They are fairly safe, but like anything, there could be some reason a particular person will have a bad reaction to a substance. Not aware of any specific cases relating to suppositories, but just bear that in mind.

The best way to use them sounds like an insult: Stick it up your butt. I use a little Vaseline when I need one (and I'm old so I actually have some for non-ABDL purposes). It takes a bit of practice but you will figure it out eventually how to get them in properly.

As for the experience, it generally will cause you to start to empty the contents of your bowels. The glycerin makes more water come into the intestines, which helps trigger a bowel movement.

One thing to do is to ensure you have some contents in your digestive system to have eliminated when you use your suppository. There are fiber supplements you can use to increase the bulk and amount of stool, or you can eat high fiber foods - bran cereals, multigrain breads, fruit, etc. Otherwise you may end up pooping out very little besides some water.