Methotrexate is a powerful medication used to treat various conditions, from cancers like leukemia to autoimmune diseases like rheumatoid arthritis and severe psoriasis [1.2.4]. It works by interfering with the growth of rapidly dividing cells and by decreasing the activity of the immune system [1.2.4, 1.7.1]. However, its potent effects mean it is not suitable for everyone. A thorough evaluation of a patient's health status is critical to determine if they are a good candidate.
Absolute Contraindications: When Methotrexate is Strictly Avoided
Certain conditions are considered absolute contraindications, meaning the drug should not be used.
- Pregnancy and Breastfeeding For non-neoplastic diseases, methotrexate is strictly contraindicated in pregnancy due to its potential to cause embryo-fetal toxicity, birth defects, and fetal death [1.2.1, 1.2.2]. Both male and female patients of reproductive potential must use effective contraception during treatment and for a period after the final dose (at least three months for males and for at least one ovulatory cycle for females) [1.2.2, 1.4.4]. It is also contraindicated in nursing mothers because the drug passes into breast milk, posing a risk of serious adverse reactions in the infant [1.2.2, 1.8.2].
- Known Hypersensitivity Patients with a history of severe hypersensitivity or allergic reactions to methotrexate, including anaphylaxis, should not receive the drug [1.2.1, 1.4.1].
- Significant Pre-existing Conditions (for RA/Psoriasis) For patients with rheumatoid arthritis or psoriasis, several other conditions are absolute contraindications:
- Alcoholism or Chronic Liver Disease Methotrexate can cause severe liver damage (hepatotoxicity), and patients with alcoholism, alcoholic liver disease, or other chronic liver diseases are at high risk [1.2.2, 1.5.2].
- Immunodeficiency Syndromes Patients with overt or laboratory evidence of immunodeficiency syndromes should not take methotrexate [1.2.2].
- Pre-existing Blood Dyscrasias This includes conditions like bone marrow hypoplasia, significant anemia, leukopenia (low white blood cell count), or thrombocytopenia (low platelet count) [1.2.2].
Relative Contraindications and High-Risk Groups
Beyond absolute contraindications, several conditions require extreme caution and may make a patient a poor candidate. In these cases, a physician must weigh the potential benefits against the significant risks.
- Kidney (Renal) Impairment Methotrexate is primarily cleared by the kidneys, so impaired renal function can lead to toxic accumulation of the drug [1.6.3]. Dose reduction is often necessary for patients with mild-to-moderate kidney disease, and the drug is generally avoided in those with severe kidney disease (creatinine clearance <30 mL/min) [1.4.3, 1.6.1, 1.6.3].
- Liver (Hepatic) Impairment Patients with any liver condition are at higher risk for methotrexate-related adverse reactions due to altered drug elimination [1.2.1]. Long-term therapy is associated with the development of fatty liver, progressive fibrosis, and even cirrhosis [1.5.2]. Regular monitoring of liver function is essential for anyone taking the drug [1.10.1].
- Active Infections Because methotrexate suppresses the immune system, it can increase the risk of getting an infection or worsen an existing one [1.4.2]. It is generally not recommended for people with active infections [1.2.3].
- Gastrointestinal Issues Patients with peptic ulcer disease or ulcerative colitis should use methotrexate with extreme caution, as the drug can cause severe gastrointestinal toxicity, including stomatitis (mouth sores) and diarrhea [1.2.2].
- Planned Vaccinations Patients should not receive "live" vaccines while using methotrexate, as this could lead to a serious infection [1.2.4].
Drug Interactions of Concern
A patient's current medication list is also a critical factor. Many drugs can interact with methotrexate, increasing the risk of toxicity:
- Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Commonly used pain relievers like ibuprofen and naproxen can reduce the renal clearance of methotrexate, leading to elevated and potentially toxic blood levels [1.9.1, 1.9.2].
- Proton Pump Inhibitors (PPIs) Medications like omeprazole, used for acid reflux, can also interfere with methotrexate clearance [1.9.1, 1.9.2].
- Certain Antibiotics Penicillins and tetracyclines can reduce renal clearance or decrease intestinal absorption of methotrexate [1.2.2, 1.9.2].
- Alcohol Consumption of alcohol should be avoided as it significantly increases the risk of methotrexate-induced liver damage [1.4.4, 1.10.3].
| Contraindication Category | Specific Conditions & Factors | Rationale for Concern |
|---|---|---|
| Absolute | Pregnancy, Breastfeeding, Known Hypersensitivity [1.2.1, 1.2.2] | High risk of fetal death, birth defects, and severe allergic reactions [1.7.1]. |
| Absolute (for RA/Psoriasis) | Alcoholism, Chronic Liver Disease, Immunodeficiency, Blood Dyscrasias [1.2.2] | Increased risk of fatal liver toxicity and severe bone marrow suppression [1.4.4, 1.5.2]. |
| High-Risk (Relative) | Kidney Disease, Active Infections, Peptic Ulcer Disease [1.2.2, 1.4.3, 1.6.2] | Drug can accumulate to toxic levels or worsen underlying conditions [1.6.3]. |
| Drug Interactions | NSAIDs, PPIs, Certain Antibiotics, Alcohol [1.9.1, 1.9.2] | These substances can increase methotrexate levels and/or enhance liver toxicity [1.4.4]. |
Conclusion: The Importance of Physician Oversight
Deciding whether a patient is a candidate for methotrexate is a complex process that requires meticulous care from a physician experienced in its use [1.4.5]. It involves a thorough review of the patient's medical history, current health status, lifestyle factors like alcohol use, and a complete list of other medications [1.10.3]. Due to the potential for severe and even fatal toxicities affecting the liver, kidneys, lungs, and bone marrow, patients must be under a doctor's care throughout therapy and adhere to a strict schedule of monitoring tests [1.2.2, 1.10.1]. These precautions are essential to mitigate the risks and ensure the safe use of this effective medication.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Consult with a qualified healthcare professional before making any decisions about your health or treatment.
Explore further information on Methotrexate from the National Institutes of Health.
