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Systemic Anti-Cancer Therapy Regimen Library

Home > LYM NHL B-cell PCNSL - MT-R [metHOTREXate, temozolomide and RITUximab] followed by EA [etoposide and cytarabine] > LYM - MT-R
This regimen is a component of LYM NHL B-cell PCNSL - MT-R [metHOTREXate, temozolomide and RITUximab] followed by EA [etoposide and cytarabine]

MT-R [metHOTREXATe, temozolomide and RITUximab] Remission Induction (LYM NHL B-cell PCNSL - MT-R [metHOTREXate, temozolomide and RITUximab] followed by EA [etoposide and cytarabine])

Treatment Overview

Evaluate following cycle 6:

  • If complete response (CR) proceed to cycles 7 and 8 of this regimen, followed by Consolidation.
  • If partial response (PR) treat with 3 to 5 additional cycles of Remission Induction therapy before Consolidation.

High dose metHOTREXATe

  • metHOTREXATe levels MUST be measured once every 24 hours.
  • Intravenous alkalinized fluids MUST be commenced at least 6 hours before the start of metHOTREXATe infusion and MUST continue until the metHOTREXATe serum level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Additional oral alkalinization can be considered as Ural® 2 sachets orally the night before and 2 sachets the morning of high dose metHOTREXATe infusion.
  • Before commencing the high dose metHOTREXATe infusion, urinary pH MUST be 7.5 or above (pH 7.5 to 8.0).
  • Closely monitor renal function, electrolytes, fluid balance, and weight.
  • foliNIc acid MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).

This regimen contains a medicine where one or more biosimilars may exist. Any biosimilars used have been reviewed by the regulator (Medsafe) and relevant specialists were consulted nationally. Where regulators, in consultation with relevant specialists, have agreed that there are no clinically significant differences in either safety or effectiveness between a biosimilar and originator product, these drugs may be used interchangeably.

Cycle 1 - 14 days - metHOTREXATe, temozolomide and RITUximab (first dose)

Cycle length:
14

RITUximab, first dose:

  • Consider withholding routine anti-hypertensives for 12 hours prior to first RITUximab dose.
  • For patients at high risk of infusion related reaction consider using additional pre-medications such as an extra antihistamine dose the day before, an H2 receptor antagonist and montelukast.

foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Cycle 2 - 14 days - metHOTREXATe and RITUximab

Cycle length:
14

RITUximab, subsequent doses: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.


foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Cycle 3 - 14 days - metHOTREXATe, temozolomide and RITUximab

Cycle length:
14

RITUximab, subsequent doses: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.


foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Cycle 4 - 14 days - metHOTREXATe and RITUximab

Cycle length:
14

RITUximab, subsequent doses: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.


foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Cycle 5 - 14 days - metHOTREXATe, temozolomide and RITUximab

Cycle length:
14

RITUximab, subsequent doses: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.


foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Cycle 6 - 14 days - metHOTREXATe and RITUximab

Cycle length:
14

RITUximab, subsequent doses: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.


foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Evaluate after cycle 6:

  • If complete response (CR) proceed to cycles 7 and 8, followed by Consolidation.
  • If partial response (PR) treat with 3 to 5 additional cycles of Remission Induction therapy before Consolidation. 

Cycle 7 - 14 days - metHOTREXATe and temozolomide (If CR after cycle 6)

Cycle length:
14

foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Cycle 8 - 14 days - metHOTREXATe (if in CR after cycle 6)

Cycle length:
14

foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Cycle details

Cycle 1 - 14 days - metHOTREXATe, temozolomide and RITUximab (first dose)

Medication Dose Route Days Max Duration
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous 1 to 4
sodium bicarbonate 50 mmol intravenous 1 to 4
acetazolamide * 250 mg Four times daily oral administration 1 to 4
metHOTREXATe * 8000 mg/m² intravenous 1 4 hours
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2, 3, 4 2 minutes
paracetamol * 1000 mg flat dosing oral administration 3
loratadine * 10 mg oral administration 3
dexamethasone * 12 mg flat dosing intravenous 3 15 minutes
RITUximab * 375 mg/m² intravenous 3 6 hours
temozolomide * 150 mg/m² Once daily oral administration 7 to 11

RITUximab, first dose:

  • Consider withholding routine anti-hypertensives for 12 hours prior to first RITUximab dose.
  • For patients at high risk of infusion related reaction consider using additional pre-medications such as an extra antihistamine dose the day before, an H2 receptor antagonist and montelukast.

foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Cycle 2 - 14 days - metHOTREXATe and RITUximab

Medication Dose Route Days Max Duration
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous 1 to 4
sodium bicarbonate 50 mmol intravenous 1 to 4
acetazolamide * 250 mg Four times daily oral administration 1 to 4
metHOTREXATe * 8000 mg/m² intravenous 1 4 hours
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2, 3, 4 2 minutes
paracetamol * 1000 mg flat dosing oral administration 3
loratadine * 10 mg oral administration 3
RITUximab * 375 mg/m² intravenous 3 6 hours

RITUximab, subsequent doses: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.


foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Cycle 3 - 14 days - metHOTREXATe, temozolomide and RITUximab

Medication Dose Route Days Max Duration
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous 1 to 4
sodium bicarbonate 50 mmol intravenous 1 to 4
acetazolamide * 250 mg Four times daily oral administration 1 to 4
metHOTREXATe * 8000 mg/m² intravenous 1 4 hours
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2, 3, 4 2 minutes
paracetamol * 1000 mg flat dosing oral administration 3
loratadine * 10 mg oral administration 3
RITUximab * 375 mg/m² intravenous 3 6 hours
temozolomide * 150 mg/m² Once daily oral administration 7 to 11

RITUximab, subsequent doses: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.


foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Cycle 4 - 14 days - metHOTREXATe and RITUximab

Medication Dose Route Days Max Duration
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous 1 to 4
sodium bicarbonate 50 mmol intravenous 1 to 4
acetazolamide * 250 mg Four times daily oral administration 1 to 4
metHOTREXATe * 8000 mg/m² intravenous 1 4 hours
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2, 3, 4 2 minutes
paracetamol * 1000 mg flat dosing oral administration 3
loratadine * 10 mg oral administration 3
RITUximab * 375 mg/m² intravenous 3 6 hours

RITUximab, subsequent doses: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.


foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Cycle 5 - 14 days - metHOTREXATe, temozolomide and RITUximab

Medication Dose Route Days Max Duration
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous 1 to 4
sodium bicarbonate 50 mmol intravenous 1 to 4
acetazolamide * 250 mg Four times daily oral administration 1 to 4
metHOTREXATe * 8000 mg/m² intravenous 1 4 hours
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2, 3, 4 2 minutes
paracetamol * 1000 mg flat dosing oral administration 3
loratadine * 10 mg oral administration 3
RITUximab * 375 mg/m² intravenous 3 6 hours
temozolomide * 150 mg/m² Once daily oral administration 7 to 11

RITUximab, subsequent doses: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.


foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Cycle 6 - 14 days - metHOTREXATe and RITUximab

Medication Dose Route Days Max Duration
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous 1 to 4
sodium bicarbonate 50 mmol intravenous 1 to 4
acetazolamide * 250 mg Four times daily oral administration 1 to 4
metHOTREXATe * 8000 mg/m² intravenous 1 4 hours
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2, 3, 4 2 minutes
paracetamol * 1000 mg flat dosing oral administration 3
loratadine * 10 mg oral administration 3
RITUximab * 375 mg/m² intravenous 3 6 hours

RITUximab, subsequent doses: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.


foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Evaluate after cycle 6:

  • If complete response (CR) proceed to cycles 7 and 8, followed by Consolidation.
  • If partial response (PR) treat with 3 to 5 additional cycles of Remission Induction therapy before Consolidation. 

