Although Hoffman was found with a syringe in his arm, the cause of his death remained undetermined and more study was needed, said Julie Bolcer, a spokeswoman for New York City's Chief Medical Examiner.
The four were arrested on Tuesday (local time) during a raid on a building in lower Manhattan after police traced what they believed to have been the source of the heroin suspected of killing the Oscar-winning actor.
New York police Sergeant Thomas Antonetti, without linking the arrests to Hoffman's death, named the four as Robert Vineberg, 57; Thomas Cushman, 48; Max Rosenblum and Juliana Luchkiw, both 22.
Vineberg and Cushman were charged with felony drug possession and Rosenblum and Luchkiw with misdemeanor drug possession, he said.
Separate police sources said the raid was conducted in connection with Hoffman's death and scores of bags of what appeared to be heroin were recovered.
A police spokesman told Reuters on Tuesday evening that heroin found in Hoffman's apartment after his death was not cut or mixed with fentanyl, a synthetic narcotic believed by health authorities to be responsible for scores of overdose deaths in recent months.
"There was no fentanyl found in the drugs," the spokesman said.
"ACE OF SPADES"
The 46-year-old actor was found unresponsive on the bathroom floor of his Manhattan apartment on Sunday by police responding to an emergency 911 call.
Police found Hoffman with a syringe in his arm and recovered plastic bags containing a substance believed to be heroin. Law enforcement sources have told Reuters he died of an apparent drug overdose.
Dozens of small, glassine drug pouches were discovered in the apartment, many of them stamped with the words "Ace of Spades" in white lettering inside, according to a third law enforcement source involved in the Hoffman investigation.
Others were stamped with an ace of hearts playing card image.
Hoffman, who is survived by his partner, Mimi O'Donnell, and their three children, had detailed his struggles with substance abuse in the past.
The actor, who won an Academy Award for his portrayal of Truman Capote in the 2006 drama "Capote" and was considered one of the most gifted film stars of his generation, had sought treatment last year after more than 20 years of sobriety.
A representative for Hoffman said the actor, who also appeared in blockbusters such as "Twister" and "The Hunger Games," will be buried after a private service, with a public memorial planned for later this month.
