Can methotrexate be used with amoxicillin (amoxicillin)

Methotrexate and Amoxicillin Interaction: Safety Considerations

Caution is warranted when using methotrexate with amoxicillin as penicillins may increase methotrexate toxicity by reducing protein binding and renal elimination, potentially leading to serious adverse effects including myelosuppression and nephrotoxicity. 1

Mechanism of Interaction

The interaction between methotrexate (MTX) and amoxicillin occurs through several mechanisms:

1. Protein binding displacement: Amoxicillin can displace MTX from serum albumin, increasing free MTX levels 1
2. Reduced renal elimination: Penicillins like amoxicillin may compete with MTX for renal tubular secretion 1
3. Risk amplification: The interaction is more significant in patients with reduced renal function, particularly the elderly 1

Risk Assessment Algorithm

High-Risk Situations (Consider Avoiding Combination)

• Patients with renal impairment (eGFR <60 mL/min)
• Elderly patients
• High-dose MTX regimens (>500 mg/m²)
• Concomitant use of other drugs that may increase MTX toxicity
• History of MTX toxicity

Management Options

1. For mild infections with low urgency:

   • Consider alternative antibiotics without known MTX interactions
   • If amoxicillin is necessary, temporarily hold MTX until antibiotic course is complete

2. For severe infections requiring immediate treatment:

   • Stop MTX until the infection resolves and antibiotic course is complete 1
   • Monitor renal function, complete blood count, and MTX levels more frequently
   • Consider leucovorin (folinic acid) rescue if signs of toxicity develop

3. For patients on long-term antibiotics:

   • Increase monitoring frequency of blood counts and renal function 1
   • Consider dose adjustment of MTX

Monitoring Recommendations

When concurrent use cannot be avoided:

• Monitor complete blood count before and during treatment
• Check renal function (BUN, creatinine) before and during treatment
• Watch for early signs of MTX toxicity:
  • Mucositis, stomatitis
  • Nausea, vomiting
  • Unexplained fatigue
  • Skin rash
  • Fever

Warning Signs of Toxicity

Be vigilant for symptoms of MTX toxicity, which may include:

• Oral ulcers or mucositis
• Myelosuppression (leukopenia, thrombocytopenia, anemia)
• Acute kidney injury
• Hepatotoxicity
• Pulmonary symptoms

Key Considerations

• The risk of interaction appears higher with high-dose MTX regimens, though caution is warranted even with low-dose MTX 1, 2
• Case reports have documented severe toxicity when high-dose MTX was administered with amoxicillin, including renal failure, myelosuppression, and mucositis 2
• Patients with existing renal impairment are at particularly high risk for this interaction 1, 3

While the guidelines note that the interaction "does not appear to be an issue in clinical practice" with low-dose MTX, the potential for serious adverse outcomes warrants a cautious approach, especially in high-risk patients 1.