Methotrexate

Methotrexate interferes with the growth of certain cells of the body, especially cells that reproduce quickly, such as cancer cells, bone marrow cells, and skin cells.

Methotrexate is used to treat:

• acute lymphoblastic leukemia (ALL) in adults and children, as part of a combination chemotherapy maintenance regimen
• mycosis fungoides (cutaneous T-cell lymphoma) in adults
• relapsed or refractory non-Hodgkin lymphoma in adults, as part of a combination regimen
• rheumatoid arthritis in adults
• polyarticular juvenile idiopathic arthritis (pJIA) in children
• severe psoriasis in adults.
• meningeal leukemia in adults and children

In conditions such as psoriasis, rheumatoid arthritis, and polyarticular juvenile idiopathic arthritis, methotrexate is not taken every day. Some people with these conditions have died from taking methotrexate every day.

Methotrexate is sometimes given when other medicines have not been effective.

You may not need to take methotrexate every day. This medicine is sometimes taken only once per week, or 2 to 4 times per week. Some conditions are treated daily for just a few days followed by a rest period of 1 week or longer before taking the medicine again.

You must use the correct dose. Some people have died after incorrectly taking methotrexate every day. Do not take more methotrexate than prescribed.

Take methotrexate exactly as it was prescribed for you. Follow all directions on your prescription label and read all medication guides or instruction sheets. Taking more methotrexate than prescribed or taking methotrexate more often than prescribed can lead to severe side effects and cause death. If you are not sure how often to take methotrexate, ask your healthcare provider or pharmacist.

If you take too much methotrexate, call your healthcare provider or go to your nearest hospital emergency room right away. You will need to receive a medicine as soon as possible to help reduce side effects that could be severe and could cause death.

If you miss taking a dose of methotrexate, call your healthcare provider for instructions about when to take your next dose of methotrexate.

If you are taking methotrexate for treatment of severe psoriasis, rheumatoid arthritis, or polyarticular juvenile idiopathic arthritis:

• Take your methotrexate dose 1 time each week (on the same day of the week).
• Do not take methotrexate every day. Severe side effects and death have happened in people who have mistakenly taken methotrexate every day instead of 1 time each week.
• Take a folic acid or folinic acid supplement every day during treatment, as instructed by your healthcare provider, to help reduce the chance of developing certain side effects such as mouth sores.

If you are taking methotrexate to treat cancer, do not take folic acid or folinic acid during treatment unless your healthcare provider tells you to. Taking folic acid or folinic acid with methotrexate may make your treatment less effective.

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. You will need frequent medical tests, and you may need an occasional liver biopsy or chest X-ray. Your cancer treatments may be delayed based on the results.

If you need to be sedated for dental work, tell your dentist you currently use methotrexate.

Store methotrexate at room temperature away from moisture, heat, and light.

You may store Xatmep in a refrigerator or at room temperature. Avoid freezing or high heat. Throw away any unused Xatmep after 60 days if kept at room temperature. If you use Jylamvo oral solution, use it within 3 months of first opening the bottle and throw away any unused medicine after 3 months.

Methotrexate carries a Boxed Warning for embryo-fetal toxicity, hypersensitivity reactions, severe adverse reactions, risk of medication errors, and benzyl alcohol toxicity.

Methotrexate may cause injury or death to an unborn baby and should not be used during pregnancy to treat arthritis or psoriasis. Methotrexate is sometimes used to treat cancer during pregnancy. Tell your doctor if you are pregnant or plan to become pregnant.

Methotrexate may cause an allergic reaction. Get emergency medical help if you have signs of an allergic reaction to methotrexate: (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).

Methotrexate can cause serious or fatal side effects. Tell your doctor if you have diarrhea, mouth sores, cough, shortness of breath, upper stomach pain, dark urine, numbness or tingling, muscle weakness, confusion, seizure, or skin rash that spreads and causes blistering and peeling.

Risk of death from taking methotrexate the wrong way. Methotrexate is taken 1 time each week for rheumatoid arthritis, polyarticular juvenile idiopathic arthritis (pJIA), and severe psoriasis. Deaths have happened when methotrexate was taken every day instead of 1 time weekly. You must use the correct dose for your condition. See "How should I take methotrexate?" for instructions on taking this medicine correctly.

