With Statin, Fenofibrate Safer Than Gemfibrozil : Risk for rhabdomyolysis increased significantly when gemfibrozil was combined with most statins.

NEW YORK — The combination of fenofibrate and a statin appears to be safer than gemfibrozil and a statin, according to an analysis of adverse event reports to the Food and Drug Administration.

In January 1998 through March 2002, the FDA received 0.6 reports of rhabdomyolysis for the combination of fenofibrate plus any statin except cerivastatin per every million prescriptions written for this drug combination, Peter H. Jones, M.D., said at an international symposium on triglycerides and HDL.

During the same period, the FDA received 8.6 reports of rhabdomyolysis for the combination of gemfibrozil plus any statin except cerivastatin per every million prescriptions written for this combination, a rate that is more than 14 times higher than for fenofibrate plus a statin, said Dr. Jones, codirector of the lipid metabolism and atherosclerosis clinic at Baylor College of Medicine, Houston.

Treatment with gemfibrozil appears to boost the maximum concentration and the area under the curve for any concurrently administered statin, an effect that is not seen with fenofibrate, Dr. Jones said.

Statins and gemfibrozil are metabolized by the same liver enzymes, which means that gemfibrozil competes with statins for these enzymes and thus acts as a competitive inhibitor of statin metabolism. Fenofibrate is metabolized by a different set of liver enzymes and hence has little impact on statin metabolism, said Dr. Jones at the symposium, sponsored by the Giovanni Lorenzini Medical Foundation.

The adverse report analysis by Dr. Jones and his collaborator excluded cerivastatin because treatment with that statin was associated with an unusually high number of cases of rhabdomyolysis. Inclusion of patients who were treated with cerivastatin did not affect the safety disparity between fenofibrate and gemfibrozil.

The study found that the FDA received two reports of rhabdomyolysis in patients treated with fenofibrate plus a statin other than cerivastatin out of more than 3.4 million prescriptions for the drug combination written during the 4-year study period. In comparison, 57 reports of rhabdomyolysis were submitted to the FDA regarding patients treated with gemfibrozil plus any statin but cerivastatin out of more than 6.6 million prescriptions written for this combination.

Dr. Jones receives research support from Pfizer Inc., which markets gemfibrozil (Lopid), and from Abbott Laboratories, which markets fenofibrate (Tricor). He is also a consultant to Abbott. He does not have a relationship with the companies that market the two other brand formulations of fenofibrate (Antava and Lofibra).

Based on the results of several studies, the combination of a statin and a fibrate (either gemfibrozil or fenofibrate) appears to be very effective for normalizing serum lipid levels in patients who have diabetes, metabolic syndrome, or atherogenic dyslipidemia, which features a high level of serum triglycerides and a low level of HDL cholesterol. However, there are not yet any study results to prove that treatment with a statin-fibrate combination leads to fewer clinical events than treatment with a statin alone. A study designed to address this question is currently in progress.

The usual starting and maintenance dosage of fenofibrate when used in combination with a statin is 160 mg/day, Dr. Jones said.

NEW YORK — The combination of fenofibrate and a statin appears to be safer than gemfibrozil and a statin, according to an analysis of adverse event reports to the Food and Drug Administration.

In January 1998 through March 2002, the FDA received 0.6 reports of rhabdomyolysis for the combination of fenofibrate plus any statin except cerivastatin per every million prescriptions written for this drug combination, Peter H. Jones, M.D., said at an international symposium on triglycerides and HDL.

During the same period, the FDA received 8.6 reports of rhabdomyolysis for the combination of gemfibrozil plus any statin except cerivastatin per every million prescriptions written for this combination, a rate that is more than 14 times higher than for fenofibrate plus a statin, said Dr. Jones, codirector of the lipid metabolism and atherosclerosis clinic at Baylor College of Medicine, Houston.

Treatment with gemfibrozil appears to boost the maximum concentration and the area under the curve for any concurrently administered statin, an effect that is not seen with fenofibrate, Dr. Jones said.

Statins and gemfibrozil are metabolized by the same liver enzymes, which means that gemfibrozil competes with statins for these enzymes and thus acts as a competitive inhibitor of statin metabolism. Fenofibrate is metabolized by a different set of liver enzymes and hence has little impact on statin metabolism, said Dr. Jones at the symposium, sponsored by the Giovanni Lorenzini Medical Foundation.

