A guide to monitoring methotrexate prescribing in primary care.
Folic acid antagonist – antimetabolite cytotoxic agent Inhibits dihydrofolate reductase – prevents DNA and RNA synthesis Anti-inflammatory effect Immunosuppressive action Tablets of 2.5 mg strength – once weekly Metoject® 7.5 mg , 10 mg , 12.5 mg , 15 mg , 17.5 mg , 20 mg , 22.5 mg and 25 mg Oral solution Folic acid @ 5 mg is given ( separate day to MTX ) to reduce SEs
Indications – Disease modifying agent Wide range of neoplastic conditions such as ○ leukaemias ○ Non-Hodgkins’s lymphoma ○ soft-tissue and osteogenic sarcomas ○ solid tumours particularly breast , lung , head and neck , bladder , cervical , ovarian and testicular tumours Psoriasis and psoriatic arthritis ( severe ) First line in active rheumatoid arthritis or ○ In combination with other DMARDSs for e.g sulfasalazine , leflunomide or hydroxychloroquine ○ parenteral – s/c or im Neurology for conditions as ○ myasthenia gravis ○ inflammatory myopathies and neuropathies ○ vasculitis ○ other immune mediated CNS and PNS system diseases Inflammatory bowel disease e.g Crohn’s ( NICE recommends not to use for ulcerative colitis unless no other alternative ) Interstitial lung disease , sarcoidosis and pulmonary vasculitis Scleritis ,vasculitis or mixed connective tissue diseases
Mucosal damage Nausea , vomiting , anorexia Ulcerative stomatitis- may be the first sign of GI toxicity Affects gametogenensis – ↓ fertility. Bone marrow suppression Hepatotoxicity Pulmonary toxicity – methotrexate pneumonitis
Contraindications –Pregnancy- teratogenic Breast feeding Severe renal impairment Significant hepatic impairment Blood disorders e.g untreated folate deficiency , leucopenia , thrombocytopenia , bone marrow hypoplasia or significant anaemia Alcoholism Severe acute or chronic infections and immunodeficiency syndrome Stomatitis , ulcers of the oral cavity and known gastrointestinal ulcer disease Hypersensitivity to methotrexate No live vaccinations should be used during methotrexate treatment Avoid using other antifolate medications with methotrexate
drug interactions –Phenytoin ( ↑ ed anti-folate effect of methotrexate) Probenecid , Penicllin , NSAIDs ( ↓ ed methotrexate excretion ↑ed levels Sig interaction between NSAIDS and methotrexate rare Tolbutamide ( ↑ serum conc of methotrexate ) Trimethoprim , Co-trimaxazole ( ↑ ed antifolate effect of methotrexate greatly increasing the risk of marrow aplasia ) Clozapine ( ↑ed risk of agranulocytosis) Ciprofloxacin (reduced excretion ↑ ed risk of toxicity- Monitor) Topical fluorouracil (toxic skin reaction) Neomycin oral ( ↓ ed levels of methotrexate ) Tetracycline / Doxycycline ( ↑ ed ed risk of toxicity )
FBC , U-Es and LFT-Every 2 weeks until dose is stable for 6 weeks Then monthly for 3 months Thereafter atleast every 12 weeks More frequent monitoring is appropriate in patients at higher risk of toxicity
References ; Further reading Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis M Cutolo , A Sulli , C pizzorni , B Seriolo Ann Rheum Dis 2001;60:729-735 doi:10.1136/ard.60.8.729 An update on Methotrexate accessed via http://www.medscape.com/viewarticle/706105_9 Medicine Compendium accessed via http://www.medicines.org.uk/emc/medicine/12034/SPC/ Methotrexate+10+mg+Tablets+(Hospira+UK+Ltd) Gwent Shared Care Protocol ; Oral Methotrexate for adults with Rheumatoid Arthritis ( RA ) , Psoriasis and Inflammatory Bowel Disease CKS NHS DMARDs accessed via http://cks.nice.org.uk/dmards#!scenario:8 The Top 100 Drugs – Andrew Hitchings , Dagan Lonsdale , Daniel Burrage , Emma Baker Rapid Clinical Pharmacology – Andrew Batchelder , Charlene Rodrigues , Ziad Alfrifai Oxford University Hospital NHS Trust -Clinical Commissioning Group- Methotrexate July 2015 Basingstoke Southampton & Winchester District Prescribing Committee – Shared Care Guideline for Methotrexate GP Summary