Katie E. Cardone, PharmD, BCACP

1
Medication-Related Problems in Patients on
Hemodialysis

• Katie E. Cardone, PharmD, BCACP
• Assistant Professor, Dept. of Pharmacy Practice
• Albany College of Pharmacy and Health Sciences

2
Objectives

• Upon 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.

3
Medication Regimens in Dialysis
4
CKD Stages
Stage Definition GFR
1 Kidney damage normal or increased GFR gt90
2 Kidney damage Mild decrease GFR 60-89
3 Moderate decrease GFR 30-59
4 Severe decrease GFR 15-29
5 Kidney failure lt15 / dialysis
NKF KDOQI. Am J Kidney Dis 200239(2Supp1)S1-266.
5
Medical Conditions in CKD

• Diseases causing initiation and progression of
  CKD
• Complications of CKD

• DM
• HTN
• Fluid overload
• HF
• CKD-MBD
• Anemia
• Infection
• Others

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Medication Regimen in Dialysis

• Consists of

• Complicated by

• Treatments of underlying diseases
• Prevention of CKD Progression
• CKD Complications
• Meds for other conditions

• Complicated Dosing schemes
• Altered PK properties
• Limited dosing data
• Drug interactions
• Multiple prescribers
• Poor adherence
• Confusing schedule

7
Resulting medication list

• Home Medications

• Dialysis Meds

1. ESA
2. Iron
3. Vitamin D
4. Heparin
5. Others

1. EMLA Cream
2. Nephplex Rx
3. PhosLo
4. Gabapentin
5. Flomax
6. Novolog
7. Lantus
8. Vitamin B12
9. Omeprazole
10. Nexium
11. Lisinopril
12. Metoprolol succinate
13. Midodrine
14. Amiodarone
15. Pramipexole
16. ASA

8
Medication-Related Problem

• any aspect of a patients drug therapy that is
  interfering with a desired, positive patient
  outcome.

Cipolle, Strand, Morley. Pharmaceutical Care
Practice a clinicians guide, 2nd ed. New York,
NY McGraw-Hill2004.
9
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 drug

Strand LM et al. DICP 1990241093-7.
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Patients at High Risk for MRPs

• ? 5 medications in regimen
• ? 12 medication doses per day
• ? 4 changes in medication regimen per year
• gt 3 comorbid conditions
• Non-adherence
• Taking medications requiring therapeutic drug
  monitoring

Koecheler JA et al. Am J Hosp Pharm 1989 46
729 32.
11
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
2004191842-8. USRDS ADR 2011. Bleyer et al.
JAMA 19992811211-3. Long et al. ANNA J
19982543-9. Curtin et al. ANNA J
199926307-16. Bander et al. Curr Opin Nephrol
Hypertens 19987649-53. Leggat et al. Am J
Kidney Dis 199832139-45. Denhaerynck et al. Am
J Crit Care 200716222-35. Manley et al.
Pharmacotherapy 200323231-9.
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Patient Example

• Home Medications

• Dialysis Meds

1. ESA
2. Iron
3. Vitamin D
4. Heparin
5. Others

1. EMLA Cream
2. Nephplex Rx
3. PhosLo
4. Gabapentin
5. Flomax
6. Novolog
7. Lantus
8. Vitamin B12
9. Omeprazole
10. Nexium
11. Lisinopril
12. Metoprolol succinate
13. Midodrine
14. Amiodarone
15. Pramipexole
16. ASA

13
State of the Literature in Dialysis

• Scant data
• Few RCT
• Changing standards

14
Changing Standards e.g. Anemia
2011 ESA PI Updated no defined Hb target
2006 KDOQI Anemia CPG
2009 TREAT
1998 Higher HCT study
1995 2000 2005 2010 2015
2000 K/DOQI Anemia CPG
2007 KDOQI updates Hb target
2006 CHOIR CREATE
15
Current Best Practices

• Medication Use in Dialysis

16
Common Complications of CKD

• Anemia
• CKD-MBD
• Hypertension

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Causes of Anemia in CKD

• Blood Loss (esp. dialysis patients)
• Hemodialysis tubing
• Numerous blood tests
• Bleeding (anticoagulation)
• Hemolysis
• Decreased RBC lifespan
• HD process
• Decreased Production of RBC
• Decreased EPO production

LOSS
DESTRUCTION
LOW PRODUCTION
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Anemia of CKD

• Goals
• Prevent transfusion
• Prevent CV events
• Maintain QOL
• Pharmacotherapy
• Iron
• Erythropoiesis Stimulating Agents

