Hepatic & Renal dose adjustments of Chemotherapy Drugs

The Drugs which are in bold, details of dose reductions are mentioned below table, scroll down. 

GuideLines for Chemotherapy Dosage Adjustment

Adjust if Function Impaired
Hepatic Renal
Alemtuzumab No No
Arsenic trioxide Yes Yes
Asparaginase (E coli) +/- +/-
Asparaginase (Erwinia) +/- +/-
Azacitidine Yes Yes
Hepatic Renal
Bendamustine Yes Yes
Bleomycin sulphate +/- Yes
Bortezmib Yes +/-
Brentuximab vedotin No No
Busulfan +/- No
Hepatic Renal
Carboplatin No Yes
Carfilzomib +/- No
Carmustine +/- Yes
Chlorambucil +/- Yes
Cisplatin No Yes
Cladribine +/- No
Clofarabine +/- +/-
Cytarabine Yes Yes
Cytarabine lipid complex No No
Cyclophosphamide  Yes  Yes
Hepatic Renal
Dacarbazine +/- Yes
Denosumab +/- +/-
Dasatinib +/- +/-
Daunorubicin Yes Yes
Daunorubicin citrate liposomal Yes Yes
Decitabine +/- +/-
Doxorubicin HCl Yes No
Doxorubicin HCl liposomal Yes No
Darbopoetin alpha No No
Hepatic Renal
Etoposide phosphate Yes Yes
Epoetin alpha No No
Filgrastim No No
Fludarabine +/- Yes
Fluorouracil +/- +/-
Hepatic Renal
Gemcitabine HCI Yes No
Gemtuzumab ozogamycin +/- No
Hydroxyurea +/- Yes
lbrutinib Yes No
Idarubicin HCl Yes Yes
Ifosfamide +/- No
Imatinib mesylate Yes Yes
Interferon alf-2b No No
Hepatic Renal
Lenalidomide No Yes
Leucovorin calcium No No
Melphaan No Yes
Mercaptopurine +/- Yes
Mesna +/- +/-
Methotrexate Yes Yes
Mitoxantrone HCl +/- No
Nelarabine +/- +/-
Nilotinib Yes No
Hepatic Renal
Obinutuzumab +/- +/-
Ofatumumab No No
Omacetaxine +/- +/-
Pamidronate +/- Yes
Pegaspargase No No
Plerixafor No Yes
Pomalidomide +/- +/-
Ponatinib HCI +/- +/-
Procarbazine HCI No Yes
Hepatic Renal
Rituximab No No
Thalidomide No No
Thioguanine +/- No
Vinblastine Yes No
Vincristine Yes No
Vincristine Liposomal +/- +/-
Vinorelbine Yes No
Zolendronic Acid +/- Yes

Specific dose reductions are mentioned below.

 

Arsenic trioxide
  • Child-Pugh Class C (severe hepatic impairment) = Limited data available, Monitor closely for toxicity
  • CrCI <30 m L/min = Monitor closely; may require dosage reduction
Azacitidine
  • Hepatic impairment = No data available, Monitor dose closely for toxicity.
  • Elevations of BUN or SCr = Delay next cycle until values return to normal or baseline and reduce dosage by 50%
Asparginase
  • Specific guidelines for dosage adjustments in hepatic impairment are not available; however, these patients may be at increased risk for toxicity. Evaluate hepatic enzymes and bilirubin pretreatment and periodically during retreatment. Use caution in patients with a history of coagulopathy.
  • Specific guidelines for dosage adjustments in renal impairment not available, it appears that no dosage adjustments are needed
Bendamustine
  • Bilirubin =  1.5-3 X ULN &  AST or ALT 2.5-10 X ULN = Do Not administer
  • Bilirubin =  > 3 X ULN = Do Not administer
  • CrCI = 40-60 mL/min = Use with caution
  • CrCI <40 mL/min = Do not administer
Bleomycin sulfate
  • Not studied in patients with hepatic impairment; adjustment for hepatic impairment may be needed.
  • Dosage recommendations using Cockcroft & Gault formula
    CrCI >50 mL/min = Administer 100% of dosage
    CrCI 40-49 mL/min = Administer 70% of dosage
    CrCI 30-39 mL/min = Administer 60% of dosage
    CrCI 20-29 mL/min = Administer 55% of dosage
    CrCI 10-19 ml/min = Administer 45% of dosage
    CrI 5-9 mL/min = Administer 40% of dosage
  • Continuous renal replacement therapy (CRRT) = Administer 75% of dose
Bortezomib & Carfilzomib
  • Renal: No dosage adjustment necessary
  • Note: Dialysis may reduce concentrations, so the drug should be administered postdialysis
Chlorambucil
  • Hepatic metabolism into active and inactive metabolites. Dosage adjustment may be needed in patient with hepatic impairment.
  • Renal Impairment
  • CrCI 10-50 mL/min = Administer 75% of dosage
  • CrCI <10 mL/min = Administer 50% of dosage
  • Hemodialysis = Administer 50% of dosage
Cisplatin
  • Renal Impairment
  • CrCI 10-50 mL/min = Administer 75% of dosage
  • CrCI <10 mL/min = Administer 50% of dosage
  • Hemodialysis = Administer 50% of dosage
Cladribine
The manufacturer recomends repeat courses should not be given until SCr < 1.5 mg/dL and/or BUN <25.

CrCI 10-50 mL/min = Administer 75% of dosage
CrCI <10 mL/min = Administer 50% of dosage

 

Cytarabine
  • Dosage adjustments may be necessary, but no specific guidelines a available. Administer 50% of dose if >2 mgdl; may increase subsequent doses in the absence of toxicities.

