The Dialysis of Drugs 2011

2011Dialysis of Drugs

George R. Bailie, PharmD, PhDAlbany College of Pharmacy and Health Sciences

Nancy A. Mason, PharmDUniversity of Michigan College of Pharmacy

Renal Pharmacy Consultants, LLCSaline, Michigan USA

The sections on continuous renal replacementtherapy and extracorporeal therapies fortreatment of drug overdose were written by:

Marc Ghannoum, MDDepartment of Nephrology Verdun HospitalUniversity of Montreal

2011 Dialysis of Drugs

2 SEE DISCLAIMER REGARDING USE OF THIS GUIDE

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 identifi ed 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 specifi c 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 This material may not be published, rewritten or redistributed.

SEE DISCLAIMER REGARDING USE OF THIS GUIDE 3

I FOREWORD

ForewordDialysis 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 fi rst 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 confi dent that Dialysis of Drugs will continue to be a valuable resource in the future.Curtis A. Johnson, PharmDDecember 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.



PrefaceDrug 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 effi cacy 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 briefl y 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.


I PREFACE

Molecular WeightDialysis is dependent upon the use of a dialytic membrane: either a synthetic membrane with fi 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 BindingAnother 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.



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 effl uent during episodes of peritonitis.

Volume of DistributionA 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 SolubilityThe 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 ClearanceThe inherent metabolic clearance—the sum of renal and nonrenal clearance—is often termed


I PREFACE

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 MembraneAs 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 RatesThe hemodialysis prescription includes the desired blood and dialysate fl ow rates. As drugs normally move from blood to dialysate, the fl ow rates of these two substances may have a pronounced effect on dialyzability. In general, increased blood fl ow rates during hemodialysis will deliver greater amounts of drug to the dialysis membrane. As the drug concentration increases in the dialysate, the fl ow rate of the dialysis solution also becomes important in



overall drug removal. Greater dialysis can be achieved with faster dialysate fl ow rates that keep the dialysate drug concentration at a minimum.

During peritoneal dialysis, little can be done to alter blood fl ow rates to the peritoneum. However, dialysate fl ow 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 ConsiderationsHIGH 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 fl ow rates. These technologies are often referred to as “high permeability,” “high-effi ciency,” and “high-fl ux” dialysis. The United States Food and Drug Administration has classifi ed high permeability dialysis membranes as those whose in vitro ultrafi ltration coeffi cient (KUf) is greater than 8 mL/hour/mm Hg.


I SPECIAL CONSIDERATION

S

Commonly included in this group of dialysis membranes are polysulfone, polyacrylonitrile, and high-effi ciency cuprammonium rayon dialyzers. Changes in dialysis membranes and changes in blood and dialysis fl 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 confi rm 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



(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 (ultrafi ltrate) via positive hydrostatic pressure. Continuous venovenous hemodialysis (CVVHD) is the major diffusive technique, while continuous venovenous hemofi ltration (CVVH) or slow continuous ultrafi ltration (SCUF) are convection-based. Continuous venovenous hemodiafi ltration (CVVHDF) has the advantage of combining both principles. Veno-venous procedures have largely replaced arterio-venous procedures by providing higher ultrafi ltration (UF) rates with decreased complications.

As for ICD, many factors contribute to drug clearance in CRRT.

Effl uent fl ow: Effl uent fl ow rate is determined by the sum of both ultrafi ltration (UF) and dialysate fl ow 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 effl uent 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 fl uconazole.



S

Post-dilution vs pre-dilution: If hemofi ltration is performed in post-dilution, the replacement fl uid is administered distal to the fi lter whereas it is administered before the fi lter in pre-dilution. 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 fi lter and can therefore be used for high UF. Newer machines can incorporate both functions, rendering drug clearance estimation more complex.

Blood fl ow: As opposed to ICD, blood fl ow has little impact on drug clearance in CRRT. There is no signifi cant increase in urea clearance when blood fl ow is increased from 100 mL/min to 250 mL/min. However, blood-fl ow dependent clearance may be observed at high effl uent fl ow rates.

Filters: Filters have various physical characteristics that provide different advantages when compared to one another. In general, newer hemofi lters have larger surface areas and higher convective permeability. Adsorption of certain drugs, like aminoglycosides and levofl oxacin, may occur with polyacrylonitrile (PAN) membranes while other drug-membrane interactions, such as the charge of the fi lter material, will also further infl uence clearance. Finally, hemofi lter drug permeability is at its highest right after installation; as the fi lter ages, clotting and blood components coating the fi lter’s surface reduce solute removal. These factors are diffi cult to quantify and predict clinically.



Drug molecular weight: Although molecular weight is an important limiting determinant of drug dialyzability in ICD, it becomes less signifi cant during CRRT because of the use of high-fl ux hemofi lters 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 signifi cant removal during CRRT because the drug-protein complex surpasses pore size of the fi lter. 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 coeffi cient, defi ned as the ratio of drug concentration in the ultrafi ltrate to the pre-fi lter 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 confi ned 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 signifi cant. 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 re-equilibration process provides a continuous drug pool that can be readily cleared by CRRT.



S

Competing elimination pathways: Extracorporeal clearance of any drug must be weighed against its endogenous clearance in order to predict effi ciency 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 signifi cant (not unusual on initiation of CRRT) it becomes important, albeit diffi cult, 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 signifi cantly 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 modifi cation). Considering all the numerous factors infl uencing 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 fl ow and sieving coeffi cient are rarely constant during treatment). The following simpler equation offers an acceptable estimation of the required dose:



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 studiesUnfortunately, 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 methodTotal 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.



S

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 effl uent rate is 25 mL/min, CRRT clearance can be estimated by:

Equation 2) ClCRRT=FREC25*Clanuric/(1-FREC25)

(FREC25 and Clanuric may be taken from the table)

