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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: Methotrexate is indicated in the treatment of neoplastic disease, such as trophoblastic neoplasms and leukaemia, and the symptomatic treatment of severe recalcitrant disabling psoriasis which is not adequately responsive to other forms of therapy.
Verbatim from this product's MHRA label. Tap a section to expand.
Methotrexate injection may be given by the intramuscular, intravenous or intra-arterial routes.
Note:
Methotrexate injection 1000mg/10ml and 5000mg/50ml presentations are hypertonic and therefore are not suitable for intrathecal use. In the treatment of Psoriasis, Methotrexate must only be used 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. Antineoplastic Chemotherapy Methotrexate is active parenterally. Methotrexate injection may be given by the intramuscular, intravenous or intra-arterial routes.
Dosage is related to the patient‘s body weight or surface area. Methotrexate has been used with beneficial effect in a wide variety of neoplastic diseases, alone and in combination with other cytotoxic agents.
Note:
Methotrexate injection 1000mg/10ml and 5000mg/50ml presentation are hypertonic and therefore are not suitable for intrathecal use. Choriocarcinoma and Similar Trophoblastic Diseases Methotrexate is administered intramuscularly in doses of 15–30mg daily for a five day course.
Such courses may be repeated 3–5 times as required, with rest periods of one or more weeks interposed between courses until any manifesting toxic symptoms subside. The effectiveness of therapy can be evaluated by 24 hours quantitative analysis of urinary chorionic gonadotrophin hormone (HCG).
Combination therapy with other cytotoxic drugs has also been reported as useful. Hydatidiform mole may precede or be followed by choriocarcinoma, and methotrexate has been used in similar doses for the treatment of hydatidiform mole and chorioadenoma destruens.
Breast Carcinoma Prolonged cyclic combination with cyclophosphamide, methotrexate and fluorouracil has given good results when used as adjuvant treatment to radical mastectomy in primary breast cancer with positive axillary lymph nodes.
Methotrexate dosage was 40mg/m2 intravenously on the first and eighth days. Leukaemia Acute granulocytic leukaemia is rare in children but common in adults and it is not particularly sensitive to methotrexate but responds to other combination chemotherapy agents.
The most common adverse reactions include ulcerative stomatitis, leukopenia, nausea and abdominal distress. Although very rare, anaphylactic reactions to methotrexate have occurred. Others reported are malaise, undue fatigue, chills and fever, dizziness and decreased resistance to infection.
g. fatal sepsis) have also been reported in patients receiving methotrexate therapy for neoplastic and non-neoplastic diseases, Pneumocystis carinii pneumonia being the most common. Other reported infections include, pneumonia, nocardiosis, histoplasmosis, cryptococcosis, Herpes Zoster, Herpes Simplex, hepatitis and disseminated Herpes Simplex and cytomegalovirus infection, including cytomegaloviral pneumonia.
In general, the incidence and severity of side effects are considered to be dose- related.
Adverse reactions as reported for the various systems are as follows:
General disorders and administration site conditions Not known: Injection site necrosis Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome, epidermal necrolysis, erythematous rashes, pruritus, urticaria, photosensitivity, pigmentary changes, alopecia, ecchymosis, telangiectasia, acne, furunculosis.
Lesions of psoriasis may be aggravated by concomitant exposure to ultraviolet radiation. Skin ulceration in psoriatic patients and rarely painful erosion of psoriatic plaques have been reported. The recall phenomenon has been reported in both radiation and solar damaged skin.
Photosensitivity, Skin exfoliation / dermatitis exfoliative has also been reported (not known frequency).
Blood and lymphatic system disorders:
Bone marrow depression, leukopenia, thrombocytopenia, pancytopenia, anaemia, hypogammaglobulinaemia, haemorrhage from various sites, septicaemia. Lymphoproliferative disorders (see “description” below), very rare Description of selected adverse reactions Lymphoma/Lymphoproliferative disorders: there have been reports of individual cases of lymphoma and other lymphoproliferative disorders which subsided in a number of cases once treatment with methotrexate had been discontinued Musculoskeletal and connective tissue: Osteonecrosis of jaw (secondary to lymphoproliferative disorders), frequency unknown Alimentary System: Gingivitis, pharyngitis, stomatitis, anorexia, vomiting, diarrhoea, haematemesis, melaena, gastrointestinal ulceration and bleeding, enteritis, hepatic toxicity resulting in active liver atrophy, necrosis, fatty metamorphosis, periportal fibrosis, or hepatic cirrhosis.
