Drug Action
Methotrexate inhibits the enzyme dihydrofolate reductase, essential for the synthesis of purines and pyrimidines.
Source page 985
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Individual generic drug information
Extracted information for Methotrexate only.
Methotrexate inhibits the enzyme dihydrofolate reductase, essential for the synthesis of purines and pyrimidines.
Source page 985
Severe Crohn’s disease ▶BY INTRAMUSCULAR INJECTION ▶Adult: Initially 25 mg once weekly until remission induced; maintenance 15 mg once weekly Maintenance of remission of severe Crohn’s disease ▶BY MOUTH ▶Adult: 10–25 mg once weekly Moderate to severe active rheumatoid arthritis ▶BY MOUTH ▶Adult: 7.5 mg once weekly, adjusted according to continued → response; maximum 20 mg per week Severe active rheumatoid arthritis ▶BY INTRAMUSCULAR INJECTION, OR BY SUBCUTANEOUS INJECTION ▶Adult: Initially 7.5 mg once weekly, then increased in steps of 2.5 mg once weekly, adjusted according to response; maximum 25 mg per week Neoplastic diseases ▶BY MOUTH, OR BY INTRAVENOUS INJECTION, OR BY INTRAVENOUS INFUSION, OR BY INTRA-ARTERIAL INFUSION, OR BY INTRAMUSCULAR INJECTION, OR BY INTRATHECAL INJECTION ▶Adult: (consult product literature) Immune system and malignant disease Severe psoriasis unresponsive to conventional therapy (specialist use only) ▶BY MOUTH, OR BY INTRAMUSCULAR INJECTION, OR BY INTRAVENOUS INJECTION, OR BY SUBCUTANEOUS INJECTION ▶Adult: Initially 2.5–10 mg once weekly, then increased in steps of 2.5–5 mg, adjusted according to response, dose to be adjusted at intervals of at least 1 week; usual dose 7.5–15 mg once weekly, stop treatment if inadequate response after 3 months at the optimum dose; maximum 30 mg per week l UNLICENSED USE Not licensed for use in severe Crohn’s disease.
Source pages 985, 986
Active infection. ascites. immunodeficiency syndromes. significant pleural effusion
Source page 986
Photosensitivity—psoriasis lesions aggravated by UV radiation (skin ulceration reported). diarrhoea. extreme caution in blood disorders (avoid if severe). peptic ulceration. risk of accumulation in pleural effusion or ascites— drain before treatment. ulcerative colitis. ulcerative stomatitis CAUTIONS, FURTHER INFORMATION ▶Blood count Bone marrow suppression can occur abruptly; factors likely to increase toxicity include advanced age, renal impairment, and concomitant use with another anti- folate drug (e.g. trimethoprim). A clinically significant drop in white cell count or platelet count calls for immediate withdrawal of methotrexate and introduction of supportive therapy. ▶Gastro-intestinal toxicity Withdraw treatment if stomatitis develops—may be first sign of gastro-intestinal toxicity. ▶Liver toxicity Liver cirrhosis reported. Treatment should not be started or should be discontinued if any abnormality of liver function tests or liver biopsy is present or develops during therapy. Abnormalities can return to normal within 2 weeks after which treatment may be recommenced if judged appropriate. ▶Pulmonary toxicity Pulmonary toxicity may be a special problem in rheumatoid arthritis (patient to seek medical attention if dyspnoea, cough or fever); monitor for symptoms at each visit—discontinue if pneumonitis suspected.
Source page 986
Exclude pregnancy before treatment. Patients should have full blood count and renal and liver function tests before starting treatment.
Source page 987
Folinic acid following methotrexate administration helps to prevent methotrexate-induced mucositis and myelosuppression. The licensed routes of administration for parenteral preparations vary—further information can be found in the product literature for the individual preparations.
Source page 987
Extracted information for Methotrexate only.
