My first month on azathioprine had me trudging through every day for a month! I was so lethargic at only 50mg I just didn't do anything but work and sleep. After about a month, my body adjusted somewhat and I found that tenaciously working out every day I had time, whether I felt like it or not, made a big difference in my overall well-being (naturally) and gave me the stamina to persevere.
50mg did not put my ulcerative colitis into complete remission, but bumping it up to 75mg daily did, and I don't recall feeling more tired for it. I missed the month of June I slept through, but the rest of the year was worth it to be largely symptom free from the colitis. With all of its issues, I wish my doctor had prescribed azathioprine years ago. I feel as though I may have undergone a lot of unnecessary suffering.
A year later, I had a relapse that wouldn't respond to anything else, so the azathioprine dose was increased to 100mg, then to 150mg daily (after checking my blood thioprine levels to see if I could expect to tolerate it well, of course). At this increased dose, it's kicking my butt again. Now I'm having vision problems, I'm always tired, I lost my libido, I have frequent indigestion, and I get muscle cramps night and day. Still, its starting to put my ulcerative colitis into remission again, so it's worth it!
In the meantime, I try to stay well hydrated and physically active. I also have learned that avoiding alcohol (I love a fine ale) helps with the tiredness and avoiding caffeine helps with the vision problems. I avoid sugar, too, since my body doesn't control yeast on it's own very well now.
In the grand scheme of things, I list azathioprine as one of the things for which I am truly grateful. It's not nearly as incapacitating as the ulcerative colitis it helps control.