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Hundreds of Australians were given water instead of pain-killing medication after thieves syphoned off the drugs from ambulance supplies and refilled the empty vials from the tap, officials say.

Authorities in the state of Victoria said large amounts of the drug fentanyl had been taken and an investigation was under way.

"We can confirm that Victoria Police are investigating allegations of theft from a number of Ambulance Victoria response stations," a police spokesman said, adding that two men had been questioned over the theft.

Ambulance Victoria chief executive Greg Sassella said hundreds of patients were affected by the switch.

"We have been able to identify all those patients that may have come into contact with this issue and we have been in direct contact with them and we can assure them they are safe," he said.

"We apologise for any sub-optimal pain relief they had."

Sassella said Victoria's ambulance service had changed its protocols for the use of fentanyl, which would now be stored in vials that contained less of the drug and had a more robust steel cap.

Fentanyl is a potent opioid often used by paramedics as a fast-acting pain-killer and usually administered as a nasal spray. It can be addictive and is used by some drug abusers as a substitute for heroin.

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