Tofacitinib, baricitinib, and upadacitinib get new warnings for heart attack, stroke, and more

The FDA is requiring updated warning labels for three Janus kinase (JAK) inhibitors indicated for arthritis, ulcerative colitis, and other inflammatory conditions due to an increased risk for serious cardiovascular (CV) events.

The decision was based on an agency review of a large, randomized safety clinical trial, which found that patients treated with tofacitinib (Xeljanz and Xeljanz XR) for rheumatoid arthritis faced an increased risk for heart attack, stroke, cancer, blood clots, and CV mortality.

The updated warnings also apply to two other JAK inhibitors indicated for inflammatory conditions—baricitinib (Olumiant) and upadacitinib (Rinvoq). According to the FDA, neither of these drugs has been evaluated in a similarly large safety trial, and their risks have not been adequately evaluated—however, since they have the same mechanism of action as tofacitinib, the agency concluded that they may pose similar risks.

“We are requiring revisions to the Boxed Warning, FDA’s most prominent warning, for [tofacitinib, baricitinib, and upadacitinib] to include information about the risks of serious heart-related events, cancer, blood clots, and death,” the agency wrote in its statement. “Recommendations for health care professionals will include consideration of the benefits and risks for the individual patient prior to initiating or continuing therapy. In addition, to ensure the benefits of these three medicines outweigh the risks in patients who receive them, we are limiting all approved uses to certain patients who have not responded or cannot tolerate one or more TNF blockers. Changes will also be made to several sections of the prescribing information and to the patient Medication Guide.”

All three drugs already carry Boxed warnings due to increased risks of serious infection, thrombosis, and lymphoma and other malignancies among patients taking the drugs.

Two other JAK inhibitors, ruxolitinib (Jakafi) and fedratinib (Inrebic), are not indicated for arthritis or other inflammatory conditions and thus are not part of the required updates. These two drugs “are used to treat blood disorders and require different updates to their prescribing information,” the agency explained. “If FDA becomes aware of any additional safety information or data that warrants updates to the prescribing information for these medicines, we may take further action and will alert the public.”

For patients taking tofacitinib, baricitinib, or upadacitinib, the FDA recommended they speak to their physician if they are a current or past smoker or a history of heart attack or other health problems. The agency also urged patients to seek immediate emergency care should they develop any of the following symptoms:

  • “Discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back.
  • “Severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw.
  • “Unusual pain or discomfort in your arms, back, neck, jaw, or stomach.
  • “Shortness of breath with or without chest discomfort.
  • “Breaking out in a cold sweat.
  • “Nausea or vomiting.
  • “Feeling lightheaded.
  • “Weakness in one part or on one side of your body.
  • “Slurred speech.
  • “Drooping on one side of your mouth.
  • “Swelling of a leg or arm.
  • “Leg pain or tenderness, or red or discolored skin in the painful or swollen leg or arm.”

John McKenna, Associate Editor, BreakingMED™

Cat ID: 158

Topic ID: 90,158,408,183,730,192,725,158,68,925