The level of wastage varies widely across the country, with some primary care trusts overspending by millions of pounds, while others barely overspend at all, the report concludes (see list below).
According to a list drawn up by the NAO, Surrey PCT could save almost£7m each year if its GPs prescribed more efficiently, while GPs in Redcar and Cleveland PCT prescribe so efficiently that they could only improve by£371 a year.
The report calls for PCTs to offer help to GPs and to benchmark themselves against other PCTs.
It also wants them to 'make more active use of the medicines management indicators in the quality and outcomes framework to promote efficient prescribing'.
Prescribing advisers should, the report states, maximise their face-to-face contact time with under-performing practices, and PCTs could also bring in financial incentives for practices to improve.
NHS Confederation chief executive Gill Morgan said: 'PCTs need to challenge GP practices to design the right incentives in the system to help this happen.
'Individual GPs need to consider what medicines they prescribe when alternatives are available.'
The report also looked at how GPs' relationships with the pharmaceutical industry affect their choices of prescription drugs.
It notes: 'Both official NHS prescribing advisers and the pharmaceutical industry influence GPs' prescribing decisions, with the industry spending more than£850m a year marketing its products to GPs.'
One in five of the 1,000 GPs surveyed said pharmaceutical companies had more influence than prescribing advisers.
This prompted Commons public accounts committee chair Edward Leigh MP to call for GPs to be 'less influenced by the blandishments of the drugs industry'.
The British Medical Association responded by saying UK general practice is the most efficient in the world.
BMA clinical and prescribing sub-committee member Dr Brian Dunn said: 'We would welcome increased prescribing support, appropriate efficiency incentives, measures to cut waste and better prescribing co-ordination between primary and secondary care.'
Last of the big spenders
PCTs that could make biggest savings:
And the smallest:
Redcar and Cleveland:£371
Great Yarmouth and Waveney:£381
Read the NAO report here