UWHC Clinical Directive for Renal Function-Based Dose Adjustments in Adults

UWHC Clinical Directive for Renal Function-Based Dose Adjustments in Adults Guidelines developed by UWHC Center for Drug Policy (CDP) Coordination: Lee Vermeulen, MS, RPh, FCCP Authors: William D. Simmons RPh, and Amy M. Hopkins PharmD Updated by: Jacob Spangler, PharmD Reviewed by: Barry Fox MD, Cindy Gaston PharmD, Kim Holdener PharmD, R. Michael Hofmann MD, Paul Kellerman MD, Pharmacokinetics Committee Approved by P&T Committee: January 21, 1999 Last Reviewed and Revised by P&T:October 2009 Next Scheduled for Review: October 2010 A. Background This clinical directive provides dose adjustments for adults based upon the degree of renal impairment or the need for hemodialysis (HD). The medications were chosen based on their high volume of use, complicated dosing regimens, or past reports of adverse drug reactions when not adjusted for renal impairment. These dosing regimens are intended to establish and maintain therapeutic dosing concentrations, while avoiding excessive accumulation of the drug or its metabolites and minimizing toxicity. This protocol reduces costs by tailoring the amount of drug required to each patient s current condition, and avoiding costs incurred with iatrogenic toxicity. The dosing regimens were designed to provide simplicity of administration. This diminishes the possibility of administration errors by eliminating difficult dosing regimens (e.g. 18 or 36 hours). Where practical, dosing intervals were lengthened rather than utilizing smaller doses to decrease the total number of doses. This curtails the opportunity for preparation, administration, or timing errors. Commercially available packages or standard doses are used to minimize acquisition, production, and distribution costs. This clinical directive must be used in conjunction with clinical evaluation, and adjustments must be made to account for the individual patient. Factors to consider include age, body weight, drug interactions, hepatic insufficiency, and other concurrent disease states. The severity, type, and site of infection, host immunocompetency, as well as the results of cultures and susceptibilities influence administration of antibiotics. A loading dose is often necessary to arrive at therapeutic drug concentrations in patients with renal impairment, as the volume of distribution is often not significantly altered. Cardiovascular and anti-diabetic agents should be used cautiously, with doses titrated to the desired clinical response (e.g., blood pressure, heart rate, blood glucose). Dose modifications are based upon changing creatinine clearance (CrCl), which can be measured directly or estimated with equations such as the Cockcroft-Gault (CG) equation 1 : [(140-age) X Actual Body Weight (kg) / (Serum Cr X 72)] multiply the result by 0.85 for females For patients with a BMI 30 kg/m 2, the Salazar-Corcoran equation is the preferred equation for estimating creatinine clearance. 2 For Men: For Women: (137-age) X [(0.285 x ABW (kg)) + (12.1 x Ht(m) 2 )] (146-age) X [(0.287 x ABW(kg)) + (9.74 x Ht(m) 2 )] (51 x SCr) (60 x SCr) The equation derived from the Modification of Diet in Renal Disease (MDRD) study that estimates glomerular filtration rate (egfr) is routinely used to screen and monitor function in chronic kidney disease (obtainable at www.kidney.org), as it is most accurate for patients with GFR < 40 ml/min/m 2. Traditionally, renal dosing recommendations provided by drug manufacturers (and contained in this protocol) are based on the CG equation. Though the MDRD equation has been shown to more accurately predict GFR, the majority of data regarding drug dosing in renal dysfunction is based on the CG equation, as the FDA Guidance for Industry suggests. 3 The National Institute of Diabetes and Kidney Diseases and The National Kidney Disease Educational Program recommend dosing of either CrCl or egfr. Serum creatinine or estimated creatinine clearance may be misleading indicators of renal function in certain situations. Calculated clearances may be inaccurate in patients with chronic kidney disease, obesity, volume overload, diabetes, low creatinine, hypoalbuminemia, hypermetabolic conditions, advanced age, decreased muscle mass (as seen in cirrhotics or debilitation). Renal function may be overestimated in situations associated with rapidly rising serum creatinines, which includes all cases of acute kidney injury (such as hepato-renal syndrome, ischemic injury, or druginduced nephrotoxicity. It can also be underestimated in periods of rapidly falling serum creatinine, such as after renal transplant. 1