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Iron Preparations

• Iron Dextran
• Sodium Ferric Gluconate
• Iron Sucrose
• Ferumoxytol

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ESA Therapy

• Epoetin Alfa
• Darbepoetin Alfa
• Peginesatide

21
Anemia of CKD Resources

• FDA approved labeling
• Clinical Practice Guidelines
• KDIGO to be released soon

22
Common Complications of CKD

• Anemia
• CKD-MBD
• Hypertension

23
CKD-MBD

• Goal Prevent CV and fracture events,
  hospitalizations, QOL
• Bone Disease and Vascular Calcification
• PTH, Vitamin D, Phosphorus and Calcium
• Pharmacotherapy
• Phosphate Binders
• Vitamin D
• Calcimimetic

KDIGO. Kidney Int Suppl. 2009 Aug(113)S1-130.
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Phosphate Binders

• Calcium-based
• Calcium Carbonate
• Calcium Acetate
• Non-Calcium based
• Sevelamer salts
• Lanthanum

KDIGO. Kidney Int Suppl. 2009 Aug(113)S1-130.
25
Vitamin D

• 25(OH) D
• D2
• D3
• 1,25(OH) D
• D2
• D3
• Analogs
• Doxercalciferol
• 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.
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Calcimimetic

• Cinacalcet

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Common Complications of CKD

• Anemia
• CKD-MBD
• Hypertension

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Blood Pressure Management in Dialysis

• BP Goal Unclear
• KDOQI CV in Dialysis
• PreHD lt 140/90 mmHg
• PostHD lt 130/80 mmHg
• KDOQI Adequacy
• No Specific Goal
• Which BP should be used for assessment?

KDOQI. Am J Kidney Dis 2005 45S1-153. KDOQI .
Am J Kidney Dis 2006 48 S2-90.
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Blood Pressure Management in Dialysis

• Goal
• Prevent CV events
• No clear BP target
• Pharmacotherapy must be used in conjunction with
  non-pharmacologic methods.
• Sodium
• Fluid
• Medication selection individualized to patient

Levin et al. Kidney Int. 201077(4)273-84.
30
Blood Pressure Management in Dialysis

• Medication Selection should be individualized
• BB, ACEi, ARB, DRI, CCB, Vasodilator, Diuretics,
  Etc.
• Selection based on
• Co-morbid conditions
• Known adverse effects of each class and/or
  individual drug
• Cost
• Drug Interactions
• Dialyzability
• Duration of action
• Dosage and schedule must be individualized.

Levin et al. Kidney Int. 201077(4)273-84.
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Special Considerations

• Patients on Dialysis

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Medication Considerations in Dialysis

• Dialysis Factors
• Removal of Drugs
• Intradialytic complications
• Schedule
• Patient Factors
• Co-morbid conditions
• Finances
• Transportation
• Attitudes
• Adherence

• Healthcare System Factors
• Record Keeping
• Communication
• Many Providers
• Provider Education
• Medication Protocols
• ESRD PPS
• Misc.
• Lack of dosing data
• Lack of evidence for drug efficacy or safety
• Access to information

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Dialysis Removal of Drugs

• Molecular Weight / Size
• Protein Binding
• Volume of Distribution
• Water Solubility
• Plasma Clearance
• Dialysis Membrane
• Blood and Dialysate Flow Rates

Johnson CA. 2010 Dialysis of Drugs.
www.ckdinsights.com
34
Key Roles of Dialysis Staff

• Update records
• Medication reconciliation
• Diagnosis reconciliation
• Post-hospitalization coordination
• Aid Patients
• Education
• Identify concerns/questions
• Help patients understand insurance
• Communication
• Referral

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Medication Regimen Review

1. Obtain accurate medication list
2. Evaluate necessity of each medication
3. Determine whether each medication is the optimal
   choice
4. Assess dosage and dosing regimen
5. Review the medication list for interactions,
   adverse effects
6. Ensure proper monitoring
7. Assess medication adherence
8. Update medication list in record

Mason NA, Bakus J. Semin Dial 20092355-61.
36
Drug Information for Dialysis Staff

• Primary Literature
• Secondary Literature
• Tertiary Literature

Malone, Keir, Stanovich, eds. Drug information a
guide for pharmacists, 3rd ed. New York, NY
McGraw-Hill2006.
37
Common Tertiary Sources in Dialysis

• Physicians Desk Reference
• Drugs Information Handbook
• Dialysis of Drugs

38
Johnson CA. 2009 Dialysis of Drugs.
www.ckdinsights.com/downloads/DialysisDrugs2009.pd
f
39
Useful Online Sources

• 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/

40
Objectives

• Upon 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.

41
Katie Cardone, PharmD, BCACP

• Assistant Professor, Dept. of Pharmacy Practice
• Albany College of Pharmacy and Health Sciences
• katie.cardone_at_acphs.edu