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

Acyclovir 15% 0.7 40 20%

Amantadine 67% 4.5 10 65%

Amikacin 5% 0.3 4 90%

Amiodarone 99% 66 130 0%Amphotericin B liposomal 95% 4 20 2%

Ampicillin 19% 0.3 35 35%

Amrinone 40% 1.3 200 6%

Atracurium 82% 0.2 400 4%

Aztreonam 60% 0.3 30 25%

Bretylium 1% 5.9 163 10%

Caspofungin 97% 4.6 ND 0%




Captopril 30% 0.8 500 8%

Cefazolin 87% 0.2 13 15%

Cefepime 10% 0.7 15 42%

Cefotaxime 36% 0.3 70 12%

Cefoxitin 50% 0.3 20 10%

Ceftazidime 21% 0.3 15 48%

Ceftriaxone 80% 0.2 10 30%

Cefuroxime 37% 0.2 10 80%

Chloramphenicol 53% 0.9 150 6%

Chloroquine 55% 150 400 2%

Cilastin 35% 0.2 3 80%

Ciprofl oxacin 35% 1.5 200 9%

Cisplatin 95% 0.5 2 48%

Clindamycin 85% 1 200 4%

Clonidine 20% 2.1 170 5%

Colistin 55% 0.3 38 20%

Cyclophosphamide 60% 0.8 120 11%

Cyclosporine 97% 5 400 0%

Daptomycin 8% 0.5 7 23%

Digoxin 25% 6 45 20%

Diltiazem 78% 3 820 0%

Disopyramide 50% 0.6 38 30%

Dobutamine 0% 0.3 4000 0%

Dopamine 0% 0.3 4000 0%

Doripenem 9% 0.2 2 23%

Doxorubicin 85% 22 113 8%

Doxycycline 95% 0.8 50 12%

Enalapril 35% 1.7 41 10%



S


Enoxacin 40% 1.6 200 5%

Erythromycin 84% 0.8 100 3%

Esmolol 55% 1.9 12000 0%

Ethambutol 25% 1.6 120 10%

Famotidine 20% 1.1 35 25%

Fentanyl 80% 4 837 0%

Flecainide 60% 4.9 222 4%

Fluconazole 12% 0.7 7 75%

Flucytosine 5% 0.7 2 95%

Furosemide 95% 0.2 54 2%

Gancyclovir 2% 0.6 20 50%

Gentamicin 2% 0.3 5 82%

Hydralazine 87% 1.5 500 1%

Imipenem 15% 0.3 100 20%

Isoniazid 17% 0.8 75 18%

Itraconazole 99% 11 400 0%

Ketamine 30% 2 90 10%

Ketoconazole 99% 2.4 580 0%

Labetolol 50% 9.4 1700 1%

Levofl oxacin 31% 1.2 22 42%

Lidocaine 70% 1.1 630 1%

Linezolid 25% 0.7 40 32%

Lisinopril 2% 1.5 1 100%

Lorazepam 90% 1 85 2%

Melphalan 90% 0.6 250 1%

Meropenem 2% 0.4 35 30%

Methotrexate 50% 0.8 9 52%

Metoprolol 11% 4.2 950 2%




Metronidazole 15% 0.8 70 25%

Micafungin 99% 0.2 22 7%

Midazolam 95% 1.1 120 5%

Milrinone 85% 0.3 80 8%

Morphine 30% 3.5 1200 7%

Moxifl oxacin 40% 2.2 200 7%

Nifedipine 96% 0.8 500 0%

Nitroglycerin 0% 3.3 16100 0%

Norepinephrine 0% 0.3 900 2%

Ofl oxacin 15% 2 33 35%

Omeprazole 95% 0.4 620 0%

Oxacillin 95% 0.2 50 3%

Phenobarbital 50% 0.5 6 65%

Phenytoin 90% 0.7 20 10%

Piperacillin 20% 0.2 40 20%

Prednisolone 60% 2 66 10%

Procainamide 16% 1.9 107 8%

Propafenone 96% 3 1100 0%

Propofol 96% 20 1000 0%

Propranolol 87% 4.3 1120 0%

Quinine 90% 1.8 16 1%

Ranitidine 15% 1.3 226 10%

Rifampin 89% 1 200 2%

Streptomycin 35% 0.3 2 85%

Sulfamethoxazole 62% 0.2 20 27%

Tacrolimus 99% 1.5 45 5%

Tazobactam 20% 0.3 20 42%

Teicoplanin 90% 0.7 2 27%



S


Tetracycline 70% 1 15 50%

Theophylline 50% 0.5 40 20%

Ticarcillin 58% 0.2 11 44%

Tobramycin 2% 0.3 4 82%

Trimethoprim 42% 1.7 50 16%

Vancomycin 30% 0.5 5 55%

Verapamil 90% 5 1020 2%

Voriconazole 55% 5 200 6%

Zidovudine 10% 1.4 1490 0%

PB=Protein bindingVd=Volume of distributionCLanuric=Endogenous drug clearance in anuric patientsFREC25= Fractional extracorporeal clearance at

effl uent 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 specifi c 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 from these studies should be applied with caution to other dialysis conditions.

About This GuideThese 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 newly-approved 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 confl ict. Conditions of dialysis used in published studies may not necessarily refl ect current dialysis procedures and technology. Variations in the duration of dialysis, fl ow 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 high-


I ABOUT THIS GUIDE

fl ux) 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 specifi c 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 confi rmed 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 fl ow rates or in the presence of peritonitis.



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 signifi cant 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 signifi cant 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-fl ux, dialysis membrane, however the type of membrane is not specifi ed. A designation of “NS” indicates membrane type is not specifi ed.


I ABOUT THIS GUIDE

KeyYes 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 signifi cant 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 signifi cant 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 specifi ed* Removed with haemoperfusion

Note: In these tables, conventional hemodialysis is defi ned as the use of a dialysis membrane whose in vitro coeffi cient of ultrafi ltration (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 defi ned 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.



HEMODIALYSIS Drug

Conventional(KUf)

High Permeability(KUf)

PeritonealDialysis

Abacavir U No (40) NDAbatacept U U UAbciximab U ND UAcamprosate ND ND NDAcarbose ND ND NDAcebutolol (diacetolol) Yes (NS) L NDAcenocoumarol U U UAcetaminophen Yes (NS) L NoAcetazolamide U ND NoAcetohexamide U ND UAcetophenazine U ND UAcetylcysteine Yes (7.5) ND NDAcitretin No (NS) U UAcyclovir Yes (NS) L NoAdalimumab U U UAdefovir Yes (NS) ND NDAdenosine U ND UAdipiodone ND ND NDAgalsidase alfa No (7.5) No (10) UAgalsidase beta U U UAlbendazole No (NS) ND UAlbumin U ND UAlcaftadine ND ND NDAldesleukin ND ND NDAlefacept ND ND NDAlemtuzumab U U UAlendronate No (NS) ND NDAliskiren ND ND NDAlfacalcidol ND ND NDAlfentanil U ND U


