Methotrexate

Cancer Treatment

Methotrexate is used to treat various forms of cancer by slowing the growth of cancer cells. It is indicated for conditions including:

• Leukemias (cancers of the white blood cells)
• Lymphomas (cancers that start in the lymph system)
• Breast cancer and lung cancer
• Cancers of the head, neck, and uterus
• Osteosarcoma (bone cancer)
• Mycosis fungoides (a type of skin cancer)

Autoimmune and Inflammatory Conditions

This medication is also used to manage certain autoimmune conditions where the immune system is overactive. It is commonly used for:

• Rheumatoid arthritis: Used in adults with severe, active disease.
• Polyarticular juvenile idiopathic arthritis: Used in children who have active disease in multiple joints.
• Psoriasis: Used for severe, disabling psoriasis that has not responded to other therapies, such as topical treatments or ultraviolet light.

Mechanism of Action

Methotrexate belongs to a class of medications known as antimetabolites. It works differently depending on the condition being treated:

• Cancer and Psoriasis: In these conditions, certain cells in the body grow and divide too quickly. Methotrexate interferes with the growth of these rapidly reproducing cells, such as cancer cells or skin cells, to slow down the progression of the disease.
• Rheumatoid Arthritis: For autoimmune conditions, methotrexate works by decreasing the activity of the immune system. This helps reduce the inflammation and swelling that cause joint pain and damage.

By targeting these specific processes, the medication helps manage symptoms and prevent further complications associated with cell overgrowth or an overactive immune response.

Common Side Effects

Common side effects of methotrexate may include:

• Nausea, vomiting, and stomach pain
• Loss of appetite
• Mouth sores or swollen gums
• Dizziness or drowsiness
• Headache
• Feeling tired or weak
• Temporary hair loss

Serious Side Effects

Seek medical attention immediately if you experience any of the following serious symptoms:

• Signs of infection, such as fever, chills, or persistent sore throat
• Dry cough, shortness of breath, or chest pain
• Yellowing of the skin or eyes (jaundice) and dark urine
• Unusual bleeding or bruising
• Severe skin rash, blistering, or peeling
• Bloody or black, tarry stools
• Changes in the amount or color of urine
• Blurred vision or other vision changes
• Seizures or confusion

Boxed Warnings

Methotrexate carries several boxed warnings due to the risk of severe and potentially fatal reactions. These toxicities can occur even at low doses used for conditions like rheumatoid arthritis or psoriasis.

• Organ Toxicity: Serious damage can occur to the liver, lungs, kidneys, and bone marrow.
• Pregnancy Risks: Methotrexate can cause fetal death or severe birth defects. It is contraindicated for use in pregnant women with non-cancerous conditions.
• Skin Reactions: Severe, sometimes fatal skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported.
• Infections and Lymphoma: The drug may increase the risk of serious opportunistic infections and the development of certain types of lymphoma.

Liver and Lung Health

Long-term use of methotrexate is associated with liver toxicity, including fibrosis and cirrhosis. Liver function is monitored closely, as damage may occur without immediate symptoms. Additionally, methotrexate-induced lung disease, such as pneumonitis, can occur at any time during treatment and may be fatal. Symptoms such as a dry, non-productive cough should be reported immediately.

Bone Marrow Suppression

Methotrexate can cause a severe decrease in blood cell production in the bone marrow. This may lead to anemia, increased risk of infection due to low white blood cell counts, and easy bruising or bleeding due to low platelet counts.

Gastrointestinal and Kidney Risks

Severe gastrointestinal toxicity, including intestinal perforation, may occur. Patients with impaired kidney function are at a higher risk for methotrexate toxicity because the drug is primarily cleared through the kidneys. Dehydration can also increase the risk of kidney damage.

