The drugs - Enbrel, Remicade, Humira and Cimzia - work by suppressing the immune system to keep it from attacking the body. For patients with rheumatoid arthritis, the treatment provides relief from swollen and painful joints, but it is "a double-edged sword," the FDA's Jeffrey Siegel said. The drugs also lower the body's defenses to various kinds of infections.

Remicade is made by Horsham-based Centocor Inc., a unit of Johnson & Johnson, and Schering-Plough Inc., of Kenilworth, N.J.; Humira is made by Abbott Laboratories Inc., of North Chicago, Ill.; Cimzia by UCB S.A., of Belgium; and Enbrel by Amgen Inc., of Thousand Oaks, Calif., and Wyeth, of Madison, N.J.

Highlighting the drugs' risks in prescribing information and in communications with doctors will help medical professionals "be more vigilant in watching for these adverse events and better assess the various benefits and risks for their patients," J&J said in a statement.

Siegel, who heads the office that oversees arthritis drugs, said the FDA became concerned after discovering that doctors seemed to be overlooking a fungal infection called histoplasmosis. Of 240 cases reported to the FDA in which patients taking one of the four drugs developed this infection, 45 died - almost 20 percent.

Siegel said the FDA's order yesterday means that the risk of histoplasmosis will be flagged in a "black box," the strongest warning information in a drug's prescribing literature. The four medications already have black-box warnings about the risk of infections, but the language varies from drug to drug.

Patients should call their doctors if they develop persistent fever, cough, shortness of breath or fatigue, which can be signs of the fungal infection.

The FDA is urging doctors to consider aggressive use of antifungal drugs in patients who develop such symptoms, even if the infection has not been confirmed by a lab test. Siegel said such a decision should not be taken lightly, since antifungal drugs can have dangerous side effects.

The four drugs belong to a class known as TNF-alpha blockers and are considered a mainstay for treating rheumatoid arthritis. They also are used to treat Crohn's disease, juvenile arthritis, certain types of psoriasis, and other immune-system disorders.

Separately, the FDA is investigating a possible link between the four medications and cancer in young patients.

Three of the drugs - Enbrel, Humira and Remicade - are considered blockbusters, with annual sales of more than $1 billion each. Cimzia is newer and less widely used.