NHS NEVER EVENT: OVERDOSE OF METHOTREXATE FOR NON- CANCER TREATMENT (JANUARY 2018) Patients given methotrexate, by any route, for non- cancer treatment should not be given more than their intended weekly dose. WEEKLY DOSING Note that the dose is a weekly dose. To avoid error with low-dose methotrexate, it is recommended that: . the patient is carefully advised of the dose and frequency and the reason for taking methotrexate and any other prescribed medicine (e.g. folic acid); . only one strength of methotrexate tablet (usually 2.5 mg) is prescribed and dispensed; . the prescription and the dispensing label clearly show the dose and frequency of methotrexate administration; . the patient is warned to report immediately the onset of any feature of blood disorders (e.g. sore throat, bruising, and mouth ulcers), liver toxicity (e.g. nausea, vomiting, abdominal discomfort, and dark urine), and respiratory effects (e.g. shortness of breath).
Source page 986
→Appendix 1: methotrexate
Source page 986
▶Common or very common ▶With intrathecal use Necrotising demyelinating leukoencephalopathy. neurotoxicity ▶With oral use Anaemia. appetite decreased. diarrhoea. drowsiness. fatigue. gastrointestinal discomfort. headache. increased risk of infection. leucopenia. nausea . oral disorders. respiratory disorders. skin reactions. throat ulcer. thrombocytopenia. vomiting ▶With parenteral use Anaemia. appetite decreased. chest pain. cough. diarrhoea. drowsiness. dyspnoea. fatigue. fever. gastrointestinal discomfort. headache. leucopenia. malaise. nausea. oral disorders. respiratory disorders. skin reactions. throat complaints. thrombocytopenia. vomiting ▶Uncommon ▶With oral use Agranulocytosis. alopecia. arthralgia. bone marrow disorders. chills. confusion. cystitis. depression. diabetes mellitus. dysuria. fever. gastrointestinal disorders. haemorrhage. healing impaired. hepatic disorders. myalgia. neoplasms. nephropathy. osteoporosis. photosensitivity reaction. rheumatoid arthritis aggravated. seizure. severe cutaneous adverse reactions (SCARs). vasculitis. vertigo. vulvovaginal disorders ▶With parenteral use Agranulocytosis. alopecia. arthralgia. bone marrow disorders. confusion. cystitis. depression. diabetes mellitus. drug toxicity. dysuria. gastrointestinal disorders. haemorrhage. healing impaired. hepatic disorders. increased risk of infection. lipoatrophy. local reaction. myalgia. neoplasms. osteoporosis. pain. paraesthesia. photosensitivity reaction. rheumatoid arthritis aggravated. seizure. severe cutaneous adverse reactions (SCARs). sterile abscess. vasculitis. vertigo. vulvovaginal disorders ▶Rare or very rare ▶With oral use Azotaemia. brain oedema. cognitive impairment. conjunctivitis. cough. dyspnoea. eosinophilia. gynaecomastia. hypotension. immune deficiency. infertility. insomnia. lymphadenopathy. meningitis aseptic. menstrual disorder. mood altered. muscle weakness. nail discolouration. neutropenia. oligozoospermia. pain. pancreatitis. paresis. pericardial disorders. pericarditis. proteinuria. psychosis. radiation injuries. renal impairment. retinopathy. sensation abnormal. sepsis. sexual dysfunction. speech impairment . stress fracture. taste metallic. telangiectasia. tinnitus. visual impairment ▶With parenteral use Apnoea. asthma-like conditions. azotaemia. conjunctivitis. embolism and thrombosis. eosinophilia. gynaecomastia. hypotension. immune deficiency. infertility. influenza like illness. insomnia. lymphadenopathy. meningism. meningitis aseptic. menstrual disorder. mood altered. muscle weakness. nail discolouration. necrosis. neutropenia. paralysis. pericardial disorders. pericarditis. proteinuria. reactivation of infection. renal impairment. retinopathy. sepsis. sexual dysfunction. sperm abnormalities. stress fracture. taste altered. telangiectasia. vision disorders ▶Frequency not known ▶With oral use Encephalopathy ▶With parenteral use Aphasia. chills. cognitive disorder. defective oogenesis. dizziness. hemiparesis. leukoencephalopathy. metabolic change. mucositis. nephropathy. pancreatitis. pulmonary oedema. skin ulcer . sudden death. tinnitus SIDE-EFFECTS, FURTHER INFORMATION Give folic acid to reduce side-effects. Folic acid decreases mucosal and gastrointestinal side-effects of methotrexate and may prevent hepatotoxicity; there is no evidence of a reduction in haematological side-effects. Withdraw treatment if ulcerative stomatitis develops— may be first sign of gastro-intestinal toxicity. Treatment with folinic acid (as calcium folinate) may be required in acute toxicity.
