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Intrathecal methotrexate-induced neurotoxicities

R W Nelson, J T Frank

American Journal of Hospital Pharmacy

|January 1, 1981

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Intrathecal methotrexate provides effective cerebrospinal fluid (CSF) drug concentrations. Careful administration minimizes neurotoxicity risks, making it a safe chemotherapy option when proper techniques are followed.

Area of Science:

Oncology
Pharmacology
Neurology

Background:

Intrathecal methotrexate administration bypasses the blood-brain barrier for direct central nervous system (CNS) chemotherapy.
High-dose intravenous methotrexate may cause systemic toxicity, necessitating alternative delivery methods.

Purpose of the Study:

To review the pharmacokinetics, therapeutic index, neurotoxicities, administration methods, and dosages of intrathecal methotrexate.
To assess the safety and efficacy of intrathecal methotrexate in achieving therapeutic CSF concentrations.

Main Methods:

Literature review of studies on intrathecal methotrexate.
Analysis of reported neurotoxicities and their associated risk factors.

Main Results:

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Intrathecal methotrexate achieves therapeutic CSF concentrations, avoiding high-dose intravenous administration.
Neurologic complications occur in 3-40% of patients, influenced by dose, CSF concentration, patient age, CNS abnormalities, vehicle, and prior radiation/methotrexate therapy.
Evidence does not strongly link preservatives or breakdown products to increased neurotoxicity risk.

Conclusions:

Intrathecal methotrexate is a safe and effective chemotherapy for CNS conditions when administered correctly.
Understanding and managing risk factors is crucial for minimizing neurotoxicity associated with intrathecal methotrexate.