Methotrexate

How it works

     * Methotrexate interferes with DNA synthesis and has more of an
       effect against cells that are proliferating faster than normal
       (these types of cells typically occur in cancer and psoriasis). It
       has been shown to inhibit dihydrofolate reductase (DHFR), an enzyme
       that participates in the folic acid synthesis. Folic acid is
       essential in the synthesis of purines and pyrimidines, vital for
       protein, DNA, and RNA synthesis
     * Experts are not sure how methotrexate works in rheumatoid arthritis
       but believe it may have multiple mechanisms including an effect on
       immune function.
     * Methotrexate belongs to the class of medicines called
       antimetabolites. It may also be called a folic acid antagonist.
       Methotrexate is also called an immunosuppressant.

Upsides

     * May be used for the treatment of severe, disabling psoriasis or
       rheumatoid arthritis that is not responsive to other forms of
       treatment.
     * May be used in the treatment of some life-threatening cancers
       including osteosarcoma, hydatidiform mole, and acute lymphocytic
       leukemia.

Downsides

   If you are between the ages of 18 and 60, take no other medication or
   have no other medical conditions, side effects you are more likely to
   experience include:
     * Mouth lesions, low blood counts, poor appetite, nausea and
       abdominal discomfort are the most common side effects of
       methotrexate. Tiredness, dizziness, skin rash, hair loss, and an
       increased susceptibility to infection have also been reported.
     * May cause bone marrow, liver, lung and kidney disease; deaths have
       been reported from methotrexate use. Periodic liver biopsies are
       recommended for people taking methotrexate long-term.
     * May cause a potentially fatal and irreversible lung condition;
       incidence does not depend on the dosage of methotrexate or length
       of treatment.
     * May not be suitable for people with anemia, poor kidney function,
       immunodeficiency, bone marrow disorders, gastrointestinal
       conditions, liver disease, fluid in the lungs, or with alcoholism.
       Methotrexate is more likely to cause toxicity in these people.
       Should not be used with NSAIDs as it may cause bone marrow
       suppression, anemia, and damage the stomach and intestinal lining.
       Methotrexate may also not be suitable for people with folate
       deficiency, stomach ulcers, lung disease, who are receiving
       radiation treatment or with any type of infection.
     * Not recommended for women of childbearing age unless benefits
       clearly outweigh risks as can cause fetal death or birth defects.
       May affect a person's future ability to have children, whether they
       are a man or a woman. Women should not breastfeed while taking
       methotrexate.
     * May occasionally cause severe, potentially fatal skin reactions.
       These may occur following single or multiple doses of methotrexate.
     * Interacts with many drugs, particularly those that also bind to
       blood proteins such as aspirin, sulfonamides, tetracyclines, and
       phenytoin.

   Notes: In general, seniors or children, people with certain medical
   conditions (such as liver or kidney problems, heart disease, diabetes,
   seizures) or people who take other medications are more at risk of
   developing a wider range of side effects. For a complete list of all
   side effects, [84]click here.

Bottom Line

   Methotrexate may be considered for the treatment of psoriasis or
   rheumatoid arthritis if other treatments have failed. It may also be
   used in certain cancers. Side effects can be severe and potentially
   fatal so a full assessment of the risks versus benefits is required
   before methotrexate is prescribed. Ongoing monitoring of blood counts,
   liver and kidney function is also required.

Tips

     * There are significant risks associated with the use of methotrexate
       and your physician should fully inform you of the risks before
       starting treatment. During treatment, you should be monitored
       regularly.
     * Carefully read dosage instructions. For psoriasis and rheumatoid
       arthritis, methotrexate is usually prescribed WEEKLY, not daily. If
       your label instructs you to take it daily, double check with your
       doctor that these are the correct instructions.
     * Report any instance of a dry, nonproductive cough to your doctor
       for further investigation.
     * Also report any instances of fever, unusual bleeding or bruising,
       loss of appetite, clay-colored stools, yellowing of the skin or
       eyes, swelling, diarrhea, skin reactions, vomiting, or mouth ulcers
       to your doctor.
     * Keep up a good level of hydration while taking methotrexate. If you
       become dehydrated, methotrexate may need to be temporarily
       discontinued until you have recovered.
     * Continued treatment with methotrexate may depend on the results of
       blood, kidney function, and other tests.
     * Keep up fluid levels while taking methotrexate; do not allow
       yourself to become dehydrated.
     * May make your skin more sensitive to the sun. Cover up and wear
       sunblock on exposed areas of skin when outside.
     * Do not take any over-the-counter NSAIDs including aspirin while you
       are on methotrexate unless your doctor permits this. Also, ask your
       doctor before taking any vitamin supplements or other medications
       purchased over-the-counter, or before receiving immunizations.
     * You may be at an increased risk of infection while taking
       methotrexate so avoid crowded areas and people who are unwell if
       you can. Wash your hands often.
     * Take good care of your mouth to help prevent mouth sores. Use a
       soft toothbrush and a mouthwash.
     * Avoid drinking alcohol or keep alcohol intake to a minimum while
       taking methotrexate.
     * If you are a woman with child-bearing potential, you should always
       use a reliable form of contraception while you are taking
       methotrexate. Your doctor may request that you take a pregnancy
       test before starting methotrexate. Methotrexate may also cause
       changes in your menstrual cycle. Men taking methotrexate should
       continue to use condoms for at least three months after stopping
       methotrexate.
     * Tell other healthcare providers that you are taking methotrexate.
       You should not receive any live vaccines while taking methotrexate.
     * If you are caring for somebody who is taking methotrexate, wear
       gloves when cleaning up body fluids or handling contaminated
       laundry or diapers, because methotrexate can transfer into urine,
       feces, and vomit. Wash any soiled items separately.

Response and Effectiveness

     * Peak levels are reached within one to two hours following an oral
       dose. Absorption of methotrexate depends on dosage; at a higher
       dosage, less methotrexate is absorbed. Toxicity of methotrexate
       appears to depend on how fast the drug is eliminated from the body.
       People with poor kidney function and certain other conditions are
       more likely to eliminate the drug slowly. The coadministration of
       leucovorin may help reduce toxicity.
     * Reduction in symptoms of rheumatoid arthritis such as joint
       swelling and tenderness may occur within 3 to 6 weeks. Also,
       reduces inflammation and pain; however, does not cause remission of
       rheumatoid arthritis nor prevent long-term joint damage. Most
       studies have been short-term, but limited studies suggest
       beneficial effects on symptoms persist for up to two years with
       continued treatment.
     * Methotrexate usually shows some benefit in psoriasis within six to
       eight weeks; however, full effects may not be seen for five to six
       months. In chronic plaque psoriasis, 50-70% report a good result.
     * When given to treat cancer, the length of time for an effect
       depends on the type of cancer and patient response to methotrexate.

References

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