Source pages 986, 987
Manufacturer advises effective contraception during and for at least 6 months after treatment in men and women.
Source page 987
Avoid (teratogenic; fertility may be reduced during therapy but this may be reversible).
Source page 987
Discontinue breast-feeding—present in milk.
Source page 987
When used for malignancy, avoid in severe hepatic impairment—consult local treatment protocol for details. Avoid with hepatic impairment in non-malignant conditions—dose-related toxicity.
Source page 987
Risk of nephrotoxicity at high doses. Avoid in severe impairment. Dose adjustments Reduce dose.
Source page 987
▶In view of reports of blood dyscrasias (including fatalities) and liver cirrhosis with low-dose methotrexate patients should: . have full blood count and renal and liver function tests repeated every 1–2 weeks until therapy stabilised, thereafter patients should be monitored every 2–3 months. . be advised to report all symptoms and signs suggestive of infection, especially sore throat ▶Local protocols for frequency of monitoring may vary. ▶Treatment with folinic acid (as calcium folinate) may be required in acute toxicity.
Source page 987
Extracted information for Methotrexate only.
There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: oral suspension, oral Immune system and malignant disease solution, solution for injection Tablet ▶Methotrexate (Non-proprietary) Methotrexate 2.5 mg Methotrexate 2.5mg tablets | 24 tablet P £1.29–£3.75 | 28 tablet P £3.82 DT = £2.34 | 100 tablet P £5.39–£14.10 Methotrexate 10 mg Methotrexate 10mg tablets | 100 tablet P £55.74 DT = £52.64 ▶Maxtrex (Pfizer Ltd) Methotrexate 2.5 mg Maxtrex 2.5mg tablets | 24 tablet P £2.39 | 100 tablet P £9.96 Methotrexate 10 mg Maxtrex 10mg tablets | 100 tablet P £45.16 DT = £52.64 Solution for injection ▶Methotrexate (Non-proprietary) Methotrexate (as Methotrexate sodium) 2.5 mg per 1 ml Methotrexate 5mg/2ml solution for injection vials | 5 vial P £36.00 (Hospital only) Methotrexate (as Methotrexate sodium) 25 mg per 1 ml Methotrexate 500mg/20ml solution for injection vials | 1 vial P £48.00–£726.28 (Hospital only) Methotrexate 50mg/2ml solution for injection vials | 1 vial P £72.63 (Hospital only) | 5 vial P £35.00 (Hospital only) Methotrexate (as Methotrexate sodium) 100 mg per 1 ml Methotrexate 1g/10ml solution for injection vials | 1 vial P £85.00 (Hospital only) | 1 vial P £80.75 ▶Methofill (Accord Healthcare Ltd) Methotrexate 50 mg per 1 ml Methofill 12.5mg/0.25ml solution for injection pre-filled injector | 1 pre-filled disposable injection P £14.34 DT = £14.35 Methofill 22.5mg/0.45ml solution for injection pre-filled injector | 1 pre-filled disposable injection P £16.10 DT = £16.11 Methofill 30mg/0.6ml solution for injection pre-filled injector | 1 pre- filled disposable injection P £16.55 DT = £16.56 Methofill 27.5mg/0.55ml solution for injection pre-filled injector | 1 pre-filled disposable injection P £16.49 DT = £16.50 Methofill 7.5mg/0.15ml solution for injection pre-filled injector | 1 pre-filled disposable injection P £12.86 DT = £12.87 Methofill 20mg/0.4ml solution for injection pre-filled injector | 1 pre- filled disposable injection P £15.55 DT = £15.56 Methofill 10mg/0.2ml solution for injection pre-filled injector | 1 pre- filled disposable injection P £13.25 DT = £13.26 Methofill 15mg/0.3ml solution for injection pre-filled injector | 1 pre- filled disposable injection P £14.40 DT = £14.41 Methofill 17.5mg/0.35ml solution for injection pre-filled injector | 1 pre-filled disposable injection P £15.24 DT = £15.25 Methofill 25mg/0.5ml solution for injection pre-filled injector | 1 pre- filled disposable injection P £16.12 DT = £16.13 