Cytarabine = 100-200 mg/m2

  • No dosage adjustment necessary

High dose Cytarabine = 1000-3000 mg/m2

  • CrCI = 46-60 mL/min = Administer 60% of dosage
  • CrCI = 31-45 mL/mjn = Administer 50% of dosage
  • CrCI <30 mL/min = Consider use of alternative drug

 

Cyclophosphamide
Hepatic Dose

  • 3.1-5.0 mg/dL = Administer 75% of dosage
  • >5 mg/dL = Hold therapy

Renal Dose

Renal impairment: CrCl <10 mL/min, give 75% of normal dose; CrCl >10 mL/min, give full dose

 

Daunorubicin and Daunorubicin citrate Liposomal
Hepatic Dose

  • 1.2-3.0 mg/dL = Administer 75% of dosage
  • >3 mg/dL = Administer 50% of dosage
  • >5 mg/dL = Hold therapy

Renal Dose

  • SCr >3 mg/dL = Administer 50% of dosage

 

Doxorubicin and Doxorubicin HCI liposomal
Hepatic Dose

  • 1.2-3.0 mg/dL = Administer 50% of dosage
  • >3 mg/dL = Administer 25 % of dosage
  • >5 mg/dL = Hold therapy

Renal Dose = Dose modification not needed.

 

Etoposide
1.5-3.0 mg/dL or SGOT > 180 units = Administer 50% dosage

Decreased albumin increases unbound drug concentration and increases hematologic toxic eects.

Renal

  • CrCI = 10-50 mL/min = Administer 75% of dosage
  • CrCI = < 10 mL/min = Administer 50% of dosage
  • Hemodialysis = Administer 50% of dosage

 

Fludarabine
Hepatic impairment- Dosage adjustments may be necessary, No specific guidelines are available

Renal Impairment – IV doses

  • CrCl 50-79 mL/min in adult = Administer 80% of IV dosage
  • CrCl 30-49 mL/min in adult = Administer 60-75% of IV dosage
  • CrCI <30 mL/min in adults = Administer 0-50% of IV dosage
  • CrCl 30-50 mL/min in children = Administer 80% of IV dosage
  • CrCI <30 mL/min in children = Do not Administer
  • Hemodialysis = Administer IV dose after dialysis

Renal Impairment – Oral Doses

  • CrCl 30-70 mL/min in adult = Administer 80% of Oral dosage
  • CrCI <30 mL/min in adults = Administer 50% of Oral dosage

 

Gemcitabine
  • Hepatic Dose: if Bill > 5 mg/dl = Reduce dose by 20%
  • Renal dose: No dosage adjustment necessary, Discontinue if severe renal toxicity or hemolyic uremic syndrome (HUS) occur during treatment

 

Hydroxyurea
Renal

  • CrCI = 10-50 mL/min = Administer 50% of dosage
  • CrCI = < 10 mL/min = Administer 20% of dosage

 

Idarubicin
Hepatic Dose

  • 1.2-3 mg/dL or AST/SGOT 60-180 units/L= Administer 75% of dosage
  • 3-5 mg/dL or AST/SGOT >180 units/L= Administer 50% of dosage
  • >5 mg/dL = Hold therapy

Renal

  • CrCI = 10-50 mL/min = Administer 75% of dosage
  • CrCI = < 10 mL/min = Administer 50% of dosage

 

Ifosfamide
Hepatic

Bilirubin >3 mg/dL = Administer 25% dosage

Renal

  • CrCI = 46-60 mL/min = Administer 80% of dosage
  • CrCI = 31-45 mL/min = Administer 75% of dosage
  • CrCI = < 30 mL/min = Administer 70% of dosage

 

Lenalidomide
Renal

  • CrCI = 30-60 mL/min = Administer 10 mg daily in MM and 5 mg in MDS
  • CrCI = < 30 mL/min = Administer 10 mg every 48 h in MM and 5 mg every 48 h in MDS

 

Melphalan
Renal

  • CrCI = 10-50 mL/min = Administer 75% of dosage
  • CrCI = < 10 mL/min = Administer 50% of dosage
  • BUN >/= 30 mg/dl = Administer 50% of dosage

 

Mercaptupurine
  • Hepatic: Dose adjustment may be necessary, but no specific guidelines are available
  • Renal: CrCI <50 mL/min = Dose every 48 hours
Thioguanine: No hepatic or renal adjustment required
Methotrexate
Hepatic Dose

  • 3-5 mg/dL or AST/SGOT >3 ULN = Administer 75% of dosage
  • >5 mg/dL = Hold therapy

Renal

  • CrCI = 10-60 mL/min = Administer 50% of dosage both in adults and children
  • CrCI = < 10 mL/min = Administer 30% of dosage in children and hold in adults

 

Vinblastine
Hepatic Dose

  • 1.5-3 mg/dL and AST/SGOT 60-180 units/L= Administer 50% of dosage
  • > 3 mg/dl = Administer 50% of dosage
  • >3 mg/dL and AST/SGOT >180 units/L= Hold therapy

Renal Dose: No adjustment needed.

 

Vincristine
Hepatic Dose

  • 1.5-3 mg/dL and AST/SGOT 60-180 units/L= Administer 50% of dosage
  • >3 mg/dL and AST/SGOT >180 units/L= Hold therapy

Renal Dose: No adjustment needed.

 

Vinorelbine
Hepatic Dose

  • 2.1-3 mg/dL = Administer 50% of dosage
  • 3.1-5 mg/dl = Administer 25% of dosage
  • >5 mg/dL = Hold therapy

Renal Dose: No adjustment needed.

 



Categories: Drug Review, Hepatic & Renal dose - Chemotherapy Drugs

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