From Monday, patients will be able to access antibiotic treatments for uncomplicated urinary tract infections over the counter at dozens of pharmacies across the state.
The trial will include 100 NSW pharmacies, including about a third in Sydney, as well as in Byron Bay, Narrabri and Albury.
Women will be able to purchase the medication if they are between the ages of 18 and 65 and are showing symptoms of an uncomplicated urinary tract infection.
Further community pharmacies will be included after July, when the second phase of the trial will also allow women to access the oral contraceptive pill over the counter at pharmacies, except if it is the first time they have taken the medication.
Some $8.8 million will be spent by the state government on funding the trial over the coming 12 months, Health Minister Ryan Park said on Thursday.
"We want to ensure this is done so safely - and we are determined to get it right," Mr Park told reporters.
"This will not only improve access to medications - but it will also alleviate the pressure on GPs and primary care services."
Medical experts worked over the past five months to ensure the trial received ethical approval, including a rigorous consultation process, Sarah Dineen-Griffin from the University of Newcastle said on Thursday.
"This trial is a really well designed trial to actually show the evidence about safety for patients," Charlotte Hespe from the Royal Australian College of GPs said.
Part of the trial includes a protocol used by pharmacists during consultation, where women are assessed to ensure they have a UTI, and their case is not complex.
Pharmacists will be trained to refer women with more serious cases to doctors or emergency departments.
"One of the concerns that we've had as GPs that we don't want to have antibiotics inappropriately prescribed," Professor Hespe said.
"So I'm very happy that the protocol that's been developed for this trial is really good in that it is collecting the right data.
"The protocol is appropriate. But most importantly, it's about ensuring me as a patient, that I will feel safe about what actually happens."
The $5 million trial was originally announced by former premier Dominic Perrottet before the state election, and welcomed by federal Health Minister Mark Butler.
"At a time when the country's got skyrocketing demand for good health care and a constrained supply of workers, it doesn't make sense not to have everyone operating to the full extent of their skills and training," Mr Butler told ABC Radio Perth earlier this year.
"I'm very keen to see these trials continue and to build an evidence base for using our health workforce smarter and more effectively."
Doctor advocacy groups have criticised the trial, saying it could create new patient safety risks.
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