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Pharmacokinetic interaction between high-dose methotrexate and amoxycillin
C L Ronchera1, T Hernández, J E Peris
1Department of Pharmacy, Hospital Dr Peset, Valencia, Spain.
Therapeutic Drug Monitoring
|October 1, 1993
Summary
Concurrent use of amoxycillin with high-dose methotrexate significantly increases methotrexate levels, leading to severe toxicity. Close patient monitoring is crucial when these drugs are co-administered.
Area of Science:
- Oncology
- Pharmacology
- Nephrology
Background:
- High-dose methotrexate is a critical chemotherapy agent for osteogenic sarcoma.
- Concurrent medications require careful evaluation for potential drug interactions.
Observation:
- A case report details a 16-year-old male treated with high-dose methotrexate (8 g/m2) for osteogenic sarcoma.
- During the 10th cycle, oral amoxycillin (1 g/6 h) was co-administered.
Findings:
- Amoxycillin coadministration markedly prolonged and enhanced methotrexate serum levels.
- Pharmacokinetic analysis revealed decreased total plasma clearance and altered residence time and half-life.
- Amoxycillin impaired methotrexate renal clearance, likely via tubular secretion competition and induced renal impairment.
Implications:
- This interaction can lead to severe acute and subacute toxicities, including renal failure, myelosuppression, and mucositis.
- Clinicians must closely monitor patients receiving amoxycillin concurrently with high-dose methotrexate.
- Awareness of this interaction is vital for optimizing cancer treatment safety and efficacy.