If you are given an aeroplane and told to fly from A to B and have nothing but the FCOM, DDG, QRH, etc. then I could see it being an issue. Who does that? Every outfit I’ve heard of that flies large transport aircraft has some sort of flight planning system that takes account of en-route performance (in my case LIDO). If there is a problem with MEL items that compromises MSA, drift down, etc. then it will be flagged up or it simply won’t produce a plan.
From a safety POV, your plan will be OK as long as the correct inputs have been made. Now you want the information presented to you in flight to be representative of operating with the particular defect: a simple way is to add the performance weight penalty to the ZFW in the FMC so things like OEI ceiling are displayed correctly (and probably reasonably conservatively). Job done.