Trexan

MTX

Adults w/ severe & active RA who are unresponsive or intolerant to conventional therapy. Polyarticular juvenile idiopathic arthritis in ped patients. Severe psoriasis unresponsive to other therapy. Produce regression in wide range of neoplastic conditions including acute leukaemias, non-Hodgkin's lymphoma, soft-tissue & osteogenic sarcomas, & solid tumours particularly breast, lung, head & neck, bladder, cervical, ovarian, & testicular carcinoma.

Adult Severe, active, classical or definite RA unresponsive or intolerant to conventional therapy 7.5-15 mg once wkly. May increase total wkly dose to 20-25 mg as necessary. Psoriasis Test dose of 2.5-5 mg. Initiate treatment 1 wk later if lab tests are normal. Usual dose: 7.5-15 mg once wkly. May increase total wkly dose to 20-25 mg as necessary in severe psoriasis. Polyarticular juvenile idiopathic arthritis Initially 10 mg/m² once wkly. Max: 30 mg/m² once wkly. Cancer Adjust dose based on BSA. Test dose of 5-10 mg parenterally 1 wk prior to therapy. Max: 30 mg/m² on 5 successive days, then at least 2 wk interval thereafter. Give doses in excess of 100 mg parenterally & in excess of 70 mg/m² w/ leucovorin rescue or assay of serum MTX level 24-48 hr. Ped Polyarticular juvenile idiopathic arthritis 5-20 mg/m² or 0.1-0.65 mg/kg once wkly.

May be taken with or without food.

Hypersensitivity. Pre-existing blood dyscrasias eg, bone marrow hypoplasia, leukopenia, thrombocytopenia or significant anaemia; severe acute or chronic infections & immunodeficiency syndrome; stomatitis, oral cavity ulcers & known active GI ulcer disease. Alcoholism. Concurrent vaccination w/ live vaccines. Concomitant use w/ drugs w/ antifolate properties eg, co-trimoxazole. Hepatic impairment. Renal function (CrCl <30 mL/min) for doses <100 mg/m² & moderate renal impairment (CrCl <60 mL/min) for doses >100 mg/m². Pregnancy & lactation.

W/draw treatment from patients w/ pulmonary symptoms; if clinically significant drop in white cell or platelet count develops. Not to be restarted in suspected MTX-induced lung disease. Stop treatment if profound leukopenia occurs. Interrupt therapy in diarrhoea & ulcerative stomatitis; other conditions leading to dehydration eg, emesis. Discontinue treatment following occurrence of haematemesis, black coloured stools or blood in stools; if any abnormality of LFTs, or liver biopsy, is present or develops. Consider dose reduction or discontinuation in case of constant increase in liver-related enzyme. Not to be given if CrCl is <30 mL/min & doses >100 mg/m² (if CrCl <60 mL/min). Not to be initiated w/ doses >100 mg/m² in urinary pH value <7. Acute or chronic interstitial pneumonitis, often associated w/ blood eosinophilia. Monitor patients for dyspneoa, cough (especially dry non-productive cough) & fever. Restricted to severe recalcitrant for treatment of psoriasis. Presence/history of infection, peptic ulcer, ulcerative colitis, debility & in extreme youth & old age. May lead to fatal toxicity w/ mistaken daily use. Liver atrophy, necrosis, cirrhosis, fatty changes & periportal fibrosis. Increased risk for liver toxicity in diabetic patients. Renal damage leading to acute renal failure. Inactive chronic infections eg, herpes zoster, TB, hepatitis B or C. May trigger tumour lysis syndrome in patients w/ rapidly growing tumour; malignant lymphomas; encephalopathy/leukoencephalopathy. Pulmonary alveolar haemorrhage. May cause adverse urinary tract reactions eg, cystitis & haematuria. May exacerbate psoriatic lesions during UV-irradiation & therapy; SJS, TEN. Patients w/ psychiatric disorders. Patients w/ pleural effusions & ascites should be drained prior to treatment initiation. Strictly monitor patient prior RT (especially of pelvis), functional impairment of haematopoietic system (eg, following prior RT or chemotherapy), impaired general condition, advanced age & in very young childn. Avoid skin & mucosal contact. Determine any increase in active substance levels w/in 48 hr of therapy. Use Ca folinate &/or acute, intermittent haemodialysis w/ high-flux dialyzer as corrective measures; folic acid or folinic acid supplementation to reduce toxicity (check vit B₁₂ levels prior to administration). Require history, physical exam & lab tests for chest x-ray, renal & liver function assessment, & blood elements before treatment. Perform full CBC, renal & LFTs repeated wkly until therapy is stabilised; monitor every 2-3 mth or before, during & after treatment. Avoid or reduce alcohol consumption. Closely monitor liver enzymes in patients taking other liver- or haematotoxic medicinal products; renal function tests & urinalyses. Test alkalinisation of urine by repeated pH monitoring (value ≥6.8) for at least 1st 24 hr after administration. Adequate hydration, urine alkalinization by oral or IV administration of Na bicarbonate or acetazolamide. Concomitant use w/ hepatotoxic or haematotoxic DMARDs eg, leflunomide; medicinal products affecting MTX elimination, or causing kidney damage (eg, NSAIDs) or potentially leading to haematopoiesis impairment; RT; antirheumatic drugs eg, gold, penicillamine, hydroxychloroquine, sulfasalazine or cytotoxic agents; trimethoprim/sulfamethoxazole. Not to be taken w/ additional hepatotoxic medicinal products. Not recommended in combination w/ NSAIDs in mild renal impairment. Avoid concomitant use w/ PPIs. Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. May affect ability to drive & use machines. Impaired kidney function. Liver disease (particularly if alcohol-related). Embryotoxicity, abortion & foetal malformations; impairment of fertility, oligospermia, menstrual dysfunction & amenorrhoea after treatment discontinuation. Female of childbearing age should be advised of possible effects on reproduction, pregnancy loss & congenital malformations; to use effective contraception during treatment & for at least 6 mth after. Men should be advised of possibility of sperm preservation before starting therapy; not to donate semen during therapy or for 6 mth following treatment discontinuation. Not to be administered during pregnancy (particularly during 1st trimester). Not to be used during lactation. Very young childn. Elderly.

