Experts at the UK's medicine regulator expressed serious worries over high doses of controversial cholesterol-lowering drug Crestor just two months before it went on the market, confidential documents seen by the Guardian reveal.

Their concerns were overruled by a European-wide decision to allow the high dose, 40mg, on the market.

The drug's manufacturer, AstraZeneca, has consistently stated that it produces no more side-effects than other similar drugs on the market, known as statins.

Minutes of the UK's Medicines and Healthcare products Regulatory Agency reveal that it had seen higher rates of a dangerous muscle-wasting disease in patients on Crestor compared with other statins. The disease is a rare side-effect of all statins.

This prompted a change in the recommendation on the drug, also known as rosuvastatin, last June, to restrict the 40mg dose to extreme cases, and ensure patients start on the 10mg dose. The 40mg dose had been given to as many as 4,500 patients in the UK at the time. AZ says this prompted a fall in the rate of side-effects, although it is not clear whether the regulator has arrived at this conclusion.

The original advice from experts on the Committee on Safety of Medicines, the body that decides a drug's fate within the MHRA, said this dose should not go on the market. They made an exception for patients with an extremely rare genetic disorder, but only about 50 people in the UK suffer from this. The relevant section of the minutes appears on the right.

The 40mg dose is still on sale in the US, where there has been a long-running campaign to ban the drug by lobby group Public Citizen.

The concerns about the drug have weighed on AZ's share price. There are a number of studies into the safety of Crestor being carried out, and results should be published in the first half of this year.

The minutes of the MHRA and the CSM related to the safety of high dosages of Crestor were obtained by a request from the Guardian under the Freedom of Information Act.

Many sections of the minutes have been blacked out. The reason given for this is because the information "relates to discussions and regulatory actions currently ongoing in relation to Crestor, and we consider its release may harm the commercial interests of the company." Due to the controversy surrounding the drug, AZ regularly publishes the incidence of the muscle-wasting disease, rhabdomyolysis. These show a similar incidence to other statins.

The confidential minutes show that, since December 2003 at least, the UK regulators have been concerned that there is a "signal" of a higher rate of these side-effects.

They say this could be due to the drug being more toxic, or other reasons, including bias on the level of reporting following the withdrawal of the statin Baycol from the market in 2001.

The company stated last night that the minutes are only a "snapshot" of the discussion on the drug's safety and therefore are misleading. It points out that it has been approved by more than 70 regulatory authorities worldwide and has been prescribed over 17m times to over 4.3 million patients.

The product was approved in the UK in March 2003 under the European process for putting a drug on the market, despite the CSM's recommendation. "Under European law, the only alternative would have been for Crestor not to be licensed in the UK at all and therefore depriving thousands of patients of the benefits of this medicine," said a statement from the MHRA.

A statement from AZ said: "Caution should be used with historical documents such as MHRA/CSM minutes. These should not be used in isolation to determine the current view of regulators. Within the drug approval process it is usual that there will be different views expressed by member states at different time points, and that they may change based on additional examination of data."

It continues: "AstraZeneca wants to ensure that rosuvastatin is used both safely and effectively and believes that whilst appropriate caution should be used when titrating to its highest approved dose (40mg) the true clinical benefit of this treatment in patients with previously uncontrollable and potentially life threatening lipid disorders make it an important clinically useful and effective medicine for the prevention of cardiovascular disease."