What antibiotics are safe to take for a patient with rheumatoid arthritis or psoriasis who is currently taking methotrexate?

Antibiotics Safe to Take While on Methotrexate

Most antibiotics are safe to prescribe with methotrexate for patients with rheumatoid arthritis or psoriasis, but trimethoprim-sulfamethoxazole (Bactrim) at therapeutic doses must be avoided entirely due to severe risk of pancytopenia and mucositis. 1

Safe Antibiotics with Appropriate Monitoring

The following antibiotics can be used safely in patients on low-dose methotrexate with appropriate monitoring:

Penicillins (including Amoxicillin)

• Penicillins are safe for use in patients on low-dose methotrexate for dermatologic or rheumatologic conditions. 1
• While penicillins can theoretically increase methotrexate levels by competing at renal tubular secretion, this does not appear to be a significant clinical issue in low-dose regimens used for psoriasis and rheumatoid arthritis. 2, 1
• Enhanced monitoring is recommended for elderly patients or those with renal impairment, as these populations are at increased risk of methotrexate accumulation. 1, 3

Tetracyclines

• Tetracyclines are safe for use with methotrexate. 1
• Listed potential interactions exist in high-dose methotrexate contexts, but these are not clinically significant in practice for low-dose regimens. 1

Fluoroquinolones (Ciprofloxacin)

• Ciprofloxacin is safe to prescribe with methotrexate, showing a favorable safety profile even in complex patient populations. 1
• Despite being listed in older guidelines as potentially increasing methotrexate toxicity, ciprofloxacin has proven safe in clinical practice. 2, 1

Antibiotics to AVOID

Trimethoprim-Sulfamethoxazole (Bactrim, Co-trimoxazole)

• High-dose Bactrim (800 mg/160 mg twice daily) poses significant risk and should be avoided entirely due to potential for severe pancytopenia, mucositis, and renal toxicity. 4, 1
• Both trimethoprim and sulfamethoxazole are folic acid antagonists that dramatically increase methotrexate toxicity. 2, 4
• Prophylactic dosing (single-strength daily or double-strength three times weekly) for Pneumocystis prophylaxis may be tolerated but requires extremely close monitoring. 4
• Consider alternative agents such as atovaquone or dapsone (after G6PD screening) when Pneumocystis prophylaxis is needed. 4

Sulfonamides

• Sulfonamides decrease methotrexate binding to albumin and reduce renal tubular excretion, leading to increased serum methotrexate levels. 2
• Serious toxic reactions can occur with concomitant use. 5

Monitoring Recommendations When Prescribing Antibiotics

Standard Monitoring

• Check CBC and liver function tests every 2-4 weeks initially, then every 1-3 months if stable. 1
• Monitor renal function (BUN and creatinine) every 2-3 months, or more frequently if risk factors are present. 1

Enhanced Monitoring for High-Risk Patients

High-risk patients requiring more frequent monitoring include:

• Elderly patients with age-related decline in renal function 1, 3
• Patients with pre-existing renal impairment 1, 3
• Patients on multiple interacting medications 2

Patient Education on Toxicity Signs

Educate patients to immediately report:

• Unusual bruising or bleeding 1
• Mouth sores (mucositis) 1
• Severe nausea/vomiting 1
• Dark urine or signs of renal dysfunction 1
• Signs of infection (fever, chills) 1

When to Temporarily Stop Methotrexate

Stop methotrexate temporarily if prescribing antibiotics for:

• Severe infections 1
• Infections not responding to standard treatment 1
• Resume only after the patient recovers and completes the antibiotic course 1

Do not routinely stop methotrexate for minor infections requiring standard antibiotic courses. 1

Critical Pitfalls to Avoid

Don't Confuse Low-Dose with High-Dose Methotrexate

• Most interaction data comes from high-dose methotrexate studies (used in oncology) and does not apply to the low-dose regimens used in rheumatologic/dermatologic conditions. 1
• Weekly doses for psoriasis/RA typically range from 7.5 to 25 mg, which is vastly different from oncologic dosing. 2

Never Prescribe Probenecid Concurrently

• Probenecid inhibits renal tubular secretion and dramatically increases methotrexate toxicity. 2, 3

Assess Renal Function Before Prescribing

• Always check renal function before prescribing any antibiotic to patients on methotrexate, as declining renal function is the most important predictor of methotrexate toxicity. 1, 3
• Up to 85% of methotrexate is renally excreted, making renal impairment a critical risk factor. 2

Consider Alternative Antibiotics When Feasible

• When multiple antibiotic options exist for treating an infection, choose those with the lowest interaction potential (tetracyclines, ciprofloxacin) over penicillins in high-risk patients. 1

Additional Drug Interactions to Remember

Beyond antibiotics, the following medications also increase methotrexate toxicity and should be used with caution:

• NSAIDs (salicylates, naproxen, ibuprofen, indomethacin) 2
• Proton pump inhibitors (omeprazole) - consider switching to H2-receptor antagonists 6
• Other hepatotoxic agents (alcohol, statins, leflunomide, retinoids, azathioprine, minocycline) 2