The US Food and Drug Administration is invoking its new powers granted in 2007 to demand that the makers of four tumour necrosis factor blockers beef up warnings on the drugs' labels to cover the risk of opportunistic fungal infections.

The products in question are Johnson & Johnson/Schering-Plough's Remicade (infliximab), Abbott Laboratories' Humira (adalimumab), Amgen and Wyeth's Enbrel (etanercept) and UCB's Cimzia (certolizumab pegol). The FDA said that the prescribing information for the drugs already includes data about the risk of serious infections but "healthcare professionals are not consistently recognising cases of histoplasmosis and other invasive fungal infections, leading to delays in treatment".

The agency specified that it has reviewed 240 cases of histoplasmosis in patients being treated with Enbrel, Humira, or Remicade. The majority of the reports involved people in the Ohio River and Mississippi River valleys, where the fungus is commonly found, and in at least 21 of the reports, histoplasmosis was initially not recognised by doctors. Twelve of those patients died.

The FDA reviewed one reported case of histoplasmosis in a patient taking Cimzia and added that it has received reports of cases of coccidioidomycosis and blastomycosis, including deaths, in patients treated with TNF blockers. Now the drugmakers are required to submit safety labelling changes within 30 days or to provide a reason why they do not believe such changes are necessary.

If there is a dispute, the FDA Amendments Act of 2007 provides strict timelines for resolving the labelling changes. Bob Rappaport, director of the Division of Anesthesia, Analgesia and Rheumatology Products at the Center for Drug Evaluation and Research, said that under the FDA's new authorities, “we can require safety label changes and a risk evaluation and mitigation strategy…when the agency becomes aware of new safety information”. He added that “requiring the risks to be highlighted will help healthcare professionals be more vigilant in watching for these adverse events and is necessary to ensure that the benefits of these drugs outweigh their risks.”

In response, Amgen said that it "will work with the agency to finalise and communicate revised product labelling for Enbrel”. The FDA stance comes after the agency said in June that it was investigating a possible link between the use of TNF blockers and the development of lymphomas and other cancers in children and young adults.