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2011

Dialysis of Drugs

George R. Bailie, PharmD, PhD Albany College of Pharmacy and Health Sciences Nancy A. Mason, PharmD University of Michigan College of Pharmacy Renal Pharmacy Consultants, LLC Saline, Michigan USA The sections on continuous renal replacement therapy and extracorporeal therapies for treatment of drug overdose were written by: Marc Ghannoum, MD Department of Nephrology Verdun Hospital University of Montreal

2011 Dialysis of Drugs

DISCLAIMER—These 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 identified 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 specific 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 Renal Pharmacy Consultants, LLC. nor Amgen Canada 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 Renal Pharmacy Consultants, LLC. nor Amgen Canada 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 © 2011, Renal Pharmacy Consultants, LLC. Printed in the U.S.A. All rights reserved. This material may not be published, rewritten or redistributed.

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Foreword
Dialysis of Drugs has been a popular clinical tool for nearly two decades. This resource is used around the world by nurses, pharmacists, physicians and other professionals caring for dialysis patients. Since writing the first edition, my goal has been to provide the busy clinician the best available answer to the common question of whether a medication is removed from the blood by dialysis and whether a replacement dose may be required following dialysis. This information enhances the safe and effective use of medications in a complex and therapeutically challenging patient. With great pleasure, I now transfer responsibility for the future publication of Dialysis of Drugs to two long-time colleagues, George Bailie and Nancy Mason. Dr. Bailie and Dr. Mason are very experienced nephrology pharmacists who will continue to meet the informational needs of dialysis professionals regarding drug dialyzability. Knowing their skill and knowledge of pharmacotherapy in dialysis patients, I am confident that Dialysis of Drugs will continue to be a valuable resource in the future. Curtis A. Johnson, PharmD December 2010 Editorial note: As this booklet went to print in early 2011, Curt Johnson lost his valiant battle with cancer. We will remember Curt as the ultimate professional and friend, and we will miss him. This issue of Dialysis of Drugs is dedicated to the memory of Dr. Curt Johnson.
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I FOREWORD

2011 Dialysis of Drugs

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 efficacy and toxicity.

What Determines Drug Dialyzability?
The extent to which a drug is affected by dialysis is determined primarily by several physicochemical characteristics of the drug that are briefly described in the text that follows. These include molecular size, protein binding, volume of distribution, water solubility, and plasma clearance. In addition to these properties of the drug, technical aspects of the dialysis procedure also may determine the extent to which a drug is removed by dialysis.
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Molecular Weight
Dialysis is dependent upon the use of a dialytic membrane: either a synthetic membrane with fixed 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.

I PREFACE

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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2011 Dialysis of Drugs

Because the primary binding proteins for most drugs (albumin, α1-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 effluent during episodes of peritonitis.

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 clearance—the sum of renal and nonrenal clearance—is often termed
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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.

I PREFACE

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.

Blood and Dialysate Flow Rates
The hemodialysis prescription includes the desired blood and dialysate flow rates. As drugs normally move from blood to dialysate, the flow rates of these two substances may have a pronounced effect on dialyzability. In general, increased blood flow rates during hemodialysis will deliver greater amounts of drug to the dialysis membrane. As the drug concentration increases in the dialysate, the flow rate of the dialysis solution also becomes important in
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2011 Dialysis of Drugs

overall drug removal. Greater dialysis can be achieved with faster dialysate flow rates that keep the dialysate drug concentration at a minimum. During peritoneal dialysis, little can be done to alter blood flow rates to the peritoneum. However, dialysate flow rates are determined by the volume and frequency of dialysate exchange in the peritoneum. At low exchange rates, drug concentrations in the dialysate will increase during the time in which the dialysate resides in the peritoneum, thus slowing additional movement of drug across the membrane. More frequent exchanges will favor increased drug dialyzability, provided the drug’s physicochemical characteristics permit its movement across the peritoneal membrane.

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 flow rates. These technologies are often referred to as “high permeability,” “highefficiency,” and “high-flux” dialysis. The United States Food and Drug Administration has classified high permeability dialysis membranes as those whose in vitro ultrafiltration coefficient (KUf) is greater than 8 mL/hour/mm Hg.
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Commonly included in this group of dialysis membranes are polysulfone, polyacrylonitrile, and high-efficiency cuprammonium rayon dialyzers. Changes in dialysis membranes and changes in blood and dialysis flow 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 confirm 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 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. CONTINUOUS RENAL REPLACEMENT THERAPY Another therapeutic development that will affect drug dialyzability is continuous renal replacement therapy (CRRT). These techniques are largely used in the management of acute renal failure in critically ill patients. As compared to intermittent conventional dialysis
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I SPECIAL CONSIDERATIONS

2011 Dialysis of Drugs

(ICD), continuous therapies provide better hemodynamic stability as well as superior volume, electrolyte and acid-base status. Drug transport in CRRT is provided by diffusion and/or convection. With diffusion, a drug moves from blood to countercurrent dialysate through a concentration gradient across a semi-permeable membrane. In convection, there is removal of solvent containing the drug (ultrafiltrate) via positive hydrostatic pressure. Continuous venovenous hemodialysis (CVVHD) is the major diffusive technique, while continuous venovenous hemofiltration (CVVH) or slow continuous ultrafiltration (SCUF) are convection-based. Continuous venovenous hemodiafiltration (CVVHDF) has the advantage of combining both principles. Veno-venous procedures have largely replaced arterio-venous procedures by providing higher ultrafiltration (UF) rates with decreased complications. As for ICD, many factors contribute to drug clearance in CRRT. Effluent flow: Effluent flow rate is determined by the sum of both ultrafiltration (UF) and dialysate flow rates, depending on the type of CRRT used. Dialysis usually favors clearance of small solutes (urea, lithium) whereas larger drugs, like vancomycin, are better removed by convection. In standard CRRT, maximal drug clearance is limited by the effluent rate (usually varying between 10-75 mL/min). At high rates, drug requirements can even exceed the usual dosage administered to patients with intact renal function, as with fluconazole.
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Post-dilution vs pre-dilution: If hemofiltration is performed in post-dilution, the replacement fluid is administered distal to the filter whereas it is administered before the filter in predilution. Pre-dilution reduces solute clearance by approximately 10-20% (usually affecting larger molecules to a greater extent) but is not restricted by high-level hematocrit in the filter and can therefore be used for high UF. Newer machines can incorporate both functions, rendering drug clearance estimation more complex. Blood flow: As opposed to ICD, blood flow has little impact on drug clearance in CRRT. There is no significant increase in urea clearance when blood flow is increased from 100 mL/min to 250 mL/min. However, blood-flow dependent clearance may be observed at high effluent flow rates. Filters: Filters have various physical characteristics that provide different advantages when compared to one another. In general, newer hemofilters have larger surface areas and higher convective permeability. Adsorption of certain drugs, like aminoglycosides and levofloxacin, may occur with polyacrylonitrile (PAN) membranes while other drug-membrane interactions, such as the charge of the filter material, will also further influence clearance. Finally, hemofilter drug permeability is at its highest right after installation; as the filter ages, clotting and blood components coating the filter’s surface reduce solute removal. These factors are difficult to quantify and predict clinically.
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2011 Dialysis of Drugs