Cycle 7 - 14 days - metHOTREXATe and temozolomide (If CR after cycle 6)

Medication Dose Route Days Max Duration
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous 1 to 4
sodium bicarbonate 50 mmol intravenous 1 to 4
acetazolamide * 250 mg Four times daily oral administration 1 to 4
metHOTREXATe * 8000 mg/m² intravenous 1 4 hours
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2, 3, 4 2 minutes
temozolomide * 150 mg/m² Once daily oral administration 7 to 11

foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Cycle 8 - 14 days - metHOTREXATe (if in CR after cycle 6)

Medication Dose Route Days Max Duration
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous 1 to 4
sodium bicarbonate 50 mmol intravenous 1 to 4
acetazolamide * 250 mg Four times daily oral administration 1 to 4
metHOTREXATe * 8000 mg/m² intravenous 1 4 hours
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2, 3, 4 2 minutes

foliNIc acid:

  • MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

Full details

Cycle 1 - 14 days - metHOTREXATe, temozolomide and RITUximab (first dose)

Day: 1

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
metHOTREXATe * 8000 mg/m² intravenous 4 hours

Day: 2

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 3

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
paracetamol * 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
dexamethasone * 12 mg flat dosing intravenous 15 minutes
Instructions:

30 to 60 minutes prior to RITUximab, or as per institutional practice.
RITUximab * 375 mg/m² intravenous 6 hours
Instructions:
  • Consider withholding routine anti-hypertensives for 12 hours prior to first RITUximab dose.
  • For patients at high risk of infusion-related reaction, consider additional pre-medications such as an extra antihistamine dose the day before, an H2 receptor antagonist and montelukast.
  • Start infusion at 50 mg/hour. If tolerated, rate can be increased by 50 mg/hour every 30 minutes to a maximum rate of 400 mg/hour.

Day: 4

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.

Day: 7

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 8

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 9

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 10

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 11

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Cycle 2 - 14 days - metHOTREXATe and RITUximab

Day: 1

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
metHOTREXATe * 8000 mg/m² intravenous 4 hours

Day: 2

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 3

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
paracetamol * 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
RITUximab * 375 mg/m² intravenous 6 hours
Instructions:
  • Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated as per institutional practice.
  • Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour, or as per institutional practice.

Day: 4

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.

Cycle 3 - 14 days - metHOTREXATe, temozolomide and RITUximab

Day: 1

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
metHOTREXATe * 8000 mg/m² intravenous 4 hours

Day: 2

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 3

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
paracetamol * 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
RITUximab * 375 mg/m² intravenous 6 hours
Instructions:
  • Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated as per institutional practice.
  • Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour, or as per institutional practice.

Day: 4

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.

Day: 7

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 8

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 9

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 10

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 11

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Cycle 4 - 14 days - metHOTREXATe and RITUximab

Day: 1

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
metHOTREXATe * 8000 mg/m² intravenous 4 hours

Day: 2

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 3

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
paracetamol * 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
RITUximab * 375 mg/m² intravenous 6 hours
Instructions:
  • Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated as per institutional practice.
  • Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour, or as per institutional practice.

Day: 4

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.

Cycle 5 - 14 days - metHOTREXATe, temozolomide and RITUximab

Day: 1

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
metHOTREXATe * 8000 mg/m² intravenous 4 hours

Day: 2

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 3

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
paracetamol * 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
RITUximab * 375 mg/m² intravenous 6 hours
Instructions:
  • Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated as per institutional practice.
  • Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour, or as per institutional practice.

Day: 4

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.

Day: 7

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 8

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 9

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 10

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 11

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Cycle 6 - 14 days - metHOTREXATe and RITUximab

Day: 1

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
metHOTREXATe * 8000 mg/m² intravenous 4 hours

Day: 2

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 3

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
paracetamol * 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
RITUximab * 375 mg/m² intravenous 6 hours
Instructions:
  • Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated as per institutional practice.
  • Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour, or as per institutional practice.

Day: 4

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.

