High-Dose Methotrexate–Doxycycline Interaction

Abstract

OBJECTIVE: To report a case in which an interaction occurred between doxycycline and high-dose methotrexate (HD-MTX) and discuss its clinical, quality of life, and economic repercussions. CASE SUMMARY: A 17-year-old girl diagnosed with high-degree osteosarcoma in her left femur was admitted to our hospital to receive her eleventh postoperative cycle of HD-MTX, according to the clinical protocol approved at our hospital. Simultaneously, due to a palpebral abscess in her left eye, the patient received systemic treatment with doxycycline 100 mg every 12 hours. As in previous cycles, pharmacokinetic monitoring of methotrexate (MTX) plasma concentrations was performed to improve leucovorin calcium rescue. The biological half-life 12 and 24 hours after infusion showed that the patient was at high risk of intoxication. She then developed hematologic as well as gastrointestinal toxicity and remained hospitalized for 11 days. The patient was readmitted 48 hours after hospital discharge because of a febrile episode that required an additional hospital stay of 12 days, and the twelfth cycle of HD-MTX had to be postponed 18 days because of the results of the previous cycle. DISCUSSION: Significant differences (p < 0.05) were observed in the eleventh HD-MTX cycle for plasma concentrations and pharmacokinetic parameters compared with the previous 10 cycles. The interaction resulted in clinical, quality of life, and economic repercussions. CONCLUSIONS: The potential interaction between MTX and doxycycline may cause pharmacokinetic changes, and its clinical repercussions on the quality of life of the patient and associated costs should be considered.