It doesn't matter when you take it, and whether or not you have food as long as it is twice a day, roughly 12 hours apart, it constantly serves to thin the mucus. What is important with Mucinex and NAC is plenty of water - I drink a full glass when I take my meds morning and evening, as well as plenty throughout the day.
I have taken guaifenesin for close to 40 years, and it seems to have very few side effects, isn't known to interact with other meds, and you don't seem to become resistant and need higher doses.