The cluster of six deaths occurred over one month, but counsel assisting Peggy Dwyer said prescription opioid overdoses were at record levels in Australia with hundreds of opiate-related deaths in the state each year.

"Opioid deaths increased (nationally) by 60 per cent in 2011-2015 compared with 2001-2005," she told Glebe Coroner's Court heard on Monday.

"Pharmaceutical opioid deaths in Australia now exceed heroin deaths by a significant margin - two to 2.5 times."

Ms Dwyer said one schizophrenic overdose victim had been prescribed fentanyl - a highly potent synthetic opioid 100 times stronger than morphine.

"A particular issue, in this case, is why that drug was prescribed (and) whether it was appropriate," she said.

Illegal manufacturing of the drug in the US had caused a "public health crisis" with a significant spike in addiction rates and related deaths, Ms Dwyer said.

But the inquest is expected to hear expert evidence that fentanyl is on the rise in regional Australia, where heroin is in shorter supply.

"One high-profile case was the death of Prince, the music artist, who died after taking a counterfeit painkiller laced with fentanyl," Ms Dwyer said.

NSW Health estimates there may be up to 750,000 Australians dependent on opioids and the inquest aims to learn lessons from the deaths to prevent future tragedies.

It will explore the need for real-time prescription monitoring to avoid "doctor shopping" and the provision of supervised injection rooms.

The inquest would also consider the need for greater availability of naloxone, a "life-saving" drug that can reverse opioid overdoses, Ms Dwyer said.

Harm-reduction strategies will be examined including testing of drugs for impurities, with the inquest hoping to review an evaluation from the first trial of recreational pill testing at a recent festival in Canberra.

Australian Associated Press