Methotrexate Oral Solution Abbreviated Prescribing Information

Abbreviated Prescribing Information: Methotrexate 2mg/ml Oral Solution. Consult Summary of Product Characteristics before prescribing. Presentation: A clear yellow oral solution, each ml of oral solution contains 2.19 mg Methotrexate disodium equivalent to 2 mg Methotrexate. Therapeutic Indications: Methotrexate 2mg/ml Oral Solution is indicated in the following oncological indications: The maintenance treatment of Acute Lymphocytic Leukaemia (ALL) in children and adults. The treatment of malignant trophoblastic tumours; The treatment of severe active rheumatoid arthritis in adults; Polyarthritic forms of active, severe juvenile idiopathic arthritis (JIA) in adolescents and children aged 3 years and over when the response to non-steroidal anti-inflammatory drugs (NSAIDs) has been inadequate. The treatment of severe forms of psoriasis vulgaris including chronic plaque psoriasis, erythrodermic psoriasis, psoriatic arthritis and pustular psoriasis which are not responsive to other conventional therapies such as phototherapy, PUVA and retinoids. Posology and Method of Administration: Dosage in adult patients with rheumatoid arthritis: The usual dose is 7.5 – 15 mg (3.75 ml – 7.5 ml) once weekly. The schedule may be adjusted gradually, depending on the individual activity of the disease and tolerability by the patient to achieve an optimal response but should not exceed a total weekly dose of 20 mg (10 ml). Thereafter the dose should be reduced to the lowest possible effective dose which in most cases is achieved within 6 weeks. Dosage in children with and adolescents with polyarthritic forms of juvenile idiopathic arthritis: Patents with JIA should always be referred to a rheumatology unit specialising in the treatment of children/adolescents. The recommended dose is 10 – 15 mg (5 – 7.5 ml)/m2 body surface area (BSA)/week. In therapy-refractory cases the weekly dosage may be increased to 20 mg (10 ml)/m2 BSA/week. However, increased monitoring frequency is indicated if the dosage is increased. The treating physician will decide how long the patient should be treated. Treatment of severe active rheumatoid arthritis and severe JIA represents a longterm treatment. Dosage in oncological indications (low dose therapy: single dose < 100 mg/m2) Doses are usually based on the patient’s body surface area (BSA). Doses in excess of 100 mg are usually given parenterally, when an injectable preparation should be used. Malignant Trophoblastic Tumours: 15mg/m2, Day 1 to Day 5. Usually, such courses may be repeated 3 to 5 times as required, with rest periods of one or more weeks interposed between courses, until any manifesting toxic symptoms subside. Acute Lymphocytic Leukaemia: Low-dose methotrexate is used in the maintenance treatment of acute lymphocytic leukaemia in children and adults within complex protocols in combination with other cytostatic medicinal products for maintenance treatment. Common accepted single doses lie in the range of 20- 40mg/m2 body surface area. If methotrexate is administered in combination chemotherapy regimens, the dosage should be reduced, taking into consideration any overlapping toxicity of the other drug components. Dosage for psoriasis: Before starting treatment, it is advisable to give the patient a test dose of 2.5 – 5.0 mg to exclude unexpected toxic effects. If, one week later, appropriate laboratory tests are normal, treatment may be initiated. The usual dose is 10mg – 25mg (5ml – 12.5ml) taken once weekly. As necessary, the total weekly dose can be increased up to 25mg. Thereafter the dose should be reduced to the lowest effective dose according to therapeutic response which is most cases is achieved within 4 to 8 weeks. Elderly: Methotrexate should be used with extreme caution in elderly patients, a reduction in dosage should be considered due to reduced liver and kidney function as well as lower folate reserves which occur with increased age. Patients with hepatic impairment: Methotrexate should be administered only with the greatest caution, if at all, in patients with significant existing or previous liver disease, especially if due to alcohol. If bilirubin levels are >5 mg/dl (85.5 µmol/l), methotrexate is contraindicated. Patients with renal impairment: Since methotrexate is predominantly eliminated renally, in patients with impaired creatinine clearance, delayed elimination is to be expected, which can lead to severe side effects. In patients with impaired renal function, the dose regimens must be adjusted according to the creatinine clearance and serum methotrexate concentrations. Paediatric population: Oncological indications: Methotrexate should be used with caution in children. Non-oncological indications: Polyarthritic forms of juvenile idiopathic arthritis: Use in children under 3 years of age is not recommended. Contraindications: Hypersensitivity to the active substance or to any of