The acute management of intrathecal methotrexate overdose: Pharmacologic rationale and guidelines

Treatment of intrathecal methotrexate overdose with folinic acid rescue and lumbar cerebrospinal fluid exchange: A report of two cases

“…Nine cases were treated with folinic acid, dexamethasone and CSF exchange. No neurologic long-term sequelae were observed in any of these nine patients [20][21][22][23][24]. Three cases received 600-650 mg of IT MTX and underwent ventriculolumbar perfusion or CSF exchange, which are considered effective if performed promptly [5,6,18].…”

“…The pathophysiology of MTX-induced acute encephalopathy is largely unknown but does not appear to be related to MTX pharmacokinetics [12]. The usual dose for IT administration is 12-15 mg. Management of IT MTX overdose is not uniform and, in fact, cases described in the literature have been treated with different approaches [18][19][20][21][22][23][24]. The highest reported IT dose given to patients who survived was 650 mg [5].…”

“…IT injection of MTX is becoming more popular, and may be the only form of CNS-directed therapy in selected patients [2]. Exposure to MTX in high concentrations or for sustained periods is clearly neurotoxic, and various dosage recommendations have been suggested to avoid neurotoxicity [3,4]. Clinical studies indicate that adults should receive a maximal IT dose of 12.5 mg of MTX to avoid acute clinical neurotoxicity.…”

Targeting Folates by Carboxypeptidase G2: Potential Applications in Anticancer Therapy

“…Yet, in cases of intrathecal MTX overdose, very severe adverse effects or even death have been described [18][19][20]. Current therapeutic recommendations for patients who receive intrathecal MTX doses greater than 100 mg include immediate lumbar puncture with drainage of cerebrospinal fluid (CSF), emergency ventriculostomy placement followed by ventriculo-lumbar perfusion, administration of systemic corticosteroids, and administration of systemic leucovorin to prevent systemic MTX-toxicity [20,21]. Intrathecal administration of leucovorin should be strictly avoided as severe neurotoxicity and fatal outcome have been observed [22].…”

Accidental intrathecal methotrexate overdose

“…An intrathecal dose of 50-120 mg may cause no or mild neurologic signs. There seems to be variation in neurologic signs that may be related to differences in cerebrospinal fluid dynamics between individuals [3,4].…”