MEDICATION MANAGEMENT IN GERIATIC CKD · Geriatric CKD Jessica Goh Senior Pharmacist 1 10 SEPTEMBER...

Medication Management In Geriatric CKD

Jessica Goh

Senior Pharmacist

1

10 SEPTEMBER 2016

Pharmacokinetic-Pharmacodynamic (PK-PD) Changes In Elderly

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PHARMACOKINETICS (PK)

ABSORPTION: process of drug entering blood stream

DISTRIBUTION : dispersion/dissemination of drug to fluids and tissue in body

METABOLISM : irreversible conversion of parent compounds to metabolites

EXCRETION : elimination of metabolites from body

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PK CHANGES IN ELDERLY Absorption

PO Meds

-Vitamin B12, Calcium and iron have absorption

in elderly due to gastric pH or GI motility

-Patients with heart failure may have blood flow

to the GIT, leading to absorption

Topical

-Skin atrophies with aging reduced blood flow,

impaired transdermal absorption

IM/SC meds

-Elderly have muscle mass poorer perfusion

4 Delafuente et al. Consult Pharm 2008

PK CHANGES IN ELDERLY

Distribution

- total body water Affects water-soluble drugs (eg digoxin, theophylline, morphine) due to Vd Higher serum drug concentrations

- muscle mass Distribution to lean tissue is smaller Lower doses required

-Higher body fat Affects lipid soluble drugs (eg phenytoin,valproate, diazepam) as they have larger Vd Longer duration of action as they are bound to the body longer

-Lower dose or frequency interval required

5 Delafuente et al. Consult Pharm 2008

PK CHANGES IN ELDERLY

Distribution

- albumin concentrations (malnourished/frail/prolonged illness) More unbound drugs Higher serum concentrations of free drug

-Uremic toxins protein binding

affinity for drugs (eg penicillins,

phenytoin,Theophylline) = free

(unbound)drug concentrations

6

Delafuente et al. Consult Pharm 2008

PK CHANGES IN ELDERLY

Metabolism

-Drugs undergoes metabolism in the liver via Phase 1 and Phase 2 reactions

-Aging causes liver to be smaller poorer liver blood perfusion

-Phase 1 (oxidation/reduction/hydrolysis) liver metabolism is in older patients

-CYP system is responsible for Phase 1 reactions of many medications. >50% of drugs undergo CYP3A4 metabolism

-Phase 2 reactions : not affected with aging

7 Delafuente et al. Consult Pharm 2008

PK CHANGES IN ELDERLY

Elimination

-as CrCl drug clearance by tubular secretion and glomerular filtration

-Renal function may be “overestimated” due to low muscle mass

8 Delafuente et al. Consult Pharm 2008

PD CHANGES IN ELDERLY

-Blunted baroreflex responses

- inotropic and chronotropic responses to β1adrenergic stimulation

-Increased sensitivity to agents that act on the central nervous system (CNS)

9 Delafuente et al. Consult Pharm 2008

ADJUSTING MEDICATIONS IN GERIATRIC CKD

-General rule of thumb: Start low, Go s l o w

-Avoid long acting agents in elderly

-Some dosage adjustments may be based on CrCl (derived from Cockcroft-Gault equation) or eGFR

-Beers Criteria

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*Adjustments quoted in the following slides

are for non-dialysis CKD patients

Antibiotics In Geriatric CKD

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PO ACYCLOVIR

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Drugs Renal Fxn Dose Max Dose

Acyclovir CrCl 10-25 Recommended Dose

q8H

800mg/dose

2.4g/day

CrCl <10 Recommended Dose

q12H

800mg/dose

1.6g/day

Caution • Potential risk for crystalluria

• Nephrotoxicity risk with concurrent

nephrotoxic agents (ACE/ARB, NSAIDs,

Colchicine) or dehydration

• Potential Risk for neurotoxicity

UptoDate 2016

13 http://www.cfps.org.sg/publications/the-college-mirror/article/994

ACYCLOVIR TOXICITY IN CKD The College Mirror, Vol 42, March 2016

ACYCLOVIR NEUROTOXICITY IN CKD

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The College Mirror, Vol 42, March 2016

ANTIBIOTIC ASSOCIATED DELIRIUM

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ANTIBIOTIC ASSOCIATED DELIRIUM

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ANTIBIOTIC ASSOCIATED DELIRIUM

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DRUG ASSOCIATED WITH COGNITIVE IMPAIRMENT IN ELDERLY

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Moore AR et al .Drugs Aging 1999.

PO ANTIBIOTICS

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Drugs Renal

Function

Dose Max Dose

Amoxicillin CrCl 10-30 500mg BD 0.5-1g/day

CrCl <10 500mg OD

Augmentin CrCl 10-30 625mg BD

CrCl <10 625mg OD

Penicillin V Use with

caution in

renal

dysfunction

Usual:

500mg q6H

4g/day

UptoDate, Micromedex 2016

PO ANTIBIOTICS

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Drugs Renal Fxn Dose

Bactrim Dosed based on TMP component Single Strength:(TMP 80 mg/SMX 400 mg)=480mg

Double Strength:(TMP 160 mg/SMX 800 mg)=960mg

*Maintain adequate hydration to prevent crystalluria

CrCl 15-30 50% of

dose

CrCl <15 Avoid

Nitrofurantoin

Avoid in elderly due to risk for

pulmonary toxicity

Contraindicated in

CrCl <60ml/min

(ineffective)

UptoDate, Micromedex 2016

SULFONAMIDE CRYSTALLURIA

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UptoDate 2016

PO ANTIBIOTICS

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Drugs Renal

Function

Dose Max Dose

Cefuroxime CrCl 10-30 500mg q24H 500mg/day

CrCl <10 500mg q48H 250mg/day

Nitrofurantoin Avoid in elderly due to risk for pulmonary

toxicity

Contraindicated in CrCl <60ml/min

UptoDate, Micromedex 2016

ANTIBIOTICS NO RENAL ADJUSTMENT REQUIRED

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Drugs Max Dose

(per day)

Azithromycin 500mg

Cloxacillin 6g

Clindamycin 1.8g

Doxycycline 200mg

Ceftriaxone 4g

Metronidazole 4g**

Moxifloxacin 400mg

**varying practice UptoDate, Micromedex 2016

PO ANTIBIOTICS

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Drugs Renal Fxn Dose

Ciprofloxacin CrCl <30 500mg OM

Levofloxacin CrCl 20-49 500mg/day:

500 mg STAT, then 250 mg q24H

750mg/day:

750mg q48H

CrCl 10-19 500mg/day:

500 mg STAT, then 250 mg q48H

750mg/day:

500 mg STAT, then 500mg q48H

UptoDate, Micromedex 2016

DRUG-DRUG INTERACTIONS

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Oral Hypoglycemic Agents (OHGAs)

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METFORMIN

-First line agent for Type 2 Diabetes

-Low hypoglycemic risks

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eGFR Dose adjustments

45 to <60 mL/min Monitor renal function

3-6monthly

≥30 to <45

mL/min

Use with caution, may

consider dosage reduction

<30 mL/min Avoid

American Diabetes Association, UptoDate, Micromedex 2016

SULPHONYLUREAS Drug Duration Excretion Renal Adjustment

First Generation

Chlorpropamide 24-72h Urine (unchanged drug and as

hydroxylated metabolites)

T/12 : ~36 hrs; prolonged in

elderly .ESRD : 50-200 hrs

CrCl >50 mL/min: by50%.

CrCl <50 mL/min: Avoid use.

Tolbutamide 14 -16h Urine (75% -85% as

metabolites. Metabolism not

affected by age

No dosage adjustment

available

Second Generation

Glipizide 14 -16h Urine (<10% as unchanged

drug; 80% as metabolites)

Less hypoglycemia in renal

impairment than other SUs.

Start low dose.

Glicazide 24 h Urine (60% to 70%; <1% as

unchanged drug

Mild to Mod: Adjust slowly

Severe impairment: Avoid

Glibenclamide 20 -

24+h

Urine (50%)metabolites eGFR <60 mL/min: Avoid

Glimepiride 24+ h Urine (60%, 80% -90% as M1

and M2 metabolites)

Severe impairment: Avoid

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UptoDate, Micromedex 2016

HSA ALERT -GLIBENCLAMIDE

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DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS

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Drug Renal Function Elimination Dose

Adjustment

Sitagliptin CrCl ≥30 -49

mL/min

Excretion: Urine

87% (~79% as

unchanged drug,

16% as

metabolites)

50mg OD

CrCl <30 mL/min 25mg OD

Saxagliptin CrCl ≤50 mL/min Urine (75%) 2.5 mg OD

Linagliptin Regardless of

renal function

80% cleared in

feces

5mg OD

None required

UptoDate, Micromedex 2016

-Low hypoglycemic risks

MEGLITINIDES •Faster onset and shorter duration of effect than sulfonylureas

•Low risk of hypoglycemia

•Good for patient who are sulfonamides or sulphur allergy

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Drug Duration Renal

function

Dosage

adjustment Elimination

Repaglinide

4-6h

CrCl

20-40

Initial: 0.5 mg

with meals;

titrate carefully.

