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METHOTREXATE is a brand name for Methotrexate. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Active rheumatoid arthritis in adult patients. - Severe forms of psoriasis vulgaris, particularly of the plaque type, which cannot be sufficiently treated with conventional therapy such as phototherapy, PUVA, and retinoids, and severe psoriatic arthritis.
Verbatim from this product's MHRA label. Tap a section to expand.
Methotrexate should only be prescribed by physicians with expertise in the use of methotrexate and a full understanding of the risk of methotrexate therapy. The prescriber should ensure that patients or their carers will be able to comply with the once weekly regimen.
For doses not realisable/practicable with this strength another strength of this medicinal product is available.
Important warning about the dosage of methotrexate:
In the treatment of rheumatoid arthritis and psoriasis, methotrexate must only be taken once a week. Dosage errors in the use of methotrexate can result in serious adverse reactions, including death. Please read this section of the summary of product characteristics very carefully.
The prescriber should specify the day of intake on the prescription. 5 - 15 mg once weekly. The schedule may be adjusted gradually to achieve an optimal response but should not exceed a total weekly dose of 20 mg. Thereafter the dose should be reduced to the lowest possible effective dose which in most cases is achieved within 6 weeks.
0 mg to exclude unexpected toxic effects. If, one week later, appropriate laboratory tests are normal, treatment may be initiated. 5–15 mg taken once weekly. As necessary, the total weekly dose can be increased up to 25 mg. Thereafter the dose should be reduced to the lowest effective dose according to therapeutic response which in most cases is achieved within 4 to 8 weeks.
The patient should be fully informed of the risks involved and the clinician should pay particular attention to the appearance of liver toxicity by carrying out liver function tests before starting methotrexate treatment, and repeating these at 2 to 4 month intervals during therapy.
The aim of therapy should be to reduce the dose to the lowest possible level with the longest possible rest period. The use of methotrexate may permit the return to conventional topical therapy which should be encouraged. Use in elderly Methotrexate should be used with extreme caution in elderly patients, a dose reduction should be considered due to reduced liver and kidney function as well as lower folate reserves which occurs with increased age.
4). The health care provider may need to adjust the dose to prevent accumulation of drug. The table below provided recommended starting doses in renally impaired patients; dosing may need further adjustment due to wide intersubject pK variability.
In general, the incidence and severity of side effects are considered to be- related to the dose, the dosing frequency, the method of administration and the duration of exposure. Most adverse reactions are reversible if detected early.
When adverse reactions do occur, the drug should be reduced in dosage or discontinued and appropriate corrective measures should be taken. 4). Methotrexate therapy should only be resumed with particular caution, after careful consideration of the need for treatment and with increased vigilance for the possible recurrence of toxicity.
Most serious adverse reactions of methotrexate include bone marrow suppression, pulmonary toxicity, hepatotoxicity, renal toxicity, neurotoxicity, thromboembolic events, anaphylactic shock and Stevens-Johnson syndrome. g. g. increased Alanine aminotransferase (ALAT), Aspartate aminotransferase (ASAT), bilirubin, alkaline phosphatase).
Other frequently occurring adverse reactions are leukopenia, anaemia, thrombocytopenia, headache, tiredness, drowsiness, pneumonia, interstitial alveolitis/pneumonitis often associated with eosinophilia, oral ulcers, diarrhoea, exanthema, erythema and pruritus.
The most relevant adverse reaction is suppression of the haematopoietic system and gastrointestinal disorders.
Adverse reactions for the various systems are as follows:
Skin and subcutaneous tissue disorders: Exanthema, Stevens-Johnson Syndrome, toxic epidermal necrolysis, erythematous rashes, pruritus, urticaria, photosensitivity, pigmentary changes, erythema multiforme, onycholysis, increased pigmentation, petechia, allergic vasculitis, hidradenitis, alopecia, depigmentation, ecchymosis, telangiectasia, acne, furunculosis, painful damage to psoriatic lesions, skin ulceration, herpetiform eruptions of the skin, hyperpigmentation of the nails and acute paronychia.
