Drug
CrCl 60–46 mL/min
CrCl 45–30 mL/min
CrCl 29–10 mL/min
Dialysis
Nephrotoxicity presentation/comments
Arsenic trioxide
No adjustment needed
No adjustment needed
Drug exposure may be higher, monitor for toxicity, and lower doses may be required
Not studied in hemodialysis patients
Case reports on acute tubular necrosis has been reported
Bleomycin
No adjustment needed
50–40 mL/min reduce dose by 30 %
40–30 mL/min reduce dose by 40 %
30–20 mL/min reduce dose by 45 %
20–10 mL/min reduce dose by 55 %
CRRT: reduce dose by 25 %
Capecitabine (xeloda)
No dose reduction
25 % dose reduction
Contraindicated
Contraindicated
Note: has been used at 50–80 % dose reduction [2]
No reports of nephrotoxicity
Carboplatin
No adjustment needed
Reduce dose by 50 %
Reduce dose by 50 %
HD: reduce dose by 50 %
CAPD: Reduce dose by 75 %
CRRT: dose at 200 mg/m2
Nephrotoxicity often appears as hypomagnesemia (reversible tubular injury), and is most common in pts previously treated with cisplatin
Carfilzomib (kyprolis)
Reduced initial dose
15 mg/m2 daily on Cycle 1, 20 mg/m2 on Cycle 2, and 27 mg/m2 on Cycles 3 and beyond
Reduced initial dose
15 mg/m2 daily on Cycle 1, 20 mg/m2 on Cycle 2, and 27 mg/m2 on Cycles 3 and beyond
Reduced initial dose
15 mg/m2 daily on Cycle 1, 20 mg/m2 on Cycle 2, and 27 mg/m2 on Cycles 3 and beyond
Reduced initial dose
15 mg/m2 daily on Cycle 1, 20 mg/m2 on Cycle 2, and 27 mg/m2 on Cycles 3 and beyond; dosed after dialysis
Rises in serum creatinine appear prerenal, with rises in BUN as well.Cases of acute renal failure have also been reported in the setting of myeloma progression or renal impairment at baseline(prerenal, tumor lysis, and thrombotic microangiopathy have been reported)
Carmustine (BiCNU)
Insufficient data
Insufficient data
Avoid
Avoid
Progressive azotemia, increased serum creatinine, and renal failure reported during and after discontinuation of prolonged therapy of over 1 year and at least six cycles. Decreased kidney size, membranous nephropathy, tubular atrophy, and glomerular sclerosis have been reported after cumulative doses over 1.5 g [11–12]. Indirect nephrotoxicity may occur secondary to infusion-related hypotension
Cetuximab
No adjustment needed
No adjustment needed
No adjustment needed
No adjustment needed
Nephrotoxicity often appears as hypomagnesemia (tubular injury)
Chlorambucil (Leukeran)15
No dose adjustment
No dose adjustment
No dose adjustment
No dose adjustment
No reports of nephrotoxicity
Cisplatin
Reduce dose by 25 %
Reduce dose by 50 %
Reduce dose by 50 % or consider use of alternate agent
HD: reduce dose by 50 %, and administer after HD
CAPD: Reduce dose by 50 %
CRRT: reduce dose by 25 %
Per manufacturer recommendation cisplatin should not be administered to any pt with preexisting renal impairment
Nephrotoxicity often appears as renal failure, renal tubular acidosis, and hypomagnesemia (tubulointerstitial injury). Prevention with aggressive hydration, forced dieresis, and cytoprotective agents (amifostine)
Cladribine
No adjustment needed
Reduce dose by 25 %
Reduce dose by 25 %
CAPD: reduce dose by 50 %
Very limited data on dose adjustments in renal insufficiency. Use with caution
Clofarabine (clolar)
50 % dose reduction
50 % dose reduction
Insufficient data
Insufficient data
Nephrotoxicity can present as proteinuria or rapid-onset acute renal failure with proteinuria
Crizotinib
No adjustment needed
No adjustment needed
Administer 250 mg Qday
Not studied in dialysis patients
Tubular toxicity has been reported
Cyclophosphamide
No adjustment needed
No adjustment needed
No adjustment needed
CrCl
<10 mL/min but not on dialysis reduce dose by 25 %
HD: Reduce dose by 50 % and administer after HD
CAPD: Reduce dose by 25 %
CRRT: No adjustment needed
Nephrotoxicity often appears as hyponatremia (SIADH and increased N/V) and hemorrhagic cystits. Prevent hyponatremia with adequate hydration and mesna. Prevent hemorrhagic cystitis with adequate hydration, and morning dosing (reduces time of medication in the bladder at night)
Cytarabine (high dose 1-3 g/m2)
Reduce dose by 40 %
Reduce dose by 50 %
Consider alternative agent or dose 100–200 mg/m2/day CIV
No data
Renal adjustments are only required in high doses (1–3 g/m2)possibly for > 500 mg/m2
Dacarbazine (DTIC)
Insufficient data
Insufficient data
Insufficient data
Insufficient data
Case report of successful use of 100 mg IV x 5 days every 4 weeks
Mild to moderate azotemia without permanent damage
Daunorubicin
No adjustment needed
No adjustment needed
No adjustment needed
No adjustment needed