To accommodate the administration of drugs that are removed by standard hemodialysis, administer the indicated dose soon after hemodialysis is complete. This avoids the need for partial or increased supplemental doses. For example a drug listed as Q 24H/ daily / 3X/week post HD should be scheduled for 1600. A drug listed as Q 12H post HD could be scheduled at 1200 and 2400 if morning HD is anticipated, or at 0600 and 1800 if afternoon HD is anticipated. If the HD schedule is altered, then a dose should be administered soon after the patient returns from HD, and then adjusted to approximately 12 hours from this time. If the schedule is Q 6H/ Q 8H, no special scheduling needs to be done, since the time is frequent enough that HD does not need to be scheduled around it. Anti-hypertensive medications should be held prior to HD to allow for greater ultrafiltrate removal without precipitating hypotension during the procedure. Standard hemodialysis technology includes routine use of high permeability dialysis membranes. High permeability membranes are defined as those membranes whose in vitro ultrafiltration coefficient (KUf) is greater than 8 ml/hr/mm Hg. dosing information contained in this protocol has been obtained from studies conducted under conditions where conventional dialysis membranes have been used. Drug removal from plasma is often enhanced with the use of high permeability membranes as compared to conventional membranes. In some cases, patients receiving high permeability dialysis may require more drug than those receiving dialysis with conventional filters. Individualized therapeutic drug monitoring may be necessary in these instances; the reader is referred to the primary literature for further details. Note: this is not a comprehensive list of renally eliminated drugs, merely drugs that are frequently used or are difficult to dose. Absence of a drug from the chart does not mean that the drug is not renally eliminated. Drug removal by peritoneal dialysis (PD) or continuous renal replacement therapy (CVVHD, CAVHD, etc.) is not equivalent to hemodialysis removal. For these procedures another source of information should be consulted Continuous Renal Replacement Dosing Guideline. Questions concerning this protocol should be directed to the Center for Drug Policy. B. Procedure 1.0 Policies 1.1 The UWHC Medical Staff, through the Pharmacy and Therapeutics Committee, shall establish and maintain a list of medications and their dosing regimens approved for pharmacist dosing in renal impairment (see Table 1). 1.2 The clinical pharmacist is responsible for reviewing each patient s drug therapy for proper dosing in renal impairment and, where appropriate, converting the prescribed dose to one consistent with the patient s renal function. Doses may be adjusted up or down based on patient s renal function. 1.3 This dose conversion may be overridden, at any time, by the prescriber writing Dose as Written or other equivalent orders with the medication order. 1.4 This procedure does not apply to the first dose of a medication, or medications not listed on the renal dosing chart. 1.5 Requests to add, change, or delete a medication from the list may be made to the Center for Drug Policy. Then, if appropriate as determined by reviewing manufacturer s guidelines, clinical dosing markers, or published primary literature, the dosing regimen will be forwarded to the Pharmacy and Therapeutics Committee for final approval. 1.6 Any changes to the approved dose adjustment list will be communicated to the medical and pharmacy staff. 2.0 Managing the Interchange Program 2.1 The pharmacist is responsible for reviewing the drug therapy of each patient on a routine basis. 2.2 If the patient is receiving a medication on the approved drug list, the pharmacists will review the dose and the patient s renal function. If a serum creatinine is not available, the pharmacist may order a serum creatinine concentration based on their clinical judgment for its need. 2.3 If the dose of a drug differs from that on the approved dose adjustment list, the pharmacist will: 2.3.1 Write an order in HealthLink and indicate Protocol without Cosign in the order mode field and document this change in the administration instruction section of the medication order by indicating "Modification made per renal dosing protocol" or write a progress note documenting the adjustment OR Contact the physician to record a verbal order. 2.3.2 If the prescriber determines no renal adjustment should be made, they must enter Dose as Written in the administration instructions section of the order. 2.3.3 If an order is changed per the protocol, this should be documented in HealthLink. 2

2.3.4 If a medication is not on the renal dosing chart, the prescriber must be contacted directly, and a verbal order must be written before any dosing adjustment can be made. C. Key The guidelines were adapted from the following references: A = McEvoy G, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, Inc; 2009. B = Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults. 5 th ed. Philadelphia, PA: American College of Physicians; 2007. D = Klasco RK (Ed): DRUGDEX System (electronic version). Thomson Micromedex, Greenwood Village, Colorado, USA. Available at: http://www.thomsonhc.com. Accessed 9/20/09. F = Drug Fact and Comparisons. efacts [serial online], Wolters Kluwer Health, Inc., St. Louis, MO. Available at: http://www.efactsweb.com/index.asp. Accessed 9/19/09. 39 All hemodialysis information is from: Johnson CA. 2008 Dialysis of Drugs. Ann Arbor, MI: CKD Insights, LLC. 2009. Available online at: http://www.ckdinsights.com/downloads/dialysisdrugs2009.pdf References: 1. Cockroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. 2. Salazar DE, Corcoran GB. Predicting creatinine clearance and renal drug clearance in obese patients from estimated fat-free body mass. Am J Med. 1988;84:1053-60. 3. Stevens LA, Nolin TD. Comparison of Drug Dosing Recommendations Based on Measured GFR and Kidney Function Estimating Equations. Am J Kid Dis. 2009;54:33-42. 4. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis. 2002;39:S1-S266. 3

Table 1. Drugs Approved For Pharmacist Dosing in Renal Impairment A B C D E F G H I J K L M N O P Q R S T U V W X Y Z Drug CrCl (ml/min) Dosing Regimen Acyclovir (IV) D > 50 5-10 mg/kg every 8H 25-49 5-10 mg/kg every 12H 11-24 5-10 mg/kg every 24H < 10 5-10 mg/kg load, then 2.5-5 mg/kg every 24H 5-10 mg/kg load, then 2.5-5 mg/kg every 24H or post hemodialysis or 5-10 mg/kg 3X/week post hemodialysis Acyclovir (PO) AD Herpes zoster infections > 10 200 mg every 4H 5X/day < 10 200 mg twice daily 200 mg twice daily post hemodialysis Acyclovir (PO) AD Varicella infections > 25 800 mg every 4H 5X/Day 10-25 800 mg three times daily < 10 800 mg twice daily 800 mg twice daily post hemodialysis Allopurinol (PO) D > 20 200 mg daily to 300 mg twice daily 11-19 200 mg daily or 100 mg twice daily < 10 200 mg load, then 100 mg daily 200 load, then 100 mg daily post hemodialysis Amantadine (PO) AD > 50 200 mg daily or 100 mg twice daily 30-49 200 mg load, then 100 mg daily 15-29 200 mg load, then 100 mg every other day < 15 200 mg load, then 200 mg every week Amikacin (IV) Monitor concentrations closely Consult unit pharmacist for dosing adjustment recommendations. Refer to extending interval dosing nomograms. Amoxicillin (PO) AB > 30 250-500 mg three times daily or 875 mg twice daily 11-29 250-500 mg twice daily < 10 250-500 mg daily 250-500 mg daily post hemodialysis Amoxicillin/Clavulanate (Augmentin ) (PO) AD > 30 250-500 mg three times daily or 875 mg* twice daily 11-29 250-500 mg twice daily < 10 250-500 mg daily 250-500 mg daily post hemodialysis *Amoxicillin/Clavulanate 875 mg dose is non-formulary 4

