8.1.3 Antimetabolites

Azacitidine
  • Injection powder for reconstitution 100mg vial

Notes

  1. NICE TA218: Azacitidine recommended for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukaemia and acute myeloid leukaemia (March 2011)
  2. NICE TA399: Azacitidine is not recommended for treating acute myeloid leukaemia with more than 30% bone marrow blasts (July 2016)
Capecitabine
  • Tablets 150mg, 500mg

Notes

  1. NICE TA61: Capecitabine and tegafur with uracil are recommended for metastatic colorectal cancer (May 2003)
  2. NICE TA100: Capecitabine and oxaliplatin are recommended in the adjuvant treatment of stage III (Duke's C) colon cancer (April 2006)
  3. NICE TA191: Capecitabine is recommended for the treatment of advanced gastric cancer (July 2010)
  4. MHRA Drug Safety Update (October 2020): 5-fluorouracil (intravenous), capecitabine, tegafur: DPD testing recommended before initiation to identify patients at increased risk of severe and fatal toxicity
Cladribine
  • Tablets 10mg
  • Solution for injection vials 2mg/1ml

Notes

  1. NICE TA616: Cladribine tablets (Mavenclad) are recommended as an option for treating highly active multiple sclerosis in adults, only when the criteria of the NICE TA are met (December 2019)
  2. MHRA Drug Safety Update (March 2022): Cladribine (Mavenclad): new advice to minimise risk of serious liver injury
    1. urgently check liver function tests (including bilirubin) in patients with symptoms or signs of liver injury
    2. discontinue or interrupt cladribine treatment in patients with hepatic dysfunction or unexplained increases in liver enzymes
    3. See the safety update for advice to give to patients
Clofarabine

Not routinely commissioned. It has been approved for use for certain conditions where all the criteria set out by the Cancer Drugs Fund are met.

Cytarabine
  • Solution for injection 20mg in 1ml, 100mg in 1ml
Fludarabine phosphate
  • Tablets 10mg
  • Powder for solution for injection vials 50mg

Notes

  1. NICE TA29: Guidance on the use of fludarabine for B-cell chronic lymphocytic leukaemia (September 2001):
    1. Fludarabine is recommended as second-line therapy for B-cell chronic lymphocytic leukaemia (CLL) for patients who have either failed, or are intolerant of, first-line chemotherapy, and who would otherwise have received combination chemotherapy of either:
      • cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP)
      • cyclophosphamide, doxorubicin and prednisolone (CAP) or
      • cyclophosphamide, vincristine and prednisolone (CVP)
  2. NICE TA119: Fludarabine (Fludara) monotherapy is not recommended for the first-line treatment of chronic lymphocytic leukaemia (February 2007)
  3. NICE TA174: Rituximab in combination with fludarabine and cyclophosphamide is recommended as an option for the first-line treatment of chronic lymphocytic leukaemia in people for whom fludarabine in combination with cyclophosphamide is considered appropriate (July 2009)
  4. NICE TA640: Treosulfan with fludarabine is recommended as an option for conditioning treatment before allogeneic haematopoietic stem cell transplant (allo-HSCT) for people with malignant diseases for whom a reduced intensity regimen, such as low-dose busulfan with fludarabine, would be suitable (August 2020)
Fluorouracil
  • Capsules 250mg (named patient only – unlicensed preparation)
  • Injection 25mg/ml, 50mg/ml

Notes

  1. MHRA Drug Safety Update (October 2020): 5-fluorouracil (intravenous), capecitabine, tegafur: DPD testing recommended before initiation to identify patients at increased risk of severe and fatal toxicity
Gemcitabine hydrochloride
  • Concentrate for solution for infusion vials 200mg, 1g, 2g
  • Powder for solution for infusion vials 200mg, 1g, 2g

Notes

  1. NICE TA116: Gemcitabine in combination with paclitaxel, is recommended as an option for the treatment of metastatic breast cancer only when docetaxel monotherapy or docetaxel plus capecitabine are also considered appropriate (January 2007)
  2. NICE TA285: Bevacizumab (Avastin) in combination with gemcitabine and carboplatin is not recommended for treating people with the first recurrence of platinum-sensitive advanced ovarian cancer (including fallopian tube and primary peritoneal cancer) who have not received prior therapy with bevacizumab or other vascular endothelial growth factor (VEGF) inhibitors or VEGF receptor-targeted agents (May 2013)
  3. NICE TA389: Topotecan, pegylated liposomal doxorubicin hydrochloride (Caelyx), paclitaxel, trabectedin (Yondelis) and gemcitabine for treating recurrent ovarian cancer (April 2016):
    1. Gemcitabine in combination with carboplatin is not recommended for treating the first recurrence of platinum-sensitive ovarian cancer
  4. NICE TA476: Paclitaxel as albumin-bound nanoparticles (nab paclitaxel; Abraxane) with gemcitabine is recommended as an option for untreated metastatic adenocarcinoma of the pancreas in adults, only if:
    1. other combination chemotherapies are unsuitable and they would otherwise have gemcitabine monotherapy
Mercaptopurine
  • Tablets 50mg (£49.95 = 25 tablets)
  • Oral suspension 100mg in 5ml (£170.00 = 100ml)
  • Capsules/ tablets 10mg (unlicensed preparation)