the excipients; severe renal impairment (creatinine clearance less than 30 ml/min, see section 4.2); significant hepatic impairment; alcoholism; active infectious disease; overt or laboratory evidence of immunodeficiency syndrome(s); pre-existing blood dyscrasias, such as bone marrow hypoplasia, leucopenia, or thrombocytopenia or serious anaemia; severe, acute or chronic infections such as tuberculosis and HIV; stomatitis, ulcers of the oral cavity and known active gastrointestinal ulcers; breast-feeding; during methotrexate therapy concurrent vaccination with live vaccines must not be carried out; Pregnancy. Special Warnings and Precautions for use: The oral solution contains 2 mg of methotrexate in each ml of solution; the scaling of the dosing syringe is in ml and not mg; care should be taken that the correct dosing volume is prescribed. Patients with rheumatological or dermatological diseases must be informed unequivocally that treatment is to be taken just once a week and not daily. Incorrect use of methotrexate can result in severe and even fatal adverse reactions. Medical staff and patients must be clearly instructed. Warnings regarding non-oncological indications: The prescriber should specify the day of intake on the prescription. The prescriber should make sure patients understand that methotrexate should only be taken once a week. Patients should be instructed on the importance of adhering to the once-weekly intakes as incorrect intake of methotrexate can lead to severe, including potentially lethal, side effects, especially in elderly patients. Due to the risk of severe potentially life-threatening adverse reactions, methotrexate should only be used in patients with severe active rheumatoid arthritis or severe forms of psoriasis vulgaris including chronic plaque psoriasis, erythrodermic psoriasis, psoriatic arthritis and pustular psoriasis which are not responsive to other conventional therapies. Warnings regarding all indications: Patients undergoing methotrexate therapy should be closely monitored to prevent intoxication and to ensure fast identification of toxic side effects. Especially strict monitoring of the patient is indicated following prior radiotherapy (especially of the pelvis), functional impairment of the haematopoietic system (e.g., following prior radio- or chemotherapy), impaired general condition as well as advanced age and in very young children. Patients should be fully informed by the physician about the risks and benefits of the therapy, of the need to inform the physician immediately if toxic signs occur and about necessary examinations and safety measures during treatment. Discontinuation of methotrexate therapy did not always result in a complete recovery from toxic effects. Methotrexate has been reported to cause impairment of fertility, oligospermia, menstrual dysfunction and amenorrhoea in humans during and for a short period after the discontinuation of treatment, Methotrexate causes embryotoxicity, abortion and foetal malformations in humans. Vitamin preparations or other products containing folic acid, folinic acid or their derivatives may decrease the effectiveness of methotrexate. Precautions: Before administration of methotrexate, the following check-up examinations and safety precautions are recommended: renal and hepatic function tests; a complete blood picture; urinalysis should be performed as part of the prior and follow-up examinations; chest x-ray; hepatitis A, B, C serology; tuberculosis diagnostics. Liver biopsies may also be required. Respiratory Strict monitoring is necessary in patients with pulmonary dysfunction, smokers and/or patients with certain bronchopulmonary diseases, particularly bronchiectasis or fibrosis. Hepatic: Hepatic toxicity has been observed, usually associated with chronic hepatic disease. The administration of low doses of methotrexate for prolonged periods may give rise, in particular, to hepatic toxicity. Liver function should be closely monitored. Gastrointestinal: Care and possible cessation of treatment are indicated if stomatitis or GI toxicity occurs as haemorrhagic enteritis due to the danger of potentially fatal intestinal perforation. Renal: Renal lesions may develop if the urinary flow is impeded and urinary pH is low, especially if large doses have been administered. Renal function should be closely monitored before, during and after treatment. Blood, Infection, and Immunosuppression: Haematopoietic suppression caused by methotrexate may occur abruptly and with apparently safe dosages. Full blood counts should be closely monitored before, during and after treatment. The immunosuppressive effect of methotrexate should be taken into account when immune responses of patients are important or essential. Special attention should be paid in cases of inactive chronic infections (e.g., herpes zoster, tuberculosis, hepatitis B or C) because of their potential activation. Progressive  multifocal leukoencephalopathy (PML): Cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients receiving methotrexate, mostly in combination with other immunosuppressive medication. Malignancy: Malignant lymphomas may occur in patients receiving low dose methotrexate, in which case therapy must be discontinued. Fertility: Methotrexate has been reported to cause impairment of fertility in both males and females. Teratogenicity – Reproductive risk: Methotrexate causes embryotoxicity, abortion and foetal malformations in humans. In non-oncologic indications, the absence of pregnancy must be confirmed before methotrexate is used. If women of a sexually mature age are treated, effective contraception must be used during treatment and for at least six months after. Skin toxicity: Severe, occasionally fatal, dermatologic reactions, including toxic epidermal necrolysis (Lyell’s Syndrome) or Stevens Johnson syndrome have been reported after single or multiple doses of methotrexate. Folic acid supplementation: If acute methotrexate toxicity occurs, patients may require treatment with folinic acid. It is recommended to check levels of vitamin B12 prior to initiating folic acid supplementation, particularly in adults aged over 50 years, as folic acid intake may mask a vitamin B12 deficiency. Methotrexate given concomitantly with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis. Exposure to intense sunlight or to UV rays should be avoided, as photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking methotrexate. Patients are advised to use adequate sun-protection to protect themselves from intense sunlight. Psoriatic lesions can worsen during UV radiation and co-administration of methotrexate. Any warning from the MC, CHM, CSM or MHRA: Patients with rheumatological or dermatological diseases must be informed unequivocally that treatment is to be taken just once a week and not daily. Incorrect use of methotrexate can result in severe and even fatal adverse reactions (see above for further details). Black Triangle notice: Not applicable. Undesirable Effects: A list of very common, common, and serious adverse reactions are presented below: Very common adverse reactions include: Loss of appetite, nausea, vomiting, abdominal pain, inflammation and ulceration of mucosa of mouth and throat, stomatitis, dyspepsia and increase in liver-related enzymes (ALAT [GPT], ASAT [GOT], alkaline phosphatase and bilirubin).Common adverse reactions include: infections, leucopenia, thrombocytopenia, anaemia, headache, dizziness, fatigue, drowsiness, pneumonitis, interstitial pneumonitis (can be fatal), anorexia, diarrhoea, erythema, exanthema and pruritus. Serious adverse reactions include: haematopoietic disorders, allergic reactions, herpes soster, megaloblastic anaemia, cytomegalovirus-induced infections, cryptococcosis, immuno-suppression, haemorrhages, hypogamma-globulinaemia, confusion, paresis, acute aseptic meningitis, acute aseptic meningitis with meningism, dysarthria, muscular asthenia, psychoses, severe visual disturbances, pericarditis, pericardial tamponade, thromboembolic reactions, vasculitis, bronchial asthma, chronic interstitial obstructive lung disease, chronic obstructive pulmonary disease, pleural effusion, bleeding of gastrointestinal tract, gastrointestinal ulcerations and haemorrhage, fibrosis and cirrhosis, periportal fibrosis, liver cirrhosis, lymphoma, bone marrow suppression, depression, convulsions, leukoencephalopathy, cerebral oedema, pericarditis, pericardial effusion, pneumonitis, pulmonary fibrosis, gastrointestinal ulcer, gastrointestinal haemorrhage, pancreatitis, severe skin reactions, osteoporosis, haematemesis, haematorrhoea, toxic megacolon, liver failure, opportunistic infection, sepsis, agranulocytosis, anaphylactic shock, anuria, aplastic anaemia, azotaemia, cerebral thrombosis, dermatitis exfoliative, diabetes mellitus, disseminated herpes simplex, encephalopathy, erythema multiforme, hemiparesis, hepatic cirrhosis, hepatic fibrosis, hepatic necrosis, hepatic steatosis, hepatitis, acute liver degeneration, reactivation of chronic hepatitis, osteonecrosis of jaw, nephropathy, proteinuria, hepatotoxicity, histoplasmosis, lymphoproliferative disorder, melaena, myelosuppression, renal toxicity, neurotoxicity, neutropenia, nocardiosis, opportunistic infections (sometimes fatal), osteonecrosis, pancytopenia, pneumocystis jiroveci pneumonia, pulmonary alveolar haemorrhage, pulmonary embolism, pulmonary toxicity, renal failure, respiratory paralysis, retinopathy, Stevens-Johnson syndrome, and toxic epidermal necrolysis (Lyell’s syndrome). Refer to the SmPC for full details of other adverse reactions. Legal Category: POM. Pack Size and NHS Price: 35ml – £95.00, 65ml – £125.00. Marketing Authorisation Number: PL 00427/0233. Marketing Authorisation Holder: Rosemont Pharmaceuticals Ltd, Rosemont House, Yorkdale Industrial Park, Braithwaite Street, Leeds, LS11 9XE, UK. Date of Preparation: Jul 2025.