Ampicillin (IV) ABF > 50 1-2 G every 4-6H 30-49 1-2 G every 6H 11-29 1-2 G every 8H < 10 1-2 G every 12H 1-2 G every 12H post hemodialysis Ampicillin/Sulbactam (Unasyn ) (IV) AB > 50 1.5-3 G every 6H 30-49 1.5-3 G every 6-8H 15-29 1.5-3 G every 12H < 14 1.5-3 G every 24H 1.5 G every 12H or 3 G every 24H post hemodialysis Argatroban (IV) in renal dysfunction alone Non-Formulary Drug Refer to UWHC Heparin-Induced Thrombocytopenia guidelines. Atenolol (PO) ADF * >35 25-200 mg daily 15-35 50 mg daily <15 25 mg daily *Consider every HS dosing in CAD patients Atorvastatin D 10-80 mg daily permeability Aztreonam (IV) AD > 30 1-2 G every 8H 11-29 1-2 G every 12H < 10 1-2 G every 24H 1-2 G every 24H post hemodialysis Azithromycin (IV) D Azithromycin (PO) D Captopril (PO) B Normal Dose Caspofungin (IV) D 500 mg every 24H removal unknown 500 mg load, then 250 mg daily X 4 days removal unknown 6.25-50 mg three times daily 6.25-50 mg daily post hemodialysis Requires ID approval 70 mg load, then 50 mg daily Not removed by conventional hemodialysis; unlikely removed by high 5

Cefazolin (IV) B Mild or moderate infection > 50 1 G every 8H 11-49 1 G every 12H < 10 1 G every 24H 1 G every 24H post hemodialysis Cefazolin (IV) B Severe infection > 50 2 G every 8H 11-49 2 G every 12H < 10 2 G every 24H 2 G every 24H post hemodialysis Cefdinir (PO) BD 30 300 mg every 12H < 30 300 mg daily 300 mg every other day and 300 mg post hemodialysis Cefepime (IV) D Mild or moderate infection > 60 1-2 G every 12H 30-59 1-2 G every 24H 11-29 1-2 G load, then 500 mg -1 G every 24H < 10 1-2 G load, then 500 mg every 24H 1-2 G load, then 250-500 mg every 24H post hemodialysis Cefepime (IV) D Severe infection and febrile neutropenia > 60 2 G every 8H 30-59 2 G every 12H 11-29 2 G every 24H < 10 2 G load, then 1 G every 24H 2 G load, then 1 G every 24H post hemodialysis Cefoxitin (IV) AD > 50 1-2 G every 6-8H 30-49 1-2 G every 8-12H 10-29 1-2 G every 12-24H 5-9 Load 1-2 G, then 500 mg -1 G every 12-24H < 5 Load 1-2 G, then 500 mg -1 G every 24H Load 1-2 G, then 1 G every 24H post hemodialysis Cefpodoxime (PO) D > 30 100-400 mg twice daily 11-29 100-400 mg daily < 10 100 mg daily 100-200 mg 3X/week or 100 mg daily post hemodialysis Ceftazidime (IV) AD** Non-Formulary Drug/Mild to moderate infection > 50 1 G every 8H 31-49 1 G every 12H 16-30 1 G every 24H < 15 1 G load, then 500 mg every 24H 1 G 3X/week or load 1 G, then 500 mg daily post hemodialysis ** Per therapeutic interchange policy, cefepime is the third generation IV cephalosporin formulary product 6

Ceftazidime (IV) AD** Non-Formulary Drug/Severe infection > 50 2 G every 8H 31-49 2 G every 12H 16-30 2 G every 24H < 15 2 G load, then 1 G every 24H 2 G 3X/week or load 2 G, then 1 G daily post hemodialysis ** Per therapeutic interchange policy, cefepime is the third generation IV cephalosporin formulary product Ceftriaxone (IV) D* *Clin Infec Dis 2004;39:1267-1284. Ceftriaxone (IV) D* Meningitis or severe infection 2 G every 12H - meningitis, 2G every 24 H - severe infection permeability Community acquired pneumonia or moderate infection 1 G every 24H permeability Cefuroxime (IV) D > 20 750 mg-1.5 G every 8H or 1.5 G every 12H for prophylaxis 11-19 750 mg every 12H < 10 750 mg every 24H 750 mg every 24H post hemodialysis Cephalexin (PO) AB > 40 250-500 mg four times daily 31-39 250-500 mg three times daily 11-30 250-500 mg twice daily < 10 250 mg twice daily 250 mg twice daily or 500 mg daily post hemodialysis Chloramphenicol (IV) D Monitor levels if severe renal impairment 12.5-18.75 mg/kg every 6H (Max dose = 4 grams) 12.5-18.75 mg/kg every 6H post hemodialysis Ciprofloxacin (IV) D Mild to moderate infection > 30 200-400 mg every 12H < 30 200-400 mg every 24H Ciprofloxacin (IV) D Severe infection >60 400 mg every 8H or 600 mg every 12H 30-59 400 mg every 12H <30 400 mg every 24H Ciprofloxacin (PO) D UTI or Mild to moderate infection > 30 250-500 mg every 12H < 30 250-500 mg every 24H 7

