Two people in Italy and five U.S. residents have been charged in a fraud and drug trafficking conspiracy to distribute opioids in Florida and Tennessee, leading to hundreds of deaths, federal prosecutors said Friday.

The indictments were unsealed by federal officials Friday in Knoxville but handed down earlier. They allege the defendants were involved in a widespread scheme to operate "pill mills" in the U.S.

Prosecutors say defendants ran the Urgent Care & Surgery Center Enterprise, which distributed enough oxycodone, oxymorphone and morphine to generate clinic revenue of at least $21 million.

About 700 center patients are dead, prosecutors said. A Justice Department news release says a "significant percentage of those deaths, directly or indirectly, were the result of overdosing on narcotics" prescribed by the center. The scheme involved illegal kickbacks and money laundering, prosecutors said.

"Throughout this country, and certainly in Tennessee and Florida, the illegal and unconscionable mass-distribution of prescription opioids through the operation of illegal pain clinics has taken a heavy toll on our citizens, families and communities," U.S. Attorney General Jeff Sessions said in the news release. "This sort of profiteering effectively trades human lives for financial riches."

Two Italians, Luca Sartini and Luigi Palma, were arrested Friday in Rome by Italian authorities. U.S. officials are seeking extradition. Federal court records posted online do not show if they have lawyers.

Also charged were Benjamin Rodriguez of Delray Beach, Florida, and four Knoxville residents: Sylvia Hofstetter, Courtney Newman, Cynthia Clemons, and Holli Womack.

Rodriguez is set to surrender to authorities. Court records do not show if he has a lawyer. Lawyers for Hofstetter and Womack did not immediately return calls seeking comment.

Clemons' lawyer, Randall Reagan, said she has pleaded not guilty and has a trial scheduled in October. He declined to comment on details of the case. Newman's lawyer, Chris Oldham, said his client is fighting the charges.

Sartini, Palma, Rodriguez, Hofstetter and a co-conspirator charged in another indictment, ran the center's opioid-based pain management clinics from about April 2009 to March 2015, prosecutors said.

The defendants hired medical providers with Drug Enforcement Agency registration numbers, which would allow the providers to prescribe drugs. The clinics did not accept insurance and ordered unnecessary drug screenings defrauding Medicare, the indictments said. Meanwhile, shell companies were set up to launder proceeds, prosecutors said.

Many patients arrived in groups and were sponsored by drug dealers who paid for the clinic visits and prescriptions to get the opioids, prosecutors said. Patients would receive a portion of prescribed narcotics for free in return.

The Justice Department said about 30 drug traffickers have been charged and convicted and about 80 to 90 smaller narcotics distributers have also been charged and convicted as part of the investigation by the Opioid Fraud and Abuse Task Force Initiative. The superseding indictment announced Friday is among 35 related indictments charging about 140 people, including medical providers who worked at the pill mills.