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Alfuzosin U U UAlitretanoin ND ND NDAllopurinol Yes (NS) L NDAlprazolam No (NS) ND UAlprostadil U No (11.1) NDAlteplase U ND UAltretamine ND ND NDAmantadine No (NS) ND NoAmbrisentan U U UAmdinocillin No (NS) ND NoAmifostine ND ND NDAmikacin Yes (NS) L YesAmiloride ND ND NDAminocaproic acid Yes (NS) ND YesAminoglutethimide Yes (NS) L NDAminosalicylic acid Yes (NS) L NDAmiodarone No (NS) ND NoAmitriptyline No (NS) ND NoAmlexanox ND ND NDAmlodipine No (NS) U NoAmoxapine U ND UAmoxicillin Yes (NS) L NoAmphetamine ND ND NDAmphotericin B No (NS) No (10.1, 36) NoAmphotericin B lipid complex No (NS) ND U

Ampicillin Yes (NS) L NoAmprenavir U ND UAmrinone U ND NoAmsacrine U U U



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Anagrelide ND ND NDAnakinra No (NS) ND NoAnastrozole ND ND NDAncestim ND ND NDAncrod ND ND NDAnidulafungin No (NS) U UAnisoylated plasminogen streptokinase activator complex

ND ND ND

Anistreplase U ND UAntithymocyte globulin (ATG) U ND U

Aprepitant No (NS) U UAprotinin U ND UArbutamine ND ND NDArgatroban U No (10.7-36) NDAripiprazole U U UArticaine ND ND NDAscorbic acid Yes (5.5) Yes (8.8) YesAsenapine U U UAsparaginase U ND UAspirin Yes (NS) L YesAtazanavir U U UAtenolol Yes (NS) L NoAtomoxetine U U UAtorvastatin No (NS) ND UAtovaquone U ND UAtracurium U ND UAtropine No (NS) ND NDAuranofi n No (NS) ND ND


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Azacitidine ND ND NDAzathioprine Yes (NS) L NDAzithromycin ND ND NoAzlocillin Yes (NS) L NoAztreonam Yes (NS) L NoBacampicillin Yes (NS) L NoBaclofen ND Yes (60) NDBasiliximab U ND UBenazepril (benazeprilat) No (NS) ND ND

Bendrofl umethiazide No (NS) ND UBenzquinamide U ND NDBenztropine ND ND NDBepotastine besylate ND ND NDBepridil No (NS) ND UBeractant U U UBesifl oxacin ND ND NDBetahistine ND ND NDBetaine ND ND NDBetamethasone ND ND NDBetaxolol No (NS) ND NoBethanechol ND ND NDBevacizumab U No (NS) UBezafi brate No (NS) ND NoBiapenem Yes (NS) Yes (NS) NDBicalutamide U ND UBiperiden ND ND NDBisoprolol No (NS) ND NDBivalirudin Yes (NS) ND NDBleomycin No (NS) ND No



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Bortezomib ND ND NDBosentan U No (11.1) UBretylium Yes (NS) L NDBromazepam ND ND NDBromfenac No (NS) ND UBromocriptine U ND UBudesonide U U UBufl omedil No (NS) No (20) UBumetanide U U UBupivacaine U U UBuprenorphine U U UBupropion No (NS) No (10) NoBuserelin ND ND NDBuspirone No (NS) ND NDBusulfan Yes (NS) Yes (8.1) NDButalbital ND ND NDButorphanol U ND UCabazitaxel U U UCabergoline ND ND NDCaffeine ND ND NDCalcitonin U U UCalcitriol No (4.2-5.3) No (31) UCalcium polystyrene sulfonate U U U

Canakinumab U U UCandesartan No (NS) No (8.1) NDCapecitabine ND ND NDCapreomycin Yes (NS) L NDCaptopril Yes (NS) L NoCarbamazepine No (NS) Yes (22, 55) No


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Carbenicillin Yes (NS) L NoCarbidopa/levodopa ND/U ND/U ND/UCarboplatin Yes (NS) L NoCarboprost ND ND NDCarglumic acid ND ND NDCarisoprodol Yes (NS) L YesCarmustine No (NS) ND NDCarprofen U ND UCarteolol ND ND NDCarumonam Yes (NS) L NDCarvedilol No (NS) ND NDCaspofungin No (NS) U UCefaclor Yes (NS) L YesCefadroxil Yes (NS) L NoCefamandole Yes (NS) L NoCefazolin Yes (6, 8) Yes (8.1-36) NoCefdinir ND Yes (NS) NDCefepime Yes (NS) Yes (40) YesCefi xime No (NS) ND NoCefmenoxime Yes (NS) L NDCefmetazole Yes (NS) L NoCefodizime No (NS) ND NoCefonicid No (NS) ND NoCeforanide Yes (NS) L NoCefotaxime Yes (NS) L NoCefoxitin Yes (NS) L NoCefpirome Yes (NS) Yes (40) NoCefpodoxime Yes (NS) L NoCefprozil Yes (NS) L NDCefradine Yes (NS) L Yes



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Cefroxadine ND ND NDCefsulodin Yes (NS) L YesCeftazidime Yes (NS) L YesCeftibuten Yes (NS) L NDCeftizoxime Yes (NS) L NoCeftobiprole ND ND NDCeftriaxone No (NS) ND NoCefuroxime Yes (NS) L NoCelecoxib U ND UCephalexin Yes (NS) L NoCephalothin Yes (NS) L NoCephapirin Yes (NS) L NoCertolizumab U U UCetirizine U No (18.7-66.7) UCetuximab U U UChloral hydrate Yes (5.5) L NDChlorambucil No (NS) ND NoChloramphenicol Yes (NS) L NoChlordiazepoxide No (NS) ND UChlormethine U U UChloroprocaine ND ND NDChloroquine No (NS) ND NoChlorpheniramine Yes (NS) L NoChlorpromazine No (NS) ND NoChlorpropamide No* (NS) ND NoChlorprothixene U ND UChlorthalidone No (NS) ND UChlorzoxazone ND ND NDCholestyramine U U UChoriogonadotropin U U U


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Cidofovir ND Yes (60) NoCilastatin Yes (NS) L NDCilazapril Yes (NS) L NDCilostazol U ND UCimetidine No (NS) ND NoCinacalcet No (NS) U NoCinoxacin No (NS) ND UCiprofl oxacin No (NS) ND NoCisatracurium U ND UCisplatin No (NS) Yes (NS) NoCitalopram No (8) No (40) UCladribine ND ND NDClarithromycin ND ND NDClavulanic acid Yes (NS) L YesClemastine ND ND NDClindamycin No (NS) ND NoClobazam No (4.2) ND NDClodronate ND Yes (8.1) NoClofarabine ND ND NDClofazimine No (NS) ND NoClofi brate No (NS) ND NoClomiphene ND ND NDClomipramine U ND UClonazepam No (NS) ND UClonidine No (NS) ND NoClopidogrel U ND UClorazepate No (NS) ND UClotrimazole U U UCloxacillin No (NS) ND NoClozapine No (NS) ND U