It should be emphasized to the patient that the recommended dose must be taken only once a week. The prescriber should specify the day of intake on the prescription. 9). Methotrexate should be used with extreme caution in patients with haematological depression, renal impairment, diarrhoea, and ulcerative disorders of the GI tract and psychiatric disorders.
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.
If hepatic function abnormalities develop, methotrexate dosing should be suspended for at least two weeks. It is only appropriate to restart methotrexate provided the abnormalities return to normal and the re-exposure is deemed appropriate.
Particular care and possible cessation of treatment are indicated if stomatitis or GI toxicity occurs as haemorrhagic enteritis and intestinal perforation may result. Reversible eosinophilic pulmonary reactions and treatment resistant, interstitial fibrosis may occur, particularly after long-term treatment.
Methotrexate therapy in patients with impaired renal function should be undertaken with extreme caution because impairment of renal function will decrease methotrexate elimination. Renal function should be monitored by renal function tests and urinalyses.
If serum creatinine levels are increased, the dose should be reduced. 3). 0. 8) for at least the first 24 hours after the administration of methotrexate is started. Renal lesions may develop if the urinary flow is impeded and urinary pH is low, especially if large doses have been administered.
Methotrexate may cause renal damage that may lead to acute renal failure. Close attention to renal function including adequate hydration, urine alkalinization, and measurement of serum methotrexate and renal function are recommended.
g. 5).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Other brands of Methotrexate in United Kingdom.
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Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
4). Use in a patient with a third distribution space (pleural effusions, ascites) As the half-life of Methotrexate can be prolonged to 4 times the normal length in patients who possess a third distribution space dose reduction or, in some cases, discontinuation of methotrexate administration may be required.
Special note If changing the oral application to parenteral administration a reduction of the dose may be required due to the variable bioavailability of methotrexate after oral administration. Method of Administration Oral.
Skin exfoliation / dermatitis exfoliative (frequency not known). The recall phenomenon has been reported in both radiation and solar damaged skin. Lesions of psoriasis may worsen with concomitant UV therapy. Radiation dermatitis and sunburn may be “recalled”.
Blood and the lymphatic system disorders:
Megaloblastic anaemia, hematopoietic disorders, eosinophilia, lymphoproliferative disorder (partly reversible), lymphadenopathy, bone marrow depression (especially at high-dose of methotrexate) is most frequently manifested by thrombocytopenia (which are usually reversible), neutropenia, leukopenia, pancytopenia, agranulocytosis, anaemia, aplastic anaemia, immunosuppression, lymphoproliferative disorders frequency very rare) or any combination may occur.
Infection or hypogammaglobulinaemia, haemorrhage from various sites. Bone marrow depression may lead to decreased resistance to infection and sepsis.
Gastrointestinal disorder:
Mucositis, stomatitis, gingivitis, hematemesis, melena, pancreatitis, enteritis, gastrointestinal ulceration (including oral ulcers) and bleeding, malabsorption, toxic megacolon. Dyspepsia, abdominal pain, anorexia, nausea, vomiting, diarrhoea.
Gastrointestinal disorders frequently require dosage adjustment. Ulcerative stomatitis and diarrhoea require interruption of therapy; otherwise hemorrhagic enteritis and death from intestinal perforation may occur.
Hepatobiliary disorders:
Hepatic toxicity resulting in increase of transaminases (ASAT, ALAT), alkaline phosphatase and bilirubin, decrease in serum albumin, acute hepatitis, periportal fibrosis, hepatic cirrhosis, hepatic failure, fatty degeneration of liver, reactivation of chronic hepatitis or death.
Renal and urinary disorders:
Renal failure, ulceration of the urinary bladder, disturbed micturition, oliguria, haematuria, dysuria, anuria, proteinuria, electrolyte disturbance, nephropathy.
Respiratory, thoracic and mediastinal disorders:
Pneumonia, acute or chronic interstitial alveolitis/pneumonia which can be fatal and is often associated with eosinophilia, acute pulmonary oedema, interstitial/pulmonary fibrosis, chronic interstitial obstructive pulmonary disease, pharyngitis, pleurisy, non-productive cough, dyspnoea, pleural effusion, bronchial asthma, epistaxis, respiratory paralysis.
