The number of people receiving hospital treatment for paracetamol poisoning is estimated to have risen in the UK from around 33,000 to 49,000 since updated guidelines were introduced 18 months ago, research found.
In a bid to save more lives, the UK's medicines regulator lowered the threshold to include patients with "relatively low" levels of the drug in their system, the study said.
A team at Edinburgh University said the change is putting extra pressure on hospital emergency departments and the public purse.
The researchers say the treatment - where the antidote acetylcysteine is administered - could also place patients at unnecessary risk of side effects, including a severe allergic reaction.
Paracetamol is said to be the most common cause of overdose in the UK, with many people mistakenly taking too high a dose because of confusion about which over-the-counter medicines contain the drug.
Patients with a life-threatening level of paracetamol in their blood are given acetylcysteine by intravenous drip.
Professor Nick Bateman, from Edinburgh University's British Heart Foundation Centre for Cardiovascular Science, said: "Changes to treatment guidelines for paracetamol overdoses are increasing the pressure on hard-pressed emergency departments.
"A full review of present UK approaches is required."
The study is published in the British Journal of Clinical Pharmacology.