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Codeine/metabolites (morphine-3 and morphine-6 glucuronides, codeine-6 glucuronide)

No/Y (NS) ND U

Colchicine No (NS) ND NoColestipol U U UColistin No (NS) ND NoCollagenase Clostridium histolyticum

U U U

Cortisone No (NS) ND NoCromolyn sodium U U UCyanocobalamin No (NS) No (40, 65) NDCyclacillin Yes (NS) L NoCyclobenzaprine U U UCyclophosphamide Yes (6.4) L NDCycloserine ND Yes (30, 52) NDCyclosporine No (NS) ND NoCyproheptadine ND ND NDCyproterone ND ND NDCystadane ND ND NDCysteamine ND ND NoCytarabine ND Yes (NS) NoDabigatran Y (NS) L NDDacarbazine ND ND NDDaclizumab U ND UDactinomycin ND ND NDDalfampridine ND L NDDalteparin U ND NoDanaparoid ND ND ND


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Danazol ND ND NDDantrolene ND ND NDDapsone Yes (NS) L NDDaptomycin No (11) Yes (62) NoDarbepoetin alfa U No (11.1-55) NoDarifenacin U U UDarunavir Yes (NS) L UDasatinib U U UDaunorubicin ND ND NDDeferasirox U U UDeferoxamine Yes (NS) L NDDefl azacort No (NS) ND UDegarelix U U UDelavirdine U ND UDemeclocycline ND ND NDDenosumab U U UDesipramine No (NS) ND NoDesloratadine No (NS) ND NoDesmopressin ND ND NDDesogestrel U U UDesvenlafaxine No (NS) U UDexamethasone No (NS) ND NoDexfenfl uramine ND ND NDDexlansoprazole U U UDexmedetomidine U U UDexmethylphenidate ND ND NDDexrazoxane ND ND NDDextroamphetamine ND ND NDDextropropoxyphene No (NS) ND NoDezocine ND ND ND



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Diazepam No (NS) ND UDiazoxide Yes (NS) L YesDibekacin Yes (NS) L NDDiclofenac U ND UDicloxacillin No (NS) ND NoDicyclomine ND ND NDDicycloverine ND ND NDDidanosine No (7.9) No (40) NoDiethylpropion ND ND NDDiethylstilbesterol (fosfestrol) No (NS) ND ND

Difl unisal No (NS) ND UDigitoxin No (NS) ND NoDigoxin No (NS) ND NoDigoxin immune Fab No (NS) U NoDihydroergotamine ND ND NDDiltiazem No (NS) ND NoDimenhydrinate ND ND NDDinoprostone ND ND NDDiphenhydramine U ND UDiphenoxylate/Atropine ND ND ND

Dipyridamole U ND NDDirithromycin No (NS) ND NoDisodium etidronate ND ND NDDisopyramide No (NS) U UDisulfi ram U U UDivalproex No (NS) ND NoDobutamine No (NS) ND NoDocetaxel No (NS) U U


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Dolasetron ND ND NDDomperidone U U UDonepezil U ND UDopamine No (NS) ND UDoripenem Yes (NS) ND NDDoxacurium No (NS) ND UDoxapram ND ND NDDoxazosin No (NS) ND NoDoxepin No (NS) ND NoDoxercalciferol No (NS) U UDoxorubicin No (NS) ND NDDoxorubicin, pegylated liposomal ND ND ND

Doxycycline No (NS) ND NoDoxylamine ND ND NDDronabinol U ND UDronedarone HCl U U UDroperidol U ND UDrospirenone U U UDrotrecogin alfa U U UDuloxetine U U UDutasteride U U UEcallantide ND ND NDEculizumab U U UEdetate calcium (ETDA) Yes (NS) L Yes

Edrophonium ND ND NDEfalizumab U U UEfavirenz No (NS) ND NoEletriptan ND ND ND



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Emtricitabine Yes (NS) ND NDEnalapril (enalaprilat) Yes (NS) L YesEncainide No (NS) ND NDEnfuvirtide No (NS) U UEnoxacin No (NS) ND NoEnoxaparin No (NS) Yes (11.5-55) NoEntacapone U U UEntecavir No (NS) ND NoEphedrine ND ND NDEpinephrine ND ND NDEpirubicin ND ND NDEplerenone No (7) ND NDEpoetin alfa No (NS) No (11.1-55) NoEpoprostenol ND ND NDEprosartan U No (60) UEptacog alfa U U UEptifi batide ND ND NDErgocalciferol ND ND NDErgotamine ND ND NDErlotinib U No (NS) UErtapenem Yes (NS) L NDErythromycin No (NS) ND NoEscitalopram ND ND NDEsmolol (ASL-8123) Yes (NS) L YesEsomeprazole U U UEstazolam U ND UEstradiol No (NS) ND NDEstramustine ND ND NDEstropipate ND ND NDEtanercept No (NS) U U


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Ethacrynic acid No (NS) U UEthambutol No (NS) No (80) UEthchlorvynol No* (NS) ND NoEthinyl estradiol U U NoEthopropazine ND ND NDEthosuximide Yes (NS) L NDEthynodiol diacetate ND ND NDEtodolac No (NS) ND UEtoposide No (NS) No (NS) NoEtravirine No (NS) U UEverolimus ND ND NDExemestane U U UEzetimibe U U UFamciclovir (penciclovir) Yes (NS) L ND

Famotidine No (NS) ND NoFelbamate ND ND NDFelodipine No (NS) ND UFenfl uramine ND ND NDFenofi brate No (NS) U UFenoldopam U ND NoFenoprofen No (NS) ND UFenoterol ND ND NDFentanyl U No (10.1) NDFerric gluconate No (NS) ND UFerrous (iron) salts U ND UFerumoxytol No (NS) ND NDFexofenadine No (NS) ND UFilgrastim No (NS) ND UFinasteride U ND U



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Flavoxate ND ND NDFlecainide No (NS) ND UFleroxacin U No (8.1, 22) NoFloctafenine ND ND NDFloxuridine ND ND NDFluconazole Yes (NS) L YesFlucytosine Yes (NS) L YesFludarabine ND ND NDFludrocortisone ND ND NDFlumazenil ND ND NDFluorouracil/FBAL No (NS)/ND Yes (71)/Yes (40) NDFluoxetine No (NS) ND NoFluoxymesterone ND ND NDFlupentixol decanoate ND ND NDFluphenazine U ND UFlurazepam No (NS) ND UFlurbiprofen ND ND NoFlutamide No (NS) ND UFluticasone U U UFluvastatin No (NS) ND UFluvoxamine U No (NS) UFolic acid Yes (NS) L NDFollitropin alfa ND ND NDFollitropin beta ND ND NDFomepizole Yes (NS) L NDFondaparinux No (NS) ND UFosaprepitant No (NS) U UFoscarnet Yes (4.1) Yes (18-60) NDFosfomycin Yes (NS) L NDFosinopril (fosinoprilat) No (NS) ND No


