Download COMMON PACE MEDICATIONS THAT REQUIRE RENAL DOSING

COMMON PACE
MEDICATIONS
THAT REQUIRE RENAL
DOSING
NPA Conference October 20,2015
Presented by
Lauren Staley, PharmD
Nicole Hermansader, PharmD
OBJECTIVES
 Why Do We Renally Dose Medications?
 The Aging Kidney
 Calculating Renal Clearance
 Renal Dosing for the Elderly
 Common PACE Medications That Require Renal Dosing
WHY DO WE RENALLY DOSE MEDICATIONS?
 Adverse Drug Reactions
are 3-10 times higher
in those with CKD
compared to those
without 1
 Many drugs and drug
metabolites eliminated
by kidney filtration
 Few medications well
studied in elderly and
CKD
THE AGING KIDNEY
Changes in kidney
structure 1
 Decrease in size and areas
of filtration
 Decrease in the number of
nephrons
 Nephron sclerosis
Decreased renal
blood flow 2
THE AGING KIDNEY
 CVD, hypertension, diabetes, tobacco use, and high
protein diet add to renal stress 1
 High incidence in the elderly in the United States
 Changes absorption, protein binding, volume of distribution and
clearance
 Other factors
 Drug interactions
 Nephrotoxic drugs
 Dehydration
CALCULATING RENAL FUNCTION
MDRD Study Equation
Cockcroft-Gault Equation 3,4
CrCl= (140 - age) x IBW x (0.85 if F)
( 7 2 x SC r )
 Used to calculate eGFR
when a SCr lab test is
ordered
 Used for staging CKD
 Best estimate of renal
function in the elderly
 Used to determine dosing for
drug labeling
 Developed using “average” men
 Healthy, middle-aged, approximately
70 kg
 IBW ver sus actual
 Using IBW can underestimate CrCl
 Using ABW in obese (BMI >30) can
overestimate CrCl
 Production/elimination of SCr
decreases with age 1
 May overestimate CrCl in older adult
RENAL DOSING FOR THE ELDERLY
 Medical History

