The MHRA said research now suggests treatment with simvastatin 80mg provides no additional benefit over a 20mg dose and greatly raises the risk of myopathy.
In this month's Drug Safety Update, the agency highlighted NICE's recommendation that GPs should only consider an 80mg dose for patients who have severely high cholesterol and are at high risk of cardiovascular complications.
The MHRA's advice followed a review of the SEARCH trial, which compared efficacy of treatment with simvastatin 80mg versus 20mg in 12,064 patients.
Researchers found similar levels of major vascular events in both groups, although there was no evidence of increased mortality, risk of cancer or stroke risk between the treatments.
But myopathy occurred in 52 patients taking simvastatin 80mg compared with just one in the 20mg group.
As a result, the MHRA advised that GPs treating patients with simvastatin 80mg, or considering an up-titration to that dose, may need to reconsider in light of the new evidence.
Regulators stressed that patients currently taking simvastatin 80mg should continue taking their medicine, but be advised to report any unexplained muscle pain.
British Cardiology Society member Dr George Kassianos criticised NICE's original decision to recommend simvastatin 80mg and called for the institute to retract the guidance.
'The decision to recommend simvastatin 80mg after simvastatin 40mg was not based on evidence - no such evidence exists - but purely on cost,' he said.
'It was associated with increase in possible harm while we had other statins, much safer and much more effective than simvastatin 80mg.'