Methotrexate
What is methotrexate?
Initially used to treat cancer, methotrexate was discovered to be effective in clearing psoriasis in the 1950s and was eventually approved for this use by the FDA in the 1970s. It is usually sold as a generic.
How does methotrexate work?
Methotrexate binds to and inhibits an enzyme involved in the rapid growth of cells. In people with psoriasis, the drug slows down the rate of skin cell growth.
Who is a candidate for methotrexate?
Methotrexate is indicated for use in adults with severe psoriasis. Methotrexate is often prescribed for severe plaque psoriasis, erythrodermic psoriasis and acute pustular psoriasis. In addition, the drug can be used to treat psoriatic arthritis. Methotrexate can be highly effective in reducing the painful symptoms of psoriatic arthritis.
The use of methotrexate is not recommended for people with the following medical conditions or histories:
- Pregnancy–pregnant women, or women and their partners who are trying to conceive a child (conception should be avoided during methotrexate treatment and for at least 12 weeks afterward)*
- Blood disorders
- Active peptic ulcers
- Severe anemia
- Cirrhosis of the liver
- Active hepatitis
- Significant liver or kidney abnormalities
- Active infectious disease
- Excessive alcohol consumption
- Unreliability in taking medications correctly
*To learn about other treatment options for pregnant and nursing women, see conception, pregnancy and psoriasis.
How effective is methotrexate?
In most psoriasis patients, improvement can begin within four to six weeks of using methotrexate. Most people see some improvement within two or three months of starting methotrexate.
How is methotrexate used?
Methotrexate is taken once a week, either by mouth or by injection. It is most commonly taken orally, either in pill or liquid form. The liquid form may be mixed with fruit juice. The drug can be taken in single or divided doses, split up over a period of 24 hours. For example, a person can take a portion Saturday morning, a portion Saturday evening and the
remainder Sunday morning.
A test dose of methotrexate is given first to see if the patient tolerates the drug. If the patient tolerates methotrexate, the dosage is increased to achieve clearance. Once clearance is achieved, the dose is gradually reduced to the lowest level capable of maintaining a reasonable improvement. If doing well, a person may be taken off methotrexate until symptoms return. However, some people must continue a maintenance dose to sustain clearance.
Patients taking methotrexate need to have regular blood tests to ensure that the drug is being safely processed by the body and is not negatively affecting the liver, blood or bone marrow. Methotrexate can cause a reduced white blood cell count, which can make a person more at risk for infection.
Normally, a doctor will not increase the dose of methotrexate if a few stubborn lesions remain. Instead, another treatment such as ultraviolet light B (UVB), laser treatment, topical steroids, Dovonex, Tazorac (also known by its generic name tazarotene) or anthralin may be added to clear the remaining lesions.
Rotational therapy
Methotrexate is sometimes rotated with other treatments such as PUVA, Soriatane also known by
its generic name acitretin) or cyclosporine in order to decrease side effects or get better results.
Combination therapy
Methotrexate can be used with PUVA or UVB to reduce the amount of UV light needed to clear the skin. In unresponsive cases of generalized pustular psoriasis, methotrexate has been used with either Soriatane or cyclosporine. It has also been used with some biologics to decrease the side effects of each medication or get better results.
What are the possible side effects of methotrexate?
Taking methotrexate can cause the following potential side effects:
- Nausea*
- Tiredness
- Difficulty sleeping
- Lightheadedness
- Mouth ulcers**
- Vomiting
- Headache
- Easy bruising and bleeding
- Fever
- Diarrhea with blood in the stool
- Chills
*Sometimes nausea can be helped by drinking milk or eating before taking the medication. Severe nausea may mean the dose is too high. Studies have shown that taking folic acid in doses of 1 to 5 milligrams (mg) per day can reduce nausea and other side effects associated with methotrexate. However, other studies have shown that folic acid may reduce methotrexate's effectiveness. Folic acid should not be taken on the same days that methotrexate is used. Check with your doctor.
**If sores appear in the mouth, the dose may be too high.
These side effects are generally manageable with careful monitoring and patient education.
The main risk of long-term methotrexate treatment is the potential for liver damage. A small percentage of patients, generally estimated to be one out of 200, will develop reversible liver scarring. This means after methotrexate is discontinued, the liver will return to normal. This is a risk after a cumulative dose of 1.5 grams (g). How long it takes to reach 1.5 g depends on the patient's dose, treatment schedule and rest periods
from the drug. For example, a patient taking 15 mg per week will reach an accumulated dose of 1.5 g after approximately two years (1 g equals 1,000 mg).
When a patient reaches a cumulative dose of 1 g to 1.5 g, doctors may perform a liver biopsy to test for liver damage. In this procedure, a thin needle is inserted through the skin to extract a small sample of liver tissue. If significant liver damage has developed, methotrexate is usually discontinued. A large-scale European study suggested that liver damage caused by methotrexate frequently improves once the drug is discontinued. Liver biopsies will be repeated at regular intervals.
The above scenario is based on patients who do not have any other risk factors for liver disease. The risk of liver damage can increase if a patient has one or more of the following risk factors:
- Drinks alcohol
- Has abnormal kidney function
- Has diabetes
- Has had prior liver disease
Rarely, some side effects may not occur until years after the drug is used, including certain types of cancer, such as lymphoma and bone marrow toxicity.
Interactions
The doctor prescribing methotrexate should always be aware of any other medications, therapies or supplements you are using.
Methotrexate may increase sensitivity to light. This reaction can occur even when methotrexate is taken several days after exposure to ultraviolet light, causing a "sunburn recall."
Patients should not take medications for inflammation or pain (including aspirin and ibuprofen) without checking with their doctor first. These medications may increase the effects of methotrexate, which could be harmful.
Patients must not drink alcohol; alcohol increases the chance of liver damage with methotrexate.
Sulfa drugs, especially Septra or Bactrim, also should not be taken while on methotrexate. The drug interaction of the sulfa drugs and methotrexate could be fatal.
Updated January 2007
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