Ciprofloxacin (PO) D Severe infection > 30 750 mg every 12H < 30 750 mg every 24H Clarithromycin (PO) A Non-formulary Drug > 30 250-500 mg twice daily 11-29 250-500 mg daily < 10 Load 500 mg, then 250 mg daily removal unknown Clindamycin (IV) A 600-900 mg every 6-8H Clindamycin (PO) A Clonidine (PO) D* *JAMA 2003;289:2560-2572. 150-300 mg four times daily 50-400 mcg twice daily Colistimethate sodium (IV) ** Monitor closely for nephrotoxicity and neurotoxicity > 80 2.5 mg/kg every 12H 50-80 2 mg/kg every 12H 10-50 2 mg/kg every 24H <10 2.5 mg/kg load, then 1.5 mg/kg every 36H Colistimethate (Coly-Mycin M) Package Insert, February 2004; Ann Pharmacother 1999;33:960-967. Am J Health Syst Pharm 2007;64:2462-2466. Dalteparin (SC) D DVT prophylaxis > 30 5,000 units every 24H < 30 5,000 units every 24H* Unlikely to be removed by conventional hemodialysis; no data for high *If patient < 50 kg: 2,500 units every 24H Dalteparin (SC) D * DVT/PE treatment > 30 100 units/kg every 12H or 200 units/kg every 24H < 30 Not recommended** Unlikely to be removed by conventional hemodialysis; no data for high *Chest 2008;133:141S-159S **Dalteparin is not recommended in renal failure due to lack of information. Heparin is the drug of choice. 8

Dalteparin (SC) D * VTE treatment in cancer patients > 30 200 units/kg daily (max = 18,000 units) for 30 days, then 150 units/kg daily (max = 18,000 units) for 5 months < 30 Not recommended** Unlikely to be removed by conventional hemodialysis; no data for high *Lower doses may be used in patients at an increased risk of bleeding. **Dalteparin is not recommended in renal failure due to lack of information. Heparin is the drug of choice. Dalteparin (SC) D * Unstable angina/non-q wave MI > 30 120 units/kg every 12H < 30 Not recommended** Unlikely to be removed by conventional hemodialysis; no data for high * Chest 2008;133:141S-159S **Dalteparin is not recommended in renal failure due to lack of information. Heparin is the drug of choice. Daptomycin (IV) ADF Needs ID approval 30 4-6 mg/kg every 24H < 30 4-6 mg/kg every 48H 4-6 mg/kg every 48H. Not removed by conventional hemodialysis; no data for high Dexrazoxane (IV) ADF > 40 500 mg/m 2 < 40 250 mg/m 2 5 mg daily, dose after hemodialysis Dicloxacillin (PO) A 250-500 mg four times daily Digoxin (IV/PO) D Monitor concentrations closely 125-500 mcg every 24H Renal insufficiency Consider every 48H or 3X weekly dosing Consult unit pharmacist for dosing adjustment recommendations. Diltiazem (PO) D Diltiazem CD (PO) D 30-90 mg three to four times daily 120-360 mg daily Doripenem (IV) BD Non-formulary Drug >50 500 mg every 8H 30-49 250 mg every 8H 10-29 250 mg every 12H Removed by hemodialysis, but insufficient data to make recommendation on dosing adjustment 9

Doxycycline (PO) A 100-200 mg load, then 100 mg daily or twice daily Enalapril (PO) D > 30 5-40 mg daily < 30 Initial dose 2.5 mg Enalaprilat (IV) ADF > 30 1.25 mg every 6H < 30 Initial dose of 0.625 mg, may repeat in 1 hour if inadequate response. Then 1.25 mg every 6 hours Enoxaparin (SC) D Non-Formulary Drug; DVT/PE treatment, Unstable angina/non-q wave MI > 30 1 mg/kg every 12H or 1.5 mg/kg every 24H* < 30 1 mg/kg every 24H* *Per therapeutic interchange policy, dalteparin is the LMWH formulary product Entecavir (PO) AD Non-Formulary Drug, Nucleoside treatment-naïve > 50 0.5 mg every 24H 30-50 0.25 mg every 24H or 0.5 mg every 48H 10-30 0.15 mg every 24H or 0.5 mg every 72H < 10 0.05 mg every 24H or 0.5 mg every 7 days 0.05 mg every 24H or 0.5 mg every 7 days, Dose post dialysis Entecavir (PO) AD Non-Formulary Drug, Lamivudine-refractory > 50 1 mg every 24H 30-50 0.5 mg every 24H or 1 mg every 48H 10-30 0.3 mg every 24H or 1 mg every 72H < 10 0.1 mg every 24H or 1 mg every 7 days 0.1 mg every 24H or 1 mg every 7 days Ertapenem (IV) ADF Non-Formulary Drug 30 1 G daily < 30 500 mg daily Erythromycin (IV) A ** > 10 250 mg-1 G every 6H < 10 Max dose is 2 G per day **Ototoxicity has occurred in patients with severe renal failure. Monitor for signs of ototoxicity. Erythromycin Base (PO) A ** 250-500 mg four times daily < 10 Max dose is 2 G per day **Ototoxicity has occurred in patients with severe renal failure. Monitor for signs of ototoxicity. 10

Erythromycin EC (PO) A ** 333 mg three times daily < 10 Max dose is 2 G per day **Ototoxicity has occurred in patients with severe renal failure. Monitor for signs of ototoxicity. Famotidine (IV) > 50 20 mg every 12H < 50 20 mg every 24H Fluconazole (IV/PO) A > 50 200-800 mg load, then 100-400 mg daily < 50 200-800 mg load, then 50-200 mg daily 200-800 mg load, then 100-400 mg 3X/week post hemodialysis or 100 mg daily Flucytosine (PO) BD Monitor concentrations closely** > 40 12.5-37.5 mg/kg every 6H 21-39 12.5-37.5 mg/kg every 12H 11-20 12.5-37.5 mg/kg every 24H < 10 12.5-37.5 mg/kg every 48H 25-50 mg/kg 3X/week post hemodialysis ** Should be used with great caution, if at all, in renal failure. Levels should be monitored closely. Fluoxetine (PO) A > 10 20-40 mg daily < 10 10-20 mg daily Fluvastatin D. Monitor closely** 20-80 mg daily Fondaparinux (SQ) * Non-Formulary Drug 50-80 Reduce dose by 25% 30-50 Reduce dose by 40% < 30 Contraindicated Removed by hemodialysis * Refer to UWHC Heparin-Induced Thrombocytopenia guidelines for more dosing information Fomepizole (IV) BD Consult unit pharmacist for dosing recommendations. Dose every 4H during hemodialysis 11