Drug molecular weight: Although molecular weight is an important limiting determinant of drug dialyzability in ICD, it becomes less significant during CRRT because of the use of high-flux hemofilters and the added effect of convection that permit passage of larger molecules up to 50,000 Da. Protein binding: Drugs that are highly bound to plasma proteins are not subject to significant removal during CRRT because the drug-protein complex surpasses pore size of the filter. Hyperbilirubinemia, hypoalbuminemia, renal failure and blood pH (all common variables in intensive care patients) can affect the fraction of unbound drug which will further change the likelihood of drug removal. The unbound fraction of drug is often correlated with the sieving coefficient, defined as the ratio of drug concentration in the ultrafiltrate to the pre-filter plasma water concentration of the drug. Volume of distribution: As is true with ICD, drugs with a large volume of distribution (Vd) are unlikely to be removed to a great extent during CRRT. Drugs with an elevated Vd are essentially confined outside the plasma compartment and hence little of total body stores will be eliminated during CRRT, even if reported drug plasma clearance and extraction are significant. However, since CRRT is a slower process than ICD, once drug is removed from the vascular component, there is more time for transfer of drug from tissues. This reequilibration process provides a continuous drug pool that can be readily cleared by CRRT.
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Competing elimination pathways: Extracorporeal clearance of any drug must be weighed against its endogenous clearance in order to predict efficiency of CRRT removal. If a drug has a high hepatic clearance (in excess of 150 mL/ min), it is unnecessary to adjust dose for CRRT. Similarly, if residual renal function is significant (not unusual on initiation of CRRT) it becomes important, albeit difficult, to factor its effect on total clearance. Unfortunately, few in vivo studies have been published regarding drug removal in CRRT and even fewer were done using newer membranes and higher UF rates (up to 75 mL/min) as advocated by recent survival studies. Although hourly drug removal is generally significantly lower than ICD, hence less attractive for overdose situations, weekly drug extraction in CRRT can be up to 5 times greater than ICD. Only the maintenance dose needs to be adjusted in CRRT (the drug loading dose mainly depends on the Vd and usually doesn’t require modification). Considering all the numerous factors influencing pharmacokinetics in CRRT, drug dosing in the intensive care setting is very unpredictable but can be roughly estimated by the following methods, all of which have unavoidable shortcomings: A) Mathematical estimation of drug clearance While several complex formulas do exist in the literature, they are handicapped by unstable parameters (blood flow and sieving coefficient are rarely constant during treatment). The following simpler equation offers an acceptable estimation of the required dose:
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2011 Dialysis of Drugs

Equation 1) D=Dn*(Clanur+Clcr*(Cln-Clanur)/100+ClCRRT)/Cln
D=Adjusted dose, Dn=Usual dose in patients with intact renal function, Clanur=endogenous drug clearance in anuric patients (see next table), Clcr=residual creatinine clearance (=0 if patient is anuric), ClCRRT=CRRT clearance of a drug (see formula 2), Cln=normal drug clearance (all clearances expressed in mL/min).

B) Available data retrieved from case reports or, preferably, prospective studies Unfortunately, available data are sparse and are not always readily applicable in intensive care patients with extreme characteristics and comorbidities (hepatic failure, shock, sepsis, etc.). Furthermore, technical equipment and prescription parameters have greatly evolved in the last years, making older reports unusable for dosing estimations. C) The total creatinine clearance method Total creatinine clearance during CRRT can be measured as the sum of creatinine clearances from both CRRT and residual renal function. This total can then be correlated with drug dosing tables for patients with impaired renal function. Unfortunately, this method is not applicable for drugs that undergo tubular reabsorption or secretion (as with penicillin antibiotics, for example). Whatever the method chosen, it is advisable, when available, to monitor plasma levels of drugs with a low therapeutic index to guide prescriptions.

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Standardized tables for ICD should never be used to estimate CRRT clearance because of the notable differences between both procedures. This practice could ultimately lead, for example, to antibiotic failure in the septic patient. The following table is a summary of commonly used drugs in the CRRT setting, with respect to protein binding, volume of distribution, endogenous non-renal clearance and fractional clearance of extracorporeal therapy (CRRT clearance divided by total clearance). Little data exists with higher replacement therapies (in excess of 50 mL/min). If effluent rate is 25 mL/ min, CRRT clearance can be estimated by: Equation 2) ClCRRT=FREC25*Clanuric/(1-FREC25)
Drug PB

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(FREC25 and Clanuric may be taken from the table)
Vd (L/kg) Clanuric (mL/min) FREC25

Acyclovir Amantadine Amikacin Amiodarone Amphotericin B liposomal Ampicillin Amrinone Atracurium Aztreonam Bretylium Caspofungin

15% 67% 5% 99% 95% 19% 40% 82% 60% 1% 97%

0.7 4.5 0.3 66 4 0.3 1.3 0.2 0.3 5.9 4.6

40 10 4 130 20 35 200 400 30 163 ND

20% 65% 90% 0% 2% 35% 6% 4% 25% 10% 0%

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2011 Dialysis of Drugs

Drug

PB

Vd (L/kg) Clanuric (mL/min) FREC25

Captopril Cefazolin Cefepime Cefotaxime Cefoxitin Ceftazidime Ceftriaxone Cefuroxime Chloramphenicol Chloroquine Cilastin Ciprofloxacin Cisplatin Clindamycin Clonidine Colistin Cyclophosphamide Cyclosporine Daptomycin Digoxin Diltiazem Disopyramide Dobutamine Dopamine Doripenem Doxorubicin Doxycycline Enalapril
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30% 87% 10% 36% 50% 21% 80% 37% 53% 55% 35% 35% 95% 85% 20% 55% 60% 97% 8% 25% 78% 50% 0% 0% 9% 85% 95% 35%

0.8 0.2 0.7 0.3 0.3 0.3 0.2 0.2 0.9 150 0.2 1.5 0.5 1 2.1 0.3 0.8 5 0.5 6 3 0.6 0.3 0.3 0.2 22 0.8 1.7

500 13 15 70 20 15 10 10 150 400 3 200 2 200 170 38 120 400 7 45 820 38 4000 4000 2 113 50 41

8% 15% 42% 12% 10% 48% 30% 80% 6% 2% 80% 9% 48% 4% 5% 20% 11% 0% 23% 20% 0% 30% 0% 0% 23% 8% 12% 10%

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I SPECIAL CONSIDERATIONS

Drug

PB

Vd (L/kg) Clanuric (mL/min) FREC25

Enoxacin Erythromycin Esmolol Ethambutol Famotidine Fentanyl Flecainide Fluconazole Flucytosine Furosemide Gancyclovir Gentamicin Hydralazine Imipenem Isoniazid Itraconazole Ketamine Ketoconazole Labetolol Levofloxacin Lidocaine Linezolid Lisinopril Lorazepam Melphalan Meropenem Methotrexate Metoprolol

40% 84% 55% 25% 20% 80% 60% 12% 5% 95% 2% 2% 87% 15% 17% 99% 30% 99% 50% 31% 70% 25% 2% 90% 90% 2% 50% 11%

1.6 0.8 1.9 1.6 1.1 4 4.9 0.7 0.7 0.2 0.6 0.3 1.5 0.3 0.8 11 2 2.4 9.4 1.2 1.1 0.7 1.5 1 0.6 0.4 0.8 4.2

200 100 12000 120 35 837 222 7 2 54 20 5 500 100 75 400 90 580 1700 22 630 40 1 85 250 35 9 950

5% 3% 0% 10% 25% 0% 4% 75% 95% 2% 50% 82% 1% 20% 18% 0% 10% 0% 1% 42% 1% 32% 100% 2% 1% 30% 52% 2%
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2011 Dialysis of Drugs

Drug

PB

Vd (L/kg) Clanuric (mL/min) FREC25

Metronidazole Micafungin Midazolam Milrinone Morphine Moxifloxacin Nifedipine Nitroglycerin Norepinephrine Ofloxacin Omeprazole Oxacillin Phenobarbital Phenytoin Piperacillin Prednisolone Procainamide Propafenone Propofol Propranolol Quinine Ranitidine Rifampin Streptomycin Sulfamethoxazole Tacrolimus Tazobactam Teicoplanin
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15% 99% 95% 85% 30% 40% 96% 0% 0% 15% 95% 95% 50% 90% 20% 60% 16% 96% 96% 87% 90% 15% 89% 35% 62% 99% 20% 90%

0.8 0.2 1.1 0.3 3.5 2.2 0.8 3.3 0.3 2 0.4 0.2 0.5 0.7 0.2 2 1.9 3 20 4.3 1.8 1.3 1 0.3 0.2 1.5 0.3 0.7