Do not use this medicine to treat psoriasis or rheumatoid arthritis if you have low blood cell counts, a weak immune system, alcoholism, or chronic liver disease, or if you are breastfeeding.

Some forms of methotrexate injection contain a preservative called benzyl alcohol, which can cause severe or fatal nervous system problems in premature babies and low birth weight infants. Only preservative-free methotrexate should be used in these patients or for injection into the spine.

You should not use methotrexate if you are allergic to it. You may not be able to take this medicine if you have:

• alcoholism, cirrhosis, or chronic liver disease
• low blood cell counts
• a weak immune system or bone marrow disorder
• if you are pregnant or breastfeeding.

Methotrexate is sometimes used to treat cancer in people who have a condition listed above. Your doctor will decide if this treatment is right for you.

To make sure this medicine is safe for you, tell your doctor if you have ever had:

• liver problems, especially fluid in your stomach (ascites)
• kidney disease or are receiving dialysis
• lung problems, especially fluid in the lungs (pleural effusion)
• radiation treatments
• a stomach ulcer (peptic ulcer disease) or ulcerative colitis
• trouble swallowing tablets
• a recent or scheduled vaccine. You should not receive live vaccines during treatment with methotrexate.

Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant. Methotrexate may cause injury or death to an unborn baby and should not be used during pregnancy to treat arthritis or psoriasis. However, methotrexate is sometimes used to treat cancer during pregnancy.

Methotrexate can harm an unborn baby if the mother or the father is using this medicine.

If you are a woman, you may need to have a negative pregnancy test before starting this treatment. Use effective birth control to prevent pregnancy while you are using methotrexate and for at least 6 months after your last dose.

If you are a man, use effective birth control if your sex partner is able to get pregnant. Keep using birth control 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 using methotrexate.

This medicine may affect fertility (ability to have children) in both men and women. It can cause reduced sperm production in men and menstrual problems in women, and it is not known if these effects are reversible. However, it is still important to use birth control to prevent pregnancy, because methotrexate may harm the baby if a pregnancy does occur.

Breastfeeding

Do not breastfeed while using this medicine, and for at least 1 week after your last dose.

Do not give this medicine to a child without the advice of a doctor.

Common side effects

Common methotrexate side effects may include:

• fever, chills, tiredness, not feeling well
• low blood cell counts
• mouth sores
• nausea, stomach pain, upset stomach
• abnormal liver function tests
• hair loss
• burning skin lesions
• being more sensitive to light.

Serious side effects

Get emergency medical help if you have signs of an allergic reaction to methotrexate (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).

Methotrexate can cause serious or fatal side effects. Call your doctor at once if you have:

• sudden chest pain, wheezing, dry cough, cough with mucus, feeling short of breath
• fever, chills, swollen lymph glands, night sweats, weight loss
• blisters or ulcers in your mouth, red or swollen gums, trouble swallowing
• vomiting, diarrhea, severe stomach pain that will not go away, severe constipation, vomiting blood, or blood in your urine or stools
• skin changes such as redness, warmth, swelling, or oozing
• low blood cell counts - fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath
• kidney problems - a big change (either increase or decrease) in the amount of urine you produce, shortness of breath, tiredness, swelling in your legs, ankles, or feet, or weight gain
• liver problems - swelling around your midsection, right-sided upper stomach pain, nausea, loss of appetite, dark urine, jaundice (yellowing of the skin or eyes)
• nerve problems - confusion, weakness, drowsiness, coordination problems, feeling irritable, headache, neck stiffness, vision problems, loss of movement in any part of your body, seizure
• signs of tumor cell breakdown - tiredness, weakness, muscle cramps, nausea, vomiting, diarrhea, fast or slow heart rate, tingling in your hands and feet or around your mouth.

Serious infections

People who take methotrexate have an increased risk of developing infections that can be life-threatening or cause death. These may include bacterial, fungal, or viral infections, including Pneumocystis jiroveci pneumonia, invasive fungal infections, hepatitis B infection that comes back (reactivation), tuberculosis that may be new or reactivated, and herpes zoster or cytomegalovirus (CMV) that spreads throughout the body. Tell your healthcare provider right away if you develop a new fever or any symptoms of infection during treatment.

