What is the interaction between Methotrexate and augmentation?

From the Guidelines

Methotrexate and augmentin should not be taken together due to a potentially dangerous drug interaction that can increase methotrexate toxicity, and alternative antibiotics should be considered to minimize the risk of adverse effects. When methotrexate and augmentin are used together, augmentin can interfere with methotrexate elimination by inhibiting renal tubular secretion, leading to higher methotrexate blood levels and increased risk of serious side effects, such as severe nausea, mouth sores, unusual bleeding or bruising, and extreme fatigue 1.

Key Considerations

• The combination of methotrexate and other medications, including antibiotics like augmentin, requires careful consideration to minimize the risk of adverse effects 1.
• Patients with reduced kidney function are at higher risk of methotrexate toxicity, and laboratory monitoring of methotrexate levels may be necessary if no alternative antibiotic can be used 1.
• Regular laboratory monitoring, including complete blood counts and liver function tests, is recommended to detect potential toxicities associated with methotrexate therapy 1.

Management Strategies

• If a patient on methotrexate develops an infection requiring antibiotics, the healthcare provider should select an alternative antibiotic without this interaction to minimize the risk of adverse effects 1.
• Patients should be educated on the signs of methotrexate toxicity and instructed to contact their healthcare provider immediately if they experience any of these symptoms while taking methotrexate and augmentin 1.
• The use of folate and/or folinic acid in conjunction with low-dose methotrexate treatment may help prevent gastrointestinal and mucocutaneous adverse events, but this should be discussed with a healthcare provider 1.

From the FDA Drug Label

Methotrexate: MTX reduced adalimumab apparent clearance after single and multiple dosing by 29% and 44% respectively, in patients with RA [see Drug Interactions (7.1)]. The interaction between methotrexate and adalimumab is that methotrexate reduces adalimumab apparent clearance. This means that when methotrexate is given with adalimumab, the levels of adalimumab in the body may be higher than expected, potentially augmenting its effects or increasing the risk of side effects. Key points to consider:

• Reduced clearance: Methotrexate decreases the rate at which adalimumab is removed from the body.
• Increased adalimumab levels: This interaction may lead to higher-than-expected levels of adalimumab in the body.
• Potential for increased effects or side effects: The increased levels of adalimumab may enhance its therapeutic effects or increase the risk of adverse reactions 2.

From the Research

Methotrexate and Augmenting Interaction

• Methotrexate is a commonly used drug for the treatment of rheumatoid arthritis, and its effectiveness can be augmented by combination therapy with other drugs 3, 4, 5, 6.
• Studies have shown that combination therapy with methotrexate and other disease-modifying antirheumatic drugs (DMARDs) such as sulfasalazine and hydroxychloroquine is more effective than methotrexate alone in patients with rheumatoid arthritis 3, 6.
• The use of methotrexate in combination with leflunomide and hydroxychloroquine has also been shown to be effective in patients with methotrexate-refractory rheumatoid arthritis 5.
• Methotrexate monotherapy has been shown to be effective in improving symptoms and slowing disease progression in patients with rheumatoid arthritis, although it is associated with a higher risk of adverse events compared to placebo 7.
• The optimal dosing and duration of methotrexate treatment, as well as the use of subcutaneous delivery, can improve treatment outcomes and reduce the risk of adverse events 4.

Key Findings

• Combination therapy with methotrexate and other DMARDs is more effective than methotrexate alone in patients with rheumatoid arthritis 3, 6.
• Methotrexate monotherapy is effective in improving symptoms and slowing disease progression in patients with rheumatoid arthritis, although it is associated with a higher risk of adverse events compared to placebo 7.
• The use of methotrexate in combination with leflunomide and hydroxychloroquine is effective in patients with methotrexate-refractory rheumatoid arthritis 5.
• Optimal dosing and duration of methotrexate treatment, as well as the use of subcutaneous delivery, can improve treatment outcomes and reduce the risk of adverse events 4.