• If you are allergic to anything, including medicines, dyes, additives, or foods.

• If you have any medical conditions such as kidney disease, liver disease (including hepatitis), heart disease, congestive heart failure, diabetes, gout, infections, or if you have had kidney stones. These conditions may require that your medicine dose, regimen, or timing be changed.

• If you have stomach ulcers or ulcerative colitis. Methotrexate may worsen these problems.

• If you are pregnant, trying to get pregnant, or if there is any chance of pregnancy. It is not known if this drug might cause problems if either the male or female is taking it at the time of conception or during pregnancy. If you're sexually active while taking this drug, you should use some kind of birth control. It is important to check with your doctor about what kinds of birth control can be used with this medicine.

• If you are breast-feeding. The drug may pass into breast milk and harm the baby.

• If you think you might want to have children in the future. This drug may cayse sterility. Talk with your doctor about the possible risk associated with this drug and the options that may preserve your ability to have children.

• If you have previously been treated for cancer with radiation or chemotherapy. Some of these treatments may affect your response to this medicine.

• If you drink heavily, or if you have abused alcohol in the past. This can increase your chances of liver damage with methotrexate.

• About any other prescription or over-the-counter medicines you are taking, including vitamins and herbs.

Penicillins, probenicid, phenylbutazone, and the anti-seizure drug phenytoin can also worsen methotrexate's side effects.

Trimethoprim-sulfa (Bactrim, Septra) and other sulfa drugs may worsen methotrexate's effects on blood counts.

People taking retinoids such as etretinate along with methotrexate may have a higher risk of liver damage.

Other antibiotics may block methotrexate from being absorbed when methotrexate is taken in pill form. Vitamins that contain folic acid may interfere with methotrexate. Theophylline levels may be increased by methotrexate, which can worsen the side effects of theophylline.

Check with your doctor, nurse, or pharmacist about other medicines, vitamins, herbs, and supplements that may cause problems with this medicine.

If you're receiving medium or high doses of methotrexate, you will be given leucovorin calcium 24 hours later, then every 6 hours for up to 8 doses to "rescue" normal cells. Your doctor will determine your dose based on several factors: your size, the type of cancer being treated, and how well your kidneys are working.

If you are taking methotrexate pills, take them exactly as directed by your doctor. If you have any questions or do not understand the instructions, talk to your doctor or nurse. Store the medicine in a tightly closed container away from heat and moisture and out of the reach of children and pets.

This drug can cause the rapid killing of tumor cells, which in some cases has led to serious kidney damage within the first 24 hours of treatment (a condition known as tumor lysis syndrome). This is more likely if you have a very large number of cancer cells in the body. If your doctor feels you might be at risk, he or she will give you medicines and/or fluids to help prevent this.

Your doctor will likely test your blood throughout your treatment, looking for possible effects of the drug on blood counts (described below) or on other body organs. Based on the test results, you may be given medicines to help treat any effects. Your doctor may also need to reduce or delay your next dose of this drug, or even stop it altogether.

This drug can lower your white blood cell count, especially in the weeks after the drug is given. A low white blood cell count increases your chance of getting an infection. Be sure to let your doctor or nurse know right away if you have any signs of infection, such as fever (100.5° or higher), chills, pain when passing urine, a new cough, or bringing up sputum.

This drug may lower your platelet count in the weeks after it is given, which can increase your risk of bleeding. Speak with your doctor before taking any drugs or supplements that might affect your body's ability to stop bleeding, such as aspirin or aspirin-containing medicines, warfarin (Coumadin), or vitamin E. Tell your doctor right away if you have unusual bruising, or bleeding such as nosebleeds, bleeding gums when you brush your teeth, or black, tarry stools.

This drug may lower your red blood cell count. If this occurs, it is usually a few months after starting treatment. A low red blood cell count (known as anemia) can cause shortness of breath, or make you to feel weak or tired all the time. Your doctor may give you medicines to help prevent or treat this condition, or you may need to get blood transfusions.

Do not get any immunizations (vaccinations), either during or after treatment with this drug, without your doctor's OK. This drug may affect your immune system, which could make vaccinations ineffective, or could even lead to serious infections. Try to avoid contact with people who have recently received a live virus vaccine, such as the oral polio vaccine or smallpox vaccine. Check with your doctor about this.

While receiving high-dose methotrexate, you will receive extra intravenous fluid with a medicine called sodium bicarbonate to flush the medicine through your kidneys. After the treatment, drink extra liquids and take the bicarbonate tablets as directed by your nurse or doctor.

While you're taking this drug, you will likely be very sensitive to sunlight or bright ultraviolet light. When possible, avoid being outdoors between the hours of 10 and 4. Wear sunglasses, hat, and protective clothes when outside, even on hazy days. Always apply sunscreen half an hour before going out in the sun, and follow the instructions for repeat applications. Avoid tanning beds.

Methotrexate can also cause radiation recall. When a person receives this drug, the skin or tissue damage from prior radiation therapy can become red and appear damaged again. Tell your doctor or nurse if your skin gets red in areas where radiation was given.

Let your doctor know right away if you have cough, shortness of breath, fever, vomiting, diarrhea, stomach pain, or mouth ulcers.

While taking this medicine, and for a few days afterward, there is a slight chance of a serious skin reaction. Symptoms often start as a skin rash with redness or blistering in the mouth, nose, or eyes, along with fever and body aches. If this happens, stop the drug and get emergency help.

Methotrexate is an effective drug for many cancers, and is given at low, medium, and high doses. At medium and high doses, severe side effects are prevented by giving it with leucovorin. Leucovorin MUST be taken exactly as directed. Leucovorin is also given when methotrexate is injected into the spinal canal to kill cancer cells in the spinal fluid.

• nausea (high dose)
• vomiting (high dose)
• sores in mouth or on lips*
• diarrhea
• increased risk of sunburn*
• skin changes in areas previously treated with radiation*
• loss of appetite

• decreased white blood cell count with increased risk of infection*
• decreased platelet count with increased risk of bleeding*
• kidney damage (high dose)

• nausea (low and medium dose)
• vomiting (low and medium dose)*
• liver damage that can cause poor appetite, weakness, yellow skin and eyes (usually only with prolonged use)
• lung collapse (high dose)
• inflammation of the lung (high dose) with fever, cough, and shortness of breath*
• hair loss
• rash, itching
• severe skin reaction that can blister and become burn-like*
• dizziness
• blurred vision
• stroke-like symptoms (high dose) such as seizures, paralysis, confusion, or coma

*See Precautions section for more detailed information.