Methotrexate is a powerful medication used to treat certain types of cancer and autoimmune diseases like rheumatoid arthritis and psoriasis. However, because of its mechanism of action—interfering with rapidly growing cells—it carries significant risks and must be used with caution. Knowing exactly when to avoid or temporarily stop this medication is essential for preventing potentially life-threatening complications.
Absolute Contraindications: Conditions to Never Take Methotrexate
Certain health conditions and life stages represent absolute contraindications for using methotrexate for non-cancerous conditions. These risks are not negotiable and require immediate discontinuation of the medication if they apply.
Pregnancy and Breastfeeding
- Pregnancy: Methotrexate is known to cause serious birth defects and fetal death. It is strictly contraindicated in pregnant women being treated for conditions like arthritis or psoriasis. Women of childbearing age must use effective contraception while taking the drug and for a significant period after stopping it (typically 6 months). If a pregnancy occurs, the medication should be stopped immediately.
- Breastfeeding: The drug is excreted into breast milk and is considered unsafe for infants, though some newer research suggests minimal transfer at low amounts. The standard recommendation remains to avoid breastfeeding during treatment and for a period after the last administration, as methotrexate can harm a rapidly developing infant.
Severe Organ Impairment
- Liver Disease: Patients with significant liver conditions, such as chronic liver disease, cirrhosis, or alcoholism, should not take methotrexate. The drug is metabolized in the liver, and combining it with pre-existing liver damage significantly increases the risk of hepatotoxicity, fibrosis, and fatal liver failure.
- Kidney Disease: Since the kidneys excrete 60% to 95% of methotrexate, impaired renal function can lead to toxic levels of the drug in the body. The medication is contraindicated in patients with moderate to severe kidney disease, and adjustments or discontinuation are necessary if kidney function declines.
Blood and Immune System Disorders
- Blood Dyscrasias: Pre-existing blood disorders, including low blood cell counts (leukopenia, thrombocytopenia) or bone marrow hypoplasia, prevent the safe use of methotrexate. The drug suppresses hematopoiesis, worsening these conditions.
- Immunodeficiency Syndromes: Patients with weakened immune systems, such as those with HIV/AIDS, should not receive methotrexate due to the high risk of severe and opportunistic infections.
Important Precautions: When to Pause or Adjust Methotrexate
In addition to absolute contraindications, several scenarios require careful consideration and potential temporary cessation of methotrexate.
Infections and Vaccinations
- Current Infections: If you develop a fever or a serious infection, you should temporarily stop taking your methotrexate and contact your doctor. Continuing an immunosuppressant like methotrexate can exacerbate the infection and lead to severe complications.
- Live Vaccines: You should not receive live vaccines (e.g., MMR, nasal flu vaccine, shingles) while on methotrexate. The drug suppresses the immune response, making live vaccines potentially dangerous.
Surgery
- Before and After Surgery: Many doctors recommend pausing methotrexate treatment before and after surgery to reduce the risk of infection and allow for proper wound healing. The exact timeline depends on the type of surgery and your overall health, so you should always discuss this with your surgeon.
Gastrointestinal Symptoms
- Mouth Sores or Diarrhea: If you experience severe diarrhea, vomiting, or stomatitis (mouth sores), you should stop methotrexate and contact your healthcare provider. These can be signs of gastrointestinal toxicity, and continuing the medication can worsen the condition.
Alcohol Consumption
- Excessive Alcohol Intake: Alcohol can increase the risk of liver damage when combined with methotrexate. While some studies suggest moderate drinking may be acceptable for those with no underlying liver problems, many experts still advise significant limitation or complete abstinence. Your doctor will provide specific guidance based on your health status.
Drug Interactions: Avoid Taking These with Methotrexate
Several common medications can dangerously interact with methotrexate by increasing its plasma concentration and toxicity.
Comparison of Common Drug Interactions
| Medication Type | Example Medications | How it Interacts with Methotrexate | Risk Level | Action Recommended |
|---|---|---|---|---|
| Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) | Ibuprofen (Advil, Motrin), Naproxen (Aleve) | Can increase methotrexate levels by affecting renal clearance, especially at higher administrations. | High, especially with high amounts of methotrexate. | Use caution or avoid; monitor closely with low amounts. |
| Proton Pump Inhibitors (PPIs) | Omeprazole (Prilosec), Lansoprazole (Prevacid) | Can reduce the clearance of methotrexate from the body, increasing toxicity. | Moderate to High | Use alternative acid reducers (like famotidine) or monitor closely. |
| Certain Antibiotics | Trimethoprim/Sulfamethoxazole (Bactrim), Penicillins | Impair methotrexate clearance and increase toxicity. Also have additive antifolate effects. | High | Avoid if possible; seek alternative antibiotics. |
| Folic Acid (as supplement) | Folic acid supplements | While often used to mitigate side effects, high amounts can reduce methotrexate's effectiveness for neoplastic diseases. | Variable | Follow your doctor's exact instructions for administration and timing relative to your methotrexate administration. |
Other Drug Interactions
- Salicylates (e.g., aspirin): Can displace methotrexate from plasma proteins, increasing free drug levels and risk of toxicity.
- Phenytoin: Increases free methotrexate levels through protein displacement.
- Sulfonamides: Increase free methotrexate levels through protein binding competition.
- Nitrous Oxide: Exacerbates methotrexate's effect on folate metabolism, increasing the risk of severe side effects.
Conclusion
Methotrexate is a valuable and effective medication, but its use requires careful consideration of potential risks and interactions. Absolute contraindications like pregnancy, severe liver or kidney disease, and immune deficiencies must be strictly observed for non-cancer indications. Temporary adjustments or discontinuation may be necessary during active infections, surgical procedures, or when experiencing severe gastrointestinal side effects. It is also crucial to manage lifestyle factors, especially alcohol consumption, and to be aware of significant drug interactions with medications like NSAIDs, PPIs, and certain antibiotics. Always maintain open communication with your healthcare provider and pharmacist about your medical history and any other medications you are taking to ensure the safest and most effective treatment plan.
For more information on drug interactions, the UCSF Health website provides a detailed patient education guide.