). Reduce dose in patients with renal impairment. 3 Contraindications Significantly impaired renal function. Significantly impaired hepatic function Pre-existing blood dyscrasias, such as significant marrow hypoplasia, leukopenia, thrombocytopenia or anaemia.
Methotrexate is contraindicated in pregnancy. Because of the potential for serious adverse reactions from methotrexate in breast fed infants, breast feeding is contra-indicated in women taking methotrexate; additionally, for non-oncological indications.
Patients with a known allergic hypersensitivity to methotrexate or any of the other ingredients should not receive methotrexate. 4 Special warnings and precautions for use WARNINGS Methotrexate must be used only by physicians experienced in antimetabolite chemotherapy.
Because of the possibility of fatal or severe toxic reactions, the patient should be fully informed by the physician of the risks involved and be under his constant supervision. Deaths have been reported with the use of methotrexate in the treatment of psoriasis.
In the treatment of psoriasis, methotrexate should be restricted to severe recalcitrant, disabling psoriasis which is not adequately responsive to other forms of therapy, and only when the diagnosis has been established by biopsy and/or after dermatological consultation.
1. 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 should be withdrawn immediately. Patients should be advised to report all symptoms or signs suggestive of infection.
2. Methotrexate may be hepatotoxic, particularly at high dosage or with prolonged therapy. Liver atrophy, necrosis, cirrhosis, fatty changes, and periportal fibrosis have been reported. Since changes may occur without previous signs of gastrointestinal or haematological toxicity, it is imperative that hepatic function be determined prior to initiation of treatment and monitored regularly throughout therapy.
Significantly impaired renal function. Significantly impaired hepatic function Pre-existing blood dyscrasias, such as significant marrow hypoplasia, leukopenia, thrombocytopenia or anaemia. Methotrexate is contraindicated in pregnancy.
Because of the potential for serious adverse reactions from methotrexate in breast fed infants, breast feeding is contra-indicated in women taking methotrexate; additionally, for non-oncological indications. Patients with a known allergic hypersensitivity to methotrexate or any of the other ingredients should not receive methotrexate.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Methotrexate is not generally a drug of choice for induction of remission of lymphoblastic leukaemia. M. injection has been administered twice weekly. Twice weekly doses appear to be more effective than daily drug administration. V. every 14 days.
Meningeal Leukaemia Some patients with leukaemia are subject to leukaemic invasions of the central nervous system and the CSF should be examined in all cases of acute lymphoblastic leukaemia and some cases of acute myeloblastic leukaemia.
Methotrexate may be given in a prophylactic regimen in all cases of acute lymphoblastic leukaemia. Methotrexate is administered by intrathecal injection in doses of 200–500 microgram/kg body weight. The administration is at intervals of two to five days and is usually until clearance of blasts in the CSF.
At this point one additional dose is advised. Alternatively, methotrexate 12mg/m2 can be given once weekly for two weeks, and then once monthly. Large doses may cause convulsions and untoward side effects, may commonly neurological in character, occur as with any intrathecal injection.
Note:
Methotrexate injection 1000mg/10ml and 5000mg/50ml presentation are hypertonic and therefore are not suitable for intrathecal use. Lymphomas In stage 3, methotrexate is commonly given concomitantly with other antitumour agents. 5mg/kg daily.
Hodgkin's Disease does not usually respond to methotrexate but can have a substantial response to the use of other combination chemotherapy agents. Mycosis Fungoides Therapy with methotrexate appears to produce clinical remissions in one half of the cases treated adjusted according to the patient‘s response and haematological monitoring.
Methotrexate has been given intramuscularly in doses of 50mg once weekly or 25mg twice weekly. M. V. doses of 10–25mg per week, adjusted according to the patient‘s response. An initial test dose one week prior to initiation of therapy is recommended to detect any idiosyncrasy.
A suggested dose range is 5–10mg. 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 two to four 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. Renal Impairment (see
In rare cases the effect of methotrexate on the intestinal mucosa has led to malabsorption or toxic megacolon.
Hepatic:
Hepatic toxicity resulting in significant elevations of liver enzymes, acute liver atrophy, necrosis, fatty metamorphosis, periportal fibrosis or cirrhosis or death may occur, usually following chronic administration.