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Fosphenytoin U ND UFrovatriptan ND ND NDFulvestrant U U UFurosemide No (NS) U UFusidic acid No (NS) ND NoGabapentin Yes (NS) L NDGadobenate ND ND NDGadobutrol Yes (5.5) L NDGadodiamide Yes (NS) L NoGadofosveset ND ND NDGadopentetate ND ND NDGadoversetamide ND Yes (NS) NDGadoxetate Yes (NS) L NDGalantamine ND ND NDGallamine ND ND NDGallium ND ND NDGallopamil U ND UGanciclovir Yes (NS) L NDGanirelix ND ND NDGatifl oxacin ND ND NDGefi tinib U No (20) UGemcitabine Yes (7) Yes (53, 58) NDGemfi brozil No (NS) ND NoGemifl oxacin No (NS) ND NDGentamicin Yes (NS) Yes (13.2, 60) YesGlatiramer ND ND NDGliclazide U U UGlimepiride U ND UGlipizide U ND UGlucagon U ND U



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Glutethimide No* (NS) ND NoGlyburide No (NS) ND UGlycopyrrolate ND ND NDGold sodium thiomalate No (NS) ND U

Golimumab U U UGoserelin ND ND NDGranisetron ND ND NDGriseofulvin ND ND NDGuaifenesin ND ND NDGuanabenz U ND NDGuanadrel ND ND NDGuanethidine ND ND NDGuanfacine No (NS) ND NoH1N1 Vaccine ND ND NDHalofantrine ND ND NDHaloperidol No (NS) ND NoHeparin No (NS) ND NoHexobarbital No (NS) ND UHirudin No (4.3-6.5) Yes (20-90) NDHuman Growth Hormone U U U

Hydralazine No (NS) ND NoHydrochlorothiazide No (NS) ND UHydrocodone ND ND NDHydrocortisone U ND UHydromorphone/hydromorphone-3-glucuronide

No/Yes (7.5) ND ND

Hydroxycarbamide No (NS) ND UHydroxychloroquine ND ND ND


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Hydroxyurea No (NS) ND UHydroxyzine No (NS) ND NoIbandronate ND Yes (8.1) NDIbritumomab U U UIbuprofen No (NS) ND UIbutilide ND ND NDIdarubicin U ND UIdebenone U U UIdursulfase U U UIfosfamide Yes (1.6) L NDImatinib No (NS) U UImiglucerase U U UImipenem Yes (NS) L YesImipramine No (NS) ND NoImmune globulin (human) U ND U

Indapamide No (NS) ND UIndinavir U No (40) NDIndomethacin No (NS) ND UInfl iximab U U UInsulin No (NS) ND NoInsulin aspart U ND UInsulin detemir No (NS) U NDInsulin glargine U ND UInsulin glulisine U ND NDInsulin lispro U ND UInterferons No (NS) Yes (20-33) NoIodixanol Yes (3.1, 4.2) L NDIohexol Yes (NS) Yes (15.5) NDIopamidol Yes (4.8) L Yes



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Iopromide Yes (5.5-6.8) Yes (8.1-62) NDIotrolan Yes (NS) L NDIoversol Yes (6.3) L NDIoxaglic acid L Yes (15.5) NDIoxilan Yes (NS) L NDIoxitalamic acid ND ND NDIrbesartan No (NS) ND NDIrinotecan (SN-38 metabolite) Yes/No (NS) No (8.5)/L ND/U

Iron dextran U No (8.1-10.1) UIron sorbitol-citric acid complex ND ND ND

Iron sucrose (saccharate) U No (10.1-55) U

Isocarboxazid ND ND NDIsoniazid No (NS) No (80) NoIsoproterenol ND ND NDIsosorbide dinitrate No (NS) ND NoIsosorbide mononitrate Yes (NS) L NoIsotretinoin U U UIsradipine No (NS) ND NoItraconazole No (NS) No (65) UKanamycin Yes (NS) L YesKetamine No (NS) ND UKetoconazole No (NS) ND NoKetoprofen U ND UKetorolac U ND UKetotifen ND ND NDLabetolol No (NS) ND NoLacosamide No (NS) ND U


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Lactulose U U ULamivudine No (NS) No (11.4) NoLamotrigine No (NS) ND ULansoprazole No (NS) ND ULanthanum carbonate No (NS) U ULapatinib U U ULaronidase U U ULefl unomide No (NS) No (8.1) NoLenalidomide Yes (NS) ND NDLepirudin No (4.3-6.2) Yes (20-90) NDLetrozole ND ND NDLeucovorin ND ND NDLeuprolide ND ND NDLeuprorelin ND ND NDLevamisole ND ND NDLevetiracetam Yes (NS) L NDLevobupivacaine U ND ULevocarnitine Yes (NS) L NDLevodopa U U ULevofl oxacin U No (13.2) NoLevonorgestrel U ND ULevorphanol ND ND NDLevothyroxine U ND ULidocaine No (NS) ND ULincomycin No (NS) ND NoLinezolid Yes (NS) Yes (9.3-65) NDLiothyronine ND ND NDLiraglutide U U ULisdexamfetamine ND ND NDLisinopril Yes (NS) L ND



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Lithium Yes (NS) Yes (40, 70) YesLomefl oxacin No (NS) ND NoLomustine No (NS) ND ULoperamide ND ND NDLopinavir U No (NS) ULoracarbef Yes (NS) L NDLoratadine No (NS) ND NoLorazepam No (NS) ND ULosartan No (NS) No (10.1-52) NoLoteprednol etabonate U U ULovastatin U ND ULoxapine ND ND NDL-tryptophan U No (8.1-40) NDMangafodipir ND ND NDMannitol Yes (NS) L YesMaprotiline No (NS) ND UMaraviroc ND ND NDMazindol ND ND NDMechlorethamine U U UMeclofenamate U ND UMedroxyprogesterone U U UMefenamic acid No (NS) ND UMefl oquine U ND UMegestrol acetate ND ND NDMelatonin/6-sulfatoxymelatonin Yes (NS) L ND

Meloxicam No (NS) U UMelphalan No (NS) ND NDMemantine HCl ND ND NDMenotropins ND ND ND


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Meperidine/normeperidine No (NS)/ND No (8.1)/Yes (8.1) U/ND