Brain and spinal cord (nervous system) problems

Methotrexate can cause nervous system problems that can be severe and last for a short or long time. These problems can get progressively worse, may not get better (irreversible), and can cause death. The risk of a nervous system problem called leukoencephalopathy is higher in people who have had radiation treatment to the head (cranial radiation). Tell your healthcare provider about any new nervous system symptoms during treatment.

Secondary cancers

New (secondary) cancers can happen in people who take methotrexate. In people with psoriasis, the risk of new skin cancers is increased, and is further increased if you take cyclosporine after methotrexate treatment. Certain blood cancers can also happen during treatment; in some cases these may completely go away after methotrexate is stopped.

Tumor lysis syndrome (TLS)

TLS is caused by the fast breakdown of cancer cells and can cause kidney failure and the need for dialysis, abnormal heart rhythm, seizure, and sometimes death. If you are receiving methotrexate as a cancer treatment, your healthcare provider may do blood tests to check you for TLS.

Skin reactions

Severe skin reactions can happen with methotrexate, which can be serious and can lead to death.

• In people with psoriasis, their psoriasis may get worse if they are exposed to sunlight or other types of ultraviolet light.
• Methotrexate can cause reactivation of skin reactions that can happen after radiation therapy (radiation recall), cause sunburns to come back (photodermatitis), and cause severe sunburn reactions.

Limit sunlight exposure during treatment with methotrexate. Use a broad-spectrum ultraviolet sunscreen and lip balm with a Sun Protection Factor (SPF) of 30 or greater, and wear a hat and protective clothing when you will be exposed to sunlight during treatment. Tell your healthcare provider right away about any new or worsening skin rash.

Fertility problems (infertility)

Methotrexate can cause fertility problems in both males and females. It can cause sperm production to stop in males and menstrual problems in females. Males may not be able to father a child and females may not be able to become pregnant. It is not known if fertility will return. Talk with your healthcare provider about your risk of infertility if this is a concern for you.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Note: Methotrexate dosing varies considerably by condition. The dose for cancer is different from the dose for autoimmune conditions. Always follow the dose prescribed by your healthcare provider.

Usual adult dose for rheumatoid arthritis

• Recommended starting dose: 7.5 mg orally once weekly, adjusted to achieve an optimal response.
• Doses of more than 20 mg once weekly may increase the risk of serious side effects, including bone marrow suppression.

Usual pediatric dose for polyarticular juvenile idiopathic arthritis (pJIA)

• Recommended starting dose: 10 mg/m² orally once weekly, adjusted to achieve an optimal response.
• Doses of more than 30 mg/m² once weekly may increase the risk of serious side effects.

Usual adult dose for severe psoriasis

• Recommended dose: 10 to 25 mg orally once weekly until an adequate response is achieved; do not exceed 30 mg per week. Once an optimal response is achieved, the dose should be reduced to the lowest effective amount.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of methotrexate can be fatal.

Overdose symptoms may include bruising or unusual bleeding, mouth sores, vomiting, little or no urination, bloody or tarry stools, or coughing up blood or vomit that looks like coffee grounds.

Avoid drinking alcohol. It may increase your risk of liver damage.

Do not receive a "live" vaccine while using methotrexate, or you could develop a serious infection. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Methotrexate could make you sunburn more easily. Avoid sunlight or tanning beds. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Tell your doctor about all your other medicines, especially:

• an antibiotic or sulfa drug
• folic acid
• mercaptopurine
• theophylline
• NSAIDs (nonsteroidal anti-inflammatory drugs) - aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others
• stomach acid reducers (proton pump inhibitors) - esomeprazole, lansoprazole, omeprazole, pantoprazole, Nexium, Prilosec, Protonix, and others.

Coadministration with hepatotoxic (liver-harming) or nephrotoxic (kidney-harming) medicines, or with medicines that affect the blood cells, may increase the risk of methotrexate side effects. Nitrous oxide anesthesia should be avoided in people receiving methotrexate, as it may increase the risk of severe side effects.

Many drugs can interact with methotrexate. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any medicine you start or stop using.

Store methotrexate tablets at room temperature between 68°F and 77°F (20°C and 25°C). Keep the tablets away from light and out of the reach of children.

Active ingredient: methotrexate.

Inactive ingredients: lactose, magnesium stearate, pregelatinized starch, and sodium hydroxide (pH adjuster).

Note: inactive ingredients may vary by manufacturer and product (tablets, oral solution).