Methotrexate (as Methotrexate sodium) 50 mg per 1 ml Methofill 15mg/0.3ml solution for injection pre-filled syringes | 1 pre-filled disposable injection P £12.40 Methofill 25mg/0.5ml solution for injection pre-filled syringes | 1 pre- filled disposable injection P £14.24 Methofill 30mg/0.6ml solution for injection pre-filled syringes | 1 pre- filled disposable injection P £14.55 Methofill 10mg/0.2ml solution for injection pre-filled syringes | 1 pre- filled disposable injection P £11.25 Methofill 7.5mg/0.15ml solution for injection pre-filled syringes | 1 pre-filled disposable injection P £10.86 Methofill 17.5mg/0.35ml solution for injection pre-filled syringes | 1 pre-filled disposable injection P £13.24 Methofill 27.5mg/0.55ml solution for injection pre-filled syringes | 1 pre-filled disposable injection P £14.49 Methofill 22.5mg/0.45ml solution for injection pre-filled syringes | 1 pre-filled disposable injection P £14.10 Methofill 12.5mg/0.25ml solution for injection pre-filled syringes | 1 pre-filled disposable injection P £12.34 Methofill 20mg/0.4ml solution for injection pre-filled syringes | 1 pre- filled disposable injection P £13.55 ▶Metoject PEN (medac UK) Methotrexate 50 mg per 1 ml Metoject PEN 27.5mg/0.55ml solution for injection pre-filled pens | 1 pre-filled disposable injection P £16.50 DT = £16.50 Metoject PEN 17.5mg/0.35ml solution for injection pre-filled pens | 1 pre-filled disposable injection P £15.25 DT = £15.25 Metoject PEN 30mg/0.6ml solution for injection pre-filled pens | 1 pre- filled disposable injection P £16.56 DT = £16.56 Metoject PEN 12.5mg/0.25ml solution for injection pre-filled pens | 1 pre-filled disposable injection P £14.35 DT = £14.35 Metoject PEN 10mg/0.2ml solution for injection pre-filled pens | 1 pre- filled disposable injection P £13.26 DT = £13.26 Metoject PEN 15mg/0.3ml solution for injection pre-filled pens | 1 pre- Immune system and malignant disease filled disposable injection P £14.41 DT = £14.41 Metoject PEN 22.5mg/0.45ml solution for injection pre-filled pens | 1 pre-filled disposable injection P £16.11 DT = £16.11 Metoject PEN 7.5mg/0.15ml solution for injection pre-filled pens | 1 pre-filled disposable injection P £12.87 DT = £12.87 Metoject PEN 25mg/0.5ml solution for injection pre-filled pens | 1 pre- filled disposable injection P £16.13 DT = £16.13 Metoject PEN 20mg/0.4ml solution for injection pre-filled pens | 1 pre- filled disposable injection P £15.56 DT = £15.56 ▶Nordimet (Nordic Pharma Ltd) Methotrexate 25 mg per 1 ml Nordimet 15mg/0.6ml solution for injection pre-filled pens | 1 pre-filled disposable injection P £14.92 DT = £14.92 Nordimet 20mg/0.8ml solution for injection pre-filled pens | 1 pre- filled disposable injection P £16.06 DT = £16.06 Nordimet 22.5mg/0.9ml solution for injection pre-filled pens | 1 pre- filled disposable injection P £16.61 DT = £16.61 Nordimet 12.5mg/0.5ml solution for injection pre-filled pens | 1 pre- filled disposable injection P £14.85 DT = £14.85 Nordimet 10mg/0.4ml solution for injection pre-filled pens | 1 pre- filled disposable injection P £13.77 DT = £13.77 Nordimet 17.5mg/0.7ml solution for injection pre-filled pens | 1 pre- filled disposable injection P £15.75 DT = £15.75 Nordimet 25mg/1ml solution for injection pre-filled pens | 1 pre-filled disposable injection P £16.64 DT = £16.64 Nordimet 7.5mg/0.3ml solution for injection pre-filled pens | 1 pre- filled disposable injection P £13.37 DT = £13.37 ▶Zlatal (Nordic Pharma Ltd) Methotrexate (as Methotrexate sodium) 25 mg per 1 ml Zlatal 17.5mg/0.7ml solution for injection pre-filled syringes | 1 pre-filled disposable injection P £15.75 DT = £15.75 Zlatal 10mg/0.4ml solution for injection pre-filled