Precautions and Monitoring

Regular laboratory testing is essential during treatment. This typically includes complete blood counts, liver enzyme tests, and kidney function assessments. Patients are also advised to avoid excessive sun exposure, as methotrexate can increase sensitivity to UV light and may worsen psoriasis symptoms or cause severe sunburn. Both men and women should use effective contraception during treatment and for a specific period after the final dose as directed by a healthcare provider.

Pregnancy

Methotrexate can cause fetal death or severe birth defects. It is contraindicated for use during pregnancy when treating non-cancerous conditions such as psoriasis or rheumatoid arthritis. For cancer treatment, the potential benefits must be weighed against the significant risks to the fetus.

Effective contraception is necessary for both men and women during treatment and for a period after the last dose:

• Women should use effective birth control during therapy and for at least one ovulatory cycle after treatment ends.
• Men should use effective birth control during therapy and for at least three months after the final dose.

A pregnancy test is usually performed before starting this medication to confirm the patient is not pregnant. If pregnancy occurs during treatment, a healthcare provider should be notified immediately.

Breastfeeding

Methotrexate is present in breast milk and can cause serious side effects in a nursing infant. Because of the potential for toxicity, breastfeeding is generally not recommended during treatment. Patients should consult with their healthcare provider regarding the risks and the best way to feed their infant while taking this medication.

Oral Forms

Methotrexate is available in the following oral preparations:

• Tablets: These are commonly prescribed for conditions such as rheumatoid arthritis and psoriasis.
• Oral Solution: A liquid form of the medication is available for patients who prefer it or have difficulty swallowing tablets.

Injectable Forms

Methotrexate can be administered through several types of injection:

• Solution for Injection: This form can be given into a muscle (intramuscular), into a vein (intravenous), or under the skin (subcutaneous).
• Auto-injectors and Pre-filled Syringes: These are designed for subcutaneous injection and are often used by patients for self-administration at home.
• Powder for Injection: This is a concentrated form that a healthcare provider must mix with liquid before it is administered.

FDA Approval and Indications

Methotrexate is FDA-approved for the treatment of several types of cancer, including leukemia, breast cancer, lung cancer, and certain lymphomas. It is also approved for the management of severe, treatment-resistant psoriasis and rheumatoid arthritis, including polyarticular juvenile idiopathic arthritis.

Boxed Warnings

The FDA requires boxed warnings for methotrexate due to the potential for severe and life-threatening adverse reactions. These warnings specify that the drug should only be used for life-threatening neoplastic diseases or for patients with severe, recalcitrant, disabling psoriasis or rheumatoid arthritis that is not adequately responsive to other forms of therapy.

Key boxed warnings include:

• Fetal Toxicity: Methotrexate can cause embryo-fetal toxicity, including fetal death and congenital malformations. It is contraindicated in pregnant women being treated for non-cancerous conditions.
• Organ Damage: There are significant risks of hepatotoxicity (liver damage), pulmonary toxicity (lung damage), and nephrotoxicity (kidney damage).
• Bone Marrow Suppression: The medication can cause severe suppression of the immune system and blood cell production, which may lead to serious infections or anemia.
• Gastrointestinal and Skin Reactions: Severe, sometimes fatal, gastrointestinal toxicity and skin reactions, such as Stevens-Johnson syndrome, have been documented.

Because of these risks, the FDA mandates that patients be closely monitored by a healthcare provider for signs of toxicity throughout their treatment.

Drinking alcohol while taking methotrexate is generally discouraged because it significantly increases the risk of liver damage. Both alcohol and methotrexate are processed by the liver, and combining them can lead to serious complications, such as liver scarring (cirrhosis) or liver failure.

Healthcare providers typically recommend avoiding alcohol entirely during treatment. In some cases, a doctor may allow very limited alcohol consumption, but this depends on the dose of methotrexate, the condition being treated, and the results of regular liver function tests.

Seek medical attention if you experience symptoms of liver toxicity, such as:

• Yellowing of the eyes or skin
• Dark urine
• Pain in the upper right abdomen
• Persistent nausea or vomiting
• Extreme fatigue