Meprobamate Yes (NS) L YesMercaptopurine Yes (NS) L NDMeropenem Yes (NS) L NDMesalamine (5-ASA) Yes (5.5) ND UMesalazine Yes (5.5) ND UMesna ND ND NDMesoridazine U ND UMesuximide ND ND NDMetaproterenol ND ND NDMetformin Yes (NS) L NDMethadone No (NS) ND NoMethaqualone No (NS) ND NoMethenamine ND ND NDMethicillin No (NS) ND NoMethimazole No (NS) ND NoMethocarbamol ND ND NDMethotrexate Yes (NS) Yes (20, 60) YesMethotrimeprazine ND ND NDMethoxsalen ND ND NDMethoxy polyethylene glycol-epoetin beta U U U

Methyl aminolevulinate HCl U U U

Methyldopa Yes (NS) L YesMethylnaltrexone ND ND NDMethylphenidate U ND UMethylprednisolone Yes (NS) L NDMethysergide ND ND ND



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Metoclopramide No (NS) ND NoMetolazone No (NS) ND UMetoprolol Yes (NS) L NDMetronidazole Yes (NS) Yes (56) NoMexiletine Yes (NS) L NoMezlocillin Yes (NS) L NoMicafungin U U UMiconazole No (NS) ND NoMidazolam No (NS) ND UMidodrine (de-glymidodrine) ND Yes (8.1) ND

Miglitol ND ND NDMiglustat ND ND NDMilrinone ND ND NDMinocycline No (NS) ND NoMinoxidil Yes (NS) L YesMirtazapine U ND UMisoprostol U ND UMitomycin ND ND NDMitotane ND ND NDMitoxantrone No (NS) ND NoMivacurium ND ND NDMoclobemide ND ND NDModafi nil ND ND NDMoexipril ND ND NDMolindone U ND UMontelukast U ND UMoricizine U ND UMoroctocog alfa U U UMorphine ND Yes (8.1, 10.1) No


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Moxifl oxacin ND ND NoMuromonab-CD3 U ND UMycophenolate (mycophenolic acid) No (NS) ND No

Nabilone ND ND NDNabumetone No (NS) ND NDNadolol Yes (NS) L NDNadroparin ND ND NDNafarelin ND ND NDNafcillin No (NS) ND NoNalbuphine ND ND NDNalidixic acid U U UNalmefene No (4.1-5.9) ND UNaloxone ND ND NDNaltrexone No (NS) ND NDNandrolone ND ND NDNaproxen No (NS) ND UNaratriptan ND ND NDNatalizumab U U UNateglinide/M1 metabolite U/Yes (NS) U/Yes (NS) U/ND

Nebivolol U U UNedocromil ND ND NDNelarabine U U UNelfi navir U No (71) NoNeomycin Yes (NS) L YesNetilmicin Yes (NS) L YesNevirapine ND Yes (40) YesNiacin ND ND NDNiacinamide ND ND ND



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Nicardipine No (NS) ND UNicotine ND ND NDNicotinic acid ND ND NDNifedipine No (NS) ND NoNilotinib U U UNilutamide ND ND NDNimodipine No (NS) ND NoNisoldipine No (NS) ND NoNitrazepam ND ND NDNitrendipine No (NS) ND UNitrofurantoin Yes (NS) L NDNitroglycerin No (NS) ND NoNitroprusside Yes (NS) L YesNizatidine No (NS) ND NoNomifensine ND ND NDNorelgestromin ND ND NDNorepinephrine ND ND NDNorethindrone ND ND NoNorethistrone ND ND NDNorfl oxacin No (NS) ND UNorgestimate U U UNorgestrel ND ND NDNortriptyline No (NS) ND NoNylidrin ND ND NDNystatin U U UOctreotide Yes (NS) L NDOfatumumab U U UOfl oxacin Yes (6.0) Yes (8.5) NoOlanzapine No (NS) ND NoOlmesartan U No (NS) U


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Olsalazine U ND UOmapatrilat No (NS) ND NDOmeprazole U ND UOndansetron U ND UOrbofi ban Yes (NS) L NDOrlistat U U UOrnidazole Yes (NS) L NoOrnipressin U U UOrphenadrine ND ND NDOseltamivir Yes (2.8-4.0) ND YesOxacillin No (NS) ND NoOxaliplatin ND Yes (71) NDOxaprozin No (NS) ND UOxazepam No (NS) ND UOxcarbazepine ND ND NDOxtriphylline Yes (NS) L NoOxybutynin ND ND NDOxycodone ND Yes (48) NDOxymetholone ND ND NDOxymorphone ND ND NDPaclitaxel No (NS) ND NoPaliperidone ND ND NDPalivizumab U U UPamidronate Yes (6.4) L NDPancuronium ND ND NDPanitumumab U U UPantoprazole No (5.1) ND NDPapaverine U U UPara-aminosalicylate U No (30, 60) UParicalcitol No (5.5) ND ND



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Paroxetine No (NS) ND UPazopanib U U UPefl oxacin No (NS) ND NoPegaspargase U ND UPegfi lgrastim U U U

Peginterferon alfa-2b U No (8.7) Yes (20-33) U

Pegvisomant U U UPemetrexed ND ND NDPemoline Yes (NS) L NoPenbutolol No (NS) ND NoPenicillamine Yes (NS) L NDPenicillin G Yes (NS) L NoPentamidine No (NS) ND NoPentastarch U U UPentazocine Yes (NS) L NDPentobarbital No (NS) ND UPentosan polysulfate ND ND NDPentostatin ND ND NDPentoxifylline U ND NDPerfl utren ND ND NDPergolide U ND UPericyazine ND ND NDPerindopril (perindoprilat) Yes (NS) L ND

Perphenazine U ND UPethidine/norpethidine No (NS)/ND No (8.1)/Yes (8.1) U/NDPhenacetin ND ND NDPhenazopyridine ND ND NDPhenelzine ND ND ND


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Phenobarbital Yes (NS) Yes (60) YesPhentermine ND ND NDPhentolamine ND ND NDPhenylbutazone No (NS) ND UPhenyltoloxamine ND ND NDPhenytoin No (NS) Yes (36) NoPhytonadione ND ND NDPilocarpine ND ND NDPimagedine (aminoguanidine) Yes (NS) ND ND

Pimozide ND ND NDPinaverium U U UPindolol ND ND NDPioglitazone No (NS) ND UPiperacillin Yes (NS) L NoPipotiazine ND ND NDPiroxicam U ND UPitavastatin calcium U U UPivmecillinam No (NS) ND UPizotifen U U UPizotyline U U UPlicamycin ND ND NDPneumococcal vaccine ND ND NDPolidocanol ND ND NDPolyethylene glycol U U UPolythiazide No (NS) ND NoPoractant alfa ND ND NDPorfi mer No (NS) U UPosaconazole No (NS) ND NDPralatrexate ND ND ND



