Four bodies, of a 32-year-old man, a 37-year-old man, a 42-year-old woman, and a 17-year-old boy, were found in a Bicknell Court home in Broadmeadows at about 2am on June 25.
Police have now said a “synthetic opioid” was found in the systems of all four.
No presence of fentanyl has been detected.
The deaths are still being treated as non-suspicious.
“There have been recent serious harms in Melbourne associated with a white powder sold as cocaine that contained protonitazene,” the department said in a statement.
Protonitazene is a highly potent synthetic opioid that can be more potent than heroin.
“The product appears to produce strong adverse effects such as loss of consciousness, respiratory depression, and life-threatening hypoxia (insufficient oxygen for normal functioning),” the statement read.
“Cocaine and protonitazene are very different substances. Cocaine produces stimulant effects, whereas protonitazene produces sedative effects and may lead to opioid overdose.”
Anybody with information about the deaths, or about the supply of illicit drugs, is asked to contact Crime Stoppers on 1800 333 000 or online.