Cycle 7 - 14 days - metHOTREXATe and temozolomide (If CR after cycle 6)

Day: 1

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
metHOTREXATe * 8000 mg/m² intravenous 4 hours

Day: 2

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 3

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 4

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.

Day: 7

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 8

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 9

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 10

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: 11

Medication Dose Route Max duration Details
temozolomide * 150 mg/m² Once daily oral administration
Instructions:
  • Take each dose on an empty stomach - one hour before OR two hours after food.
  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Cycle 8 - 14 days - metHOTREXATe (if in CR after cycle 6)

Day: 1

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
metHOTREXATe * 8000 mg/m² intravenous 4 hours

Day: 2

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 3

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 4

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
  • Administration may continue past Day 4 if metHOTREXATe level is still elevated.

Supportive Care Factors

Factor Value
Antiviral prophylaxis for hepatitis B virus: Required for anti–HBc positive patients at risk of reactivation
Antiviral prophylaxis for herpes virus: Routine antiviral prophylaxis may be considered
Emetogenicity: Variable
Folinic acid rescue for high dose methotrexate: Mandatory
Hydration: Routine hydration recommended
Hypersensitivity / Infusion related reaction risk: High - routine premedication recommended
Pneumocystis jirovecii pneumonia (PJP) prophylaxis: Routine antibiotic prophylaxis recommended
Tumour lysis syndrome prophylaxis: Tumour lysis syndrome prophylaxis may be considered

Emetogenicity:

  • MEDIUM day 1, high dose metHOTREXATe may be highly emetogenic in certain patients.
  • MINIMAL day 3, cycles 1 to 6.
  • MEDIUM to HIGH (temozolomide).

PJP prophylaxis: If trimethoprim + sulfamethoxazole is used as prophylaxis, it is recommended to withhold at least 48 hours prior to high dose metHOTREXATe administration and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (as per institutional practice).

References

Tabernero J, Vyas M, Giuliani R, Arnold D, Cardoso F, Casali PG, Cervantes A, Eggermont AMM, Eniu A, Jassem J, Pentheroudakis G, Peters S, Rauh S, Zielinski CC, Stahel RA, Voest E, Douillard JY, McGregor K, Ciardiello F. Biosimilars: a position paper of the European Society for Medical Oncology, with particular reference to oncology prescribers. ESMO Open. 2017 Jan 16;1(6):e000142. doi: 10.1136/esmoopen-2016-000142., PMID: 28848668

Lyman GH, Balaban E, Diaz M, Ferris A, Tsao A, Voest E, Zon R, Francisco M, Green S, Sherwood S, Harvey RD, Schilsky RL. American Society of Clinical Oncology Statement: Biosimilars in Oncology. J Clin Oncol. 2018 Apr 20;36(12):1260-1265. doi: 10.1200/JCO.2017.77.4893. Epub 2018 Feb 14., PMID: 29443651

* The medicines, doses, combinations, and schedule in this treatment regimen have been carefully reviewed against international best practice guidelines by specialists in medical oncology around New Zealand and this advice has been accepted for publication by Te Aho o Te Kahu (the Cancer Control Agency). Sometimes medicines that are used in routine clinical practice have not been through a formal review process by the NZ Medicines Regulator Medsafe and are therefore considered unapproved or off-label. These medicines are legally able to be prescribed through sections 25 and 29 of the Medicines Act and by obtaining informed consent from patients. All treatment regimens listed on this website have been through robust peer review and are considered an accepted standard of care, whether prescribed through sections 25 or 29 or carrying formal Medsafe Approval.

s29: This symbol indicates that some formulations of the associated medicine are legally only able to be prescribed under section 29 of the Medicines Act. You can see which formulations are section 29 by hovering over the s29 symbol. You can access full medication details from the New Zealand Formulary by clicking on the medication name. Each clinician retains full responsibility for ensuring they have complied with all relevant obligations and requirements of section 29 including obtaining informed patient consent prior to prescribing the applicable medicine.