8.1.3 Antimetabolites

Azacitidine
  • Injection

Notes

  1. NICE TA218: Azacitidine 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 for metastatic colorectal cancer (May 2003)
  2. NICE TA100: Capecitabine and oxaliplatin in the adjuvant treatment of stage III (Duke's C) colon cancer (April 2006)
  3. NICE TA191: Capecitabine for the treatment of advanced gastric cancer (July 2010)
  4. NICE CG81: metastatic breast cancer (February 2009)
  5. 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
  • Injection 25mg/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
  • Tablets 10mg (unlicenced)
  • Suspension 100mg/5ml

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.
Methotrexate
  • Injection
  • Injection (not for intrathecal use)
  • 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)

Notes

  1. Refer to individual shared care guidelines for use in Gastroenterology, Rheumatology, and Dermatology conditions
  2. To avoid confusion for patients due to differences between injection devices, subcutaneous methotrexate should be prescribed by brand
  3. Methotrexate Safety Information: Oral methotrexate is a very effective medication and acceptably safe if taken at the correct dose with the required monitoring. However, it has the potential for serious toxicity, compounded by confusion surrounding its unusual dosing schedule of once weekly. The National Patient Safety Agency has issued a safety alert with recommended actions to help reduce the number of drug errors associated with methotrexate. The full guidance can be viewed here. Some of the key points are summarised below.
    1. Patients should be issued with an information leaflet and monitoring document.
    2. Be aware that different strengths of methotrexate tablets are available. Where possible the patient should be supplied with one strength continuously which should be recorded in the monitoring booklet and can be checked by others to confirm supply details. If a patient describes their dose by the number of tablets, take care in ascertaining the strength of these tablets. Local policy is to use only 2.5mg tablets for oral once weekly methotrexate in adults varying the number of tablets to achieve the desired dose. If a different strength is stated, take extra steps to check the accuracy of this.
    3. When admitted to hospital a full medication review should be undertaken, preferably by a pharmacist, and the prescribing, monitoring and administration requirements recorded in the notes.
    4. It is the prescriber's responsibility to record the correct dose and frequency on the drug chart and to strike out the six days of the week when a dose must not be administered. Discharge prescriptions must be complete, legible and include the form, strength dose and directions in full. Staff administering oral methotrexate should confirm with the patient that the medication is required and then carefully check the details of strength, dose and timing together with their usual drug administration checks. The administration should be recorded on the drug chart at the time the dose is given.
    5. Be aware of patients who present with symptoms of breathlessness, persistent dry cough, vomiting or diarrhoea as these can be signs of methotrexate toxicity.
    6. 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.
  4. 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

Notes

  1. NICE TA135: Pemetrexed recommended for the treatment of malignant pleural mesothelioma (January 2008)
  2. NICE TA181: Pemetrexed recommended for the first-line treatment of non-small-cell lung cancer. TA181 does not replace TA124 (August 2007); 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
  • Tablets 40mg

 

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