I always draw twice as big as the intended printsize. Usually that means that I draw in A3 with a working area of 36x24cm. If the pages are full bleed, I usually cut down the paper a bit so it meassures 40x30cm. Then I work after this pattern:
Just loosely pencil up the guidelines, 5cm border on the outside and bottom, and 2,5cm border on the inside and top. And just keep all of the most important action inside the square. If I'm working on A4 i just make a 2cm wide border around the whole thing.
If anyone is interested in unusual layouts and enormous page sizes, I recommend having a look at this guy, Phillippe Druillet. He is amazing. His stuff is mostly in french. I have an Italian old Italian translation myself even though I can't read Italian.