70 22 120 80 1200 200 500 16100 900 33 620 50 6 20 40 66 107 1100 1000 1120 16 226 200 2 20 45 20 2

25% 7% 5% 8% 7% 7% 0% 0% 2% 35% 0% 3% 65% 10% 20% 10% 8% 0% 0% 0% 1% 10% 2% 85% 27% 5% 42% 27%

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I SPECIAL CONSIDERATIONS

Drug

PB

Vd (L/kg) Clanuric (mL/min) FREC25

Tetracycline Theophylline Ticarcillin Tobramycin Trimethoprim Vancomycin Verapamil Voriconazole Zidovudine

70% 50% 58% 2% 42% 30% 90% 55% 10%

1 0.5 0.2 0.3 1.7 0.5 5 5 1.4

15 40 11 4 50 5 1020 200 1490

50% 20% 44% 82% 16% 55% 2% 6% 0%

PB=Protein binding Vd=Volume of distribution CLanuric=Endogenous drug clearance in anuric patients FREC25=Fractional extracorporeal clearance at effluent rate of 25 mL/min ND=No data

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 specific pharmacokinetic effects of plasmapheresis. The procedure may
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2011 Dialysis of Drugs

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 from these studies should be applied with caution to other dialysis conditions.

About This Guide
These guidelines are designed to provide extensive, easy-to-read information regarding the dialyzability of drugs. Numerous literature sources have been used in preparing the guidelines. For many drugs, including newlyapproved medications, investigational agents and medications available in other countries, no studies have been done to determine the effect of dialysis on drug removal. In some cases, the available data may conflict. Conditions of dialysis used in published studies may not necessarily reflect current dialysis procedures and technology. Variations in the duration of dialysis, flow rates, dialysis membranes, and whether peritoneal dialysis is continuous or intermittent will all affect drug removal. This educational review will distinguish between conventional hemodialysis and high permeability (often called high20 SEE DISCLAIMER REGARDING USE OF THIS GUIDE

flux) hemodialysis where such data are available. However, the review does not contain information on drug dialyzability with CRRT (See Special Considerations) or with plasmapheresis. For additional information on specific drugs, the reader should consult the primary literature. A designation of “Yes” in the Hemodialysis and Peritoneal Dialysis columns 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. 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 confirmed 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 flow rates or in the presence of peritonitis.
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I ABOUT THIS GUIDE

2011 Dialysis of Drugs

A designation of “U” indicates that no dialysis studies have been published, or that there is very limited information (such as case reports), but that the authors of this guide have concluded that significant 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 or that there is very limited information (such as case reports). However, the authors have extrapolated data from studies using conventional dialysis to conclude that significant drug removal is likely to occur during high permeability dialysis. A designation of “ND” indicates that no (or very limited) data are available on drug dialyzability. In some cases, the literature reports the use of a high permeability, or high-flux, dialysis membrane, however the type of membrane is not specified. A designation of “NS” indicates membrane type is not specified.

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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 significant 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 significant 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 specified * Removed with haemoperfusion Note: In these tables, conventional hemodialysis is defined as the use of a dialysis membrane whose in vitro coefficient of ultrafiltration (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 defined 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. Some drugs in this table are not available in Canada.

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Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Abacavir Abatacept Abciximab Acamprosate Acarbose Acebutolol (diacetolol) Acenocoumarol Acetaminophen Acetazolamide Acetohexamide Acetophenazine Acetylcysteine Acitretin Acyclovir Adalimumab Adefovir Adenosine Adipiodone Agalsidase alfa Agalsidase beta Albendazole Albumin Alcaftadine Aldesleukin Alefacept Alemtuzumab Alendronate Aliskiren Alfacalcidol Alfentanil
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U U U ND ND Yes (NS) U Yes (NS) U U U Yes (7.5) No (NS) Yes (NS) U Yes (NS) U ND No (7.5) U No (NS) U ND ND ND U No (NS) ND ND U

No (40) U ND ND ND L U L ND ND ND ND U L U ND ND ND No (10) U ND ND ND ND ND U ND ND ND ND

ND U U ND ND ND U No No U U ND U No U ND U ND U U U U ND ND ND U ND ND ND U

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I CHART

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Alfuzosin Alitretanoin Allopurinol Alprazolam Alprostadil Alteplase Altretamine Amantadine Ambrisentan Amdinocillin Amifostine Amikacin Amiloride Aminocaproic acid Aminoglutethimide Aminosalicylic acid Amiodarone Amitriptyline Amlexanox Amlodipine Amoxapine Amoxicillin Amphetamine Amphotericin B Amphotericin B lipid complex Ampicillin Amprenavir Amrinone Amsacrine

U ND Yes (NS) No (NS) U U ND No (NS) U No (NS) ND Yes (NS) ND Yes (NS) Yes (NS) Yes (NS) No (NS) No (NS) ND No (NS) U Yes (NS) ND No (NS) No (NS) Yes (NS) U U U

U ND L ND No (11.1) ND ND ND U ND ND L ND ND L L ND ND ND U ND L ND No (10.1, 36) ND L ND ND U

U ND ND U ND U ND No U No ND Yes ND Yes ND ND No No ND No U No ND No U No U No U
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2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Anagrelide ND Anakinra No (NS) Anastrozole ND Ancestim ND Ancrod ND Anidulafungin No (NS) Anisoylated plasminogen ND streptokinase activator complex Anistreplase U Antithymocyte globulin U (ATG) Aprepitant No (NS) Aprotinin U Arbutamine ND Argatroban U Aripiprazole U Articaine ND Ascorbic acid Yes (5.5) Asenapine U Asparaginase U Aspirin Yes (NS) Atazanavir U Atenolol Yes (NS) Atomoxetine U Atorvastatin No (NS) Atovaquone U Atracurium U Atropine No (NS) Auranofin No (NS)
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ND ND ND ND ND U ND ND ND U ND ND No (10.7-36) U ND Yes (8.8) U ND L U L U ND ND ND ND ND

ND No ND ND ND U ND U U U U ND ND U ND Yes U U Yes U No U U U U ND ND

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I CHART

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Azacitidine Azathioprine Azithromycin Azlocillin Aztreonam Bacampicillin Baclofen Basiliximab Benazepril (benazeprilat) Bendroflumethiazide Benzquinamide Benztropine Bepotastine besylate Bepridil Beractant Besifloxacin Betahistine Betaine Betamethasone Betaxolol Bethanechol Bevacizumab Bezafibrate Biapenem Bicalutamide Biperiden Bisoprolol Bivalirudin Bleomycin

ND Yes (NS) ND Yes (NS) Yes (NS) Yes (NS) ND U No (NS) No (NS) U ND ND No (NS) U ND ND ND ND No (NS) ND U No (NS) Yes (NS) U ND No (NS) Yes (NS) No (NS)

ND L ND L L L Yes (60) ND ND ND ND ND ND ND U ND ND ND ND ND ND No (NS) ND Yes (NS) ND ND ND ND ND

ND ND No No No No ND U ND U ND ND ND U U ND ND ND ND No ND U No ND U ND ND ND No
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2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Bortezomib Bosentan Bretylium Bromazepam Bromfenac Bromocriptine Budesonide Buflomedil Bumetanide Bupivacaine Buprenorphine Bupropion Buserelin Buspirone Busulfan Butalbital Butorphanol Cabazitaxel Cabergoline Caffeine Calcitonin Calcitriol Calcium polystyrene sulfonate Canakinumab Candesartan Capecitabine Capreomycin Captopril Carbamazepine
28

ND U Yes (NS) ND No (NS) U U No (NS) U U U No (NS) ND No (NS) Yes (NS) ND U U ND ND U No (4.2-5.3) U U No (NS) ND Yes (NS) Yes (NS) No (NS)

ND No (11.1) L ND ND ND U No (20) U U U No (10) ND ND Yes (8.1) ND ND U ND ND U No (31) U U No (8.1) ND L L Yes (22, 55)

