Intravenous injections or infusions of methotrexate in doses up to mg every one or two weeks have been used in the treatment of bladder carcinoma with promising results, varying from only symptomatic relief to complete though unsustained regressions. The use of high doses of methotrexate with Calcium Leucovorin Rescue is currently being evaluated.
It is recommended that a test dose of mg should be administered, one week prior to therapy to detect idiosyncratic adverse reactions. In most cases of severe uncontrolled psoriasis, unresponsive to conventional therapy, mg orally once a week and adjusted by the patient's response is recommended. The prescriber may specify the day of intake on the prescription. The use of methotrexate in psoriasis may permit the return to conventional topical therapy which should be encouraged.
In adults with severe , acute, classical or definite rheumatoid arthritis who are unresponsive or intolerant to conventional therapy, 7. The schedule may be adjusted gradually to achieve an optimal response but should not exceed a total weekly dose of 20mg.
Once response has been achieved, the schedule should be reduced to the lowest possible effective dose. The prescriber may specify the day of intake on the prescription Elderly: Due to diminished hepatic and renal function and decreased folate stores, methotrexate should be used with extreme caution in elderly patients, a reduction in dosage should be considered and these patients should be closely monitored for early signs of toxicity.
Safety and effectiveness in children have not been established, other than in cancer chemotherapy. Methotrexate is contra-indicated in the presence of: Methotrexate must be used only by physicians experienced in antimetabolite Chemotherapy. Because of the possibility of fatal or severe toxicity, the physician should fully inform the patient of the risks involved and provide close medical supervision.
Monitoring prior to starting treatment — see also below Before beginning or reinstituting methotrexate after a rest period, the patient's renal, liver and bone marrow function should be assessed by history, physical examination and laboratory tests. A chest X-ray should also be taken see Respiratory effects below. If any clinically significant drop in blood cell count occurs, methotrexate should be stopped immediately and appropriate therapy instituted.
But in recent years doctors have used it successfully to treat other conditions such as rheumatoid arthritis and psoriasis. Methotrexate works well for these other conditions if you take the medicine just once or at most twice a week in smaller doses, along with your blood count being monitored. Serious harm, even death, could occur if you take methotrexate daily for conditions other than cancer.
Among other things, it causes abnormally low blood counts, mouth sores and bleeding, and can lead to serious infections. In one case a physician prescribed methotrexate 15 mg daily rather than weekly for a year-old patient. The patient received nine doses before the error was discovered. The patient later died.
We recommend a pragmatic dosing schedule of 5 mg of oral folic acid given on the morning following the day of MTX administration. Methotrexate , Folic acid , Folinic acid , Homocysteine. Methotrexate MTX has become established as the most commonly used disease-modifying anti-rheumatic drug DMARD in the treatment of rheumatoid arthritis RA and is widely used in other inflammatory conditions [ 1 ]. In recent years there has been a trend towards more aggressive use of MTX in the treatment of inflammatory arthropathies, with regard to both dose and early intervention.
This review summarizes the current data on the use of folic acid as a supplement to MTX use in RA for the prevention of adverse effects and as a potential modulator of cardiovascular risk. The folic acid analogue aminopterin was first used in the treatment of RA in [ 1 — 3 ]. By the related compound MTX Nmethylaminopterin had been shown to reduce disease activity [ 4 ], and it has subsequently become established as the DMARD of first choice in the management of RA due to its superior efficacy: Mechanism of action Despite MTX having been in use for over 30yr, its precise mechanism of action in the treatment of RA remains unknown.
MTX inhibits the enzyme dihydrofolate reductase, thereby depleting the pool of reduced folates, which act as donors of 1-carbon moieties in the formation of metabolic intermediates, including purines, deoxythymidylate monophosphate and methionine, and producing a state of effective folate deficiency [ 1 ]. In high doses, such as those used for cancer chemotherapy, MTX acts as a cytotoxic drug by interfering with purine and pyrimidine synthesis in tissues with a high rate of cellular turnover.
However, there is no evidence that the beneficial effect of MTX in a low, once-weekly dose is mediated by inhibition of the replication of immune or inflammatory cells [ 1 ]. Upon transport into cells, MTX is converted to polyglutamated forms which promote intracellular retention.
These intracellular polyglutamates are potent inhibitors not only of dihydrofolate reductase but also of a number of folate-dependent enzymes, including 5-aminoimidazolecarboxamide ribonucleotide AICAR transformylase [ 1 , 6 ]. Adenosine exhibits an anti-inflammatory effect via interaction with receptors on neutrophils and mononuclear cells [ 1 , 7 ]. While hair loss is a relatively uncommon side effect in patients who take methotrexate at such doses, up to one third develop mouth ulcers, or sores.
These side effects can often be short-circuited by taking a folic acid supplement. Folic acid is the synthetic form of folate. One study found that RA patients on methotrexate who took folic acid supplements lowered the risk of GI problems and mouth sores by 79 percent.
Ranganathan recommends taking 1 mg of folic acid daily, though for convenience some other physicians instruct patients to pop a single 5 mg dose once a week. Some doctors recommend taking folic acid 24 hours after receiving a dose of methotrexate; ask your physician for complete instructions on using folic acid supplements.
If you are a man, use a condom to keep from causing a pregnancy while you are using methotrexate. Continue using condoms for at least 3 months after your last dose. Tell your doctor right away if a pregnancy occurs while either the mother or the father is taking methotrexate.
This medicine may affect fertility ability to have children in both men and women. However, it is important to use birth control to prevent pregnancy because methotrexate may harm the baby if a pregnancy does occur. You should not breast-feed while using this medicine. Do not give this medicine to a child without the advice of a doctor. How should I take methotrexate? Take methotrexate exactly as it was prescribed for you Follow all directions on your prescription label and read all medication guides or instruction sheets.
Methotrexate is sometimes taken once or twice per week and not every day. You must use the correct dose. Ask your doctor or pharmacist if you have questions about your dose or how often to take it. Measure liquid medicine carefully. Use the dosing syringe provided, or use a medicine dose-measuring device not a kitchen spoon. Methotrexate can be toxic to your organs, and may lower your blood cell counts. Your blood will need to be tested often, and you may need an occasional liver biopsy.
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