* 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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