ND U ND ND U U U U U U U No ND ND ND ND U U ND ND U U U U ND ND ND No No

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

I CHART

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Carbenicillin Carbidopa/levodopa Carboplatin Carboprost Carglumic acid Carisoprodol Carmustine Carprofen Carteolol Carumonam Carvedilol Caspofungin Cefaclor Cefadroxil Cefamandole Cefazolin Cefdinir Cefepime Cefixime Cefmenoxime Cefmetazole Cefodizime Cefonicid Ceforanide Cefotaxime Cefoxitin Cefpirome Cefpodoxime Cefprozil Cefradine

Yes (NS) ND/U Yes (NS) ND ND Yes (NS) No (NS) U ND Yes (NS) No (NS) No (NS) Yes (NS) Yes (NS) Yes (NS) Yes (6, 8) ND Yes (NS) No (NS) Yes (NS) Yes (NS) No (NS) No (NS) Yes (NS) Yes (NS) Yes (NS) Yes (NS) Yes (NS) Yes (NS) Yes (NS)

L ND/U L ND ND L ND ND ND L ND U L L L Yes (8.1-36) Yes (NS) Yes (40) ND L L ND ND L L L Yes (40) L L L

No ND/U No ND ND Yes ND U ND ND ND U Yes No No No ND Yes No ND No No No No No No No No ND Yes
29

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2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Cefroxadine Cefsulodin Ceftazidime Ceftibuten Ceftizoxime Ceftobiprole Ceftriaxone Cefuroxime Celecoxib Cephalexin Cephalothin Cephapirin Certolizumab Cetirizine Cetuximab Chloral hydrate Chlorambucil Chloramphenicol Chlordiazepoxide Chlormethine Chloroprocaine Chloroquine Chlorpheniramine Chlorpromazine Chlorpropamide Chlorprothixene Chlorthalidone Chlorzoxazone Cholestyramine Choriogonadotropin
30

ND Yes (NS) Yes (NS) Yes (NS) Yes (NS) ND No (NS) Yes (NS) U Yes (NS) Yes (NS) Yes (NS) U U U Yes (5.5) No (NS) Yes (NS) No (NS) U ND No (NS) Yes (NS) No (NS) No* (NS) U No (NS) ND U U

ND L L L L ND ND L ND L L L U No (18.7-66.7) U L ND L ND U ND ND L ND ND ND ND ND U U

ND Yes Yes ND No ND No No U No No No U U U ND No No U U ND No No No No U U ND U U

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

I CHART

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Cidofovir Cilastatin Cilazapril Cilostazol Cimetidine Cinacalcet Cinoxacin Ciprofloxacin Cisatracurium Cisplatin Citalopram Cladribine Clarithromycin Clavulanic acid Clemastine Clindamycin Clobazam Clodronate Clofarabine Clofazimine Clofibrate Clomiphene Clomipramine Clonazepam Clonidine Clopidogrel Clorazepate Clotrimazole Cloxacillin Clozapine

ND Yes (NS) Yes (NS) U No (NS) No (NS) No (NS) No (NS) U No (NS) No (8) ND ND Yes (NS) ND No (NS) No (4.2) ND ND No (NS) No (NS) ND U No (NS) No (NS) U No (NS) U No (NS) No (NS)

Yes (60) L L ND ND U ND ND ND Yes (NS) No (40) ND ND L ND ND ND Yes (8.1) ND ND ND ND ND ND ND ND ND U ND ND

No ND ND U No No U No U No U ND ND Yes ND No ND No ND No No ND U U No U U U No U
31

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Codeine/metabolites (morphine-3 No/Y (NS) and morphine-6 glucuronides, codeine-6 glucuronide) Colchicine No (NS) Colestipol U Colistin No (NS) Collagenase Clostridium U histolyticum Cortisone No (NS) Cromolyn sodium U Cyanocobalamin No (NS) Cyclacillin Yes (NS) Cyclobenzaprine U Cyclophosphamide Yes (6.4) Cycloserine ND Cyclosporine No (NS) Cyproheptadine ND Cyproterone ND Cystadane ND Cysteamine ND Cytarabine ND Dabigatran Y (NS) Dacarbazine ND Daclizumab U Dactinomycin ND Dalfampridine ND Dalteparin U Danaparoid ND
32

ND ND U ND U ND U No (40, 65) L U L Yes (30, 52) ND ND ND ND ND Yes (NS) L ND ND ND L ND ND

U No U No U No U ND No U ND ND No ND ND ND No No ND ND U ND ND No ND

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

I CHART

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Danazol Dantrolene Dapsone Daptomycin Darbepoetin alfa Darifenacin Darunavir Dasatinib Daunorubicin Deferasirox Deferoxamine Deflazacort Degarelix Delavirdine Demeclocycline Denosumab Desipramine Desloratadine Desmopressin Desogestrel Desvenlafaxine Dexamethasone Dexfenfluramine Dexlansoprazole Dexmedetomidine Dexmethylphenidate Dexrazoxane Dextroamphetamine Dextropropoxyphene Dezocine

ND ND Yes (NS) No (11) U U Yes (NS) U ND U Yes (NS) No (NS) U U ND U No (NS) No (NS) ND U No (NS) No (NS) ND U U ND ND ND No (NS) ND

ND ND L Yes (62) No (11.1-55) U L U ND U L ND U ND ND U ND ND ND U U ND ND U U ND ND ND ND ND

ND ND ND No No U U U ND U ND U U U ND U No No ND U U No ND U U ND ND ND No ND
33

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Diazepam Diazoxide Dibekacin Diclofenac Dicloxacillin Dicyclomine Dicycloverine Didanosine Diethylpropion Diethylstilbesterol (fosfestrol) Diflunisal Digitoxin Digoxin Digoxin immune Fab Dihydroergotamine Diltiazem Dimenhydrinate Dinoprostone Diphenhydramine Diphenoxylate/ Atropine Dipyridamole Dirithromycin Disodium etidronate Disopyramide Disulfiram Divalproex Dobutamine Docetaxel
34

No (NS) Yes (NS) Yes (NS) U No (NS) ND ND No (7.9) ND No (NS) No (NS) No (NS) No (NS) No (NS) ND No (NS) ND ND U ND U No (NS) ND No (NS) U No (NS) No (NS) No (NS)

ND L L ND ND ND ND No (40) ND ND ND ND ND U ND ND ND ND ND ND ND ND ND U U ND ND U

U Yes ND U No ND ND No ND ND U No No No ND No ND ND U ND ND No ND U U No No U

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

I CHART

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Dolasetron Domperidone Donepezil Dopamine Doripenem Doxacurium Doxapram Doxazosin Doxepin Doxercalciferol Doxorubicin Doxorubicin, pegylated liposomal Doxycycline Doxylamine Dronabinol Dronedarone HCl Droperidol Drospirenone Drotrecogin alfa Duloxetine Dutasteride Ecallantide Eculizumab Edetate calcium (ETDA) Edrophonium Efalizumab Efavirenz Eletriptan

ND U U No (NS) Yes (NS) No (NS) ND No (NS) No (NS) No (NS) No (NS) ND No (NS) ND U U U U U U U ND U Yes (NS) ND U No (NS) ND

ND U ND ND ND ND ND ND ND U ND ND ND ND ND U ND U U U U ND U L ND U ND ND

ND U U U ND U ND No No U ND ND No ND U U U U U U U ND U Yes ND U No ND
35

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Emtricitabine Enalapril (enalaprilat) Encainide Enfuvirtide Enoxacin Enoxaparin Entacapone Entecavir Ephedrine Epinephrine Epirubicin Eplerenone Epoetin alfa Epoprostenol Eprosartan Eptacog alfa Eptifibatide Ergocalciferol Ergotamine Erlotinib Ertapenem Erythromycin Escitalopram Esmolol (ASL-8123) Esomeprazole Estazolam Estradiol Estramustine Estropipate Etanercept
36