In the treatment of rheumatoid arthritis, methotrexate induced lung disease is a potentially serious adverse drug reaction which may occur acutely at any time during therapy. It is not always fully reversible. Epistaxis (frequency not known) has been reported.
Pulmonary alveolar haemorrhage (frequency not known) has been reported for methotrexate used in rheumatologic and related indications.
Nervous System disorder:
Headaches, fatigue, drowsiness, dizziness, vertigo, lethargy, aphasia, irritability, hemiparesis, paresis, convulsions, encephalopathy/ leukoencephalopathy. Leukoencephalopathy has been reported especially following intravenous methotrexate in high doses, or low doses following cranial-spinal radiation.
Cerebral oedema, transient subtle cognitive dysfunction, dysarthria, unusual cranial sensations. Pain, muscular asthenia or paraesthesia/hypoaesthesia (frequency very rare), changes in sense of taste (metallic taste), meningism, acute aseptic meningitis, paralysis.
Psychiatric disorders:
Depression, confusion, Mood alterations, insomnia, psychoses.
Cardiac disorder:
Percardial effusion, Pericarditis pericardial tamponade.
Vascular disorders:
Thromboembolic events (arterial thrombosis, cerebral thrombosis, deep vein thrombosis, retinal vein thrombosis, thrombophlebitis, pulmonary embolus), vasculitis, hypotension.
Eye disorders:
Conjunctivitis, blurred/impaired vision, retinopathy.
Neoplasms benign, malignant and unspecified (including cysts and polyps):
Lymphoma, which can be reversible, Methotrexate may trigger tumour lysis syndrome in patients with […]
As methotrexate is eliminated mainly via the kidneys, increased concentrations are to be expected in the presence of renal impairment, which may result in severe adverse reactions. g. in elderly subjects), monitoring should take place at shorter intervals.
g. NSAIDs) or that can potentially lead to impairment of haematopoiesis, are administered concomitantly. If risk factors such as renal function disorders, including mild renal impairment, are present, combined administration with NSAIDs is not recommended.
Dehydration may also intensify the toxicity of methotrexate. Concomitant use of proton pump inhibitors (PPIs) and high dose methotrexate should be avoided, especially in patients with renal impairment. 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. If a clinically significant drop in white cell or platelet count develops, methotrexate therapy should be withdrawn immediately and appropriate supportive therapy given (see Undesirable Effects section).
Patients should be advised to report all symptoms or signs suggestive of infection. Malignant lymphomas may occur in patients receiving low dose methotrexate, in which case therapy must be discontinued. Failure of the lymphoma to show signs of spontaneous regression requires the initiation of cytotoxic therapy.
Progressive multifocal leukoencephalopathy (PML) Cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients receiving methotrexate, mostly in combination with other immunosuppressive medication. PML can be fatal and should be considered in the differential diagnosis in immunosuppressed patients with new onset or worsening neurological symptoms.
Liver function tests Treatment should not be initiated or should be discontinued if there are persistent or significant abnormalities in liver function tests, other non- invasive investigations of hepatic fibrosis, or liver biopsies.
Temporary increases in transaminases to two or three times the upper limit of normal have been reported in patients at a frequency of 13-20 %. Persistent elevation of liver enzymes and/or decrease in serum albumin may be indicative for severe hepatotoxicity.
In the event of a persistent increase in liver enzymes, consideration should be given to reducing the dose or discontinuing therapy. Histological changes, fibrosis and more rarely liver cirrhosis may not be preceded by abnormal liver function tests.
There are instances in cirrhosis where transaminases are normal. Therefore, non-invasive diagnostic methods for monitoring of liver condition should be considered, in addition to liver function tests. Liver biopsy should be considered on an individual basis taking into account the patient’s comorbidities, medical history and the risks related to biopsy.
Risk factors for hepatotoxicity include excessive prior alcohol consumption, persistent elevation of liver enzymes, history of liver disease, family history of hereditary liver disorders, diabetes mellitus, obesity and previous contact with hepatotoxic drugs or chemicals and prolonged methotrexate treatment.
Additional hepatotoxic medicinal products should not be given during treatment with methotrexate unless clearly necessary. Alcohol consumption should be […]