syringes | 1 pre- filled disposable injection P £13.77 DT = £13.77 Zlatal 25mg/1ml solution for injection pre-filled syringes | 1 pre-filled disposable injection P £16.64 DT = £16.64 Zlatal 20mg/0.8ml solution for injection pre-filled syringes | 1 pre- filled disposable injection P £16.06 DT = £16.06 Zlatal 12.5mg/0.5ml solution for injection pre-filled syringes | 1 pre- filled disposable injection P £14.85 DT = £14.85 Zlatal 7.5mg/0.3ml solution for injection pre-filled syringes | 1 pre- filled disposable injection P £13.37 DT = £13.37 Zlatal 22.5mg/0.9ml solution for injection pre-filled syringes | 1 pre- filled disposable injection P £16.61 DT = £16.61 Zlatal 15mg/0.6ml solution for injection pre-filled syringes | 1 pre- filled disposable injection P £14.92 DT = £14.92 Solution for infusion ▶Methotrexate (Non-proprietary) Methotrexate (as Methotrexate sodium) 100 mg per 1 ml Methotrexate 5g/50ml solution for infusion vials | 1 vial P £400.00 (Hospital only) | 1 vial P £380.00 Oral solution ▶Methotrexate (Non-proprietary) Methotrexate (as Methotrexate sodium) 2 mg per 1 ml Methotrexate 2mg/ml oral solution sugar free sugar-free | 35 ml P £114.00 DT = £95.00 sugar-free | 65 ml P £125.00 DT = £125.00 ▶Jylamvo (Intrapharm Laboratories Ltd) Methotrexate (as Methotrexate sodium) 2 mg per 1 ml Jylamvo 2mg/ml oral solution sugar-free | 60 ml P £112.50
Source pages 987, 988
Extracted information for Methotrexate only.
Patients and their carers should be warned to report immediately the onset of any feature of blood disorders (e.g. sore throat, bruising, and mouth ulcers), liver toxicity (e.g. nausea, vomiting, abdominal discomfort and dark urine), and respiratory effects (e.g. shortness of breath). Patients should be advised to avoid self-medication with over-the-counter aspirin or ibuprofen. Patients should be counselled on the dose, treatment booklet, and the use of NSAIDs. Methotrexate treatment booklets Methotrexate treatment booklets should be issued where appropriate. In England, Wales, and Northern Ireland, they are available for purchase from: 3M Security Print and Systems Limited Gorse Street, Chadderton Oldham OL9 9QH Tel: 0845 610 1112 GP practices can obtain supplies through their Local Area Team stores. NHS Hospitals can order supplies from www.nhsforms.co.uk or by emailing nhsforms@mmm.com. In Scotland, treatment booklets can be obtained by emailing stockorders.dppas@theapsgroup.com or by fax on 0131 629 9967. These booklets include advice for adults taking oral methotrexate for inflammatory conditions, and a section for recording results of blood tests and dosage information.
Source page 987
Filter the extracted dose blocks for this individual drug.
First line only; read the complete Indications and dose section above.
Initially 25 mg once weekly until remission
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 985
First line only; read the complete Indications and dose section above.
10–25 mg once weekly
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 985
First line only; read the complete Indications and dose section above.
7.5 mg once weekly, adjusted according to
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 985
First line only; read the complete Indications and dose section above.
Initially 7.5 mg once weekly, then increased in
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 986
First line only; read the complete Indications and dose section above.
(consult product literature)
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 986
First line only; read the complete Indications and dose section above.
Initially 2.5–10 mg once weekly, then increased
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 986