Yes (NS) Yes (NS) No (NS) No (NS) No (NS) No (NS) U No (NS) ND ND ND No (7) No (NS) ND U U ND ND ND U Yes (NS) No (NS) ND Yes (NS) U U No (NS) ND ND No (NS)

ND L ND U ND Yes (11.5-55) U ND ND ND ND ND No (11.1-55) ND No (60) U ND ND ND No (NS) L ND ND L U ND ND ND ND U

ND Yes ND U No No U No ND ND ND ND No ND U U ND ND ND U ND No ND Yes U U ND ND ND U

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

I CHART

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Ethacrynic acid Ethambutol Ethchlorvynol Ethinyl estradiol Ethopropazine Ethosuximide Ethynodiol diacetate Etodolac Etoposide Etravirine Everolimus Exemestane Ezetimibe Famciclovir (penciclovir) Famotidine Felbamate Felodipine Fenfluramine Fenofibrate Fenoldopam Fenoprofen Fenoterol Fentanyl Ferric gluconate Ferrous (iron) salts Ferumoxytol Fexofenadine Filgrastim Finasteride

No (NS) No (NS) No* (NS) U ND Yes (NS) ND No (NS) No (NS) No (NS) ND U U Yes (NS) No (NS) ND No (NS) ND No (NS) U No (NS) ND U No (NS) U No (NS) No (NS) No (NS) U

U No (80) ND U ND L ND ND No (NS) U ND U U L ND ND ND ND U ND ND ND No (10.1) ND ND ND ND ND ND

U U No No ND ND ND U No U ND U U ND No ND U ND U No U ND ND U U ND U U U
37

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Flavoxate ND ND Flecainide No (NS) ND Fleroxacin U No (8.1, 22) Floctafenine ND ND Floxuridine ND ND Fluconazole Yes (NS) L Flucytosine Yes (NS) L Fludarabine ND ND Fludrocortisone ND ND Flumazenil ND ND Fluorouracil/FBAL No (NS)/ND Yes (71)/Yes (40) Fluoxetine No (NS) ND Fluoxymesterone ND ND Flupentixol decanoate ND ND Fluphenazine U ND Flurazepam No (NS) ND Flurbiprofen ND ND Flutamide No (NS) ND Fluticasone U U Fluvastatin No (NS) ND Fluvoxamine U No (NS) Folic acid Yes (NS) L Follitropin alfa ND ND Follitropin beta ND ND Fomepizole Yes (NS) L Fondaparinux No (NS) ND Fosaprepitant No (NS) U Foscarnet Yes (4.1) Yes (18-60) Fosfomycin Yes (NS) L Fosinopril (fosinoprilat) No (NS) ND
38

ND U No ND ND Yes Yes ND ND ND ND No ND ND U U No U U U U ND ND ND ND U U ND ND No

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

I CHART

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Fosphenytoin Frovatriptan Fulvestrant Furosemide Fusidic acid Gabapentin Gadobenate Gadobutrol Gadodiamide Gadofosveset Gadopentetate Gadoversetamide Gadoxetate Galantamine Gallamine Gallium Gallopamil Ganciclovir Ganirelix Gatifloxacin Gefitinib Gemcitabine Gemfibrozil Gemifloxacin Gentamicin Glatiramer Gliclazide Glimepiride Glipizide Glucagon

U ND U No (NS) No (NS) Yes (NS) ND Yes (5.5) Yes (NS) ND ND ND Yes (NS) ND ND ND U Yes (NS) ND ND U Yes (7) No (NS) No (NS) Yes (NS) ND U U U U

ND ND U U ND L ND L L ND ND Yes (NS) L ND ND ND ND L ND ND No (20) Yes (53, 58) ND ND Yes (13.2, 60) ND U ND ND ND

U ND U U No ND ND ND No ND ND ND ND ND ND ND U ND ND ND U ND No ND Yes ND U U U U
39

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Glutethimide Glyburide Glycopyrrolate Gold sodium thiomalate Golimumab Goserelin Granisetron Griseofulvin Guaifenesin Guanabenz Guanadrel Guanethidine Guanfacine H1N1 Vaccine Halofantrine Haloperidol Heparin Hexobarbital Hirudin Human Growth Hormone Hydralazine Hydrochlorothiazide Hydrocodone Hydrocortisone Hydromorphone/ hydromorphone-3glucuronide Hydroxycarbamide Hydroxychloroquine
40

No* (NS) No (NS) ND No (NS) U ND ND ND ND U ND ND No (NS) ND ND No (NS) No (NS) No (NS) No (4.3-6.5) U No (NS) No (NS) ND U No/Yes (7.5) No (NS) ND

ND ND ND ND U ND ND ND ND ND ND ND ND ND ND ND ND ND Yes (20-90) U ND ND ND ND ND ND ND

No U ND U U ND ND ND ND ND ND ND No ND ND No No U ND U No U ND U ND U ND

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

I CHART

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Hydroxyurea Hydroxyzine Ibandronate Ibritumomab Ibuprofen Ibutilide Idarubicin Idebenone Idursulfase Ifosfamide Imatinib Imiglucerase Imipenem Imipramine Immune globulin (human) Indapamide Indinavir Indomethacin Infliximab Insulin Insulin aspart Insulin detemir Insulin glargine Insulin glulisine Insulin lispro Interferons Iodixanol Iohexol Iopamidol

No (NS) No (NS) ND U No (NS) ND U U U Yes (1.6) No (NS) U Yes (NS) No (NS) U No (NS) U No (NS) U No (NS) U No (NS) U U U No (NS) Yes (3.1, 4.2) Yes (NS) Yes (4.8)

ND ND Yes (8.1) U ND ND ND U U L U U L ND ND ND No (40) ND U ND ND U ND ND ND Yes (20-33) L Yes (15.5) L

U No ND U U ND U U U ND U U Yes No U U ND U U No U ND U ND U No ND ND Yes
41

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

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 (SN-38 Yes/No (NS) No (8.5)/L metabolite) Iron dextran U No (8.1-10.1) Iron sorbitol-citric acid ND ND complex Iron sucrose U No (10.1-55) (saccharate) 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) Kanamycin Yes (NS) L Ketamine No (NS) ND Ketoconazole No (NS) ND Ketoprofen U ND Ketorolac U ND Ketotifen ND ND Labetolol No (NS) ND Lacosamide No (NS) ND

ND ND ND ND ND ND ND ND/U U ND U ND No ND No No U No U Yes U No U U ND No U

42

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I CHART

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Lactulose U Lamivudine No (NS) Lamotrigine No (NS) Lansoprazole No (NS) Lanthanum carbonate No (NS) Lapatinib U Laronidase U Leflunomide No (NS) Lenalidomide Yes (NS) Lepirudin No (4.3-6.2) Letrozole ND Leucovorin ND Leuprolide ND Leuprorelin ND Levamisole ND Levetiracetam Yes (NS) Levobupivacaine U Levocarnitine Yes (NS) Levodopa U Levofloxacin U Levonorgestrel U Levorphanol ND Levothyroxine U Lidocaine No (NS) Lincomycin No (NS) Linezolid Yes (NS) Liothyronine ND Liraglutide U Lisdexamfetamine ND Lisinopril Yes (NS)

U No (11.4) ND ND U U U No (8.1) ND Yes (20-90) ND ND ND ND ND L ND L U No (13.2) ND ND ND ND ND Yes (9.3-65) ND U ND L

U No U U U U U No ND ND ND ND ND ND ND ND U ND U No U ND U U No ND ND U ND ND
43

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Lithium Lomefloxacin Lomustine Loperamide Lopinavir Loracarbef Loratadine Lorazepam Losartan Loteprednol etabonate Lovastatin Loxapine L-tryptophan Mangafodipir Mannitol Maprotiline Maraviroc Mazindol Mechlorethamine Meclofenamate Medroxyprogesterone Mefenamic acid Mefloquine Megestrol acetate Melatonin/6sulfatoxymelatonin Meloxicam Melphalan Memantine HCl Menotropins
44