Urogenital System:
Renal failure, azotaemia, cystitis, haematuria, defective oogenesis or spermatogenesis, transient oligospermia, menstrual dysfunction, infertility, abortion, foetal defects, severe nephropathy. Vaginitis, vaginal ulcers, and nephropathy have also been reported.
Pulmonary System:
Infrequently an acute or chronic interstitial pneumonitis, often associated with blood eosinophilia, may occur and deaths have been reported. Acute pulmonary oedema has also been reported after intrathecal use. Pulmonary fibrosis is rare.
A syndrome consisting of pleuritic pain and pleural thickening has been reported following high doses.
Central Nervous System:
Headaches, drowsiness, blurred vision, aphasia, hemiparesis and convulsions have occurred possibly related to haemorrhage or to complications from intra- arterial catheterization. Convulsion, paresis, Guillain-Barré syndrome and increased cerebrospinal fluid pressure have followed intrathecal administration.
Other reactions related to, or attributed to the use of methotrexate such as pneumonitis, metabolic changes, precipitation of diabetes, osteoporotic effects, abnormal changes in tissue cells, abnormal (usually ‘megaloblastic’) red cell morphology and even sudden death have been reported.
There is the potential for Non-Hodgkin’s lymphoma to develop through the use of methotrexate. There have been reports of leukoencephalopathy following intravenous methotrexate in high doses, or low doses following cranial-spinal radiation.
Adverse reactions following intrathecal methotrexate are generally classified into three groups, acute, subacute, and chronic. The acute form is a chemical arachnoiditis manifested by headache, back or shoulder pain, nuchal rigidity, and fever.
The subacute form may include paresis, usually transient, paraplegia, nerve palsies, and cerebellar dysfunction. The chronic form is a leukoencephalopathy manifested by irritability, confusion, ataxia, spasticity, occasionally convulsions, dementia, somnolence, coma, and rarely, death.
There is evidence that the combined use of cranial radiation and intrathecal methotrexate increases the incidence of leukoencephalopathy. Acute or chronic interstitial pneumonitis, often associated with blood eosinophilia, may occur and deaths have been reported.
4 Special warnings and precautions for use)
If substantial hepatic function abnormalities develop, methotrexate dosing should be suspended for at least two weeks. Special caution is indicated in the presence of pre-existing liver damage or impaired hepatic function. Concomitant use of other drugs with hepatotoxic potential (including alcohol) should be avoided.
3. Methotrexate has been shown to be teratogenic; it has caused foetal death and/or congenital anomalies. Therefore it is not recommended in women of childbearing potential unless there is appropriate medical evidence that the benefits can be expected to outweigh the considered risks.
Pregnant psoriatic patients should not receive methotrexate. 4. Renal function should be closely monitored before, during and after treatment. Caution should be exercised if significant renal impairment is disclosed. Reduce dose of methotrexate in patients with renal impairment.
High doses may cause the precipitation of methotrexate or its metabolites in the renal tubules. 0, by oral or intravenous administration of sodium bicarbonate (5 x 625mg tablets every three hours) or acetazolamide (500mg orally four times a day) is recommended as a preventative measure.
Methotrexate is excreted primarily by the kidneys. Its use in the presence of impaired renal function may result in accumulation of toxic amounts or even additional renal damage. 5. Diarrhoea and ulcerative stomatitis are frequent toxic effects and require interruption of therapy, otherwise haemorrhagic enteritis and death from intestinal perforation may occur.
6. Methotrexate affects gametogenesis during the period of its administration and may result in decreased fertility which is thought to be reversible on discontinuation of therapy. Conception should be avoided during the period of methotrexate administration and for at least six months thereafter.
Patients and their partners should be advised to this effect. 7. Methotrexate has some immunosuppressive activity and immunological responses to concurrent vaccination may be decreased. The immunosuppressive effect of methotrexate should be taken into account when immune responses of patients are important or essential.
8. Potentially fatal opportunistic infections, including Pneumocystis carinii pneumonia may occur with methotrexate therapy. When a patient presents with pulmonary symptoms the possibility of Pneumocystis carinii should be considered.
9. Pleural effusions and ascites should be drained prior to initiation of methotrexate therapy. 10. Deaths have been reported with the use of methotrexate. Serious adverse reactions including deaths have been reported with concomitant administration of methotrexate (usually in high doses) along with some non-steroidal anti-inflammatory drugs (NSAIDs), (see