Any advice on how to take the "big 3"?

Hello Sunflower, I think the best way is to experiment with when you take them. It is different for everyone. I took mine at night before bed so I could sleep through some of the discomfort. It is a long road with the big three and your body may adjust somewhat as time goes on. Perhaps keep a daily log so you can track your ups and downs and then make your doctor aware of all that is happening. I am so sorry you are struggling for now but try to hang in there and keep in touch with this group. There are a lot of people who share your experience and it helps to talk. Best to you and I hope your holidays are peaceful.

@kssunflower I agree with Carolyn ( @bluesplashgirl ) - you need to find what works for you. I was initially given a complex set of instructions - this before breakfast, that with food, something else before dinner...) and I was nauseated and headachy for 2 weeks, about ready to chuck it all.

Then I called the pulmonologist's office and spoke to his nurse. She was the one who told me "try them before bed with a few crackers" - it wasn't pleasant, but it was doable. She said in terms of treatment, this schedule might not be optimal, but it was far better than stopping! Others here have worked out other schedules for themselves.
Have you talked to the doc or their staff about your discomfort? Don't worry about sounding whiny or weak - these meds aren't east for anyone!
Sue

This worked best for me and I did 40 months.
Ethambutol all at once with breakfast, Rifampin x1 at 10am, AZ with dinner, Rifampin x1 before bed (9pm)

My ID doctor recommended that I phase in the 3 antibiotics one at a time, over the course of a couple of weeks. This was helpful as I adjusted to each individually - the rifampin caused dizziness for a couple of days after the first dose, but then I split the dose for a few days and was fine. I did experience intermittent fatigue for a few months after starting the 3 antibiotics 3 times/week but that disappeared as well. After 6 months, I moved to the daily dosing strategy, taking rifampin with black coffee when I woke up, and the other antibiotics an hour or so later, generally without food as I don't get hungry for many hours. I no longer take ethambutol as the sensitivity tests did not support continuation so I take rifampin on an empty stomach with coffee in the AM, azithromycin an hour of so later, and clofazimine with dinner. No problems or side effects other than the mild clofazimine "suntan."

You need to give ondansetron a try. My doctor prescribed it for nausea and I couldn’t manage without it. I take it as soon as I get up in the morning and it comes in a small tablet that melts in your mouth. 8 mg and 4 mg but I require 8mg. My doctor told me to take 2 rifampin as soon as I get up, one hour before eating, azithromycin after any meal and all three ethambutol one hour before dinner. I think taking the drugs on an empty stomach maximizes the effectiveness. I do this three days a week and couldn’t manage without the ondansetron. I usually only need it in the morning but sometimes afternoons as well. No matter what instructions your doctor gives you, you can only do what you your body will allow. Best of luck.

Thank you all so much for the advice. It really helped to spread them out a bit. You all helped me get through Christmas! I hope you having a good holiday season. Blessings to each of you, and thank you for your kind words and encouragement!

I don’t know if this will work for you but I take the azithromycin after bkft. An hour or so later I take ethambutol and another with lunch around 1:30 and the last with dinner. I take two rifampin on an empty stomach at 10pm with my last food intake by 8pm. Are you taking probiotics daily? I need to look into how much and what kind to take with so many antibiotics.