Yes (NS) No (NS) No (NS) ND U Yes (NS) No (NS) No (NS) No (NS) U U ND U ND Yes (NS) No (NS) ND ND U U U No (NS) U ND Yes (NS) No (NS) No (NS) ND ND

Yes (40, 70) ND ND ND No (NS) L ND ND No (10.1-52) U ND ND No (8.1-40) ND L ND ND ND U ND U ND ND ND L U ND ND ND

Yes No U ND U ND No U No U U ND ND ND Yes U ND ND U U U U U ND ND U ND ND ND

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

I CHART

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Meperidine/ normeperidine Meprobamate Mercaptopurine Meropenem Mesalamine (5-ASA) Mesalazine Mesna Mesoridazine Mesuximide Metaproterenol Metformin Methadone Methaqualone Methenamine Methicillin Methimazole Methocarbamol Methotrexate Methotrimeprazine Methoxsalen Methoxy polyethylene glycol-epoetin beta Methyl aminolevulinate HCl Methyldopa Methylnaltrexone Methylphenidate Methylprednisolone Methysergide

No (NS)/ND No (8.1)/Yes (8.1) Yes (NS) Yes (NS) Yes (NS) Yes (5.5) Yes (5.5) ND U ND ND Yes (NS) No (NS) No (NS) ND No (NS) No (NS) ND Yes (NS) ND ND U U Yes (NS) ND U Yes (NS) ND L L L ND ND ND ND ND ND L ND ND ND ND ND ND Yes (20, 60) ND ND U U L ND ND L ND

U/ND Yes ND ND U U ND U ND ND ND No No ND No No ND Yes ND ND U U Yes ND U ND ND

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

45

2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Metoclopramide Metolazone Metoprolol Metronidazole Mexiletine Mezlocillin Micafungin Miconazole Midazolam Midodrine (de-glymidodrine) Miglitol Miglustat Milrinone Minocycline Minoxidil Mirtazapine Misoprostol Mitomycin Mitotane Mitoxantrone Mivacurium Moclobemide Modafinil Moexipril Molindone Montelukast Moricizine Moroctocog alfa Morphine
46

No (NS) No (NS) Yes (NS) Yes (NS) Yes (NS) Yes (NS) U No (NS) No (NS) ND ND ND ND No (NS) Yes (NS) U U ND ND No (NS) ND ND ND ND U U U U ND

ND ND L Yes (56) L L U ND ND Yes (8.1) ND ND ND ND L ND ND ND ND ND ND ND ND ND ND ND ND U Yes (8.1, 10.1)

No U ND No No No U No U ND ND ND ND No Yes U U ND ND No ND ND ND ND U U U U No

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

I CHART

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Moxifloxacin Muromonab-CD3 Mycophenolate (mycophenolic acid) Nabilone Nabumetone Nadolol Nadroparin Nafarelin Nafcillin Nalbuphine Nalidixic acid Nalmefene Naloxone Naltrexone Nandrolone Naproxen Naratriptan Natalizumab Nateglinide/M1 metabolite Nebivolol Nedocromil Nelarabine Nelfinavir Neomycin Netilmicin Nevirapine Niacin Niacinamide

ND U No (NS) ND No (NS) Yes (NS) ND ND No (NS) ND U No (4.1-5.9) ND No (NS) ND No (NS) ND U U/Yes (NS) U ND U U Yes (NS) Yes (NS) ND ND ND

ND ND ND ND ND L ND ND ND ND U ND ND ND ND ND ND U U/Yes (NS) U ND U No (71) L L Yes (40) ND ND

No U No ND ND ND ND ND No ND U U ND ND ND U ND U U/ND U ND U No Yes Yes Yes ND ND
47

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Nicardipine Nicotine Nicotinic acid Nifedipine Nilotinib Nilutamide Nimodipine Nisoldipine Nitrazepam Nitrendipine Nitrofurantoin Nitroglycerin Nitroprusside Nizatidine Nomifensine Norelgestromin Norepinephrine Norethindrone Norethistrone Norfloxacin Norgestimate Norgestrel Nortriptyline Nylidrin Nystatin Octreotide Ofatumumab Ofloxacin Olanzapine Olmesartan
48

No (NS) ND ND No (NS) U ND No (NS) No (NS) ND No (NS) Yes (NS) No (NS) Yes (NS) No (NS) ND ND ND ND ND No (NS) U ND No (NS) ND U Yes (NS) U Yes (6.0) No (NS) U

ND ND ND ND U ND ND ND ND ND L ND L ND ND ND ND ND ND ND U ND ND ND U L U Yes (8.5) ND No (NS)

U ND ND No U ND No No ND U ND No Yes No ND ND ND No ND U U ND No ND U ND U No No U

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

I CHART

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Olsalazine U Omapatrilat No (NS) Omeprazole U Ondansetron U Orbofiban Yes (NS) Orlistat U Ornidazole Yes (NS) Ornipressin U Orphenadrine ND Oseltamivir Yes (2.8-4.0) Oxacillin No (NS) Oxaliplatin ND Oxaprozin No (NS) Oxazepam No (NS) Oxcarbazepine ND Oxtriphylline Yes (NS) Oxybutynin ND Oxycodone ND Oxymetholone ND Oxymorphone ND Paclitaxel No (NS) Paliperidone ND Palivizumab U Pamidronate Yes (6.4) Pancuronium ND Panitumumab U Pantoprazole No (5.1) Papaverine U Para-aminosalicylate U Paricalcitol No (5.5)

ND ND ND ND L U L U ND ND ND Yes (71) ND ND ND L ND Yes (48) ND ND ND ND U L ND U ND U No (30, 60) ND

U ND U U ND U No U ND Yes No ND U U ND No ND ND ND ND No ND U ND ND U ND U U ND
49

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Paroxetine Pazopanib Pefloxacin Pegaspargase Pegfilgrastim Peginterferon alfa-2b

No (NS) U No (NS) U U U

Pegvisomant U Pemetrexed ND Pemoline Yes (NS) Penbutolol No (NS) Penicillamine Yes (NS) Penicillin G Yes (NS) Pentamidine No (NS) Pentastarch U Pentazocine Yes (NS) Pentobarbital No (NS) Pentosan polysulfate ND Pentostatin ND Pentoxifylline U Perflutren ND Pergolide U Pericyazine ND Perindopril Yes (NS) L (perindoprilat) Perphenazine U ND Pethidine/norpethidine No (NS)/ND No (8.1)/Yes (8.1) Phenacetin ND ND Phenazopyridine ND ND Phenelzine ND ND
50

ND U ND ND U No (8.7) Yes (20-33) U ND L ND L L ND U L ND ND ND ND ND ND ND

U U No U U U U ND No No ND No No U ND U ND ND ND ND U ND ND U U/ND ND ND ND

SEE DISCLAIMER REGARDING USE OF THIS GUIDE

I CHART

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Phenobarbital Yes (NS) Phentermine ND Phentolamine ND Phenylbutazone No (NS) Phenyltoloxamine ND Phenytoin No (NS) Phytonadione ND Pilocarpine ND Pimagedine Yes (NS) (aminoguanidine) Pimozide ND Pinaverium U Pindolol ND Pioglitazone No (NS) Piperacillin Yes (NS) Pipotiazine ND Piroxicam U Pitavastatin calcium U Pivmecillinam No (NS) Pizotifen U Pizotyline U Plicamycin ND Pneumococcal vaccine ND Polidocanol ND Polyethylene glycol U Polythiazide No (NS) Poractant alfa ND Porfimer No (NS) Posaconazole No (NS) Pralatrexate ND
SEE DISCLAIMER REGARDING USE OF THIS GUIDE

