New drug dosages often twice as high as required

The initially recommended dosage of prescription drugs is often twice that needed for safe and effective use in clinical practice, according to two new studies.

In one study, researchers at the Food and Drug Administration (FDA) studied label changes for 354 new drugs that received FDA approval between 1980 and 1999. They discovered that the initially recommended dosage for 21 per cent of the drugs was later changed, and 70 per cent of them were dosage decreases made for safety reasons.

Although the researchers had predicted that improvements in drug development would have led to a smaller proportion of label changes after approval in recent years, they found that the opposite had occurred. New drugs approved in the late 1990s were more than three times more likely to require a dosage change than drugs approved in the early 1980s.

In the second study, researchers in the Netherlands examined data compiled from 1982 to 2000 by the World Health Organization, which monitors changes in the ‘daily defined dose’ (DDD). The DDD is a reflection of dosing regimens used in everyday clinical practice, and changes over time reveal ways in which common dosages differ from the initially recommended dosages.

The researchers found 115 instances of changes in the DDD – of which 45 (39.1 per cent) were increases and 70 (60.9 per cent) were decreases. Drug classes that most frequently had dosage changes were antibiotics and cardiovascular drugs (JAMA, 2002; 288: 1578).