FDA: Co-administration of statins and protease inhibitors increases risk of muscle injury

Thursday, FDA updated its recommendations concerning drug-drug interactions between protease inhibitors and statins, warning of an increased risk of muscle injury (myopathy). The most serious form of myopathy, rhabdomyolysis, can damage kidneys and lead to kidney failure, which can be fatal.

“The labels for both HIV protease inhibitors and the affected statins have been updated to contain consistent information about drug-drug interactions. These labels have been updated to include dosing recommendations for those statins that may be safely co-administered with HIV or HCV protease inhibitors,” according to the FDA safety communication.

Lovastatin and simvastatin are contraindicated for use with HIV protease inhibitors or HCV protease inhibitors, boceprevir and telaprevir, FDA said.

Earlier in the week, FDA approved label changes for all statins to warn patients of the potential risk of increased blood glucose levels and diabetes as well as memory loss when taking these medications. However, FDA also removed the need for routine periodic monitoring of liver enzymes in patients taking statins, according to an FDA drug safety communication.

FDA reviewed results from the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) and noted a 27% increase in investigator-reported diabetes mellitus in patients treated with rosuvastatin compared to patients receiving placebo.

In addition, worsening glycemic control was seen in patients who received high-dose atorvastatin in the Pravastatin or Atorvastatin Evaluation and Infection Therapy – Thrombolysis in Myocardial Infarction 22 (PROVE-IT TIMI 22) substudy.

Also, a review of the medical literature revealed these 3 additional reports linking statins to increased diabetes risk:

• A 2010 meta-analysis by Sattar and colleagues in Lancet reported that statin therapy was associated with a 9% increased risk for incident diabetes (OR=1.09; 95% CI, 1.02-1.17) of 91,140 participants from 13 statin trials.

• A meta-analysis in 2009 by Rajpathak and colleagues in Diabetes Care revealed a small increase in diabetes risk (RR=1.13; 95% CI, 1.03-1.23) among 57,593 participants in 6 statin trials.

• A report by Culver and colleagues, using data from the Women’s Health Initiative, found that statin use in postmenopausal women increased the risk of new-onset diabetes. The report was published this year in Archives of Internal Medicine.

Post-marketing adverse event reports of statin use found that patients who were older than 50 years may be at risk for memory loss or impairment, and cases do not appear to be associated with fixed or progressive dementia, such as Alzheimer’s disease.

FDA noted that cognitive impairment was reversible upon discontinuation of statin therapy. “Data from observational studies and clinical trials did not indicate that cognitive changes associated with statin use are common and lead to clinically significant cognitive decline,” according to the FDA statement.

Routine monitoring of liver enzymes is no longer necessary for patients taking statins, FDA reported. The label of statins have been updated to recommend liver enzyme tests before starting statin therapy and as clinically indicated thereafter.

“Serious liver injury with statins is rare and unpredictable in individual patients, and routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury,” according to FDA.

FDA also required that the lovastatin drug label be updated with new contraindications and dose limitations when taken with certain medicines that can increase the risk for muscle injury.