Higher Than Expected Risk Found with
Acne Drug Accutane

Need to Monitor Users

AP 22aug2006

[Abstract below]

CHICAGO — Accutane, the powerful acne drug known to cause birth defects, seems to raise the risk for potential heart and liver problems more than doctors had expected, according to a new study.

The findings came from lab tests on 13,772 patients taking the acne drug and underscore the need to closely monitor people taking isotretinoin, which is sold as Accutane and in three generic versions. Abnormal results for cholesterol and liver function were more common than expected.

Although those conditions can lead to problems over the long term, abnormal lab tests do not necessarily mean patients will develop heart or liver problems, said co-author Dr. Lee Zane of the University of California-San Francisco.

Further studies would be needed to determine any long-term health effects, he said, but in the study, most patients' abnormal lab tests returned to normal when they quit taking the drug.

Thirty-one percent of healthy patients in the study developed high cholesterol levels and 11 percent developed abnormal liver tests.

The patients ranged in age from 13 to 50 and were treated from March 1995 to September 2002. They were members of Kaiser Permanente in Northern California. The study appeared in Monday's Archives of Dermatology.

source: http://www.mercurynews.com/mld/mercurynews/living/health/15331272.htm 22aug2006

Accutane Linked Heart, Liver Woes

CARLA K. JOHNSON / AP 22aug2006

CHICAGO — Accutane, the powerful acne drug already known to cause birth defects, seems to raise the risk for potential heart and liver problems more than doctors had expected, according to a new study.

The findings came from lab tests on 13,772 patients taking the popular acne drug and underscore the need to closely monitor people taking isotretinoin, which is sold as Accutane and in three generic versions. Abnormal results for cholesterol and liver function were more common than expected.

While those conditions can lead to problems over the long term, abnormal lab tests don't necessarily mean patients will develop heart or liver problems, said study co-author Dr. Lee Zane of the University of California, San Francisco.

"An elevation in cholesterol doesn't guarantee a heart attack. A high level of liver enzymes doesn't mean cirrhosis of the liver," Zane said.

Further studies would be needed to determine any long-term health effects, he said, but in the current study, most patients' abnormal lab tests returned to normal when they quit taking the drug.

Patients usually take it for less than a year at a cost of $10 to $15 per daily pill. It's considered one of the most effective treatments for the severest acne.

On March 1, the U.S. Food and Drug Administration began requiring patients and doctors to register their use of the drug, a program intended to stop birth defects.

Isotretinoin can cause brain and heart defects in infants if a woman takes it during or immediately before pregnancy. More than 71,000 patients have registered in the FDA's registry. Women who take it must have pregnancy tests and use birth control or abstain from sex.

Most dermatologists already knew the drug also could increase levels of cholesterol, liver enzymes and blood fats called triglycerides that can raise the risk of heart disease. But the new study found higher than expected percentages of patients developing these abnormal lab results.

Among patients with normal lab tests before they started taking the drug, 44 percent developed high levels of triglycerides. The package insert, by contrast, cites high triglycerides in 25 percent of patients.

Thirty-one percent of healthy patients in the study developed high cholesterol levels and 11 percent developed abnormal liver tests.

The patients ranged in age from 13 to 50 and were treated between March 1995 and September 2002. They were all members of the Kaiser Permanente health plan in northern California. The findings were published in Monday's Archives of Dermatology.

Some patients in the study had more lab tests than others during their treatment with the acne drug, but, for their analysis, the researchers used only the most abnormal test result for each different test each patient had.

The researchers also looked at lab tests for levels of white blood cells, hemoglobin and platelets. They found these were rarely abnormal.

The study won't change medical practice because dermatologists already carefully test patients taking Accutane, said Dr. John Strauss, professor emeritus at the University of Iowa College of Medicine. Strauss is a former consultant for Roche Laboratories Inc., the maker of Accutane, he said.

Roche representatives did not reply to an e-mail seeking comment on the study.

The drug is sometimes the only way to treat severely disfiguring acne, Strauss said. Some risk could be acceptable for patients whose acne is severe, he said.

"I've got patients who have said to me, 'You've saved my life with this drug,'" Strauss said.

source: http://seattlepi.nwsource.com/health/1500AP_Accutane_Study.html 22augf2006

Vol. 142 No. 8, August 2006

A Population-Based Analysis of Laboratory Abnormalities During Isotretinoin Therapy for Acne Vulgaris

Lee T. Zane, MD, MAS; Wendy A. Leyden, MPH; Ann L. Marqueling, BA; M. Michele Manos, PhD, MPH, DVM

Arch Dermatol. 2006;142:1016-1022.

Objective To determine the incidence of abnormal laboratory test results among isotretinoin users.

Design Retrospective cohort.

Setting Comprehensive managed care health plan in Northern California.

Participants The study population comprised 13 772 patients aged 13 to 50 years with acne, undergoing oral isotretinoin therapy between March 1995 and September 2002.

Main Outcome Measures Laboratory values for serum triglyceride, total cholesterol, and liver transaminase levels; white blood cell count, hemoglobin level, and platelet count; and frequency of abnormal laboratory results by severity grade as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0.

Results Substantial increases in the cumulative incidence of abnormalities were seen in serum lipid and transaminase levels, but not in hematologic parameters, during isotretinoin treatment compared with the baseline period. The cumulative incidence of new abnormalities in patients with normal values at baseline was 44% for triglyceride level, 31% for total cholesterol level, and 11% for transaminase level. Moderate to severe abnormalities in lipid and transaminase levels were generally transient and reversible. New abnormalities in hematological test results were uncommon.

Conclusions The incidence of abnormally high serum lipid levels during isotretinoin treatment may be greater than previously estimated. Elevations in transaminase level are generally mild. Normal baseline values of serum lipid and transaminase levels do not preclude the development of new abnormalities during isotretinoin treatment. Routine monitoring of white blood cell count, hemoglobin level, and platelet count during isotretinoin therapy may be of little utility without clinical suspicion of an abnormality. The clinical significance of laboratory abnormalities during isotretinoin therapy remains to be determined.

Author Affiliations: Departments of Dermatology (Dr Zane and Ms Marqueling) and Epidemiology/Biostatistics (Dr Manos), University of California, San Francisco; and Division of Research, Kaiser Permanente Northern California, Oakland (Ms Leyden and Dr Manos).

source: http://archderm.ama-assn.org/cgi/content/abstract/142/8/1016 22aug2006