Feces

(~90%)

CrCl <20 Not studied

Nateglinide

4h

N/A No adjustment

required

Urine (83%)

UptoDate, Micromedex 2016

OTHER OHGAs

Drug Renal function Adjustment

Alpha-Glucosidase

Inhibitors

Eg Acarbose

CrCl <25 mL/min or Scr

>2mg/dL or 177umol/L

Avoid

Sodium-Glucose Cotransporter 2 Inhibitors

Canagliflozin eGFR 45 to <60 mL/min Max 100mg

eGFR <45 mL/min Avoid

Dapagliflozin eGFR 30 to <60 mL/min Avoid

Empagliflozin eGFR <45 mL/min Avoid

Thiazolidinediones None required. Need to

adjust for hepatic

Avoid in patients with

advanced CKD, especially

those with preexisting heart

failure, given the risk of

edema and heart failure

32 UptoDate, Micromedex 2016

SUMMARY SLIDE ON OHGAs

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CKD

Stage

eGFR Metformin SU Meglitnide DPP4 SGLT2 Acarbose Thiazolid-

inediones

3A 45-59 √ √* √ √ √ √ √

3B 30-44 √ √* √ √* X √ √

4 15-29 X √* √* √* X X √*

5 <15 X √* √* √* X X √*

*requires renal adjustment/only certain agents in drug class

recommended-conditions apply

PAINKILLERS IN GERIATRIC CKD

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PAINKILLERS

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2012 AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults

PAINKILLERS

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2012 AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults

PAINKILLERS

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2012 AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults

PAINKILLERS-START LOW

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UptoDate 2016

DRUG ASSOCIATED WITH COGNITIVE IMPAIRMENT IN ELDERLY

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Moore AR et al .Drugs Aging 1999.

Antihypertensives In Geriatric CKD

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ACEI/ARB + DIURETICS + NSAIDS & NEPHROTOXICITY

•Acute kidney injury risk increases by 31%, with the highest risk occurring in the first month of use

• Triple whammy!

41 Lapi et al. BMJ. 2013;346:e8525

WHAT BP TARGETS DO WE USE FOR ELDERLY?

Guidelines Population Goal BP, mm Hg Remarks

JNC8 2014 General ≥60 y <150/90

Diabetes <140/90

CKD <140/90

ESH/ESC 2013 General elderly <80 y <150/90 *For fragile

elderly, SBP

goals should be

adapted to

individual

tolerability

General ≥80 y <150/90

Diabetes <140/85

CKD no proteinuria <140/90

CKD + proteinuria <130/90

CHEP 2013 General ≥80 y <150/90

Diabetes <130/80

CKD <140/90

NICE 2011 General ≥80 y <150/90

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Abbreviations: CHEP, Canadian Hypertension Education Program; JNC, Joint National Committee; ESC, European Society of

Cardiology; ESH, European Society of Hypertension; NICE, National Institute for Health Clinical Excellence.

ANTIHYPERTENSIVES ARE ASSOCIATED WITH FALL RISKS!!

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ADVERSE DRUG EVENTS

44 Hanlon JT et al. J Am Geriatr Soc 1997

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POLYPHARMACY- BANE OR BOON?

TAKE HOME MESSAGES

•Start low, Go s l o w

•Avoid polypharmacy

•Consider potential drug interactions

•Review patients & medications regularly

•Keep regimens simple

46

Br J Clinc Pharmaco 1998; 46:531-533

THANK YOU!

47

goh.jessica.hf@alexandrahealth.com.sg

CASE STUDY 1

Medication list

Aspirin 100 mg OM

Metformin 250g BD

Glibenclamide 10 mg BD

Madopar 62.5mg qds during waking hours

Lactulose 10ml BD

Simvastatin 40 mg ON

68y M, was found drowsy and referred to ED for hypoglycemia.He was recently prescribed a week course of Clarithromycin 500mg BD for URTI. PMH:T2DM, Hypertension , Parkinson disease, Dyslipidaemia and CKD Stage 3 What do you think could have caused his hypoglycemia?

HSA ALERT -GLIBENCLAMIDE

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DRUG-DRUG INTERACTIONS

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CASE STUDY 2

At the clinic, he brought his own meds from GP.

Co-Diovan(Valsartan 80mg/HCTZ 12.5mg) 1/1 OM

Allopurinol 100mg OM –withheld by GP due to ARF

Colchicine 500mcg TDS prn for gout flare

Diclofenac 50mg TDS prn

70y M, taxi driver, was referred to Nephrology clinic for AKI. Serum creatinine was 131umol/L. PMH: Gout, Hypertension What do you think could have caused his AKI?

ACEI/ARB + DIURETICS + NSAIDS & NEPHROTOXICITY

•Acute kidney injury risk increases by 31%, with the highest risk occurring in the first month of use

• Triple whammy!

52 Lapi et al. BMJ. 2013;346:e8525

THANK YOU!

53

goh.jessica.hf@alexandrahealth.com.sg