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Pharmacokinetic interaction between high-dose methotrexate and oxacillin
Karine Titier1, Fabrice Lagrange, Fabienne Péhourcq
1Department of Clinical Pharmacology and Toxicology, Pellegrin Hospital and University Victor Ségalen, Bordeaux, France.
Therapeutic Drug Monitoring
|July 27, 2002
Summary
Oxacillin co-administration with high-dose methotrexate for osteosarcoma treatment led to severe toxicity and patient death. Oxacillin may inhibit methotrexate elimination, necessitating careful monitoring during combined therapy.
Area of Science:
- Oncology
- Pharmacology
- Toxicology
Background:
- High-dose methotrexate is a critical chemotherapy regimen for osteosarcoma.
- Drug interactions can significantly alter the pharmacokinetics and toxicity of chemotherapeutic agents.
Observation:
- An 18-year-old patient undergoing high-dose methotrexate therapy for osteosarcoma received oxacillin concurrently.
- This co-administration resulted in markedly elevated methotrexate plasma concentrations.
Findings:
- The patient developed severe acute toxicities, including renal failure, myelosuppression, mucitis, fever, and dermatologic issues.
- Despite folinic acid rescue and hemodialysis, the patient's condition deteriorated, leading to death.
Implications:
- Oxacillin may impede the renal elimination of methotrexate, increasing the risk of severe toxicity.
- This case highlights the potential for significant drug interactions between oxacillin and high-dose methotrexate.
- Clinicians should exercise caution and consider alternative antibiotics or vigilant monitoring when co-administering oxacillin with high-dose methotrexate.