Mainly excreted through the bile, however per FDA recommendations at 50 % dose reduction is recommended in pts with a SCr > 3
Epirubicin
No adjustment needed
No adjustment needed
No adjustment needed
No adjustment needed
Mainly excreted through the bile, however per FDA recommendations at 50 % dose reduction is recommended in pts with a SCr > 5
Eribulin
Reduce to 1.1 mg/m2/dose
Reduce to 1.1 mg/m2/dose
No data
No data
Erlotinib (Tarceva)
Insufficient data
Insufficient data
Note: hold if CrCl
<30 due to treatment
Insufficient data
Note: hold if CrCl
<30 due to treatment
Insufficient Data
Note: hold if CrCl
<30 due to treatment
Renal impairment or failure may follow hepatic impairment (hepatorenal syndrome) or severe dehydration
Etoposide
Reduce dose by 15 %
Reduce dose by 20 %
Reduce dose by 25 %
HD: reduce dose by 50 % (not removed by HD)
PD: reduce dose by 50 % (not removed by PD)
CRRT: reduce dose by 25 %
Fludarabine
Reduce dose to 20 mg/m2
Reduce dose to 20 mg/m2
Avoid use
HD: administer after hemodialysis
CAPD: Reduce dose by 50 %
CRRT: Reduce dose by 25 %
About 50 % of every dose is excreted by the urine
Gefitinib (Iressa)
No dose adjustment
No dose adjustment
No dose adjustment
Note: use caution
No dose adjustment
Note: use caution
No reports of nephrotoxicity
Note:
<4 % renal elimination
Gemcitabine
No adjustment needed
No adjustment needed
No adjustment needed
No adjustment needed
Nephrotoxicity often appears as hemolytic uremic syndrome (microangiopathic lesions)
Hydroxyurea (Droxia)
50 % dose reduction
7.5 mg/kg daily
50 % dose reduction
7.5 mg/kg daily
50 % dose reduction
7.5 mg/kg daily
50 % dose reduction
7.5 mg/kg daily; dosed after dialysis
Temporarily impaired tubular function with elevated serum uric acid, BUN, and creatinine
Ibrutinib (imbruvica)
No dose adjustment
MCL: 560 mg po daily
No dose adjustment
MCL: 560 mg po daily
Insufficient data
Insufficient data
Renal failure preceded by increases in creatinine of 1.5–3 times the upper limit of normal.
Note: < 1 % excreted renally
Ifosfamide
Reduce dose by 20 %
Reduce dose by 25 %
Reduce dose by 30 %
No data
Nephrotoxicity often appears as fanconi syndrome, renal tubular acidosis, nephrogenic diabetes insipidus, and hemorrhagic cystitis. Prevent nephrotoxic effects by maintaining adequate hydration, using mesna, and monitoring electrolytes
Imatinib
No adjustment needed
CrCl 59–40 mL/min max recommended dose of 600 mg
CrCl 39–20 mL/min reduce starting dose by 50 %, increase as tolerated. Max recommended dose 400 mg
CrCl < 20 mL/min use caution, 100 mg has been tolerated in some pts
18 % of the drug is excreted through the urine
Interferons
No adjustment needed
No adjustment needed
No adjustment needed
No adjustment needed
Nephrotoxicity often appears as proteinuria, (minimal change, and acute tubular necrosis)
Interleukin-2
No adjustment needed
No adjustment needed
No adjustment needed
No adjustment needed
Nephrotoxicity often appears as prerenal azotemia from renal hypoperfusion (capillary leak syndrome). Prevent renal complications by controlling volume and hemodynamic status. Avoid other nephrotoxins
Irinotecan
No adjustment needed
No adjustment needed
No adjustment needed
HD: reduce dose from 125 mg/m2–50 mg/m2
Use with caution in renal insufficiency. Although only small amounts of irinotecan are present in the urine several case reports have shown toxicity in pts with ESKD. Use with caution
Lenalidomide
MCL: dose 10 mg daily
MDS: dose 5 mg daily
MM: dose 10 mg daily
MCL: dose 10 mg daily
MDS: dose 5 mg daily
MM: dose 10 mg daily
MCL: dose 15 mg Q48H
MDS: dose 2.5 mg daily
MM: dose 15 mg Q48H
HD:
MCL: dose 5 mg (after HD)
MDS: dose 2.5 mg (After HD)
MM: dose 5 mg (after HD)
Patients with multiple myeloma frequently have renal insufficiency. T1/2 and AUC increase as creatinine clearance decreases
Lomustine
Reduce dose by 25 %
Reduce dose by 30 %
Avoid use
Avoid use
Nephrotoxicity often appears as a slowly progressive, chronic interstitial nephritis, which is generally irreversible, and can be induced by prolonged therapy time. First signs of renal involvement are elevations in SCr, followed by proximal tubular damage (usually proteinuria, and renal tubular acidosis). Nephrotoxicity may be delayed from several months to as long as several years after discontinuation
Melphalan
Reduce dose by 15 %
Reduce dose by 25 %
Reduce dose by 30 %
Limited data
Nephrotoxicity often appears as SIADH. Have pts maintain adequate hydration during therapy
Methotrexate
Reduce dose by 35 %
Reduce dose by 50 %
Avoid use
CRRT: reduce dose by 50 %
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