Notes

  1. Refer to individual shared care guidelines for use in Gastroenterology
  2. Avoid concomitant use of mercaptopurine with allopurinol, unless supervised by an appropriate specialist.
  3. Mercaptopurine is used in the management of acute leukaemias, chronic myeloid leukaemia and in the management of ulcerative colitis and Crohn's disease (unlicensed indication).
Methotrexate
  • Injection 2.5mg/ml, 25mg/ml
  • Injection (not for intrathecal use) 100mg/ml
  • Tablets 2.5mg (£2.09 = 28 tablets)
  • Metoject® prefilled syringe 0.15ml (7.5mg), 0.2ml (10mg), 0.25ml (12.5mg), 0.3ml (15mg), 0.35ml (17.5mg), 0.4ml (20mg), 0.45ml (22.5mg), 0.5ml (25mg), 0.55ml (27.5mg), 0.6ml (30mg) (£12.87 - £16.56 per syringe) (for South Devon patients this is provided by specialist services at Torbay Hospital)

Notes

  1. West Devon: refer to individual shared care guidelines for use in Gastroenterology, Rheumatology, and Dermatology conditions
  2. South Devon: refer to individual shared care guidelines for use in Gastroenterology, Rheumatology, or Dermatology, Ophthalmology and Respiratory conditions
    1. Prescribing and monitoring of subcutaneous methotrexate (Metoject®) is undertaken by specialist services at Torbay Hospital
  3. Methotrexate dose should be taken once weekly.
  4. To avoid confusion for patients due to differences between injection devices, subcutaneous methotrexate should be prescribed by brand
  5. To avoid errors it is recommended that:
    1. The patient is carefully advised of the dose and frequency and the reason for taking methotrexate and any other prescribed medicine (eg. folic acid)
    2. The prescription and the dispensing label clearly show the dose and frequency of administration, for example: 'methotrexate 2.5mg tablets: (number of tablets) to be taken as a single dose ONCE A WEEK on XXXDAY'
    3. Only one strength of methotrexate tablet (2.5mg) should be prescribed and dispensed
    4. Staff that encounter methotrexate prescriptions must ensure the correct dosing interval is given.
    5. Methotrexate treatment booklets should be issued where appropriate.
    6. The patient is warned to report immediately the onset of any feature of blood disorders (eg. sore throat, bruising and mouth ulcers), liver toxicity (eg. nausea, vomiting, abdominal discomfort and dark urine), and respiratory effects (e.g. shortness of breath)
    7. Patients should be co-prescribed folic acid to prevent methotrexate-induced side-effects (off-label use). Prescribe 5mg at least once weekly (more frequent dosing is often routinely recommended, refer to individual shared care guidelines / specialist advice). Folic acid should be taken at least 24 hours after previous methotrexate administration. Be aware that methotrexate and folic acid tablets look alike.
    8. Methotrexate and NSAIDs: if aspirin or other NSAIDs are given concurrently the dose of methotrexate should be carefully monitored. Patients should be advised to avoid self-medication with over-the-counter aspirin or ibuprofen.
  6. MHRA Drug Safety Update (September 2020): Methotrexate once-weekly for autoimmune diseases: new measures to reduce risk of fatal overdose due to inadvertent daily instead of weekly dosing. Advice for prescribers:
    1. Before prescribing methotrexate, make sure that the patient is able to understand and comply with once-weekly dosing
    2. Consider the patient’s overall polypharmacy burden when deciding which formulation to prescribe, especially for a patient with a high pill burden
    3. Decide with the patient which day of the week they will take their methotrexate and note this day down in full on the prescription
    4. Inform the patient and their caregivers of the potentially fatal risk of accidental overdose if methotrexate is taken more frequently than once a week; specifically, that it should not be taken daily
    5. Advise patients of the need to promptly seek medical advice if they think they have taken too much
Nelarabine

Not routinely commissioned. It has been approved for use in certain conditions where all the criteria set out by the Cancer Drugs Fund are met.

Pemetrexed
  • Injection powder for reconstitution 100mg vial, 500mg vial

Notes

  1. NICE TA135: Pemetrexed is recommended for the treatment of malignant pleural mesothelioma (January 2008)
  2. NICE TA181: Pemetrexed is recommended for the first-line treatment of non-small-cell lung cancer. TA181 does not replace TA124; this states that pemetrexed is not recommended for patients with NSCLC who have had prior chemotherapy, whilst TA181 applies to the first-line use of pemetrexed in patients with NSCLC (September 2009)
  3. NICE TA190: Pemetrexed for the maintenance treatment of non-small-cell lung cancer (August 2017)
  4. NICE TA402: Pemetrexed maintenance treatment recommended for non-squamous non-small-cell lung cancer after pemetrexed and cisplatin (August 2016)
  5. Pemetrexed is not routinely commissioned for other indications. It has been approved for the treatment of a number of conditions where all the criteria set out by the Cancer Drugs Fund are met.
  6. NICE TA124: Pemetrexed is not recommended for the treatment of non-small cell lung cancer (August 2007)
  7. NICE TA309: Pemetrexed is not recommended as maintenance treatment for people with locally advanced or metastatic non-squamous non-small-cell lung cancer after therapy with pemetrexed and cisplatin (April 2014)
Raltitrexed
  • injection 2mg vial

Notes

  1. NICE CG131: Colorectal cancer: diagnosis and management (November 2011)
Tioguanine
  • Capsules 10mg (unlicensed preparation)
  • Suspension 10mg in 1ml (unlicensed preparation)

 

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