What is the interaction between Methotrexate and Penicillin (antibiotic)?

From the Guidelines

Methotrexate and penicillin should be used with caution due to a potential interaction that can increase methotrexate levels and toxicity risk. This interaction is attributed to penicillins competing with methotrexate for renal tubular secretion, thereby reducing methotrexate elimination from the body 1. When taking these medications together, patients should be closely monitored for signs of methotrexate toxicity, such as mouth sores, severe nausea, unusual bruising, or decreased blood counts.

Key Considerations

• The interaction between methotrexate and penicillin is particularly concerning with high-dose methotrexate therapy, although the doses used for psoriasis, as outlined in the guidelines, are generally lower 1.
• To manage this interaction, healthcare providers may need to adjust the methotrexate dose, increase the frequency of monitoring, or ensure adequate hydration and urine alkalinization to promote methotrexate excretion.
• Patients on methotrexate should inform all their healthcare providers about all medications they are taking, including over-the-counter drugs and supplements, to avoid potentially harmful interactions.

Monitoring and Management

• Regular monitoring for signs of methotrexate toxicity is crucial when these medications are used concomitantly 1.
• Healthcare providers should be vigilant for any adverse effects and adjust the treatment plan as necessary to minimize risks while maintaining therapeutic efficacy.
• The guidelines for methotrexate use in psoriasis emphasize the importance of monitoring liver function, blood counts, and other potential toxicities, which becomes even more critical in the presence of potential drug interactions like the one with penicillin 1.

From the FDA Drug Label

Penicillins may reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with high and low dose methotrexate. Use of methotrexate with penicillins should be carefully monitored

• Methotrexate and penicillin interaction: The use of methotrexate with penicillins may increase the risk of hematologic and gastrointestinal toxicity due to reduced renal clearance of methotrexate.
• Key considerations:
  • Increased serum concentrations of methotrexate
  • Concomitant hematologic and gastrointestinal toxicity
  • Careful monitoring is recommended when using methotrexate with penicillins 2 2

From the Research

Methotrexate and Penicillin Interaction

• There is no direct evidence of an interaction between methotrexate and penicillin in the provided studies 3, 4, 5, 6, 7.
• Methotrexate is known to have potential toxicities, including bone marrow suppression, pulmonary toxicity, nephrotoxicity, hematologic toxicity, and an increased risk of infections 3, 4.
• The use of methotrexate in patients with rheumatoid arthritis requires careful monitoring and management of potential side effects, including renal function and liver function 3, 5, 6.
• Recommendations for the use of methotrexate in rheumatoid arthritis vary, but most agree on the importance of baseline assessment, monitoring, and folic acid supplementation 5, 6.
• The optimal dose and route of administration of methotrexate are still debated, with some studies suggesting that higher starting doses and subcutaneous administration may be more effective 7.
• However, without specific information on the interaction between methotrexate and penicillin, it is not possible to provide a definitive answer on their combined use 3, 4, 5, 6, 7.