The adverse report analysis by Dr. Jones and his collaborator excluded cerivastatin because treatment with that statin was associated with an unusually high number of cases of rhabdomyolysis. Inclusion of patients who were treated with cerivastatin did not affect the safety disparity between fenofibrate and gemfibrozil.

The study found that the FDA received two reports of rhabdomyolysis in patients treated with fenofibrate plus a statin other than cerivastatin out of more than 3.4 million prescriptions for the drug combination written during the 4-year study period. In comparison, 57 reports of rhabdomyolysis were submitted to the FDA regarding patients treated with gemfibrozil plus any statin but cerivastatin out of more than 6.6 million prescriptions written for this combination.

Dr. Jones receives research support from Pfizer Inc., which markets gemfibrozil (Lopid), and from Abbott Laboratories, which markets fenofibrate (Tricor). He is also a consultant to Abbott. He does not have a relationship with the companies that market the two other brand formulations of fenofibrate (Antava and Lofibra).

Based on the results of several studies, the combination of a statin and a fibrate (either gemfibrozil or fenofibrate) appears to be very effective for normalizing serum lipid levels in patients who have diabetes, metabolic syndrome, or atherogenic dyslipidemia, which features a high level of serum triglycerides and a low level of HDL cholesterol. However, there are not yet any study results to prove that treatment with a statin-fibrate combination leads to fewer clinical events than treatment with a statin alone. A study designed to address this question is currently in progress.

The usual starting and maintenance dosage of fenofibrate when used in combination with a statin is 160 mg/day, Dr. Jones said.

NEW YORK — The combination of fenofibrate and a statin appears to be safer than gemfibrozil and a statin, according to an analysis of adverse event reports to the Food and Drug Administration.

In January 1998 through March 2002, the FDA received 0.6 reports of rhabdomyolysis for the combination of fenofibrate plus any statin except cerivastatin per every million prescriptions written for this drug combination, Peter H. Jones, M.D., said at an international symposium on triglycerides and HDL.

During the same period, the FDA received 8.6 reports of rhabdomyolysis for the combination of gemfibrozil plus any statin except cerivastatin per every million prescriptions written for this combination, a rate that is more than 14 times higher than for fenofibrate plus a statin, said Dr. Jones, codirector of the lipid metabolism and atherosclerosis clinic at Baylor College of Medicine, Houston.

Treatment with gemfibrozil appears to boost the maximum concentration and the area under the curve for any concurrently administered statin, an effect that is not seen with fenofibrate, Dr. Jones said.

Statins and gemfibrozil are metabolized by the same liver enzymes, which means that gemfibrozil competes with statins for these enzymes and thus acts as a competitive inhibitor of statin metabolism. Fenofibrate is metabolized by a different set of liver enzymes and hence has little impact on statin metabolism, said Dr. Jones at the symposium, sponsored by the Giovanni Lorenzini Medical Foundation.

The adverse report analysis by Dr. Jones and his collaborator excluded cerivastatin because treatment with that statin was associated with an unusually high number of cases of rhabdomyolysis. Inclusion of patients who were treated with cerivastatin did not affect the safety disparity between fenofibrate and gemfibrozil.

The study found that the FDA received two reports of rhabdomyolysis in patients treated with fenofibrate plus a statin other than cerivastatin out of more than 3.4 million prescriptions for the drug combination written during the 4-year study period. In comparison, 57 reports of rhabdomyolysis were submitted to the FDA regarding patients treated with gemfibrozil plus any statin but cerivastatin out of more than 6.6 million prescriptions written for this combination.

Dr. Jones receives research support from Pfizer Inc., which markets gemfibrozil (Lopid), and from Abbott Laboratories, which markets fenofibrate (Tricor). He is also a consultant to Abbott. He does not have a relationship with the companies that market the two other brand formulations of fenofibrate (Antava and Lofibra).

Based on the results of several studies, the combination of a statin and a fibrate (either gemfibrozil or fenofibrate) appears to be very effective for normalizing serum lipid levels in patients who have diabetes, metabolic syndrome, or atherogenic dyslipidemia, which features a high level of serum triglycerides and a low level of HDL cholesterol. However, there are not yet any study results to prove that treatment with a statin-fibrate combination leads to fewer clinical events than treatment with a statin alone. A study designed to address this question is currently in progress.

The usual starting and maintenance dosage of fenofibrate when used in combination with a statin is 160 mg/day, Dr. Jones said.