News Briefs

Steroids taken with protease inhibitors linked to complications

A study by researchers at the National Institutes of Health (NIH) indicates that a steroid medication taken with an HIV protease inhibitor may increase the risk of bone damage in HIV-infected patients as well as increase the risk of Cushing’s syndrome.

Published in the Dec. 15 issue of the Journal of Acquired Immune Deficiency Syndrome, the study showed that ritonavir, a protease inhibitor used to treat HIV patients, taken with prednisone, significantly increased the concentrations of prednisolone in the systems of healthy volunteers.

Researchers gave 10 healthy volunteers a 14-day course of low-dose ritonavir. They also gave the volunteers three doses of prednisone. One dose of prednisone was given before ritonavir was started as a baseline. A second dose was given after four days on ritonavir and a third dose was given after 14 days on ritonavir. Blood samples were taken after each dose of prednisone to determine steroid levels.

Prednisolone concentrations were 41% higher than the baseline amount after the drugs were taken together four days into the ritonavir regimen and 30% higher after the drugs were taken together 14 days into the regimen.

The study team included researchers at the NIH Clinical Center and the National Institute of Allergy and Infectious Diseases. The team plans to continue studies of the blood levels of individuals on steroids and other HIV medications.

HHS agencies announce initiative to improve cancer therapy

The Food and Drug Administration (FDA), the National Cancer Institute (NCI), part of the National Institutes of Health, and the Centers for Medicare & Medicaid Services (CMS) today announced the Oncology Biomarker Qualification Initiative (OBQI) — an agreement to collaborate on improving the development of cancer therapies and the outcomes for cancer patients through biomarker development and evaluation. This initiative is the first time these three Department of Health and Human Services (HHS) agencies have focused together on biomarkers as a way of speeding the development and evaluation of cancer therapies.

The goal of OBQI is to validate particular biomarkers so that they can be used to evaluate new, promising technologies in a manner that will shorten clinical trials, reduce the time and resources spent during the drug development process, improve the linkage between drug approval and drug coverage, and increase the safety and appropriateness of drug choices for cancer patients.

Under the OBQI, biomarker research will be focused in four key areas: standardizing and evaluating imaging technologies to see in more detail how treatments are working, developing scientific bases for diagnostic assays to enable personalized treatments, instituting new trial designs to utilize biomarkers, and pooling data to ensure that key lessons are shared from one trial to another. By working with academic and industry scientists, as well as professional organizations, the OBQI teams can foster the development of key information on biomarkers through clinical trials.

The first OBQI project to be implemented will serve to validate and standardize the use of Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) scanning. PET scans are used to characterize biochemical changes in a cancer. Under the collaboration, researchers will use FDG-PET imaging technology in trials of patients being treated for non-Hodgkin’s lymphoma, to determine if FDG-PET is a predictor of tumor response. Data resulting from this type of evidence-based study will help both FDA and CMS work with drug developers based on a common understanding of the roles of these types of assessments.

Bayer, FDA warn of administration errors for nimodipine (Nimotop)

Bayer and the FDA have notified health care professionals of changes to the prescribing information for nimodipine (Nimotop), including a boxed warning to notify prescribers about medication administration errors. Nimodipine is approved for oral administration to improve neurological outcome after subarachnoid hemorrhage.

When administered intravenously or parenterally, it can cause serious adverse events, including death. Nimodipine must not be administered intravenously or by any parenteral route. For more information, see: www.fda.gov/medwatch/safety/2006/safety06.htm#Nimotop.

Hypoglycemia, hyperglycemia linked to gatifloxacin (Tequin) use

Bristol-Myers Squibb Co. has announced labeling changes for gatifloxacin (Tequin), an antibiotic indicated for the treatment of patients with pneumonia, bronchitis, uncomplicated gonorrhea, and various infections including infections of urinary tract, kidneys, and skin.

The labeling changes, announced by the gatifloxacin manufacturer in a letter to health care professionals, update the prescription information as a result of continued reports of serious cases of hypoglycemia (low blood sugar) and hyperglycemia (high blood sugar) in patients receiving gatifloxacin. Since the approval of gatifloxacin in 1999, there have been rare cases of life-threatening events reported globally in patients treated with the drug. Most of these events were reversible when properly managed, but a few had fatal outcomes.

Information about the risks of low blood sugar and high blood sugar was added to the Warnings section of the U.S. labeling in 2002. The new changes strengthen the existing warning on hypoglycemia and hyperglycemia, add a contraindication for use in diabetic patients, and include information identifying other risk factors for developing low blood sugar and high blood sugar, including advanced age, renal insufficiency, and concomitant glucose-altering medications while taking gatifloxacin.

Bosentan label revised to include liver function monitoring

Actelion and the FDA have notified health care professionals of changes to the bosentan (Tracleer) prescribing information based on cases of hepatotoxity reported. Bosentan is indicated for the treatment of pulmonary arterial hypertension. The notification underscored the need to continue monthly liver function monitoring for the duration of bosentan treatment and the need to adhere to the recommended dosage adjustment and monitoring guidelines described in the product labeling.

For more information, see: www.fda.gov/medwatch/safety/2006/safety06.htm#Tracleer.

Study of natalizumab-treated patients shows no new PML cases

An independent clinical and laboratory study of more than 3,000 people treated with the drug natalizumab (Tysabri) for multiple sclerosis (MS), Crohn’s disease, and rheumatoid arthritis has found no evidence of new cases of progressive multifocal leukoencephalopathy (PML). The laboratory component of the study was coordinated by the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH), working in conjunction with the NIH Clinical Center. Clinical and neuroradiological experts from other institutions also participated. Results of the study were published in the March 2 issue of the New England Journal of Medicine.

Natalizumab, an immune system-modifying drug, was approved by the FDA in November 2004 to treat relapsing-remitting MS. Studies have shown that it can substantially reduce the frequency of relapses in that disease. However, the drug was withdrawn from the market and from clinical trials in February 2005 after the manufacturer identified two cases of PML in MS patients who had received the drug. A person with Crohn’s disease who had received natalizumab also was diagnosed with PML. The current study was conducted to determine whether other people treated with natalizumab were at risk of PML. Symptoms of PML include mental deterioration, problems with vision, speech, balance, and movement and, in most cases, coma, and death.

Although the study did not find any evidence for new cases of PML, the researchers cannot say for certain that the patients who received natalizumab will not develop the disease in the future. The risk associated with longer-term treatment with natalizumab also is unknown.

The study also did not formally include patients who were treated with natalizumab outside of clinical trials. However, since PML is a very severe disease, it is likely that any PML in other patients who received natalizumab would have been diagnosed, the researchers say.