Foscarnet (IV) D - adjust for both renal function CMV Retinitis AND weight CrCl (ml/min/kg) (multiply by weight for For 70 kg patient (ml/min) estimated CrCl dosing > 1.4 > 98 60/kg every 8H or 90 mg/kg every 12H 1.0-1.4 70-98 45/kg mg every 8H or 70 mg/kg every 12H 0.8-1.0 56-69 50 mg/kg every 12H 0.6-0.8 42-55 40 mg/kg every 12H or 80 m/kg every 24H 0.5-0.6 35-41 60 mg/kg every 24H 0.4-0.5 28-34 50 mg/kg every 24H < 0.4 <28 not recommended Foscarnet (IV) D adjust for both renal function HSV Infections AND weight CrCl (ml/min/kg) (multiply by weight for For 70 kg patient (ml/min) estimated CrCl > 1.4 > 98 40 mg/kg every 8-12H 1.0-1.4 70-98 30 mg/kg every 8-12H 0.8-1.0 56-69 20-35 mg/kg every 12H 0.6-0.8 42-55 35 mg/kg every 24H or 25 mg/kg every 12H 0.5-0.6 35-41 25-40 mg/kg every 24H 0.4-0.5 28-34 20-35 mg/kg every 24H < 0.4 <28 Not recommended Fosphenytoin (IV) DF Consult unit pharmacist for dosing adjustment recommendations. Monitor concentrations closely Not removed by conventional hemodialysis; removed by high Gabapentin (PO) D **, use caution in renal failure. > 60 300-1200 mg three times daily 30-59 200-700 mg twice daily 15-29 200-700 mg daily < 14 100-300 mg daily 100-300 mg post hemodialysis Ganciclovir (IV) D For CMV prophylaxis load may not be necessary > 70 5 mg/kg every 12H 50-69 5 mg/kg load, then 2.5 mg/kg every 12H 25-49 5 mg/kg load, then 2.5 mg/kg every 24H 10-24 5 mg/kg load, then 1.25 mg/kg every 24H 5 mg/kg load, then 1.25 mg/kg 3X/week post hemodialysis Ganciclovir (PO) AD CMV retinitis Tx/CMV Px (Load may not be necessary for prophylaxis) > 70 1 G three times daily 50-69 1 G load, then 500 mg three times daily 25-49 1 G load, then 500 mg twice daily 10-24 1 G load, then 500 mg daily 1 G load, then 500 mg 3X/week post hemodialysis 12

Gemfibrozil (PO) D > 50 600 mg twice daily 10-50 300 mg twice daily < 10 150 mg twice daily Gentamicin (IV) Monitor concentrations closely Consult unit pharmacist for dosing adjustment recommendations. Refer to extending interval dosing nomograms. Glipizide (PO) D Glipizide XL (PO) D 5 mg daily 20 mg twice daily Unlikely to be removed by conventional hemodialysis; no data for high 5-20 mg daily Unlikely to be removed by conventional hemodialysis; no data for high Glyburide (PO) D ** > 50 1.25-20 mg daily < 50 **May need dose reduction** Glyburide micronized (PO) D ** > 50 1.25-12 mg daily < 50 **May need dose reduction Heparin (SQ) D 5,000-20,000 units every 12H or 5,000 units every 8H Hydralazine (PO) AD > 10 10 75 mg four times daily < 10 May require lower dosage Ibandronate (IV) ADF 30 3 mg once every three months < 30 Not recommended No data for conventional hemodialysis; removed by high *Restricted to the treatment of osteoporosis in patients who cannot tolerate or fail oral bisphosphonate therapy. **Oral ibandronate is non-formulary. Imipenem/Cilastatin (Primaxin ) (IV) D Non-Formulary Drug /Mild-to-moderate infections > 40 500 mg every 8H 20-40 500 mg load, then 250 mg every 8H < 20 500 mg load, then 250 mg every 12H 500 mg load, then 250 mg every 12H post hemodialysis **Per therapeutic interchange policy, meropenem is the carbepenem of choice. 13

Imipenem/Cilastatin (Primaxin ) (IV) D Non-Formulary Drug /Severe infections or Pseudomonas > 70 1 G every 6-8H 41-70 1 G load, then 750 mg every 8H 21-40 1 G load, then 500 mg every 6H < 20 1 G load, then 500 mg every 12H 1 G load, then 500 mg every 12H post hemodialysis **Per therapeutic interchange policy, meropenem is the carbepenem of choice. Isosorbide Dinitrate (PO) D Itraconazole (PO) D No adjustment needed Ketoconazole (PO) D 10-40 mg three times daily. Allow a 12 hour nitrate-free period 200 mg load three times daily X 3 days if severe 200-400 mg daily Not removed by conventional hemodialysis or high permeability filters with KUf 65 ml/hr/mm Hg. 200-400 mg daily Ketorolac (IM/IV) D Use for > 5 days increases risk of renal failure > 50 15-30 mg every 6H 49-21 15 mg every 6H to max of 60 mg daily 20 Contraindicated Unlikely to be removed by conventional hemodialysis; no data for high Labetalol (PO) D 100 mg twice daily-400 mg three times daily Lamivudine (PO) ADF Hepatitis B treatment and prophylaxis > 50 100 mg daily 30-49 100 mg x 1 dose load, then 50 mg daily 15-29 100 mg x 1 dose load, then 25 mg daily 5-14 35 mg x 1 dose load, then 15 mg daily <5 35 mg x 1 dose load, then 10 mg daily Not removed by hemodialysis; not removed by high permeability Lamivudine (PO) ADF HIV Infection > 50 150 mg twice daily or 300 mg daily 30-49 150 mg daily 15-29 150 mg X 1 dose load, then 100 mg daily 5-14 150 mg X1 dose load, then 50 mg daily <5 50 mg X1 dose load, then 25 mg daily Not removed by hemodialysis; not removed by high permeability 14