Yes (60) ND ND ND ND Yes (36) ND ND ND ND U ND ND L ND ND U ND U U ND ND ND U ND ND U ND ND

Yes ND ND U ND No ND ND ND ND U ND U No ND U U U U U ND ND ND U No ND U ND ND
51

2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Pralidoxime ND Pramipexole No (NS) Prasugrel U 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 Profenamine ND Progesterone U Proguanil No (NS) Promazine U Promethazine No (NS) Propafenone No (NS) Propantheline ND Propofol U Propoxyphene No (NS) Propranolol No (NS) Propylthiouracil No (NS)
52

ND ND U ND ND ND ND No (NS) ND L ND L U ND L/L ND ND ND ND U ND ND ND ND ND ND ND ND ND

ND U U ND U ND No U No ND ND ND U No No/No ND U ND ND U ND U ND No ND U No No ND

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Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Protriptyline Pseudoephedrine Pyrantel Pyrazinamide Pyridostigmine Pyridoxine Pyrimethamine Quazepam Quetiapine Quinapril (quinaprilat) Quinidine Quinine Quinupristin/ dalfopristin Rabeprazole Raloxifene Raltegravir Raltitrexed Ramipril (ramiprilat) Ranitidine Rasagiline Rasburicase Recainam Remifentanil Repaglinide Reserpine Reteplase Reviparin Ribavirin Rifabutin

No (NS) No (NS) ND Yes (NS) ND ND ND U ND No (NS) No* (NS) No (NS) ND U U Yes (NS) ND No (NS) No (NS) ND U No (NS) U U No (NS) ND No (NS) No (NS) U

ND ND ND Yes (80) ND Yes (36) ND ND ND U ND ND ND U ND L ND ND Yes (NS) ND U ND U No (60) ND ND ND ND No (40)

No U ND No ND ND ND U ND No No No No/No U U U ND ND No ND U U U U No ND U U U
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2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Rifampin Rifapentine Rilmenidine Riluzole Rimantadine Risedronate Risperidone Ritodrine Ritonavir Rituximab Rivaroxaban Rivastigmine Rizatriptan Rocuronium Romidepsin Romiplostim Ropinirole Ropivacaine Rosiglitazone Rosuvastatin Roxithromycin Rufloxacin Salbutamol Salcatonin Salmeterol Salsalate Sapropterin Saquinavir Sargramostim Saxagliptin
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No (NS) U No (NS) U No (NS) ND ND Yes (NS) Yes (NS) No (NS) ND ND ND ND U ND U U No (NS) No (NS) ND ND No (NS) U ND Yes (NS) ND U ND Yes (NS)

No (80) ND ND U ND ND ND L L U ND ND ND ND U ND U U ND ND ND ND ND U ND L ND No (40) ND Yes (NS)

No U U U U ND ND Yes No U ND ND ND ND U ND U U U U No ND U U ND No ND U ND ND

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Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Secobarbital Selegiline Sermorelin Sertindole Sertraline Sevelamer Sibutramine Sildenafil Silver Simethicone Simvastatin Sirolimus Sisomicin Sitagliptin Sitaxsentan sodium Sodium diatrizoate Sodium oxybate Sodium polystyrene sulfonate Solifenacin Somatropin Sorafenib Sotalol Sparfloxacin Spectinomycin Spiramycin Spirapril (spiraprilat) Spironolactone Stanozolol Stavudine

No (NS) ND ND No (NS) No (NS) U U U No (NS) U U U Yes (NS) No (NS) U L ND U U No (NS) U Yes (NS) ND Yes (NS) ND U U ND Yes (NS)

ND ND ND ND ND U ND No (65) ND U ND U L ND U Yes (NS) ND U U U U L ND L ND ND ND ND Yes (NS)

No ND ND ND U U U U U U U U ND ND U ND ND U U U U ND ND Yes ND U U ND ND
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2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Streptokinase Streptomycin Streptozocin Sucralfate Sufentanil Sulbactam Sulfadiazine Sulfamethoxazole Sulfapyridine Sulfasalazine Sulfinpyrazone Sulfisoxazole Sulindac Sumatriptan Sunitinib Tacrine Tacrolimus Tadalafil Tamoxifen Tamsulosin Tazobactam Tegafur Tegaserod Teicoplanin Telavancin Telithromycin Telmisartan Temazepam Temocillin Temozolomide
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U Yes (NS) ND No (NS) U Yes (NS) ND Yes (NS) ND U No (NS) Yes (NS) No (NS) ND U ND No (NS) No (NS) ND U Yes (NS) Yes (NS) No (NS) No (NS) ND ND No (NS) No (NS) Yes (NS) ND

U L ND ND ND L ND L ND U ND L ND ND U ND ND U ND ND L L ND ND L ND ND ND L ND

U Yes ND No U No ND No ND U ND Yes U ND U ND U U ND U No ND ND No U ND U U No ND

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Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Temsirolimus Tenecteplase Teniposide Tenofovir Terazosin Terbinafine Terbutaline Teriparatide Testosterone Tetrabenazine Tetracycline Thalidomide Theophylline Thiabendazole Thiamazole Thiamine Thiethylperazine Thioguanine Thioproperazine Thioridazine Thiotepa Thiothixene Thrombin alfa Thyrotropin alfa Tiagabine Tiaprofenic acid Ticarcillin Ticlopidine Tigecycline Tiludronate

ND U U ND No (NS) U ND ND No (NS) ND No (NS) U Yes (NS) ND No (NS) No (NS) ND ND ND U ND U U U No (NS) U Yes (NS) U No (NS) U

ND U ND Yes (50) ND U ND ND ND ND ND No (65) L ND ND ND ND ND ND ND ND ND U U ND U L ND ND ND

ND U U ND No U ND ND U ND No U No ND No U ND ND ND U ND U U U ND U No U U U
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2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Timolol Tinidazole Tinzaparin Tirofiban Tizanidine Tobramycin Tocainide Tocilizumab Tocopherol Tolazamide Tolbutamide Tolcapone Tolmetin Tolterodine Topiramate Topotecan Torsemide Tositumomab Trabectedin Tramadol Trandolapril (trandolaprilat) Tranexamic acid Tranylcypromine Trapidil Trastuzumab Trazodone Treprostinil Tretinoin Triamterene
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No (NS) Yes (NS) U Yes (NS) ND Yes (NS) Yes (NS) ND ND U No (NS) U U U Yes (NS) Yes (8.0) No (NS) U ND No (NS) Yes (NS) ND ND ND U U U ND ND

ND L ND L ND L L ND ND ND ND U ND U L L U U ND Yes (50) L ND ND ND U ND U ND ND

No ND ND ND ND Yes ND ND ND U U U U U ND ND U U ND ND ND ND ND ND U U U ND ND

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Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Triazolam Trifluoperazine Triflupromazine Trihexyphenidyl Trimebutine Trimeprazine Trimethoprim Trimetrexate Trimipramine Triprolidine Triptorelin Tropisetron Trospium Ulipristal acetate Urofollitropin Ursodiol Ustekinumab Valacyclovir Valganciclovir Valproic acid Valrubicin Valsartan Vancomycin Vardenafil Varenicline Vecuronium Velaglucerase Venlafaxine Verapamil Verteporfin

No (NS) No (NS) U ND ND ND Yes (NS) U U ND ND U ND ND ND U ND Yes (NS) Yes (NS) No (NS) ND No (NS) No (NS) ND Yes (NS) U U No (NS) No (NS) ND

ND ND ND ND ND ND L ND ND ND ND ND ND ND ND U ND L ND Yes (62) ND ND Yes (10.1-60) ND ND ND U ND ND ND

U No U ND ND ND No U U ND ND U ND ND ND U ND No ND No ND U No ND ND U U U No ND
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2011 Dialysis of Drugs

Drug

HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

Vigabatrin Vildagliptin Vinblastine Vincristine Vinorelbine Voriconazole Vorinostat Warfarin Zafirlukast Zalcitabine Zaleplon Zanamivir Zidovudine/GZDV Zileuton Zinc Ziprasidone Zoledronic acid Zolmitriptan Zolpidem Zopiclone

