FDA Updates Warning Labels for MS Products

Postmarketing case reports of injection site reactions, including abscesses and necrosis, have led the FDA to require the beta interferons that are used to treat multiple sclerosis to update the warnings and precaution section of their labels.

Case reports, including those in the medical literature and those submitted to the FDA’s Adverse Event Reporting System (FAERS), were discussed in two reviews by regulators, according to an FDA spokesperson. One review assessed the risk for abscesses with all of the beta interferon products approved for multiple sclerosis; the second review assessed injection site reactions and injection site abscesses with Avonex alone.

All of the labels for the interferon beta products with the exception of Avonex already had warnings and precautions subsections describing the risk of injection site reactions including necrosis. The FDA has approved additions to this section with language pertaining to abscesses for several products including: EMD Serono’s Rebif (interferon beta-1a), Bayer’s Betaseron (interferon beta-1b), Biogen’s Plegridy (peginterferon beta-1a), and Novartis’ Extavia (interferon beta-1b), the spokesperson said by email.

The labels for these therapies now reads (additions/revisions are underlined):

Injection site reactions, including injection site necrosis, can occur with the use of interferon beta products. Injection site necrosis (ISN) was reported in 4% of interferon beta-1b-treated patients in controlled clinical trials (compared to 0% on placebo) ….Injection site abscesses and cellulitis have been reported in the postmarketing setting with use of interferon beta products. Some cases required treatment with hospitalization for surgical drainage and intravenous antibiotics. Periodically evaluate patient understanding and use of aseptic self-injection techniques and procedures, particularly if injection site necrosis has occurred. Patients should be advised of the importance of rotating injection sites with each dose. Whether to discontinue therapy following a single site of necrosis is dependent on the extent of necrosis. For patients who continue therapy after injection site necrosis has occurred, avoid administration into the affected area until it is fully healed. If multiple lesions occur, change injection site, or discontinue therapy until healing occurs.

“We did a dedicated review of injections site reactions, including injection site abscesses, with Avonex, and concluded that a new warnings and precautions subsection in the Avonex PI describing a risk for injection site reactions, including injection site abscesses, was warranted," the spokesperson said.

Avonex (interferon beta-1a) is manufactured by Biogen. The label now includes an additional section on injection site reactions that reads:

Injection site reactions, including injection site necrosis, can occur with the use of interferon beta products, including Avonex. In controlled clinical trials, injection site reactions (e.g., injection site pain, bruising or erythema) occurred in 18% of patients receiving Avonex and 13% in the placebo group. These reactions included injection site inflammation (6%), injection site pain (8%), injection site mass (<1%), nonspecific reactions.

Injection site abscesses and cellulitis and injection site necrosis have been reported in the postmarketing setting with interferon beta products, including Avonex. Some cases required treatment with hospitalization for surgical drainage and intravenous antibiotics.Periodically evaluate patient understanding and use of aseptic self-injection techniques and procedures, particularly if injection site necrosis has occurred. Whether to discontinue therapy following a single site of necrosis is dependent on the extent of necrosis. For patients who continue therapy with Avonex after injection site necrosis has occurred, avoid administration of Avonex into the affected area until it is fully healed. If multiple lesions occur, change injection site or discontinue therapy until healing occurs.