Although methotrexate is generally very well tolerated, nausea is one of the most common side effects. This tends to occur most frequently 24-48 hours after the weekly dose is administered. There are several strategies to manage this side effect. A high dose of folic acid (leucovorin tablet) can be given 12 hours and then 24 hours after the methotrexate dose. This will combat many of the methotrexate-induce side effects. Another option, is to administer the methotrexate as an injection instead of by pills (orally). The injectable methotrexate is given weekly as well and is a very small, insulin-like needle that is administered subcutaneously. This completely bypasses the gastrointestinal tract and can completely eliminate the side effect of nausea.
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