Most persons take methotrexate only once per week. No more methotrexate would be taken until the next Wednesday when 3 pills again would be ingested. Yet, some people need larger doses for adequate control of their arthritis, and increases in the dose are made every 4 to 8 weeks. Some persons require 8 pills or more per week to treat their arthritis. Even so, all pills may be taken simultaneously.
Most people take methotrexate with food to minimize the risk of stomach upset and nausea.
However, dairy products and other foods may interfere with the ability of methotrexate to get into the blood stream. Therefore, if methotrexate is not working as well as had been expected, sometimes it is worthwhile trying the methotrexate on an empty stomach. Methotrexate is comparatively rapid in its ability to fight arthritis. Benefit may start in 3 to 6 weeks. The risk of side-effects is increased if the methotrexate is taken in large doses or on a daily rather than weekly schedule.