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Pralidoxime ND ND NDPramipexole No (NS) ND UPrasugrel U U UPravastatin No (5.3) ND NDPrazepam No (NS) ND UPraziquantel No (NS) ND NDPrazosin No (NS) ND NoPrednisolone U No (NS) UPrednisone No (NS) ND NoPregabalin Yes (NS) L NDPrimaquine No (NS) ND NDPrimidone Yes (NS) L NDProbenecid U U UProbucol No (NS) ND NoProcainamide/N-acetyl procainamide (NAPA)

Yes (NS)/ Yes (NS) L/L No/No

Procarbazine ND ND NDProchlorperazine U ND UProcyclidine ND ND NDProfenamine ND ND NDProgesterone U U UProguanil No (NS) ND NDPromazine U ND UPromethazine No (NS) ND NDPropafenone No (NS) ND NoPropantheline ND ND NDPropofol U ND UPropoxyphene No (NS) ND NoPropranolol No (NS) ND NoPropylthiouracil No (NS) ND ND


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Protriptyline No (NS) ND NoPseudoephedrine No (NS) ND UPyrantel ND ND NDPyrazinamide Yes (NS) Yes (80) NoPyridostigmine ND ND NDPyridoxine ND Yes (36) NDPyrimethamine ND ND NDQuazepam U ND UQuetiapine ND ND NDQuinapril (quinaprilat) No (NS) U NoQuinidine No* (NS) ND NoQuinine No (NS) ND NoQuinupristin/dalfopristin ND ND No/No

Rabeprazole U U URaloxifene U ND URaltegravir Yes (NS) L URaltitrexed ND ND NDRamipril (ramiprilat) No (NS) ND NDRanitidine No (NS) Yes (NS) NoRasagiline ND ND NDRasburicase U U URecainam No (NS) ND URemifentanil U U URepaglinide U No (60) UReserpine No (NS) ND NoReteplase ND ND NDReviparin No (NS) ND URibavirin No (NS) ND URifabutin U No (40) U



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Rifampin No (NS) No (80) NoRifapentine U ND URilmenidine No (NS) ND URiluzole U U URimantadine No (NS) ND URisedronate ND ND NDRisperidone ND ND NDRitodrine Yes (NS) L YesRitonavir Yes (NS) L NoRituximab No (NS) U URivaroxaban ND ND NDRivastigmine ND ND NDRizatriptan ND ND NDRocuronium ND ND NDRomidepsin U U URomiplostim ND ND NDRopinirole U U URopivacaine U U URosiglitazone No (NS) ND URosuvastatin No (NS) ND URoxithromycin ND ND NoRufl oxacin ND ND NDSalbutamol No (NS) ND USalcatonin U U USalmeterol ND ND NDSalsalate Yes (NS) L NoSapropterin ND ND NDSaquinavir U No (40) USargramostim ND ND NDSaxagliptin Yes (NS) Yes (NS) ND


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Secobarbital No (NS) ND NoSelegiline ND ND NDSermorelin ND ND NDSertindole No (NS) ND NDSertraline No (NS) ND USevelamer U U USibutramine U ND USildenafi l U No (65) USilver No (NS) ND USimethicone U U USimvastatin U ND USirolimus U U USisomicin Yes (NS) L NDSitagliptin No (NS) ND NDSitaxsentan sodium U U USodium diatrizoate L Yes (NS) NDSodium oxybate ND ND NDSodium polystyrene sulfonate U U U

Solifenacin U U USomatropin No (NS) U USorafenib U U USotalol Yes (NS) L NDSparfl oxacin ND ND NDSpectinomycin Yes (NS) L YesSpiramycin ND ND NDSpirapril (spiraprilat) U ND USpironolactone U ND UStanozolol ND ND NDStavudine Yes (NS) Yes (NS) ND



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Streptokinase U U UStreptomycin Yes (NS) L YesStreptozocin ND ND NDSucralfate No (NS) ND NoSufentanil U ND USulbactam Yes (NS) L NoSulfadiazine ND ND NDSulfamethoxazole Yes (NS) L NoSulfapyridine ND ND NDSulfasalazine U U USulfi npyrazone No (NS) ND NDSulfi soxazole Yes (NS) L YesSulindac No (NS) ND USumatriptan ND ND NDSunitinib U U UTacrine ND ND NDTacrolimus No (NS) ND UTadalafi l No (NS) U UTamoxifen ND ND NDTamsulosin U ND UTazobactam Yes (NS) L NoTegafur Yes (NS) L NDTegaserod No (NS) ND NDTeicoplanin No (NS) ND NoTelavancin ND L UTelithromycin ND ND NDTelmisartan No (NS) ND UTemazepam No (NS) ND UTemocillin Yes (NS) L NoTemozolomide ND ND ND


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Temsirolimus ND ND NDTenecteplase U U UTeniposide U ND UTenofovir ND Yes (50) NDTerazosin No (NS) ND NoTerbinafi ne U U UTerbutaline ND ND NDTeriparatide ND ND NDTestosterone No (NS) ND UTetrabenazine ND ND NDTetracycline No (NS) ND NoThalidomide U No (65) UTheophylline Yes (NS) L NoThiabendazole ND ND NDThiamazole No (NS) ND NoThiamine No (NS) ND UThiethylperazine ND ND NDThioguanine ND ND NDThioproperazine ND ND NDThioridazine U ND UThiotepa ND ND NDThiothixene U ND UThrombin alfa U U UThyrotropin alfa U U UTiagabine No (NS) ND NDTiaprofenic acid U U UTicarcillin Yes (NS) L NoTiclopidine U ND UTigecycline No (NS) ND UTiludronate U ND U



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Timolol No (NS) ND NoTinidazole Yes (NS) L NDTinzaparin U ND NDTirofi ban Yes (NS) L NDTizanidine ND ND NDTobramycin Yes (NS) L YesTocainide Yes (NS) L NDTocilizumab ND ND NDTocopherol ND ND NDTolazamide U ND UTolbutamide No (NS) ND UTolcapone U U UTolmetin U ND UTolterodine U U UTopiramate Yes (NS) L NDTopotecan Yes (8.0) L NDTorsemide No (NS) U UTositumomab U U UTrabectedin ND ND NDTramadol No (NS) Yes (50) NDTrandolapril (trandolaprilat) Yes (NS) L ND

