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Home > LEU ALL precursor B-cell - UKALL14 with RITUximab [over 40 years] [not for transplant] > LEU - UKALL14 with RITUximab [over 40 years] [not for transplant] Intensification/CNS prophylaxis
This regimen is a component of LEU ALL precursor B-cell - UKALL14 with RITUximab [over 40 years] [not for transplant]

UKALL14 with RITUximab [over 40 years] [not for transplant] - Intensification/CNS prophylaxis (LEU ALL precursor B-cell - UKALL14 with RITUximab [over 40 years] [not for transplant])

Treatment Overview

Starts after count recovery from Phase 2 Induction, with neutrophils greater than 0.75 x 109/L and platelets greater than 75 x 109/L.


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 36 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 - 28 days

Cycle length:
28

foliNIc acid: MUST start 36 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).


pegaspargase:

  • DO NOT use in BCR-ABL1+ (Philadelphia positive) patients.
  • There is limited data available for use of pegaspargase in patients 65 years and older. Strongly consider not using pegaspargase in patients 65 years and older.
  • Consideration can be given to reducing dose of pegaspargase to 500 international units/m2 for certain patients.
  • Monitor patients for one hour after administration of pegaspargase in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (e.g. adrenaline, oxygen, intravenous steroids, antihistamines).
  • See also Additional details for Further information on pegaspargase.

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

Cycle details

Cycle 1 - 28 days

Medication Dose Route Days Max Duration
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous 1 to 4,
15 to 18
sodium bicarbonate 50 mmol intravenous 1 to 4,
15 to 18
acetazolamide * 250 mg Four times daily oral administration 1 to 4,
15 to 18
metHOTREXATe 300 mg/m² intravenous 1, 15 60 minutes
metHOTREXATe 2700 mg/m² intravenous 1, 15 23 hours
foliNIc acid (as calcium folinate) 30 mg flat dosing Every three hours intravenous 2, 3, 16,
17		 2 minutes
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 3, 4, 17,
18		 2 minutes
paracetamol * 1000 mg flat dosing oral administration 2, 3, 16
loratadine * 10 mg oral administration 2, 3, 16
famotidine * 20 mg oral administration 2, 16
pegaspargase * 1000 international unit/m² intravenous 2, 16 120 minutes
RITUximab * 375 mg/m² intravenous 3 6 hours

foliNIc acid: MUST start 36 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).


pegaspargase:

  • DO NOT use in BCR-ABL1+ (Philadelphia positive) patients.
  • There is limited data available for use of pegaspargase in patients 65 years and older. Strongly consider not using pegaspargase in patients 65 years and older.
  • Consideration can be given to reducing dose of pegaspargase to 500 international units/m2 for certain patients.
  • Monitor patients for one hour after administration of pegaspargase in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (e.g. adrenaline, oxygen, intravenous steroids, antihistamines).
  • See also Additional details for Further information on pegaspargase.

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

Full details

Cycle 1 - 28 days

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 300 mg/m² intravenous 60 minutes
metHOTREXATe 2700 mg/m² intravenous 23 hours
Instructions:

Continuous infusion over 23 hours starting immediately after the 60 minute metHOTREXATe infusion.

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 three hours intravenous 2 minutes
Instructions:
  • Starting 36 hours after start of metHOTREXATe infusion and continue to administer every 3 hours for the first 5 doses, then 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 minutes prior to pegaspargase.
loratadine * 10 mg oral administration
Instructions:

30 minutes prior to pegaspargase.

famotidine * 20 mg oral administration
Instructions:

30 minutes prior to pegaspargase.
pegaspargase * 1000 international unit/m² intravenous 120 minutes
Instructions:
  • DO NOT use in BCR-ABL1+ patients.
  • Strongly consider omitting in patients 65 years and older.
  • Consider dose reduction to 500 international units/m2 for certain patients.
  • Monitor patients for one hour after administration of pegaspargase in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (e.g. adrenaline, oxygen, intravenous steroids, antihistamines).
Additional details:

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 three hours intravenous 2 minutes
Instructions:
  • Administer every 3 hours for the first 5 doses, then every 6 hours (see below) 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.
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • After 5 doses at 3 hourly intervals (see above) 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.
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 before RITUximab 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: 15

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 300 mg/m² intravenous 60 minutes
metHOTREXATe 2700 mg/m² intravenous 23 hours
Instructions:

Continuous infusion over 23 hours starting immediately after the 60 minute metHOTREXATe infusion.

Day: 16

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 three hours intravenous 2 minutes
Instructions:
  • Starting 36 hours after start of metHOTREXATe infusion and continue to administer every 3 hours for the first 5 doses, then 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 minutes prior to pegaspargase.
loratadine * 10 mg oral administration
Instructions:

30 minutes prior to pegaspargase.

famotidine * 20 mg oral administration
Instructions:

30 minutes prior to pegaspargase.
pegaspargase * 1000 international unit/m² intravenous 120 minutes
Instructions:
  • DO NOT use in BCR-ABL1+ patients.
  • Strongly consider omitting in patients 65 years and older.
  • Consider dose reduction to 500 international units/m2 for certain patients.
  • Monitor patients for one hour after administration of pegaspargase in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (e.g. adrenaline, oxygen, intravenous steroids, antihistamines).
Additional details:

Day: 17

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 three hours intravenous 2 minutes
Instructions:
  • Administer every 3 hours for the first 5 doses, then every 6 hours (see below) 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.
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • After 5 doses at 3 hourly intervals (see above) 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: 18

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 18 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 18 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 18 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 18 if metHOTREXATe level is still elevated.

Additional details

Section 1: Further information on pegaspargase

  • Pegaspargase (and asparaginase products) should only be administered by centres with appropriate expertise. 
  • There is limited data available for use of pegaspargase in patients 65 years and older. Strongly consider not using pegaspargase in patients 65 years and older.
  • Consideration can be given to reducing dose of pegaspargase to 500 international units/m2 for certain patients. 
  • Prior to using pegaspargase perform a baseline abdominal ultrasound scan is recommended to examine the biliary tract, pancreas and hepatic echotexture. Pegasparagase is contraindicated in those with a history of severe significant hepatic impairment, including alcoholic liver disease, autoimmune or viral hepatitis, and steatohepatitis/NASH.
  • If after pegaspargase there is any evidence of steatosis/liver disease, perform an ultrasound of the liver. 
  • Development of anti-asparaginase antibodies may be associated with low asparaginase activity levels. As a precaution, periodic measurement of the asparaginase activity level in serum or plasma is recommended. 
  • Routine monitoring for bone marrow suppression, coagulations abnormalities, pancreatitis, hepatic toxicity, hyperuricaemia, hyperglycaemia, ketoacidosis and hypertriglyceridaemia is required. See Additional information - pegaspargase.
  • To reduce risk of hypersensitivity to pegaspargase avoid using other pegylated products e.g. pegFILGRASTIM if there is a suitable non-pegylated form.

Supportive Care Factors

Factor Value
Antifungal prophylaxis: Routine antifungal prophylaxis recommended
Antiviral prophylaxis for hepatitis B virus: Required for anti–HBc positive patients at risk of reactivation
Antiviral prophylaxis for herpes virus: Routine antiviral prophylaxis recommended
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

Emetogenicity:

  • MEDIUM days 1 and 15, high dose metHOTREXATe may be highly emetogenic in certain patients.
  • MINIMAL days 2, 3 and 16.

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.