In order to get approval to launch nuclear material, the launch vehicle must be nuclear-rated (like human-rating, it ensures safety). With the recent retirement of the Delta II, only the Atlas V is currently nuclear-rated, but eventually others may be. Additionally, the fuel is encased in boxes designed to withstand launch failure and impact into the ocean without releasing the contents.
In the case of RTGs, the fuel is always releasing heat and is always radioactive. For fission reactors, the fuel is relatively inert and non-radioactive until it is turned on.