Vampire Mitchell (Aidan Turner) was killed off at the conclusion of the paranormal drama's third run, while Russell Tovey (George) will also exit the show.
In a new press release, Whithouse confirmed that Sinead Keenan has also quit her role as werewolf Nina.
"Not only would it be our first series without Aidan, but Russell had decided that series 4 would be his last, and Sinead had decided that her Being Human journey had come to an end after series 3," explained the writer. "The mountain before us seemed even higher than usual.
"But once we'd stopped rocking and shaking, we saw series 4 as an opportunity: we could invent new characters, expand the show in different directions, create new worlds and monsters and heroes, and add new layers to the overarching Being Human mythology."
Despite the cast departures, Whithouse insisted that Being Human has "never been in ruder health", praising new series regulars Michael Socha (Tom) and Damien Molony (Hal).
"Hand on heart, I think [Damien is] one of the most exciting and versatile actors of his generation," he said. "Watching his performance grow over the filming was a joy."
He continued: "Then there's Michael Socha. Promoted from semi-regular to lead. If you thought he was good in series 3, wait till you see what he does in series 4. Michael will break your heart this year."
Being Human will return to BBC Three with fourth series premiere 'Eve Of The War'.
> Being Human Damien Molony hints at vampire romance
> Russell Tovey: 'I was ready to leave Being Human'
Watch a brand new Being Human series four prequel below: