Can a high dose of methotrexate cause constipation?

Yes: Methotrexate can cause constipation.

Constipation is not: A typical side effect of methotrexate, even at high doses. High dose Methotrexate is often administered with aggressive hydration and with leucovorin rescue to minimize renal toxicity and mucositis. As such, Methotrexate is more commonly associated with loose stools. Constipation is more commonly associated with vincristine and othe vinca alkaloids.