Katie E. Cardone, PharmD, BCACPAssistant Professor, Dept. of

Pharmacy PracticeAlbany College of Pharmacy and

Health Sciences

Medication-Related Problems in Patients on Hemodialysis

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ObjectivesUpon completion of this session the participant will be able to:

Describe the complexity of medication regimens in CKD and discuss implications on outcomes.

Identify and discuss dialysis-specific factors affecting medication use.

Outline key roles for dialysis staff in prevention of medication-related problems.

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Medication Regimens in Dialysis

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CKD Stages

StageStage DefinitionDefinition GFRGFR

1Kidney damage +

normal or increased GFR

>90

2Kidney damage + Mild decrease GFR

60-89

3Moderate decrease

GFR30-59

4 Severe decrease GFR 15-29

5 Kidney failure <15 / dialysis

NKF KDOQI. Am J Kidney Dis 2002;39(2Supp1):S1-266.4

Medical Conditions in CKDDiseases causing initiation and progression of CKD

Complications of CKD

DMHTNFluid overloadHFCKD-MBDAnemiaInfectionOthers…

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Medication Regimen in Dialysis

Consists of… Complicated by…

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Treatments of underlying diseases

Prevention of CKD Progression

CKD ComplicationsMeds for other

conditions

Complicated Dosing schemesAltered PK propertiesLimited dosing data

Drug interactions Multiple prescribers Poor adherenceConfusing schedule

Resulting medication list…

Home Medications Dialysis Meds

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18. ESA 19. Iron20. Vitamin D21. Heparin 22. Others…

Medication-Related Problem

“any aspect of a patient’s drug therapy that is interfering with a desired, positive patient outcome.”

Cipolle, Strand, Morley. Pharmaceutical Care Practice: a clinician’s guide, 2nd ed. New York, NY: McGraw-Hill;2004.

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MRP Classification

Untreated indication

Failure to receive drug

Subtherapeutic dose

Over-dose

Inappropriate laboratory follow up

Drug use without medical indication

Adverse Drug Reaction

Drug interaction

Wrong drugStrand LM et al. DICP 1990;24:1093-7.9

Patients at High Risk for MRPs

5 medications in regimen

12 medication doses per day

4 changes in medication regimen per year

> 3 comorbid conditions

Non-adherence

Taking medications requiring therapeutic drug monitoring

Koecheler JA et al. Am J Hosp Pharm 1989; 46: 729 – 32. 10

Once a Patient is on Dialysis… Takes many medications. Has multiple disease states. Has DM. Is frequently hospitalized. Is non-adherent. Takes medications requiring close

monitoring. Has inaccurate records.

Manley et al. Nephrol Dial Transplant 2004;19:1842-8. • USRDS ADR 2011. • Bleyer et al. JAMA 1999;281:1211-3. • Long et al. ANNA J 1998;25:43-9. • Curtin et al. ANNA J 1999;26:307-16. • Bander et al. Curr Opin Nephrol Hypertens 1998;7:649-53. Leggat et al. Am J Kidney Dis 1998;32:139-45. •Denhaerynck et al. Am J Crit Care 2007;16:222-35. •Manley et al. Pharmacotherapy 2003;23:231-9.

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Patient Example

Home Medications Dialysis Meds

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18. ESA 19. Iron20. Vitamin D21. Heparin 22. Others…

State of the Literature in Dialysis

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Scant data

Few RCT

Changing standards

Changing Standards: e.g. Anemia

1995 2000 2005 2010 2015

1998 Higher HCT study

2007 KDOQI updates Hb target

2006 CHOIR CREATE

2006KDOQI Anemia CPG

2009 TREAT

2000K/DOQI Anemia CPG

2011 ESA PI Updated: no defined Hb target

Current Best Practices

Medication Use in Dialysis

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Common Complications of CKD

Anemia

CKD-MBD

Hypertension

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Causes of Anemia in CKDBlood Loss (esp. dialysis patients)

Hemodialysis tubingNumerous blood testsBleeding (anticoagulation)

HemolysisDecreased RBC lifespanHD process

Decreased Production of RBCDecreased EPO production

LOSS

DESTRUCTION

LOW PRODUCTION

Anemia of CKD Goals

Prevent transfusionPrevent CV events Maintain QOL

PharmacotherapyIronErythropoiesis Stimulating Agents

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Iron Preparations

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Iron Dextran Sodium Ferric GluconateIron Sucrose Ferumoxytol

ESA Therapy

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Epoetin AlfaDarbepoetin AlfaPeginesatide

Anemia of CKD: Resources

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FDA – approved labeling

Clinical Practice GuidelinesKDIGO to be released soon

Common Complications of CKD

Anemia

CKD-MBD

Hypertension

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CKD-MBDGoal: Prevent CV and fracture events,

hospitalizations, QOLBone Disease and Vascular Calcification

PTH, Vitamin D, Phosphorus and Calcium

Pharmacotherapy:Phosphate BindersVitamin DCalcimimetic

23KDIGO. Kidney Int Suppl. 2009 Aug;(113):S1-130.

