Methotrexate

The page therefore has two arms: (a) relapsed / metastatic head and neck cancer, intravenous, and (b) ENT manifestations of granulomatosis with polyangiitis (GPA), weekly oral or subcutaneous. Product: UK SPC via MHRA Products - METHOTREXATE 100 MG/ML CONCENTRATE FOR SOLUTION FOR INFUSION (PL200750378), Accord Healthcare Limited; §2: each ml contains 100 mg methotrexate (5 ml = 500 mg; 10 ml = 1000 mg; 50 ml = 5000 mg). §4.1 (verbatim): 'Acute lymphocytic leukaemia, Non-Hodgkin's lymphomas, osteogenic sarcoma, adjuvant and in advance disease of breast cancer, metastatic or recurrent head and neck cancer, choriocarcinoma and similar trophoblastic diseases, advanced cancer of urinary bladder.' ARM (a) IS COVERED and is the only dose written. VERBATIM §4.2: 'Methotrexate can be given as convention low dose therapy, intermediate dose therapy and high dose therapy. Conventional low dose therapy: 15-50 mg/m 2 body surface area per week intravenously or intramuscularly in one or more doses. 40-60 mg/m 2 body surface area (for head and neck cancer) once weekly as intravenous bolus injection.' 'Doses of over 100 mg methotrexate always require subsequent administration of folinic acid (See calcium folinate rescue).' 'The dosage is generally calculated per m2 body surface area or body weight.' LABEL STATUS OF THE REGIMEN (§4.2, verbatim): 'Some common dosages which have been used in different indications are given below. None of these dosages can currently be described as standard therapy. ... only the most commonly used guidelines are given, and should be considered as examples Current published protocols should be consulted for dosages and the method and sequence of administration.' §4.2 WARNING (verbatim): 'The dose must be adjusted carefully depending on the body surface area if methotrexate is used for the treatment of tumour diseases. Fatal cases of intoxication have been reported after administration of incorrectly calculated doses.' 'Treatment should be initiated by or occur in consultation with a doctor with significant experience in cytostatic treatment.' ROUTE: 'Methotrexate can be administered intramuscularly, intravenously or intra-arterial. Methotrexate 100mg/ml is hypertonic and must not be administered intrathecally.' OTHER PRINTED REGIMENS, NOT WRITTEN AS THIS PAGE'S DOSE: the SPC also prints intermediate-dose therapy (100 mg/m2 to 1000 mg/m2 in a single dose; 'In advanced squamous epithelial and bladder cancer, intermediate doses of methotrexate up to 100-200 mg/m2 can be used') and high-dose therapy (1000 mg/m2 or more over 24 hours), both of which require calcium folinate rescue and a specialist protocol - consult the full SPC and the local protocol. ARM (b) IS NOT COVERED: granulomatosis with polyangiitis (or any vasculitis) is not named anywhere in this SPC, and this product is given intramuscularly, intravenously or intra-arterially - there is no oral or subcutaneous regimen in it - so NO dose is given for the GPA / weekly oral-or-subcutaneous arm; it needs its own source (a product or guideline that names that indication). Do not read the 40-60 mg/m2 weekly figure as a GPA dose. §4.4 (verbatim): 'Because of the risk of severe toxic reactions (which can be fatal), methotrexate must only be used in life-threatening neoplastic diseases.' and 'Fatal toxicity in association with intravenous administration due to dose miscalculation has been reported.' SPECIAL POPULATIONS (§4.2): older people - dose reduction should be considered because of reduced liver and kidney function and lower folate reserves; patients with significant pathological fluid accumulation (pleural effusion, ascites) - methotrexate is eliminated slowly, so 'drainage of the fluid before treatment is started and monitoring of plasma methotrexate levels are recommended'. CHILDREN (no paediatric dose is written): §4.2 'Methotrexate should be used with caution in paediatric patients. Treatment should follow currently published therapy protocols for children (see section 4.4).' Excipient: 10.60 mg/ml (0.461 mmol/ml) sodium (§2). Section 4.4, 4.5, 4.6 and 4.8 of the retrieved text each end at the source-fetch truncation marker, so the lists below are partial.