Tranexamic acid ND ND NDTranylcypromine ND ND NDTrapidil ND ND NDTrastuzumab U U UTrazodone U ND UTreprostinil U U UTretinoin ND ND NDTriamterene ND ND ND


I CHART

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Triazolam No (NS) ND UTrifl uoperazine No (NS) ND NoTrifl upromazine U ND UTrihexyphenidyl ND ND NDTrimebutine ND ND NDTrimeprazine ND ND NDTrimethoprim Yes (NS) L NoTrimetrexate U ND UTrimipramine U ND UTriprolidine ND ND NDTriptorelin ND ND NDTropisetron U ND UTrospium ND ND NDUlipristal acetate ND ND NDUrofollitropin ND ND NDUrsodiol U U UUstekinumab ND ND NDValacyclovir Yes (NS) L NoValganciclovir Yes (NS) ND NDValproic acid No (NS) Yes (62) NoValrubicin ND ND NDValsartan No (NS) ND UVancomycin No (NS) Yes (10.1-60) NoVardenafi l ND ND NDVarenicline Yes (NS) ND NDVecuronium U ND UVelaglucerase U U UVenlafaxine No (NS) ND UVerapamil No (NS) ND NoVerteporfi n ND ND ND



HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Vigabatrin Yes (NS) L NDVildagliptin ND ND NDVinblastine ND ND NDVincristine ND ND NDVinorelbine ND ND NDVoriconazole No (NS) No (NS) NoVorinostat ND ND NDWarfarin No (NS) ND NoZafi rlukast U ND UZalcitabine ND ND NDZaleplon ND ND NDZanamivir ND ND ND

Zidovudine/GZDV No (NS)/ Yes (NS) ND/L No/Yes

Zileuton U No (8.3, 10.1) UZinc ND ND NDZiprasidone No (NS) U UZoledronic acid ND ND NDZolmitriptan ND ND NDZolpidem No (NS) ND UZopiclone No (NS) ND U


I CHART

Drugs of Abuse

HEMODIALYSIS Drug

Conventional(KUf)


PeritonealDialysis

Amphetamine ND ND NDCocaine No (NS) ND UEthanol Yes (NS) L NDHeroin U ND ULysergide (LSD) U ND UMarijuana (THC) U ND UMDMA (Ecstasy) ND ND NDMescaline (peyote) U ND UNicotine ND ND NoPhencyclidine (PCP) U ND UPsilocybin ND ND ND



Extracorporeal Therapies for Treatment of Drug OverdoseDrug 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). Benefi ts 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).


I DRUG OVERDOSE

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 signifi cantly by ECT but, in acute overdose, recently absorbed drug may not be fully distributed in tissues, hence mostly confi ned 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-fl ux 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 confi rmation of the catheter placement (hence delay), while use of the latter is associated with higher blood recirculation (loss of effi ciency).

Dialysate and blood fl ow rates should be maximized whenever possible. Volume removal



(or ultrafi ltration) 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 effi ciency unless the patient is at major risk for bleeding. In such a case, tight heparinization or saline fl ushes 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.

Hemofi ltration 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 hemofi ltration reduces the likelihood of drug rebound. Unfortunately, hourly clearance is signifi cantly inferior to high-fl ux dialysis. Therefore, hemofi ltration is usually reserved for use in


I DRUG OVERDOSE

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 suffi cient 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.



Drug

Indi

catio

ns to

initi

ate d

ialys

isW

hen

to te

rmin

ate d

ialys

isSa

licyla

tes

-Ser

um co

ncen

tratio

n >5

mm

ol/L r

egar

dless

of sy

mpt

oms

-Ser

um co

ncen

tratio

n >2

.2 m

mol/

L in

chro

nic p

oison

ing- P

rese

nce o

f hyp

otens

ion, s

ignifi c

ant m

etabo

lic ac

idosis

after

rehy

drati

on,

pulm

onar

y ede

ma,

rena

l failu

re, C

NS fe

ature

s, e.g

. hall

ucina

tions

, stu

por, c

omo

-Ser

um co

ncen

tratio

n <2

mm

ol/L

Ethy

lene

glyco

l (EG)

an

d m

ethan

ol

-EG

seru

m co

ncen

tratio

n >8

mm

ol/L

-Meth

anol

seru

m co

ncen

tratio

n >1

5mm

ol/L

- Pre

senc

e of r

enal

failur

e, ra

pid cl

inica

l dete

riora

tion,

refra

ctory

acido

sis, v

isual

signs

(in

meth

anol

toxici

ty)

-EG

seru

m co

ncen

tratio

n <3

mm

ol/L

- Meth

anol

seru

m co

ncen

tratio

n <6

mm

ol/L

-Res

olutio

n of

the a

cidos

isLit

hium

- Pres

ence

of m

assiv

e ing

estio

n, se

vere

neur

ologic

al tox

icity

(seizu

res, c

oma),

rena

l failu

re- S

erum

conc

entra

tion

>4.0

mEq

/L in

acut

e pois

oning

(Ser

um

con

cent

ratio

ns d

o not

corre

late w

ell w

ith to

xicity

in ch

ronic

pois

oning

.)

- Ser

um co

ncen

tratio

n <1

mEq

/L

(Hem

odial

ysis

may

nee

d to

be

repe

ated

beca

use o

f reb

ound

.)Th

eoph

ylline

-Ser

um co

ncen

tratio

n >5

00 µ

mol/

L in

acut

e pois

oning

-Ser

um co

ncen

tratio

n >3

00 µ

moI/

L in

chro

nic p

oison

ing- R

efrac

tory a

rrhyth

mias

or co

nvuls

ions,

patie

nts w

ho d

o not

toler

ate ac

tivate

d ch

arco

al- S

erum

conc

entra

tion

>200

µm

ol/L i

n ch

ronic

pois

oning

if pa

tient

over

60

year

s old

or p

re-e

xistin

g lun

g, ca

rdiac

, or h

epati

c dise

ase

- Unt

il sym

ptom

s disa

ppea

r or s

erum

co

ncen

tratio

n <2

00 µ

mol/

L

Valpr

oic A

cid-S

erum

conc

entra

tion

>550

0 µm

ol/L i

n ac

ute p

oison

ing-P

rese

nce o

f com

a or h

emod

ynam

ic ins

tabilit

y- S

erum

conc

entra

tion

<100

0 µm

ol/L

USE

OF E

CT F

OR S

ELEC

TED

COM

MON

OVE

RDOS

ES


I REFERENCES

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 hemofi ltration or hemodiafi ltration 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 infl uences 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.



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.

The Dialysis of Drugs 2011

Documents

Transcript of The Dialysis of Drugs 2011