Understanding Methotrexate
Methotrexate is a powerful medication classified as an antimetabolite and immunosuppressant [1.4.1, 1.4.4]. It works by interfering with the body's use of folic acid, a B vitamin essential for cell growth [1.7.1, 1.4.6]. By slowing down cell growth, it can treat certain types of cancer [1.4.1]. By decreasing the activity of the immune system and reducing inflammation, it is also highly effective for treating autoimmune conditions like rheumatoid arthritis, psoriasis, and Crohn's disease [1.4.1, 1.4.3, 1.4.4]. While highly effective, it comes with a wide spectrum of potential side effects that require careful monitoring.
Common Side Effects
Many people taking methotrexate experience mild to moderate side effects, especially when first starting the medication. Gastrointestinal issues are among the most frequent complaints, affecting between 20% and 65% of patients [1.2.5].
Commonly reported side effects include:
- Gastrointestinal Distress: Nausea, vomiting, diarrhea, and stomach pain are very common [1.2.1, 1.2.5].
- Fatigue and Drowsiness: A general feeling of tiredness or a "methotrexate fog" can occur, often the day after taking the weekly dose [1.2.5, 1.2.3].
- Mouth Sores: Sores in the mouth or on the lips (stomatitis) can develop in up to one-third of patients [1.2.5, 1.2.1].
- Headache and Dizziness: These are frequently reported neurological symptoms [1.2.2, 1.2.7].
- Hair Loss: While less common at the lower doses used for arthritis, some hair thinning can occur. This is typically not permanent [1.2.3, 1.3.4].
- Loss of Appetite: The medication can affect your desire to eat [1.2.3].
Serious Side Effects
While less common, methotrexate can cause severe and potentially life-threatening side effects. Immediate medical attention is required if any of these symptoms appear. Your doctor will perform regular blood tests to monitor for these complications before they become severe [1.2.2, 1.5.2].
- Liver Damage (Hepatotoxicity): Methotrexate can cause elevated liver enzymes, and in rare cases, long-term use can lead to liver fibrosis or cirrhosis [1.2.5, 1.3.3]. Symptoms include yellowing of the skin or eyes (jaundice), dark urine, and upper right abdominal pain [1.2.3, 1.2.4].
- Lung Disease: Inflammation of the lungs (pneumonitis) is a rare but serious risk [1.2.3]. A persistent dry cough, shortness of breath, or chest pain should be reported to a doctor immediately [1.2.3, 1.5.2].
- Bone Marrow Suppression: The drug can lower the production of blood cells, leading to a low white blood cell count (increasing infection risk), a low red blood cell count (anemia), and low platelets (increasing bleeding risk) [1.2.1, 1.2.4]. Signs include fever, chills, sore throat, unusual bruising, bleeding gums, or black, tarry stools [1.2.1, 1.2.3].
- Kidney Problems: In some cases, methotrexate can cause kidney damage or failure [1.2.2]. Symptoms may include changes in urination frequency, swelling in the legs or feet, and rapid weight gain [1.2.1, 1.2.3].
- Severe Skin Reactions: Though rare, life-threatening skin reactions like Stevens-Johnson syndrome can occur. Any fever accompanied by a rash, blisters, or peeling skin needs immediate medical evaluation [1.2.2, 1.2.6].
- Nervous System Effects: Confusion, seizures, and weakness or numbness on one side of the body are serious neurological side effects that require urgent care [1.2.2, 1.2.1].
- Increased Cancer Risk: Methotrexate may slightly increase the risk of developing certain cancers, like lymphoma and skin cancer [1.2.2, 1.3.4].
| Side Effect Category | Common Manifestations | Serious (Seek Medical Help) Manifestations |
|---|---|---|
| Gastrointestinal | Nausea, vomiting, diarrhea, mouth sores, loss of appetite [1.2.5] | Severe stomach pain, vomiting blood, black/tarry stools, inability to keep fluids down [1.2.4, 1.2.1] |
| Hematologic (Blood) | General fatigue [1.2.5] | Fever, chills, signs of infection, unusual bruising or bleeding, extreme tiredness, pale skin [1.2.3, 1.2.4] |
| Hepatic (Liver) | Mild elevation in liver enzymes (found on blood tests) [1.3.3] | Yellow skin or eyes (jaundice), dark urine, persistent nausea, abdominal pain (upper right) [1.2.3, 1.2.4] |
| Pulmonary (Lungs) | None common | Persistent dry cough, shortness of breath, chest pain, fever [1.2.3] |
| Dermatologic (Skin) | Minor hair thinning, increased sun sensitivity [1.2.3, 1.3.4] | Severe rash, blistering or peeling skin, worsening of psoriasis sores with sun exposure [1.2.2, 1.2.6] |
Long-Term Side Effects
With long-term use, the primary concerns are potential damage to the liver and lungs [1.3.2, 1.2.3]. Regular blood tests and check-ups are essential to monitor organ function [1.3.2, 1.2.2]. There is also a small increased risk of lymphoma, although this is complex as rheumatoid arthritis itself carries a higher risk [1.3.4]. Some studies suggest methotrexate may actually reduce cardiovascular mortality in RA patients [1.3.3].
Managing and Mitigating Side Effects
Fortunately, several strategies can help manage methotrexate's side effects:
- Folic Acid Supplementation: Doctors almost always prescribe folic acid to be taken with methotrexate. This B vitamin helps protect healthy cells and can significantly reduce the risk of gastrointestinal issues, mouth sores, and liver problems by up to 79% [1.2.5, 1.5.5]. It is typically taken once a week, on a different day than the methotrexate [1.5.5].
- Lifestyle Adjustments: Limiting or avoiding alcohol is crucial to protect the liver [1.2.5, 1.5.4]. Due to increased sun sensitivity, patients should use high-SPF sunscreen and wear protective clothing [1.2.3, 1.5.3].
- Dose and Administration Changes: For severe nausea, a doctor might split the oral dose (e.g., half in the morning, half at night) or switch from tablets to an injectable form, which can bypass the GI tract [1.2.5, 1.5.7].
- Drug and Food Interactions: It's important to discuss all medications with your doctor, as some, including certain non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and proton pump inhibitors (e.g., omeprazole), can increase methotrexate levels and toxicity [1.2.2, 1.6.1]. Limiting caffeine intake may also be advised as it can potentially reduce the drug's effectiveness [1.6.3].
Conclusion
Methotrexate is a cornerstone therapy for many autoimmune diseases and certain cancers, but it is not a benign drug [1.7.4]. Its side effects range from common and manageable discomforts to rare but severe organ damage. Close communication with a healthcare provider, adherence to regular blood test schedules, and proactive management strategies like taking folic acid and avoiding alcohol are essential for using this medication safely and effectively. Patients should never hesitate to report new or worsening symptoms to their doctor.
For more detailed patient information, you can visit MedlinePlus [1.2.2].