Yes (NS) ND ND ND ND No (NS) ND No (NS) U ND ND ND No (NS)/ Yes (NS) U ND No (NS) ND ND No (NS) No (NS)

L ND ND ND ND No (NS) ND ND ND ND ND ND ND/L No (8.3, 10.1) ND U ND ND ND ND

ND ND ND ND ND No ND No U ND ND ND No/Yes U ND U ND ND U U

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Drugs of Abuse
HEMODIALYSIS Conventional High Permeability Peritoneal (KUf) (KUf) Dialysis

I CHART

Drug

Amphetamine Cocaine Ethanol Heroin Lysergide (LSD) Marijuana (THC) MDMA (Ecstasy) Mescaline (peyote) Nicotine Phencyclidine (PCP) Psilocybin

ND No (NS) Yes (NS) U U U ND U ND U ND

ND ND L ND ND ND ND ND ND ND ND

ND U ND U U U ND U No U ND

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2011 Dialysis of Drugs

Extracorporeal Therapies for Treatment of Drug Overdose
Drug elimination by extracorporeal therapies (ECT) is an area of growing interest in acute overdose. Use of these techniques may provide excellent drug clearance as compared to endogenous clearance, even in patients with intact kidney function. Although ECT can readily remove the agent responsible for toxicity, there still a lack of solid data showing improved outcomes of ECT over regular supportive measures (such as hydration and gut decontamination). Benefits of ECT should be weighed against potential risks of the procedure, pharmacokinetics of the drug, time to initiate therapy, and valuable alternatives to ECT. Absolute prerequisite indications to ECT are the following: • The drug must be toxic • The drug must have properties amenable to ECT removal (e.g. low protein binding) • The overdose must be severe as suggested by serum biochemistry (toxic serum concentrations), exposure (dose ingested) or clinical status (coma, cardiovascular compromise or hypoventilation). Furthermore, ECT can also be considered if the patient’s condition deteriorates despite maximal supportive therapy, if there is no alternative effective treatment (antidotes), or if the patient has inadequate endogenous elimination mechanisms (hepatic or renal failure).

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Drug elimination by ECT is dependent upon several parameters (described starting on page 3), with some notable differences in poisoning situations: Drugs with a high Vd are usually not cleared significantly by ECT but, in acute overdose, recently absorbed drug may not be fully distributed in tissues, hence mostly confined to plasma i.e. the actual Vd is lower than expected. Furthermore, although high protein binding usually limits extracorporeal removal, in overdose, high drug concentration can saturate binding sites, permitting clearance of unbound drug by hemodialysis or other techniques. Hemodialysis is by far the most widely available ECT modality and can be organized quickly by the physician while entailing few risks. In addition to drug removal, hemodialysis has the added advantage of correcting associated metabolic abnormalities (acid-base and electrolytes), which are common in drug overdose. Generally, high-flux dialyzers are preferred in cases of poisonings because they can improve clearances of some toxins better than standard dialysis membranes. Veno-venous access is usually provided by dual-lumen catheters inserted in the internal jugular, subclavicular or femoral vein. The former two sites require X-ray confirmation of the catheter placement (hence delay), while use of the latter is associated with higher blood recirculation (loss of efficiency). Dialysate and blood flow rates should be maximized whenever possible. Volume removal
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I DRUG OVERDOSE

2011 Dialysis of Drugs

(or ultrafiltration) is rarely necessary because poisoned patients are generally hypovolemic and subject to hypotension, unless there is pulmonary edema or oliguric renal failure. Since intoxicated patients have different metabolic parameters compared to chronic kidney disease patients, notably hyperkalemia, hyperphosphatemia, and acidosis, the dialysate bath must be prescribed with care. In methanol overdoses, it is even possible to add ethanol to the dialysate. The extracorporeal circuit is fully anticoagulated in order to maximize efficiency unless the patient is at major risk for bleeding. In such a case, tight heparinization or saline flushes are practical alternatives. Duration of the dialysis session will depend on desired clinical or biochemical surrogates, but is at least 4-6 hours in most cases. Drugs that have a large Vd can be redistributed after hemodialysis, producing a rebound effect, often requiring another session for further removal. Hemofiltration uses convection compared to diffusion for hemodialysis. This technique is usually provided as a continuous veno-venous procedure, and has the particular advantage of removing larger molecules (up to 50,000 Da) and offering continuous drug removal while being better tolerated than conventional dialysis. The continuous nature of hemofiltration reduces the likelihood of drug rebound. Unfortunately, hourly clearance is significantly inferior to high-flux dialysis. Therefore, hemofiltration is usually reserved for use in
64 SEE DISCLAIMER REGARDING USE OF THIS GUIDE

situations when hemodialysis is contraindicated or unavailable. Hemoperfusion, a process by which drugs are adsorbed through a charcoal membrane, offers excellent drug clearance, especially for protein bound toxins. Unfortunately, hemoperfusion is seldom available, entails more complications (thrombocytopenia), is more costly and necessitates regular replacement of the charcoal cartridges. There is also anecdotal evidence supporting the use of plasmapheresis or molecular absorbent recirculating systems for acute overdose, but these methods are costly and have yet to show marked improvement over conventional hemodialysis. Peritoneal dialysis does not provide sufficient drug clearances to be considered for poisoning situations. Drugs or other substances for which ECT can be life-saving in intoxications include ethylene glycol, isopropranol, lithium, methanol, salicylates, valproic acid and theophylline. Drugs or other toxins for which ECT may be considered include aminoglycosides, carbamazepine, chloral hydrate, heavy metals (in association with chelation therapy), metformin, methotrexate, paraquat, phenobarbital, phenytoin, and vancomycin.

I DRUG OVERDOSE

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65

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2011 Dialysis of Drugs

USE OF ECT FOR SELECTED COMMON OVERDOSES When to terminate dialysis -Serum concentration <2 mmol/L

Drug Salicylates

Indications to initiate dialysis -Serum concentration >5 mmol/L regardless of symptoms -Serum concentration >2.2 mmol/L in chronic poisoning -Presence of hypotension, significant metabolic acidosis after rehydration, pulmonary edema, renal failure, CNS features, e.g. hallucinations, stupor, como Ethylene -EG serum concentration >8 mmol/L glycol (EG) -Methanol serum concentration >15mmol/L and methanol -Presence of renal failure, rapid clinical deterioration, refractory acidosis, visual signs (in methanol toxicity) Lithium -Presence of massive ingestion, severe neurological toxicity (seizures, coma), renal failure -Serum concentration >4.0 mEq/L in acute poisoning (Serum concentrations do not correlate well with toxicity in chronic poisoning.) Theophylline -Serum concentration >500 µmol/L in acute poisoning -Serum concentration >300 µmoI/L in chronic poisoning -Refractory arrhythmias or convulsions, patients who do not tolerate activated charcoal -Serum concentration >200 µmol/L in chronic poisoning if patient over 60 years old or pre-existing lung, cardiac, or hepatic disease Valproic Acid -Serum concentration >5500 µmol/L in acute poisoning -Presence of coma or hemodynamic instability -Serum concentration <1000 µmol/L

-EG serum concentration <3 mmol/L -Methanol serum concentration <6 mmol/L -Resolution of the acidosis -Serum concentration <1mEq/L (Hemodialysis may need to be repeated because of rebound.) -Until symptoms disappear or serum concentration <200 µmol/L

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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 hemofiltration or hemodiafiltration 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 influences 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 replace-ment 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.
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I REFERENCES

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REFERENCES FOR TREATMENT OF POISONING
1. Ghannoum M, Leblanc M. Clinical Toxicology. Chapter 18, p. 267-282. Intensive Care in Nephrology, Murray PT, Brady H, Hall JB (eds). 2006. Martin Dunitz/Taylor & Francis, London, UK. 2. Garella S, Lorch JA. Hemodialysis and hemoperfusion for poisoning. American Kidney Foundation Nephrology Letter 1993;10:1-19.

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