Lepirudin (IV)** Requires dosage adjustment in renal impairment, consult with prescriber. Pharmacist dosing NOT permitted per protocol. **Refer to UWHC Heparin-Induced Thrombocytopenia guideline. Lenalidomide (PO) DF Multiple Myeloma > 60 25 mg daily for 21 days of 28 day cycle 30-60 10 mg every 24H < 30 (not requiring dialysis) 15 mg every 48H 5 mg daily, dose after hemodialysis Lenalidomide (PO) DF Myelodysplastic Syndrome > 60 10 mg daily 30-60 5 mg every 24H < 30 (not requiring dialysis) 5 mg every 48H 5 mg three times a week, dose after hemodialysis Levetiracetam (IV/PO) D >80 500-1,500 mg every 12H 50-80 500-1,000 mg every 12H 30-49 250-750 mg every 12H <30 250-500 mg every 12H 500-1,000 mg every 24H, dose after hemodialysis Levofloxacin (IV/PO) D Non-Formulary Drug** > 50 500 mg daily or 750 mg daily 21-49 500 mg load, then 250 mg daily or 750 mg load, then 750 mg every other day < 20 500 mg load, then 250 mg every other day or 750 mg load, then 500 mg every other day 500 mg load, then 250 mg every other day or 750 mg load, then 500 mg every other day; Unlikely to be removed by conventional hemodialysis; not removed by high permeability filters with KUf of 13.2 ml/hr/mm Hg. ***Per therapeutic interchange policy, moxifloxacin is the quinolone (gram+) of choice; consider 750 mg dose regimen for nosocomial pneumonia, complicated skin structure infection or community acquired pneumonia (5 day treatment) Levothyroxine (PO) D Linezolid (IV,PO) D Lisinopril (PO) AD 25-200 mcg daily Unlikely to be removed by conventional hemodialysis; no data for high Metabolites may accumulate in renal failure 600 mg every 12H 600 mg every 12H post hemodialysis 10-40 mg daily 15

Magnesium Sulfate Sliding Scale IV 30 Serum Mg (mg/dl) Usual Dose* (g/kg) 1.6-1.8 0.05 1.0 1.5 0.1 <1.0 0.15 < 30 Usual Dose* (g/kg) Serum Mg (mg/dl) g/kg 1.6-1.8 0.025 1.0 1.5 0.05 <1.0 0.075 Contact provider for patient specific orders. *Use actual body weight unless >130% lean body weight, in which case use LBW for dose calculations. Meperidine (IV/IM) D ** * > 50 50-150 mg every 3-4H 10-49 75 % of dose < 10 50 % of dose *Refer to UWHC guideline for appropriate indications for use. **Avoid use in renal impairment due to an increased risk of seizures Not removed by conventional hemodialysis; not removed by high Metabolite normeperidine is removed by high Meropenem (IV) D Mild-to-moderate infections; Empiric Therapy > 50 500 mg every 8H 26-50 500 mg every 12H 10-25 250 mg every 12H <10 250 mg every 24H 250 mg every 24H post hemodialysis **Per therapeutic interchange policy, meropenem is the carbepenem of choice. Meropenem (IV) D Severe infections (in ICU, Transplant and Hematology wards; immunosuppressed or neutropenic; MIC 2) 36 500 mg every 6H; may be infused over 3H 26-35 500 mg every 8H; may be infused over 3H 10-25 500 mg every 12H; may be infused over 3H <10 and HD/PD 500 mg every 24H; may be infused over 3H **Per therapeutic interchange policy, meropenem is the carbepenem of choice. Metformin (PO) AD > 50 500 mg three times daily-850 mg daily < 50 Contraindicated in renal failure due to the risk of lactic acidosis. Removed by hemodialysis Metoclopramide (IV/PO) D > 40 10-20 mg four times daily < 40 5-10 mg four times daily 16

Metoprolol (PO) D Metronidazole (IV) ADF Metronidazole (PO) AF Micafungin (IV) D Moxifloxacin (IV, PO) D 25 mg daily 200 mg twice daily (Consider three times daily use in CAD patients) 25 mg daily 200 mg twice daily post hemodialysis (Consider three times daily use in CAD patients) 500 mg every 8H or 500 mg 1 G every 12H 500 mg every 8H post hemodialysis 500 mg three to four times daily 500 mg three to four times daily post hemodialysis 50-150 mg daily No data 400 mg daily No data Nafcillin (IV) AF 1-2 G every 4-6H Nitrofurantoin (PO) A > 60 50-100 mg every 6H < 60 Contraindicated Contraindicated, Removed by hemodialysis Note: 100 mg daily for prophylaxis Nitrofurantoin ER (PO) AD > 60 100 mg twice daily < 60 Contraindicated < 30 Contraindicated, Removed by hemodialysis Norfloxacin (PO) D > 30 400 mg twice daily < 30 400 mg daily Oseltamivir A Treatment of influenza >30 75 mg twice daily X 5 days 11-29 75 mg daily X 5 days <10 No data Unknown if removed by hemodialysis Oseltamivir A Prophylaxis of influenza >30 75 mg daily 11-29 75 mg every other day <10 No data Unknown if removed by hemodialysis 17

Pantoprazole (IV/PO) DF 40-80 mg once or twice daily 40-80 mg once or twice daily, not removed by hemodialysis Penicillin G (IV) AD Avoid potassium salt in renal failure > 50 1-2 million units every 4H 11-49 1-2 million units every 6H < 10 1-2 million units every 8H 1-2 million units every 8H post hemodialysis Penicillin V (PO) D > 10 250-500 mg four times daily < 10 250-500 mg three times daily 250-500 mg three times daily post hemodialysis Pentoxifylline (PO)** > 80 400 mg three times daily 31-79 400 mg twice daily < 30 400 mg daily Unlikely to be removed by conventional hemodialysis; no data for high **Ann Pharmacother 1996;30:724-9 Phenobarbital (IV/PO) Monitor concentrations closely Consult unit pharmacist for dosing adjustment recommendations. Phenytoin (PO) D Consult unit pharmacist for dosing adjustment recommendations. Monitor concentrations closely Not removed by conventional hemodialysis; removed by high Phosphate IV (sodium or potassium) Sliding Scale 30 < 30 Serum PO4 (mg/dl) Usual Dose* (mm /kg) 2.4 3.0 (mild) 0.32 1.6 2.3 (moderate) 0.64 <1.6 (severe) 1 Serum PO4 (mg/dl) Usual Dose* (mm/kg) 2.4 3.0 (mild) 0.16 1.6 2.3 (moderate) 0.32 <1.6 (severe) 0.5 Contact provider for patient specific orders. *Use actual body weight unless >130% lean body weight, in which case use LBW for dose calculations Piperacillin (IV) D > 40 3 G every 4-6H 21-39 3 G every 8H < 20 3 G every 12H 3 G every 12H post hemodialysis 18

Piperacillin/Tazobactam (Zosyn ) (IV) D Mild-to-moderate infections > 40 3.375 G every 6H 21-39 3.375 G every 8H < 20 3.375 G every 12H 3.375 G every 12H post hemodialysis Piperacillin/Tazobactam (Zosyn ) (IV) D Severe infections > 40 3.375 G every 4H or 4.5 G every 6H 21-39 3.375 G every 6H or 4.5 G every 8H < 20 3.375 G every 8H or 4.5 G every 12H 3.375 G every 8H or 4.5 G every 12H post hemodialysis Piperacillin/Tazobactam (Zosyn ) (IV) Extended Infusion Protocol > 20 3.375 G every 8H infused over 4H < 20 and HD/PD 3.375 G every 12H infused over 4H Plerixafor ADF UWHC restricted medication > 50 0.24 mg/kg once daily (not to exceed 40 mg/day) < 50 0.16 mg/kg once dailydialy (not to exceed 27 mg/day) Unknown Posaconazole D Requires ID approval 200-400 mg every 12-24H No data Potassium Chloride PO or IV Sliding Scale 30 < 30 Serum K (mmol/l) Usual Dose 3.6-3.9 20 meq 3.1 3.5 40 meq 3.0 60 meq Serum K (mmol/l) Usual Dose 3.6-3.9 10 meq 3.1 3.5 20 meq 3.0 30 meq Contact provider for patient specific orders. Pregabalin (PO) ADF 60 150-600 mg per day, divided twice daily or three times daily 30-60 75-300 mg per day, divided twice daily or three times daily 15-29 25-150 mg once daily or divided twice daily < 15 25-75 mg once daily ; removed by high Primidone (PO) Monitor concentrations closely Consult unit pharmacist for dosing adjustment recommendations. Procainamide (IV) Monitor concentrations closely Consult unit pharmacist for dosing adjustment recommendations. Propranolol (PO) D 10 160 mg four times daily 19

Ranitidine (IV)** > 50 50 mg every 8H 31-49 50 mg every 12H < 30 50 mg every 24H Not removed by conventional hemodialysis; removed by high **Eu J Clin Pharmacol, 1997;52:229-34 Ranitidine (PO) D ** > 50 150 mg once twice daily <50 150 mg every HS Not removed by conventional hemodialysis; removed by high **Eu J Clin Pharmacol, 1997;52:229-34 Rifampin (IV)/(PO) D IV restricted to ID approval 600 mg every 12-24H < 10 600 every 24H Not removed by hemodialysis Sertraline (PO) D No adjustment needed Sildenafil (PO) DF No adjustment needed 50-200 mg daily For Pulmonary Arterial Hypertension only 20 mg TID Simvastatin(PO) D 10 5-40 mg daily < 10 Initial dose = 5 mg Unlikely to be removed by conventional hemodialysis; no data for high Sotalol ADF Ventricular Arrhythmias > 60 Every 24H 30-59 Every 24H 10-29 Every 36-48H < 10 Individualize therapy Sotalol ADF Supraventricular Arrhythmias (atrial fibrillation or flutter) > 60 Every 12H 40-60 Every 24H < 40 contraindicated Spironolactone (PO) D Monitor K + Levels > 10 25-200 mg daily < 10 Not recommended Unlikely to be removed by conventional hemodialysis; no data for high Telithromycin (PO) ADF Requires ID approval 30 800 mg daily < 30 600 mg daily < 30 and coexisting hepatic impairment 400 mg daily 600 mg daily post hemodialysis 20

