Hepatic and Renal dose adjustments of Chemotherapy Drugs

GuideLines for Chemotherapy Dosage Adjustment

• 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

• 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%

• 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

• 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

• 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

• Renal: No dosage adjustment necessary
• Note: Dialysis may reduce concentrations, so the drug should be administered postdialysis

• 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

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

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

• 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

• 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

• 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

• 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.

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

Renal

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

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

• 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

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

• 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

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

• 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

• 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

• Hepatic: Dose adjustment may be necessary, but no specific guidelines are available
• Renal: CrCI <50 mL/min = Dose every 48 hours

• 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

• 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.

• 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.

• 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.