Kidney Disease




Acute vs. chronic
Etiology
Obtain comprehensive medication list
Calculate BMI
 Calculate CrCl using Cockcroft-Gault equation
 Loading Dose
 Most likely NOT adjusted in renal impairment
 Reduced if V D is significantly decreased (i.e. dialysis) 1
RENAL DOSING FOR THE ELDERLY
 Determine Maintenance Dose
 Dose reduction
 Extend dosing interval
 Therapeutic Drug Monitoring
 Peaks/troughs
 Reserved for agents with serum levels correlated with toxicity or
efficacy
 Aminoglycosides, digoxin, lithium,
phenytoin (free unbound), vancomycin 1
ANTIBIOTICS
Nitrofurantoin
 Contraindicated if est. CrCl <60 ml/min 5
 Inadequate bladder concentration
 Peripheral neuropathy, pulmonary and hepato -toxicity
Ciprofloxacin and levofloxacin
 Renal dose adjust for CrCl <50 ml/min 5
 Tendon rupture, QTc prolongation
ANTIBIOTICS
Sulfamethoxazole/trimethoprim
 For estimated CrCl <30 ml/min, reduce dose by 50% 5
 Change in mental status, hyperkalemia
Amoxicillin/clavulanate
 For CrCl <30 ml/min:
 Avoid 875 mg and XR
 Reduce to Q12H 5
 Q24H for dialysis 5
5
 Avoid serious adverse GI effects
ANTIFUNGAL
Fluconazole
 No adjustment needed for single dose vaginal candidiasis 5
 For CrCl ≤50 mL/minute (no dialysis), reduce maintenance dose by
50% 5
 No change to loading dose (maximum 400 mg)
 QTc prolongation risk
 Dose dependent clinical drug interactions due to P450 inhibition
 Strong 2C19 (clopidogrel substrate)
 Moderate 3A4 (statins)
ANTIVIRALS
Acyclovir
 800 mg PO 5 times/day herpes zoster outbreak 5
 Reduce to Q8H for CrCl <25 ml/min. 5
 Reduced to Q12H in HD or CrCl <10 ml/min.
5
Valcyclovir
 Renal dose adjustments for CrCl <50 ml/min 5
 Extending dosing interval
ANTICOAGULANTS
Injectable
 Lovenox (enoxaparin)
 Dose adjust when
CrCl <30 ml/min 6
Oral
 Pradaxa (dabigatran)
 Xarelto (rivaroxaban)
 Eliquis (apixaban)
Not adjusting the dose for reduced renal function
increases the risk of bleeding!
LOVENOX (ENOXAPARIN) 6
Indication
Recommended Dose
Dose Adjusted for
CrCl < 30 mL/min
DVT prophylaxis in abdominal
surgery
40 mg SC once daily
30 mg SC once daily
DVT prophylaxis in knee
replacement surgery
30 mg SC every 12 hours
30 mg SC once daily
DVT prophylaxis in hip
replacement surgery
30 mg SC every 12 hours or 40 mg SC
once daily
30 mg SC once daily
DVT prophylaxis in medical
patients
40 mg SC once daily
30 mg SC once daily
Inpatient treatment of acute DVT 1 mg/kg SC every 12 hours or
with or without pulmonary
1.5 mg/kg SC once daily
embolism
1 mg/kg SC once daily
Outpatient treatment of acute
DVT without pulmonary
embolism
1 mg/kg SC once daily
1 mg/kg SC every 12 hours
ORAL ANTICOAGULANTS
Medication
Indication
Pradaxa
(Dabigatran
etexilate)5
1.
Xarelto
(Rivaroxaban)
1.
5
2.
2.
3.
Eliquis
(Apixaban) 5
1.
2.
3.
Recommended
Dosing
Atrial
fibrillation
DVT and PE
1.
2.
DVT/PE
treatment
DVT
prophylaxis
Atrial
fibrillation
1.
150 mg BID
150 mg BID
Renal Dose
Adjustments
1.
2.
HD
CrCl 15 to 30ml/min: 75mg BID
CrCl <15 ml/min: Not studied
CrCl <30 ml/min: Not studied
Not
studied
1.
2.
3.
CrCl <30 ml/min: Avoid use
CrCl <30 ml/min: Avoid use
CrCl 15 to 50 ml/min: 15mg
QPM
CrCl <15 ml/min: Avoid use
Avoid Use
2.
3.
15 mg BID x 21 days
then 20 mg daily
10 mg once daily
20 mg QPM
DVT or PE
1.
treatment and
prevention
Prophylaxis
Atrial
2.
fibrillation
3.
10 mg BID x 7 days,
then 5 mg BID for at
least 6 months, then
2.5 mg BID
2.5 mg BID
5 mg BID
1.
Scr >2.5 mg/dL or CrCl <25
ml/min: Not studied
CrCl <30 ml/min: Not studied
Any 2 of the following: Age ≥80
years, weight ≤60 kg, or Scr ≥
1.5 mg/dL: 2.5 mg BID
Avoid Use
2.
3.
ACID REDUCERS
 Ranitidine



If CrCl <50 ml/min, recommend 150 mg daily 5
Titrating upward cautiously as needed
Adverse CNS effects


Vertigo, mental confusion, somnolence
Falls Risk
 Famotidine
 For CrCl <50 ml/min, give 50% of normal dose
OR
 Extend interval to every 36-48 hours 5
ANTICONVULSANTS
Levetiracetam
 Dose adjust when CrCl <80 ml/min 7
Gabapentin
 Dose adjust when CrCl <60 ml/min 5
Lyrica (pregabalin)
 Dose adjust when CrCl <60 ml/min 5
Not adjusting the dose for renal impairment
increases level of sedation, increasing falls risk!
ANTIDIABETICS
Metformin
 Use Contraindicated : SCr ≥1.5 mg/dL (males) or ≥1.4 mg/dL (females) 8
 Due to the risk of lactic acidosis
 However…
 Experts suggest use should be allowed in mild to moderate renal impairment
with stable renal function and close monitoring 8
 Incidence of lactic acidosis very rare
 ADA and other organizations agree that avoiding use with above SCr thresholds
may be overly restrictive
Approach for Prescribing Metformin in
Renal Dysfunction8
CrCl (ml/min)
Maximum Daily Dose
>60
2,550 mg
45-59
2,000 mg
30-44
1,000 mg
<30
Do not use
ANTIDIABETICS
 Januvia (sitagliptan)




