND U ND L ND ND
I CHART
Drug
Sunitinib Tacrine Tacrolimus Tadalal Talinolol Tamoxifen Tamsulosin Tazobactam Tebazumab Tegaserod Teicoplanin Telbivudine Telithromycin Telmisartan Temazepam Temocillin Temozolomide Temsirolimus Teniposide Tenofovir Terazosin Terbinane Terbutaline Teriparatide Testolactone Testosterone Tetracycline Thalidomide Thallous chloride Theophylline
U ND No (NS) No (NS) No (NS) ND U Yes (NS) No (NS) No (NS) No (NS) No (NS) ND No (NS) No (NS) Yes (NS) ND U U ND No (NS) U ND ND ND No (NS) No (NS) U ND Yes (NS)
U ND U U ND ND U No U ND No ND ND U U No ND U U ND No U ND ND ND U No U ND No
51
Drug
Thiabendazole Thiamine Thiethylperazine Thioguanine Thioproperazine Thioridazine Thiotepa Thiothixene Thyrotropin alfa Tiagabine Ticarcillin Ticlopidine Tigecycline Tilidine Tiludronate Timolol Tinidazole Tinzaparin Tipranavir Tiroban Tizanidine Tobramycin Tocainide Tocopherol Tolazamide Tolbutamide Tolcapone Tolmetin Tolterodine Topiramate
52
ND No (NS) ND ND ND U ND U U No (NS) Yes (NS) U No (NS) No (NS) U No (NS) Yes (NS) U U Yes (NS) ND Yes (NS) Yes (NS) ND U No (NS) U U U Yes (NS)
ND ND ND ND ND ND ND ND U ND L ND ND ND ND ND L ND U L ND L L ND ND ND U ND U L
ND U ND ND ND U ND U U ND No U U U U No ND ND U ND ND Yes ND ND U U U U U ND
I CHART
Drug
Topotecan Torsemide Tositumomab Tosuoxacin Tramadol Trandolapril (trandolaprilat) Tranexamic acid Tranylcypromine Trapidil Trastuzumab Trazodone Treprostinil Tretinoin Triamterene Triazolam Trientine Triuoperazine Triupromazine Trihexyphenidyl Trimeprazine Trimethobenzamide Trimethoprim Trimetrexate Trimipramine Triprolidine Triptorelin Tropisetron Trospium Trovaoxacin
Yes (8.0) No (NS) U No (NS) No (NS) Yes (NS) ND ND ND U U U ND ND No (NS) ND No (NS) U ND ND ND Yes (NS) U U ND ND U ND No (NS)
L U U ND Yes (50) L ND ND ND U ND U ND ND ND ND ND ND ND ND ND L ND ND ND ND ND ND ND
ND U U ND ND ND ND ND ND U U U ND ND U ND No U ND ND ND No U U ND ND U ND ND
53
Drug
Urofollitropin Ursodiol Valacyclovir Valganciclovir Valproic acid Valrubicin Valsartan Vancomycin Vardenal Varenicline Vecuronium Velosulin Venlafaxine Verapamil Verteporn Vigabatrin Vinblastine Vincristine Vinorelbine Voriconazole Vorinostat Warfarin Zarlukast Zalcitabine Zaleplon Zanamivir Zidovudine/GZDV Zileuton Zinc
54
ND U Yes (NS) Yes (NS) No (NS) ND No (NS) No (NS) ND Yes (NS) U U No (NS) No (NS) ND Yes (NS) ND ND ND No (NS) ND No (NS) U ND ND ND No (NS)/ Yes (NS) U ND
ND U No ND No ND U No ND ND U U U No ND ND ND ND ND No ND No U ND ND ND No/Yes U ND
I CHART
Drug
U ND ND ND ND
U ND ND U ND
Drugs of Abuse
Drug HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis
Amphetamine Cocaine Ethanol Heroin Lysergide (LSD) Marijuana (THC) MDMA (Ecstasy) Mescaline (peyote) Nicotine Phencyclidine (PCP) Psilocybin
ND ND L ND ND ND ND ND ND ND ND
ND U ND U U U ND U No U ND
55
References
1. Aronoff GR, Bennett WM, Berns JS, Brier ME, Kasbekar N, Mueller BA, Pasko DA, Smoyer WE. Drug prescribing in renal failure, 5th ed. Philadelphia: American College of Physicians; 2007. 2. Bugge JF. Pharmacokinetics and drug dosing adjustments during continuous venovenous hemoltration or hemodialtration in critically ill patients. Acta Anaesthesiol Scand. 2001; 45:929-934. 3. Clark WR, Turk JE, Kraus MA, Gao D. Dose determinants in continuous renal replacement therapy. Artif Organs. 2003;27:815-820. 4. Ibrahim RB, Liu C, Cronin SM, Murphy BD, Cha R, Swerdlow P, Edwards DJ. Drug removal by plasmapheresis: an evidence-based review. Pharmacotherapy. 2007;27:1529-1549. 5. Keller E, Reetze P, Schollmeyer P. Drug therapy in patients undergoing continuous ambulatory peritoneal dialysis: Clinical pharmacokinetic considerations. Clin Pharmacokinet. 1990;18:104-117. 6. Mueller BA, Pasko DA, Sowinski KM. Higher renal replacement therapy dose delivery inuences on drug therapy. Artif Organs. 2003;27:808-814. 7. Olyaei AJ, Bennett WM. Principles of drug usage in dialysis patients, in Nissenson AR, Fine RN (eds). Handbook of dialysis therapy, 4th ed. Philadelphia: Saunders Elsevier; 2008. 8. Pea F, Viale P, Pavan F, Furlanut M. Pharmacokinetic considerations for antimicrobial therapy in patients receiving renal replacement therapy. Clin Pharmacokinet. 2007;46:997-1038. 9. Schetz M. Drug dosing in continuous renal replacement therapy: general rules. Curr Opin Crit Care. 2007;13:645-651. 10. Schetz M, Ferdinande P, Van den Berghe G, Verwaest C, Lauwers P. Pharmacokinetics of continuous renal replacement therapy. Intensive Care Med. 1995;21:612-620. 11. Taylor CA, Abdel-Rahman E, Zimmerman SW, Johnson CA. Clinical pharmacokinetics during continuous ambulatory peritoneal dialysis. Clin Pharmacokinet. 1996;31:293-308.
56 SEE DISCLAIMER REGARDING USE OF THIS GUIDE