Stomatitis, dyspepsia, abdominal pain, nausea, loss of appetite, abnormal LFTs (increased ALT, AST, bilirubin & alkaline phosphatase); leukopenia, anaemia, thrombocytopenia, headache, tiredness, drowsiness, pneumonia, interstitial alveolitis/pneumonitis often associated w/ eosinophilia, oral ulcers, diarrhoea, exanthema, erythema & pruritus. SJS, TEN. Myelosuppression, mucositis.

Reduced excretion & increased toxicity w/ diphenylhydantoins, acidic anti-inflammatory agents, salicylates, phenylbutazone, phenytoin, barbiturates, tranquilisers, OCs, amidopyrine derivatives, p-aminobenzoic acid, thiazide diuretics, oral hypoglycaemics, doxorubicin, tetracyclines, probenecid or sulfinpyrazone. Reduced tubular secretion w/ probenecid & weak organic acids eg, loop-diuretics & pyrazoles. Concomitant use w/ potentially nephro-, hemato- or hepatotoxic agents (eg, sulphasalazine, leflunomide & alcohol); azathioprine or retinoids; aspirin, ibuprofen or indomethacin (NSAIDs); immune-modulating medicinal products. Increased risk for pancytopenia w/ leflunomide. Enhanced nephrotoxicity w/ potentially nephrotoxic chemotherapeutic agent eg, cisplatin. Reduced renal clearance w/ antibiotics eg, penicillin, glycopeptides, sulfonamides, ciprofloxacin & cefalotin. Reduced intestinal absorption or interference w/ enterohepatic circulation w/ oral antibiotics eg, tetracyclines, chloramphenicol & non-absorbable broad-spectrum antibiotics. Impaired efficacy w/ vit prep or other products containing folic acid or its derivatives. Possibility of marked haematopoietic disorders w/ sulfonamides, trimethoprim-sulfamethoxazole, chloramphenicol, pyrimethamine. Increased toxicity w/ medicinal products causing folate deficiency eg, sulfonamides, trimethoprim-sulfamethoxazole; nitrous oxide. Increased levels & severe hepatitis w/ etretinate. Bone marrow suppression & decreased folate levels w/ triamterene. Increased probability of severe haematoxic effects w/ metamizole. Prolonged elimination w/ PPIs eg, omeprazole or pantoprazole. Decreased clearance of theophylline. Reduced efficacy w/ methylxanthines, beverages containing caffeine or theophylline. Reduced blood levels w/ anticonvulsants. Increased t_½ of 5-fluorouracil. Increased non-renal elimination w/ colestyramine. Delayed clearance w/ cytostatic medicinal products. Increased risk of renal impairment w/ procarbazine. Increased risk of soft tissue or bone necrosis w/ RT. Increased plasma levels of mercaptopurine. Possible effect on immune system (falsify vaccinal & test results) w/ live vaccine. Decreased efficacy of phenytoin. Potentiated efficacy & toxicity w/ ciclosporin. Increased/prolonged blood conc w/ levetiracetam.

Cytotoxic Chemotherapy / Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

L04AX03 - methotrexate ; Belongs to the class of other immunosuppressants.

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