More than 2000 Australians are dying from drug overdoses every year, with most deaths unintentional and involving prescription medication.

More than 2000 Australians die every year from a drug overdose, mostly in simple, tragic accidents.

Australia's Annual Overdose Report shows that in 2018, 2070 people fatally overdosed, with a majoity of the deaths involving opioids, stimulants and the use of multiple substances at the same time.

The report by independent health research unit The Penington Institute was released on International Overdose Awareness Day and revealed that 1556 of drug overdoses (75 per cent) in 2018 were unintentional.

It found 70 per cent of victims were men and 400 more Australians died from an overdose than on the nation's roads - and the gap was widening.

Penington Institute CEO John Ryan says campaigning, investment in evidence-based policies and community education have done a great job of bringing down the road toll but "we must tackle our overdose crisis in the same way."

Overdose deaths cost the economy more than $13 billion every year and the number of unintentional overdose deaths that involve four or more substances have almost quadrupled, he said.

There is now a clear upward trend with more than 2000 Australians dying annually from overdoses for five consecutive years.

"Overdose is our hidden health crisis - and it's a crisis that is costing us billions. And what's worse is these deaths are preventable. We simply can't accept that 2000 of our sons and daughters, mums and dads, and brothers and sisters die every year from a drug overdose."

Mr Ryan is calling on the Commonwealth to commit to a National Overdose Prevention Strategy.

"We want Australia's Annual Overdose Report to encourage Australians from all walks of life to talk more about overdose and drug issues. That's vital if we're to bring this hidden crisis out of the shadows. The rich, middle and poor are all impacted by overdose," he said .

The report backs research by the National Drug and Alcohol Research Centre, showing heroin was once again the leading underlying opioid-induced accidental deaths.

Australian Injecting and Illicit Drug Users League CEO Melanie Walker said there had also been an increase in deaths involving synthetic opioids like fentanyl and tramadol over the past decade.

There had also been an increasing rate of deaths involving psychotropic medicines like benzodiazepines and antipsychotics as well as non-opioid medicines used for treatment of chronic pain.