Before they were arrested last year, Alabama doctors John Couch and Xiulu Ruan were prized customers of Insys Therapeutics Inc., maker of a powerful and highly addictive type of synthetic opioid known as fentanyl.

Drs. Couch and Ruan prescribed a combined $4.9 million of the painkiller, called Subsys, to Medicare patients in 2013 and 2014, among the most of any doctors in the U.S., federal data show.

Insys,...