Ticarcillin/Clavulanate (Timentin ) (IV) D > 60 3.1 G every 4-6H 30-59 3.1 G every 6-8H 11-29 3.1 G every 12H < 10 3.1 G load, then 2 G every 12H 10 and coexisting hepatic impairment 3.1 G load, then 2 G every 24H 3.1 G load, then 2 G every 12H post hemodialysis Tobramycin (IV) Monitor concentrations closely Consult unit pharmacist for dosing adjustment recommendations. Refer to extending interval dosing nomograms. Triamterene (PO) BD Monitor K+ levels > 10 50 mg daily 100 mg twice daily < 10 Not recommended Unknown. Topiramate (PO) ADF < 70 ml/min Reduce dose by 50% Supplemental dose may be required Trimethoprim/Sulfamethoxazole* (Bactrim) (IV/PO) D Pneumocystis carinii (jiroveci) pneumonia treatment > 30 15-20 mg/kg/day divided every 6-8H 16-29 15-20 mg/kg/day divided every 6-8H X 48H, then 7-10 mg/kg/day divided every 12H < 15 7-10 mg/kg/day divided every 12-24H 15-20 mg/kg, may divide dose, 3X/week, dose post hemodialysis *Based on TMP component. IV has short expiration time Trimethoprim/Sulfamethoxazole* (Bactrim) (IV/PO) D Mild to moderate infection > 30 5 mg/kg/day divided every 12H; or (1) 160/800 mg tab PO twice daily < 30 2.5 mg/kg/day; or (1) 80/400 mg tab twice daily or (1) 160/800 mg tab every 24H 5 mg/kg, 3X/week, dose post dialysis; or (2) 160/800 mg tabs, 3X/week, dose post hemodialysis Trimethoprim/Sulfamethoxazole* (Bactrim) (IV/PO) D Moderate to severe infection > 30 8-15 mg/kg/day divided every 6-12H < 30 8-15 mg/kg/day divided every 6-12H X 48H, then 4-7 mg/kg/day divided every 12H 8-15 mg/kg, may divide dose, 3X/week, dose post hemodialysis *Based on TMP component. IV has short expiration time Trimethoprim/Sulfamethoxazole* (Bactrim) (IV/PO) D Life threatening infection > 30 15-20 mg/kg/day divided every 6-12H < 30 15-20 mg/kg/day divided every 6-12H X 48H, then 4-7 mg/kg/day divided every 12H 15-20 mg/kg, may divide dose, 3X/week, dose post hemodialysis *Based on TMP component. IV has short expiration time 21

Valacyclovir (PO) F Herpes zoster > 50 1 gram every 8H 30-49 1 gram every 12H 10-29 1 gram every 24H < 10 500 mg every 24H Dose post dialysis Valacyclovir (PO) F Genital herpes (initial episode) > 50 1 gram every 12H 30-49 1 gram every 12H 10-29 1 gram every 24H < 10 500 mg every 24H Valacyclovir (PO) F Genital herpes (recurrent episodes) > 50 500 mg every 12H 30-49 500 mg every 12H 10-29 500 mg every 24H < 10 500 mg every 24H Valacyclovir (PO) F Genital herpes (suppressive therapy in immunocompetent patients) > 50 1 gram every 24H 30-49 1 gram every 24H 10-29 500 mg every 24H < 10 500 mg every 24H Valacyclovir (PO) F Genital herpes (alternative suppressive therapy in immunocompetent patients with 9 recurrences/year) > 50 500 mg every 24H 30-49 500 mg every 24H 10-29 500 mg every 48H < 10 500 mg every 48H Valacyclovir (PO) F Genital herpes (suppressive therapy in HIV-infected patients) > 50 500 mg every 12H 30-49 500 mg every 12H 10-29 500 mg every 24H < 10 500 mg every 24H Valganciclovir (PO) DF Induction therapy > 60 900 mg twice daily 40-59 450 mg twice daily 25-39 450 mg daily 10-24 450 mg every other day 450 mg every other day post hemodialysis 22

Valganciclovir (PO) DF Maintenance therapy > 60 900 mg daily 40-59 450 mg daily 25-39 450 mg every other day 10-24 450 mg twice weekly 450 mg twice weekly post hemodialysis Valganciclovir (PO) CMV prophylaxis after solid organ transplant > 60 900 mg daily 40-59 450 mg daily 39 450 mg every other day 450 mg every other day post hemodialysis Valproic Acid (IV/PO) Consult unit pharmacist for dosing adjustment recommendations. Not removed by conventional hemodialysis; removed by high Vancomycin (IV) Round doses to 500 mg, 750 mg, 1 G, or 1.5 G 100 ml/min 15-25 mg/kg load, then 10 mg/kg every 8H 80-99 ml/min 15-25 mg/kg load, then 15 mg/kg every 12H 56-79 ml/min 15-25 mg/kg load, then 10 mg/kg every 12H 40-55 ml/min 15-25 mg/kg load, then 15 mg/kg q24h 30-39 ml/min 15-25 mg/kg load, then 10 mg/kg every 24H 20-29 ml/min 15-25 mg/kg load, then 15 mg/kg every 48H <20 ml/min 15-20 mg/kg load, then monitor serum concentrations 15-20 mg/kg load, then 500-750 mg post hemodialysis, then monitor serum concentrations. Refer to UWHC guidelines. Venlafaxine (IV) ABDF > 50 Reduce dose by 25% 10-50 Reduce dose by 50% < 10 Reduce dose by 50% Reduce dose by 50%, give after dialysis Voriconazole (IV) A Requires ID approval 50 6 mg/kg every 12H x 2 doses load, then 4 mg/kg every 12H < 50 Avoid due to accumulation of IV vehicle Voriconazole (PO) A Requires ID approval 200 mg every 12H if 40 kg 100 mg every 12H if < 40 kg ADF, D, F Zoledronic Acid (IV) Adults > 60 4 mg every 3-4 weeks 50-60 3.5 mg every 3-4 weeks 40-49 3.3 mg every 3-4 weeks 30-39 3 mg every 3-4 weeks Unknown with Bone Metastases of Solid Tumors and Osteolytic Lesions of Multiple Myeloma 23

A, D, F Zoledronic Acid (IV) Osteoporosis and Paget s Disease > 35 < 35 Not recommended Unknown 24