Phosphate Binders

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Calcium-based Calcium CarbonateCalcium Acetate

Non-Calcium based Sevelamer saltsLanthanum

KDIGO. Kidney Int Suppl. 2009 Aug;(113):S1-130.

Vitamin D

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25(OH) DD2D3

1,25(OH) DD2D3

AnalogsDoxercalciferol Paricalcitol

Uses differ based on product and CKD stage

OTC vs Rx

Effect on PTH

Side effects

KDIGO. Kidney Int Suppl. 2009 Aug;(113):S1-130.

Calcimimetic

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Cinacalcet

Common Complications of CKD

Anemia

CKD-MBD

Hypertension

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Blood Pressure Management in Dialysis

BP Goal: UnclearKDOQI CV in Dialysis

PreHD < 140/90 mmHgPostHD < 130/80 mmHg

KDOQI AdequacyNo Specific Goal

Which BP should be used for assessment?

KDOQI. Am J Kidney Dis 2005; 45:S1-153.KDOQI . Am J Kidney Dis 2006; 48: S2-90.

Blood Pressure Management in Dialysis Goal

Prevent CV eventsNo clear BP target

Pharmacotherapy must be used in conjunction with non-pharmacologic methods. Sodium Fluid

Medication selection individualized to patient

29Levin et al. Kidney Int. 2010;77(4):273-84.

Blood Pressure Management in Dialysis

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Medication Selection should be individualized

BB, ACEi, ARB, DRI, CCB, Vasodilator, Diuretics, Etc.

Selection based on Co-morbid conditionsKnown adverse effects of each class and/or

individual drugCostDrug InteractionsDialyzability Duration of action

Dosage and schedule must be individualized. Levin et al. Kidney Int. 2010;77(4):273-84.

Special Considerations

Patients on Dialysis

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Medication Considerations in Dialysis

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Dialysis Factors: Removal of DrugsIntradialytic

complicationsSchedule

Patient Factors: Co-morbid conditionsFinances Transportation AttitudesAdherence

Healthcare System FactorsRecord Keeping Communication Many ProvidersProvider EducationMedication ProtocolsESRD PPS

Misc. Lack of dosing data Lack of evidence for

drug efficacy or safetyAccess to information

Dialysis Removal of DrugsMolecular Weight / SizeProtein BindingVolume of Distribution Water Solubility Plasma ClearanceDialysis MembraneBlood and Dialysate Flow Rates

Johnson CA. 2010 Dialysis of Drugs. www.ckdinsights.com 33

Key Roles of Dialysis StaffUpdate records:

Medication reconciliation “Diagnosis reconciliation” Post-hospitalization coordination

Aid Patients:Education Identify concerns/questionsHelp patients understand insurance

Communication

Referral

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Medication Regimen Review

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1. Obtain accurate medication list 2. Evaluate necessity of each medication 3. Determine whether each medication is the

optimal choice4. Assess dosage and dosing regimen5. Review the medication list for interactions,

adverse effects6. Ensure proper monitoring7. Assess medication adherence8. Update medication list in record

Mason NA, Bakus J. Semin Dial 2009;23:55-61.

Drug Information for Dialysis Staff

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Primary Literature

Secondary Literature

Tertiary Literature

Malone, Keir, Stanovich, eds. Drug information: a guide for pharmacists, 3rd ed. New York, NY: McGraw-Hill;2006.

Common Tertiary Sources in Dialysis

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Physicians’ Desk Reference

Drugs Information Handbook

Dialysis of Drugs

Johnson CA. 2009 Dialysis of Drugs. www.ckdinsights.com/downloads/DialysisDrugs2009.pdf

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Useful Online Sources

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PubMed http://www.ncbi.nlm.nih.gov/pubmed/ National Guideline Clearinghouse

http://www.guidelines.gov KDIGO http://www.kdigo.org National Kidney Foundation

http://www.kidney.org Medscape http://www.medscape.com DailyMed http://dailymed.nlm.nih.gov Medline Plus

http://www.nlm.nih.gov/medlineplus/

ObjectivesUpon completion of this session the participant will be able to:

Describe the complexity of medication regimens in CKD and discuss implications on outcomes.

Identify and discuss dialysis-specific factors affecting medication use.

Outline key roles for dialysis staff in prevention of medication-related problems.

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Katie Cardone, PharmD, BCACPAssistant Professor, Dept. of Pharmacy PracticeAlbany College of Pharmacy and Health Scienceskatie.cardone@acphs.edu

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