Toxic dose

Single acute ingestion

Methotrexate has a low oral bioavailability due to saturable absorption. Therefore, neither accidental nor acute deliberate ingestion is likely to cause toxicity. In particular, ingestions of less than 1000 mg of methotrexate in adults, or less than 5 mg/kg of methotrexate in children, are unlikely to cause toxicity in patients with normal kidney function.

The risk of toxicity from acute ingestion of methotrexate is greater in patients with impaired kidney function.

Repeated supratherapeutic ingestions

Repeated supratherapeutic ingestions of methotrexate may occur due to dosing errors. Oral methotrexate is most toxic when the dosing interval is reduced—this most commonly involves a weekly dose being inadvertently administered daily. Toxicity is more likely if weekly doses are taken daily for 3 or more consecutive days or twice daily for more than 36 hours.