FDA moves to strengthen drug safety program

The FDA announced in early November that it was strengthening its safety program for marketed drugs.

Lester M. Crawford, DVM, PhD, acting FDA commissioner, says that he has authorized the Center for Drug Evaluation and Research (CDER) to take the following measures:

Sponsor an Institute of Medicine (IOM) study of the drug safety system. The study will emphasize the post-market phase, and assess what additional steps could be taken to learn more about the side effects of drugs as they are actually used. The IOM committee will examine the FDA’s role within the health care delivery system and recommend measures to enhance the confidence of Americans in the safety and effectiveness of their drugs.

Implement a program for adjudicating differences of professional opinion. CDER will formalize a program to provide an improved process to ensure that the opinions of scientific reviewers are incorporated into its decision-making process. CDER’s program provides for a review of the involved differing professional opinions by FDA and outside experts. An ad hoc panel, whose members were not directly involved in disputed decisions, will have 30 days to review all relevant materials and recommend to the center director an appropriate course of action.

Appoint a director for the Office of Drug Safety. CDER will conduct a national search to fill the currently vacant position of director of the Office of Drug Safety, which is responsible for overseeing the post-marketing safety program for all drugs.

Conduct drug safety/risk management consultations. In the coming year, CDER will conduct workshops and advisory committee meetings to discuss complex drug safety and risk management issues. These may include emerging concerns for products that are investigational or already marketed. These consultations will include experts from the FDA, other federal agencies, academia, the pharmaceutical industry, and the health care community.

Publish risk management guidances. By the end of this year, the FDA intends to publish final versions of three guidances that have been developed by the agency to help pharmaceutical firms manage risks involving drugs and biological products. These documents are "Premarketing Guidance," covering risk assessment of pharmaceuticals prior to their marketing; "RiskMAP Guidance," which deals with the development and use of risk-minimization action plans; and "Pharmacovigilance Guidance," which discusses post-marketing risk assessment, good pharmacovigilance practices, and pharmacoepidemiologic assessment. These guidances, which were first issued as draft guidances in May 2004, are designed to assist manufacturers in the management and minimization of risks of pharmaceutical products throughout their life cycle.

Pfizer to sponsor new celecoxib clinical trial

Pfizer has announced that it is sponsoring a major clinical study to further assess its COX-2 medication celecoxib (Celebrex) in osteoarthritis patients at high risk for cardiovascular disease. This announcement came several weeks after Merck & Co. voluntarily withdrew its COX-2 inhibitor rofecoxib (Vioxx) from the market due to safety concerns of an increased risk of cardiovascular events in patients taking the drug.

The clinical trial, which will be conducted at major universities and hospitals around the world, is expected to start early in 2005. Because of recent questions raised about the cardiovascular safety of the COX-2 specific inhibitors, Pfizer will be discussing the study design with the FDA and other regulatory agencies prior to finalizing its details and start date.

The study will enroll more than 4,000 patients around the world who have had a recent heart attack and who also have a history of osteoarthritis. The study will assess the effects of celecoxib on inflammation and cardiovascular events. The multicenter, randomized, placebo-controlled study will be conducted over a period of at least two years and will include monitoring of cardiovascular safety by an independent data safety monitoring committee.

New drug safety warnings issued

The FDA, Janssen Pharmaceutica Products, and Johnson & Johnson Pharmaceutical Research & Development have notified health care professionals of reports of medication errors involving confusion between galantamine hydrobromide (Reminyl), a drug approved for the treatment of mild-to-moderate dementia of the Alzheimer’s type, and glimepiride (Amaryl), a product of Aventis Pharmaceuticals, indicated for the treatment of noninsulin-dependent (Type 2) diabetes mellitus. These reports include instances in which galantamine was prescribed but glimepiride was incorrectly dispensed and administered instead, leading to various adverse events including severe hypoglycemia and one death. For more information, see: www.fda.gov/medwatch/SAFETY/2004/safety04.htm#Reminyl.

In addition, the FDA and Centocor have notified health care professionals of revisions to the warnings and adverse reactions sections of the prescribing information for infliximab (Remicade), indicated for the treatment of rheumatoid arthritis and Crohn’s disease. In controlled studies of all TNF a-blocking agents, including infliximab, more cases of lymphoma have been observed among patients receiving the agents than among control group patients. Malignancies also have been observed in open-label, uncontrolled clinical studies at a rate several-fold higher than expected in the general population. Patients with Crohn’s disease or rheumatoid arthritis, particularly patients with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several fold) than the general population for the development of lymphoma. The FDA has recommended a warning concerning malignancy be added to the labeling for all therapeutic agents that block TNF. For more information, see www.fda.gov/medwatch/SAFETY/2004/safety04.htm#Remicade.

Finally, the FDA and Abbott Pharmaceuticals have notified health care professionals of revisions to the warnings section of the prescribing information of adalimumab (Humira), which is indicated for the treatment of rheumatoid arthritis. These warnings include serious infections with the combined use of adalimumab and anakinra; hypersensitivity reactions, including anaphylaxis; and hematologic events, including pancytopenia and aplastic anemia. For more information, see www.fda.gov/medwatch/SAFETY/2004/safety04.htm#Humira.