Dosing adjustments

Dosing & AE manage­ment

Dosing adjustments

Twice daily oral VARGATEF® has a well-defined and simple dosing regimen1​

Dosing adjustments for diarrhoea, vomiting and other non-haematological adverse reactions1​

Diarrhoea

CTCAE adverse events

  • Diarrhoea ≥ grade 2 for more than 7 consecutive day despite anti-diarrhoeal treatment

OR

  • Diarrhoea ≥ grade 3 despite anti-diarrhoeal treatment

Dose adjustment

  • Interrupt treatment and allow recovery to grade 1 or baseline
  • Then, reduce dose from 200 mg twice daily to 150 mg twice daily
  • If a 2nd dose reduction is considered necessary, reduce dose from 150 mg twice daily to 100 mg twice daily

 

Nausea/vomiting

CTCAE adverse events

  • Vomiting ≥ grade 2

AND/OR

  • Nausea ≥ grade 3 despite anti-emetic treatment

Dose adjustment

  • Interrupt treatment and allow recovery to grade 1 or baseline
  • Then, reduce dose from 200 mg twice daily to 150 mg twice daily
  • If a 2nd dose reduction is considered necessary, reduce dose from 150 mg twice daily to 100 mg twice daily

 

Elevated liver enzymes
(ALT and AST)

AST/ALT and bilirubin elevations

  • Elevation of AST and/or ALT values to > 2.5 x ULN in conjunction with total bilirubin elevation to ≥ 1.5 x ULN

OR

  • Elevation of AST and/or ALT values to > 5 x ULN

  • Elevation of AST and/or ALT values to > 3 x ULN in conjunction with an increase of total bilirubin to ≥ 2 x ULN and ALKP < 2 x ULN

Dose adjustment

  • Interrupt treatment and allow recovery of transaminase values to ≤ 2.5 x ULN in conjunction with bilirubin to normal
  • Then reduce dose from 200 mg twice daily to 150 mg twice daily
  • If a 2nd dose reduction is considered necessary, reduce dose from 150 mg twice daily to 100 mg twice daily

  • Unless there is an alternative cause established, VARGATEF ® should be permanently discontinued

 

Dose Reduction
Algorithms

CTCAE adverse events

  • Other non-haematologic or haematologic adverse reactions of ≥ grade 3

Dose adjustment

  • Interrupt treatment and allow recovery to grade 1 or baseline, then reduce dose from 200 mg twice daily to 150 mg twice daily
  • If a 2nd dose reduction is considered necessary, reduce dose from 150 mg twice daily to 100 mg twice daily

Summary of dose reduction schedule

Dose adjustments / interruption available for VARGATEF® in case of adverse events:1​

Alt Image
For full dose adjustment / interruption recommendations, see VARGATEF® SmPC

ALT = alanine transaminase
AST = aspartate transaminase

References
  1. VARGATEF® SmPC
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