100 mg if CrCl ≥50 ml/min 5
50 mg if CrCl 30-49 ml/min 5
25 mg if CrCl <30 ml/min 5
Hypoglycemic events
 Glyburide
 High Alert Drug (BEERS) 9
 Extremely long half life in
geriatrics
 Hypoglycemic events
ANTIHYPERTENSIVES
Atenolol
 Maximum 50 mg daily if CrCl between 15-35 ml/min 5
 Maximum 25 mg daily if CrCl <15 ml/min 5
 Bisoprolol
 Initiate 2.5 mg daily if CrCl <40 ml/min, titrate cautiously 5
Lisinopril
 Start 2.5 mg daily if CrCl <30 ml/min 5
Quinapril
 CrCl 10-30 ml/min, give 2.5 mg daily 5
 Recommendations differ per indication CHF vs. HTN
NMDA RECEPTOR ANTAGONIST
Namenda (memantine) 5
 Dose adjust for severe impairment CrCl 5-29 ml/min
 5 mg daily for 1 week, if tolerated increase to 5 mg twice daily
 Namenda XR maximum 14 mg daily
 Adverse GI effects, dizziness, drowsiness,
confusion, etc.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
O l ya e i , A l i , a n d W i l l i am B e n n et t . " D r ug D o s i n g a n d Re n a l Tox i ci t y i n t h e E l d e r ly
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< h t t p s : / / w w w. a s n o n l i n e . o r g / ed uc a t i o n / d is t a n c el e a r n i n g / c ur r i c ula / g e r i a t r ic s / C h a p te r 9 . p d f > .
We i n s te i n J , A n d e r s o n S . T h e A g i n g K i d n ey : P hy s i o l o g i ca l C h a n g e s . A d v C h r o n i c
K i d n ey D i s . 2 01 0 J u l ; 17 ( 4 ) : 3 0 2 – 3 07. d o i : 1 0 .1 0 5 3 / j . ac k d . 2 010 . 0 5 . 0 0 2 .
h t t p : / / w w w. n c b i. n l m. n i h .g ov / p m c/ a r t i c le s / P M C 2 9 016 2 2
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RO S T E R& s = PL & pt = 6 & f pt = 31 & d d = 2 91 1 1 2 & p b = P L & s e a rc h i d= 5 3 610 31 3 # dd .
“ Fr e q u e n t l y A s ke d Q u e s t i o n s A b o ut G F R E s t i m a te s . ” T h e N a t i o n a l K i d n ey
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" L ex i co m p O n l i n e . " C l i n i c a l D r u g I n f o r ma t i o n . We b . 8 O c t . 2 01 5 .
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Ke p p r a P a c ka g e I n s e r t
( h t t p : / / w w w. a c ce s s d a t a .f d a . g ov / d r ug s a t f d a _ d o c s / l a b el / 2 0 0 9 / 0 210 3 5 s 07 8 s 0 8 0 ,
0 21 5 0 5 s 0 21 s 0 24 l b l . p d f )
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2 01 5 . w w w.P h a r ma c i s t s L et te r.c o m .
P L D et a i l - D o c ume n t , “ Po te n t i al l y H a r m f ul D r ug s i n t h e E l d e r l y: B e e r s L i s t . ”
P h a r m a c i s t ’s L e t te r / P r e sc r i b e r ’s L e t te r. J u n e 2 01 2 .
QUESTIONS AND COMMENTS?